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Laparoscopic Approach in Management of Renal Cell Carcinoma During Pregnancy: State of the Art
Review
Laparoscopic Approach in Management of Renal Cell Carcinoma During Pregnancy: State of the Art Lucio Dell’Atti,1 Chiara Borghi,2 Andrea Benedetto Galosi1 Abstract Renal cell carcinoma (RCC) is extremely rare in pregnant women. However, this is one of the most reported urologic tumors during pregnancy. The aim of this review was to evaluate RCC during pregnancy in terms of epidemiology, risk factors, diagnosis, natural history of disease, and the safety of laparoscopic approach in the management of this tumor. RCC presentation is frequently made incidentally during an ultrasonography performed for other reasons, such as hydronephrosis owing to non-neoplastic causes. The optimal time for surgery during pregnancy and the consequences of surgery on the maternal and fetal well-being are major considerations. Risks for adverse pregnancy outcomes should be explained, and the patient’s decision about pregnancy termination should be considered. Ultrasound is good in diagnosing renal masses, with a sensitivity comparable to that of computed tomography only for exophytic masses larger than 3 cm. Magnetic resonance imaging is reproducible and a good, though expensive, alternative to computed tomography scans for the evaluation of renal lesions in pregnant women. Radical nephrectomy or nephron-sparing surgery are essential treatments for management of RCC. Laparoscopic surgery has historically been considered dangerous during pregnancy and avoided whenever possible, because of concerns regarding surgery-related risks, such as uterine injury, miscarriage, teratogenesis, preterm birth, and hypercapnia. The laparoscopic treatment during pregnancy is becoming increasingly accepted where feasible with low morbidity. However, the combination of a multidisciplinary approach, multi-specialty communication, and skilled surgeons can give the best possible outcomes for mother and fetus. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2019 Elsevier Inc. All rights reserved. Keywords: Diagnosis, Laparoscopy, Renal cancer, Surgery, Treatment
Introduction Even experienced laparoscopic surgeons may not decide on the management of cancer during pregnancy, which represents a medical dilemma.1 Renal cell carcinoma (RCC) diagnosis is extremely rare during gestation.2 However, this is one of the most reported urologic tumors in pregnant women.3 This pathologic condition is emotionally devastating for young patients and their family, overshadowing the joyfulness of pregnancy.4 1 Department of Urology, University Hospital “Ospedali Riuniti” and Polythecnic University of Marche Region, Ancona, Italy 2 Unit of Obstetrics and Gynecology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara and S. Anna Hospital of Ferrara, Ferrara, Italy
Submitted: Apr 6, 2019; Revised: May 19, 2019; Accepted: May 20, 2019 Address for correspondence: Lucio Dell’Atti, MD, PhD, Department of Urology, Marche Polytechnic University, University Hospital “Ospedali Riuniti”, 71 Conca St, 60126 Torrette, Ancona, Italy E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.clgc.2019.05.025
If renal cancer is diagnosed during the first trimester, concerns about surgery and further adjuvant therapies during pregnancy should be discussed.2,3 Risks for adverse pregnancy outcomes should be explained, and the patient’s decision about pregnancy termination should be considered.3,4 On the other hand, if the renal mass is diagnosed during the second or the third trimester, surgery could be safely performed without compromising fetal outcome but still, if possible, it is preferred to postpone it until postpartum.5 The aim of this review was to evaluate RCC during pregnancy in terms of epidemiology, risk factors, diagnosis, natural history of disease, and the safety of a laparoscopic approach in the management of this tumor. A MEDLINE search of the peer reviewed literature on diagnosis and case reports of RCC during pregnancy, published in English, was done through March 1, 2019 using the words: “renal cancer,” “pregnancy,” “gestation,” “diagnosis,” “treatment,” “laparoscopy,” and “management.” Given the rarity of this cancer, articles were not limited by design or number of reported patients. A total of 109
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Laparoscopy and Renal Carcinoma During Pregnancy documented cases of all renal malignancies during pregnancy, including 91 reported cases of RCCs, were evaluated for this review (Figure 1).
Epidemiology RCC represents the 10th most frequently diagnosed cancer in women, accounting for 3% of all oncologic diagnoses.6 Although most detected lesions are small tumors, locally advanced disease continues to be diagnosed in a notable proportion of patients, with up to 17% of patients harboring distant metastases at the time of diagnosis.7 RCC incidence rates vary substantially worldwide.8 Rates are generally higher in Europe and North America than in Asia and South America. Within a continent, rates also differ by country.9 Rates among females are generally about one-half of those among males and also vary geographically. In the United States, RCC incidence rates differ among racial/ethnic populations. Rates are lower among Asian/Pacific Islanders (4.7 per 100,000), mirroring rates of their countries of origin. However, incidence rates for white Hispanics (9.7 per 100,000) are much higher than rates reported in Latin America (6.7 per 100,000), suggesting the potential role of environmental exposures.10 The estimated incidence of cancer diagnosed in pregnant women in developed societies is 1 per 1000 pregnancies.11 The most common tumors diagnosed during pregnancy are breast cancer, melanoma, cervical cancer, and lymphomas. Lung, ovarian, gastrointestinal, urologic, and other malignancies are rarely observed.9-11 Although RCC accounts for 3% of all adult malignancies, and the mean age at diagnosis is 56 years, it is rare in gestation, despite the current tendency of women to bear children at more advanced ages.9,10 A meta-analysis of 14 studies, published in 2013, concluded that parity was associated
with an increased risk of RCC. As an example, women with a history of at least 1 pregnancy showed an increased risk up to 40% to 90% if compared with nulliparous women. Risk was higher with higher number of pregnancies.3 Moreover, RCC rates seem to be increased during pregnancy, because of the incidental detection of renal masses, owing to more frequent abdominal ultrasound imaging.3 As a matter of fact, urinary tract ultrasound is often performed at any gestational age, mainly because of ureter mechanical compression between the gravid uterus and iliopsoas muscle or ascending urinary tract infections.4
Etiology Obesity, smoking, analgesics, environmental factors, hypertension, diabetes, chronic kidney diseases, and reproductive and hormonal factors are established risk factors for RCC.12,13 Translational studies demonstrated that RCC could be induced by prolonged intake of fat.12 This is confirmed by pathologic changes observed through histologic sectioning. Macleod et al observed, on a prospective cohort of 77,260 residents of Washington, that obesity was significantly associated with RCC (body mass index 35 kg/m2 vs. < 25 kg/m2: hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.06-2.79).14 The relative risk estimates that every 5 kg of body weight gained increases the risk of RCC by 35% in women.14 The biological reasons behind this association are unclear, although recent evidence shows that the effects of circulating hormones such as estrogens, insulin-like growth factors, and adipokines might play a role. Adipose tissue in obese women is a source of estrogens that may play a role in the pathogenesis of RCC.15 Physical activity may reduce RCC risk by decreasing obesity, insulin resistance, blood pressure, and lipid peroxidation.16 A recent meta-analysis reported
Figure 1 Treatment of Patients Who Were Diagnosed With Renal Cell Carcinoma During Pregnancy
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Abbreviations: Lap ¼ Laparoscopic; N/A ¼ not available; NSS ¼ nephron sparing surgery; RN ¼ radical nephrectomy.
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Lucio Dell’Atti et al an inverse association between physical activity and RCC risk (relative risk [RR], 0.88; 95% CI, 0.79-0.97).17 Smoking has been associated with a number of common cancers, including RCC.18 Tobacco smoke includes a mix of carcinogens involved in the etiology of RCC. In the VITamin And Lifestyle (VITAL) study, smoking was independently linked with renal cancers (> 37.5 pack-years vs. never: HR, 1.58; 95% CI, 1.092.29).14 Similarly, in the PLCO trial, the number of cigarettes per day was confirmed to be significantly associated with a higher risk of developing RCC and with a higher risk of high-grade RCC.19 Epidemiological data suggest that analgesic use increases the risk of RCC. Cho et al demonstrated the relationship between analgesics and nonsteroidal anti-inflammatory drug consumption and an increased risk of RCC (pooled multivariate RR, 1.51; 95% CI, 1.12-2.04).20 A meta-analysis by Choueiri et al observed that the use of acetaminophen and nonsteroidal anti-inflammatory drugs was associated with an increased risk of RCC (pooled RR, 1.28; 95% CI, 1.15-1.44 and pooled RR, 1.25; 95% CI, 1.06-1.46, respectively).21 In terms of occupational exposure, more robust studies are needed to confirm the relation between industrial agents and risk of RCC.22 However, despite the limited evidence, exposure to x-radiation and industrial agents, such as inorganic arsenic agents, perfluorooctanoic acid, cadmium, nitrate, and radon in drinking water, may be considered as potential RCC risk factors.23,24 Hypertension is another independent risk factor for RCC. About 18% of cases diagnosed with RCC during pregnancy presented with hypertension. A number of prospective studies investigated the association between blood pressure and the risk of RCC.25 In the VITAL study, hypertension was independently associated with RCC risk (HR, 1.70; 95% CI, 1.30-2.22).14 A recent meta-analysis of 18 prospective studies further encourages an association between hypertension and RCC risk.26 A history of hypertension was associated with a 67% increased risk of RCC, and each 10-mm Hg increase in blood pressure was associated with a 10% to 22% increased risk of RCC. The biological reasons behind this relationship remain unclear, but some authors have hypothesized the involvement of chronic renal hypoxia and lipid peroxidation with formation of reactive oxygen species.27 Moreover, women with hypertensive disorders may also be more likely to get a renal imaging and therefore identify incidental renal cancers.28 Diabetes is associated with an increased risk of several types of tumors.29 However, its relationship with RCC remains unclear. In the VITAL study, there was no observed relationship between type 2 diabetes and RCC after accounting for multiple factors.14 This association was consistent across different strata of body mass indexes, smoking habit, and blood pressure values.30 Moreover, RCC risk increased with an increasing number of comorbidities, including obesity, hypertension, and type 2 diabetes. Specifically, women who had all 3 of these conditions had 4-fold higher probability of RCC development compared with women without comorbidities.31 RCC of native end-stage kidney disease or acquired cystic kidney disease are found in about 4% of patients.32 In the VITAL study, the presence of a kidney disease (HR, 2.58; 95% CI, 1.21-5.50) was independently related to RCC.14
A possible correlation between hormonal factors and RCC development exists, although the underlying mechanism is not fully understood. An increased risk of RCC has been associated with parity among women in several cohort studies.22,33 Associations with other reproductive factors, including the use of oral contraceptives and hormone replacement therapy, are not consistently seen.10
Clinical Presentation The presentation of RCC in pregnant women is frequently made incidentally during an ultrasonography performed for other reasons, such as hydronephrosis owing to non-neoplastic causes (calculi or mechanical compression of the ureter), or ascending urinary tract infection.34,35 The main reported presenting symptoms are: pain (50%), hematuria (47%), hypertension (18%), and the classical triad of hematuria, pain, and palpable mass (26%).36 Hematuria in pregnancy is usually owing to non-neoplastic causes such as infection, calculi, bladder varicosities, and glomerulonephritis. The classical triad of pain, palpable mass, and hematuria may present a diagnostic dilemma because hypertension is often seen in pregnancy and may mimic preeclampsia, causing a delay in diagnosis.37 Fever (21%), weight loss (9%), and oligemic shock from hemorrhage into the tumor (3%) also can occur. Other less frequent presentations are hemolytic anemia, hypercalcemia, or rupture of tumoral cyst.36,37 Five cases were reported with metastatic disease during pregnancy, and the remaining were diagnosed with less advanced disease, usually during the second and third trimesters of pregnancy.36,38 Few cases were reported during the first trimester.36,39
Diagnosis and Imaging In general, the use of diagnostic imaging during pregnancy is limited, because ionizing radiation used for standard radiology and computed tomography are potentially related to biological effects causing congenital malformations, central nervous system injury, mental retardation, intrauterine growth restriction, or stillbirth.40 The safest diagnostic imaging studies during all stages of gestation are ultrasound and magnetic resonance imaging (MRI), with no teratogenic effects.40,41 RCC is frequently diagnosed as an incidental finding during a routine ultrasound examination for antepartum care.36 Ultrasound is good in diagnosing renal masses, with a sensitivity comparable to that of computed tomography (CT) only for exophytic masses larger than 3 cm.42 Ultrasonography, CT, and MRI have variable sensitivity in detecting and staging RCC. Ultrasonography is less sensitive in detecting small renal lesions, especially those that do not deform the contour of the kidney.43 The sensitivity of CT and ultrasonography for detection of lesions 3 cm and less is 94% and 79%, respectively. CT and MRI have nearly 100% accuracy in the diagnosis of RCC.42,43 CT scan is the imaging modality of choice for the diagnosis of renal tumors.43 A CT scan not including the gravid uterus in the field-of-view results in negligible fetal doses and may be performed in pregnancy without risks to the fetus. A standard single CT scan through the gravid uterus results in a fetal dose of 25 mGy or less. A CT of the abdomen/pelvis exposes the uterus to 18 to 25 mGy and should be avoided, unless a medical emergency warrants it.41 Exposure to high doses of radiation (greater than 50-100 mGy)
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Laparoscopy and Renal Carcinoma During Pregnancy during the first 2 weeks after conception is thought to be an all or none phenomenon, resulting in either fetal death or no effect. Because most organogenesis takes place between weeks 2 and 8 after conception, fetal anomalies would be potentially affected by very high doses of radiation (greater than 200 mGy) during this time frame. Severe intellectual disability may occur at lower doses (greater than 60 mGy) early in pregnancy (8-15 weeks of gestation), and microcephaly may occur with doses greater than 200 mGy during this timeframe. A 10- to 20-mGy exposure may also increase the lifetime risk of leukemia 2-fold (background risk of 1:3000). Fetal gonad and thyroid injury are other areas of theoretical concern, with certain types and doses of radiation exposure generally unrelated to preoperative surgical diagnostic tests.44,45 MRI is reproducible and a good, although expensive, alternative to CT scan for the evaluation of renal lesions in pregnant women. It accurately evaluates the local tumor size and location, the involvement of the adjacent structures, and the possible development of cancer thrombus in the renal vein and inferior vena cava.46 Gadolinium, the contrast agent utilized during MRI examination, crosses the placenta barrier, but no adverse effect on the fetus has been recorded. However, it may induce fetal hypothyroidism.47 Whole body MRI is an emerging method for malignant cancer staging; its sensitivity is comparable to skeletal scintigraphy for assessment of skeletal metastasis.48 However, its sensitivity in detecting pulmonary lesions in comparison with chest CT remains unknown.49 The European Society of Radiology guideline has approved its use in all stages of pregnancy.40 The differential diagnosis of renal masses includes inflammatory, cystic, benign, and malignant lesions other than renal cell carcinoma.50
Prognosis
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Active surveillance (AS) presents a unique opportunity to observe the natural history of RCC, as most tumors are treated with a surgical approach soon after diagnosis.51 Many authors showed that small renal tumors grew slowly and seldom metastasized.51-53 Most renal neoplasms are slow-growing, with an average volume doubling time of more than 500 days.53 A meta-analysis of 234 renal tumors showed a mean growth rate of 0.28 cm/y; the tumors pathologically confirmed as RCC had a higher growth rate, up to 0.4 cm/y.54 However, RCC may have relatively aggressive growth potential compared with other benign renal tumors. Contemporary selection for AS remains a process of shared decision-making, considering patient age, pregnancy status, renal function, tumor size and complexity, and interventional risk, along with judicious renal mass biopsy use.55 To fully understand the growth kinetics of RCC, few studies have demonstrated the correlation between the immunohistochemical biomarkers and the growth rate of RCCs.56 For renal masses, AS with delayed treatment until progression is now gradually accepted especially for patients during pregnancy.57 The growth rate of renal tumors under AS is various and not wellpredicted by clinical and radiographic factors.49 On the other hand, immunohistochemistry can define the nature of tumor growth through assessment of the expression of biomarkers that reflect cell proliferation, apoptosis, and angiogenesis.58 In the case of RCC during pregnancy, timely diagnosis and management is crucial in predicting maternal-fetal prognosis. However, the timing of surgery for renal tumors during pregnancy
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is controversial.59 The surgical resection from open to laparoscopic technique remains the mainstay of treatment.60 Recommendations regarding surgery are determined by time of diagnosis, size and stage of tumor, risk of malignancy, general health of the mother, and probability of survival of the fetus.61 Therefore, it may be rational to await fetal delivery prior to treatment if the neoplasm is discovered during late stages of pregnancy.60,61 If there are suspicions of malignant renal mass in the first trimester, surgery is often not delayed despite the small increased risk of miscarriage.62 However, surgical treatment during the second trimester will need to balance the maternal and fetal risks related to invasive procedures with the risks of delaying surgery.63 Surgery-related mechanisms causing increased morbidity during abdominal surgery include direct uterine trauma, decreased uteroplacental blood flow, teratogenic effect of anesthetic agents, adverse effects of anesthesia on maternal hemodynamics and acidbase balance, enhancement of impaired ventilatory mechanics, increased thromboembolic risk, and adverse effects of postoperative medications.64 Concerns about teratogenic effects and an increased risk of abortion have been discussed widely in the literature, and an indication to postpone laparoscopic or laparotomic surgery at the second trimester if possible has been proposed.65 Actually, evidence shows that the rates of early pregnancy loss are not significantly increased by surgery itself during the first trimester of pregnancy.66 Surgical procedures performed during the second or the third trimester could predispose to uterine contractions, stillbirth, or early preterm labor.67 Nevertheless, no clear benefit from routine preoperative tocolysis has been demonstrated.66,67 If a renal tumor is discovered close to the expected date of labor, then the surgery may be postponed until that date. Resection of a tumor discovered in the third trimester is usually recommended together with a caesarean section.64 If surgery during pregnancy is essential and cannot be postponed, careful perioperative precautions are required owing to the physiological changes of cardiovascular, respiratory, and gastrointestinal systems of pregnant patients, and a multidisciplinary team including anesthesiologists, surgeons, and obstetricians should be involved in the management.65-67 In pregnancy, the kidney biopsy is not mandatory for diagnosis, as radiologic studies usually provide sufficient results for diagnosis prior to treatment.40 The timing of the biopsy can range from early pregnancy to 40 gestational weeks.50 Core biopsy is prescribed in selected cases, mainly in patients with small masses who are candidates for an AS, local ablative therapies (ie, cryosurgery or radiofrequency ablation), patients with a solitary kidney, and patients with metastatic disease before initiating targeted treatments.49,50
Laparoscopic Management in RCC Approximately 1 in 500 women will require non-obstetrical abdominal surgery during pregnancy.66,67 The most common non-obstetrical surgical emergencies complicating pregnancy are acute appendicitis and cholecystitis.44 Other diseases that may require surgical treatments during pregnancy comprise ovarian masses or torsion, symptomatic cholelithiasis, adrenal tumors, renal masses, splenic disorders, symptomatic hernias, complications of inflammatory bowel diseases, and other rare conditions.44,48
Lucio Dell’Atti et al Once the decision for a surgical treatment has been made, the modality (laparotomy vs. laparoscopy) should be offered based on the skills of the surgeon and the availability of the appropriate equipment.59,61 Benefits of laparoscopy during pregnancy appear similar to those benefits in non-pregnant patients including less postoperative ileus, less postoperative pain, decreased length of hospital stays, and faster return to work.5,36 Radical nephrectomy (RN) or nephron-sparing surgery (NSS) are essential treatments for management of RCC. Even in metastatic disease, RN is done before a systemic therapy.68 NSS is recommended in patients with T1 stage tumors.69 The laparoscopic treatment during pregnancy is becoming increasingly accepted where feasible.70 O’Connor and colleagues were the first authors to report successful laparoscopic RN during pregnancy.71 Since then, many other cases have been described. In patients with renal masses not treatable by NSS, Ljungberg et al, on behalf of the European Association of Urology, recommended laparoscopic RN as the new standard.72 Thus, the relatively little amount of data published on pregnant patients and renal tumors gets to even fewer cases in which NSS treatment has been applied. Binbay et al36 reported the case of laparoscopic partial nephrectomy observed during pregnancy for a right-sided renal tumor. Early unclamping technique was preferred. Renorraphy was completed with a barbed suture, application of Floseal, and completed with a glyconate suture. They also placed a double J catheter. The pregnancy, delivery, and oncologic follow-up was declared as uneventful and with no tumor recurrence or metastasis at 22 months after surgery. More recently (in 2018), Petrut et al73 reported a trans-peritoneal laparoscopic partial nephrectomy, using 3 trocars, performed during the 16th week of pregnancy. The patient was discharged on the 4th postoperative day. During the 36 months of follow-up, the CT and ultrasonography scan did not reveal any tumor recurrence. Laparoscopic RN can be performed via the transperitoneal or retroperitoneal approach, each providing specific advantages and disadvantages.69 The choice of the laparoscopic approach depends on the surgeon and his laparoscopic experience. Selected tumors may be approached by either route or the other, according to the surgeons’ preference, the location, and technical complexity of the renal mass. The transperitoneal approach was usually utilized for anterior or lateral masses. The retroperitoneoscopic approach was usually utilized for posterior, posteromedial, or posterolateral renal tumors.69,74 Factors in favor of the transperitoneal route are the lager working space, allowing for wider angulation and maneuverability with laparoscopic instruments, and the more accustomed orientation by anatomic landmarks. However, it requires bowel mobilization to expose the kidney.74 The retroperitoneoscopic approach, by avoiding bowel mobilization, seems to provide a more direct access to the kidney and the renal vessels. Drawbacks of the technique are the spatial limitations of the narrow retroperitoneal working space and the lack of view.75,76 However, Akin et al70 performed RN using the retroperitoneal laparoscopic approach for a renal mass with 10-cm diameter. The operation time was 46 minutes, and the estimated blood loss was 20 cc. They used only 3 trocars during the laparoscopic
retroperitoneal procedure. The patient was discharged on postoperative day 3. There is evidence observed in the literature that shows the successful implementation of robotic-assisted laparoscopic partial nephrectomy.76 Park et al have even described one case of robot-assisted partial nephrectomy in 2008 done during pregnancy and without complications reported during or after the treatment.77 This supports the notion that the laparoscopic NSS technique is a safe and feasible option during pregnancy (Table 1).
Discussion Laparoscopic surgery has historically been considered dangerous during pregnancy and avoided whenever possible because of concerns regarding surgery-related risks, such as uterine injury, miscarriage, teratogenesis, preterm birth, and hypercapnia.70,71 These concerns have proven to be false as surgical skills have increased, more experience has been gained, and the envelope has continued to be pushed with ever more elegant instrumentation.74,76 Currently, laparoscopic urologic surgical modalities are performed with increasing numbers even during pregnancy, and developing minimally invasive surgery has enabled us to improve results.77 There is a growing body of evidence that this formidable tool can be performed safely during pregnancy for gynecologic, gastrointestinal, and urologic indications.76-78 The landmark survey by Reedy et al, including 413 laparoscopic procedures performed during pregnancy for general surgical and gynecologic indications, appeared to result in no higher fetal or maternal complications rates in comparison to laparotomy.78,79 Traditionally, the recommendations for non-emergent surgical treatments during pregnancy have been to avoid surgery during the first and third trimester to minimize the risks of spontaneous abortion and preterm labor, respectively.80 This has led some authors to suggest delaying surgery until the second trimester and that the gestational age limit for successful completion of laparoscopic surgery during pregnancy should be 26 to 28 weeks. When the pregnant patient is placed in a supine position, the gravid uterus places pressure on the inferior vena cava, resulting in decreased venous return to the heart.80,81 This decrease in venous return leads to reduction in cardiac output with concomitant maternal hypotension and decreased placental perfusion during surgery. For the right kidney masses, placing the patient in a left lateral decubitus position will shift the uterus off the vena cava, improving venous return and cardiac output.80-82 Clearly, safe laparoscopic access is paramount, and we feel that the open (Hasson) technique is appropriate. If the uterus is < 18 weeks, the initial trocar placement is in the umbilicus, not subumbilical (Figure 2). CO2 pneumoperitoneum is obtained with open placement of the laparoscopic trocar that ranges from a 10-mm to 3-mm diagnostic laparoscope.67 As our technology has advanced, in the past few years, we almost exclusively have been using only the 5-mm laparoscope, even if we place a 10-mm Hasson trocar in the navel. This gives one the flexibility to move the laparoscope to virtually any other port if the pathology warrants superior visualization from another trocar site (one
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1 31 8th w T1b 25th w iNS SD 1 34 14th w T1b 16th w iNS SD
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Abbreviations: CS ¼ Cesarean section; i ¼ intraperitoneal; N/A ¼ not available; NS ¼ nephron sparing; r ¼ retroperitoneal; RN ¼ radical nephrectomy; SD ¼ spontaneous delivery; trim ¼ trimester; w ¼ week.
1 41 16th w T2b N/A eRN N/A 1 36 16th w T3a N/A iRN CS 1 32 16th w T1b 20th w iRN SD 1 32 21st w T1a 22th w eRN N/A 1 28 21st w T3b 33rd w iRN CS 1 36 14th w T1a 14th w iNS N/A 1 39 12th w T2b 19th w iRN SD 1 52 20th w T1b 25th w eRN CS 1 30 8th w T1b 16th w eRN SD 1 30 11th w T1b 13th w iRN SD 1 34 11th w T1a 19th w iRN SD Patients Age, y Age of gestation at diagnosis Pathologic stage Age of gestation at treatment Treatment Pregnancy outcomes
Domjàn et al5 Yin et al1 Bettez et al63 Park et al77 Lee et al59 Stroup et al60 Sainsbury Van Basten et al62 et al4 O’Connor et al71 Study
Table 1 Outcomes in Patients Affected by Renal Cell Carcinoma During Pregnancy and Treated With a Laparoscopic Approach
Lisowska et al37
Akin et al70
Binbay et al36
Petrut et al73
Laparoscopy and Renal Carcinoma During Pregnancy could use the 10-mm laparoscope at the Hasson port and then change to the 5-mm laparoscope for the smaller trocar sites). In pregnancies associated with a uterine size 18 weeks, the initial trocar is placed above the navel with the lateral ports being placed under direct visualization. Some authors suggested ultrasound-guided first trocar insertion to avoid enlarged uterus damage.67,80,81 Minimizing CO2 insufflation to maximize both cardiac output and maternal hepatic flow, and to minimize fetal acidosis is best accomplished by keeping intraperitoneal pressures < 12 mm Hg.82,83 Surgery during pregnancy requires an adequate anesthesia for both mother and child. Safety of the fetus implies avoidance of potentially harmful drugs at critical times of fetal development, maintenance of stable maternal hemodynamic parameters to provide adequate uteroplacental circulation, and avoidance of preterm labor.84 All general anesthetic drugs cross the placenta, and there is no optimal general anesthetic technique. Any drug given during pregnancy could potentially negatively affect the development of the fetus depending on the dosage, the route, and the time of administration.83,84 The opening of the peritoneal cavity in the intraperitoneal approach may theoretically be associated with less uterine irritation and, in turn, fewer obstetric complications, including preterm labor.78,80 However, these benefits must be weighed against the risks of laparoscopic surgery. Such risks include injury to the pregnant uterus and the technical difficulties owing to the increasing size of the gravid uterus. In addition, CO2 pneumoperitoneum causes a decrease in cardiac index, an increase in mean arterial pressure, and an increase in systemic vascular resistance. The increased intraabdominal pressure decreases venous return and cardiac output, which may lead to decreased uterine blood flow, increased intrauterine pressure, and possibly decreased fetal perfusion. Significantly, the decreased venous return seen during laparoscopic surgery owing to increased intra-abdominal pressure is volume-dependent, and in adequately resuscitated pregnant women, increased intraabdominal pressure should not lead to decreased CO2 and fetal blood flow. The low pressure of 8 mm Hg to 12 mm Hg should be used, if possible, to minimize any adverse effect on fetal perfusion. This pressure was elicited by Hunter et al when they studied pregnant ewes.83 It may lead to maternal hypercapnia, tachycardia, and hypertension, but it was only a transient effect. Though Hunter felt that CO2 was the detrimental agent in pregnant ewes, no abnormal organogenesis has been observed in laparoscopic appendectomies performed in humans in the first trimester with CO2 as the insufflation agent.78,83 A risk of hypercapnia certainly does exist with a CO2 pneumoperitoneum. Case series recommend monitoring the end-tidal CO2, with a goal of < 35 mm Hg. It is also recommended to hyperventilate the mother to keep end-tidal CO2 concentration in expired air less than 35 mm Hg.83,84 If the procedure is related to a high risk of maternal hypotension or hypoxia and the continuous fetal heart rate monitoring during surgery is technically feasible, this monitoring is generally warranted in potentially viable pregnancies. Continuous fetal monitoring is not usually necessary during abdominal surgery. If intraoperative signs of fetal distress owing to hypoxia are detected, non-surgical
Lucio Dell’Atti et al Figure 2 Laparoscopic Ports Position in Pregnancy: If the Uterus is < 18 Weeks, the Initial Trocar (Red Star) Placement is the Umbilicus. In Pregnancies Associated With a Uterine Size ‡ 18 Weeks, the Initial Trocar is Placed Above the Navel With the Lateral Ports (Blue Stars) Being Placed Under Direct Visualization
manipulation, change of patient’s position, and conservative techniques for intrauterine fetal resuscitation should be performed. Maternal oxygenation or hemodynamic support systems can be helpful in such cases and avoids indication for immediate delivery.44,83
Some authors have compared laparoscopic procedures with open procedures in the pregnant patient, comparing various outcomes, such as hospital length of stay, use of tocolytics, need for postoperative analgesia, and the time of return to a regular diet and mobilization. Curet et al85 compared 16 pregnant patients
Figure 3 Management of Small Renal Masses (cT1a) During Pregnancy
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Laparoscopy and Renal Carcinoma During Pregnancy undergoing laparoscopic procedures with 18 pregnant patients undergoing open procedures (both groups were comparable in age, trimester, intraoperative oxygenation, and end-tidal CO2) and found that gestational age at delivery, birth weight, and Apgar scores were not statistically different in the 2 groups. In addition, the laparoscopic group had a shorter hospital stay, fewer days of postoperative narcotic use, and resumed a regular diet sooner postoperatively than the open surgery group did. These differences were statistically significant. Surgical outcomes of laparoscopic procedures in pregnant patients are similar to outcomes in non-pregnant ones.44,82,85
Conclusions Laparoscopic surgery associated with pregnancy is feasible with low morbidity. Although the operative times are longer, pregnant women undergoing operative laparoscopy with the appropriately skilled laparoscopist benefit from the minimally invasive procedures with brief hospital stays, rapid postoperative recoveries, and earlier return to normal gastrointestinal function and ambulation compared with pregnant women undergoing laparotomy. We feel that less manipulation of the uterus and a decrease in delay of the diagnosis can decrease maternal and fetal/ infant mortality with subsequent successful pregnancy outcomes with fewer complications. It must be emphasized that the laparoscopic procedures should not be undertaken without a surgeon having the proper skills, constantly in communication with am anesthesiologist monitoring CO2 and arterial blood gases, as well as dedicated obstetricians and an operating room team properly skilled, knowledgeable, and comfortable with advanced minimally invasive surgery. The combination of multidisciplinary approach, multi-specialty communication, and skilled surgeons will surely give the best possible outcomes for mother and fetus (Figure 3).
Disclosure The authors have stated that they have no conflicts of interest.
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13. King SC, Pollack LA, Li J, King JB, Master VA. Continued increase in incidence of renal cell carcinoma, especially in young patients and high grade disease: United States 2001 to 2010. J Urol 2014; 191:1665-70. 14. Macleod LC, Hotaling JM, Wright JL, et al. Risk factors for renal cell carcinoma in the VITAL study. J Urol 2013; 190:1657-61. 15. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371:569-78. 16. Bergström A, Hsieh CC, Lindblad P, Lu CM, Cook NR, Wolk A. Obesity and renal cell cancer—a quantitative review. Br J Cancer 2001; 85:984-90. 17. Behrens G, Leitzmann MF. The association between physical activity and renal cancer: systematic review and meta-analysis. Br J Cancer 2013; 108:798-811. 18. Hunt JD, van der Hel OL, McMillan GP, Boffetta P, Brennan P. Renal cell carcinoma in relation to cigarette smoking: meta-analysis of 24 studies. Int J Cancer 2005; 114:101-8. 19. Liao LM, Hofmann JN, Cho E, Pollak MN, Chow WH, Purdue MP. Circulating levels of obesity-related markers and risk of renal cell carcinoma in the PLCO cancer screening trial. Cancer Causes Control 2017; 28:801-7. 20. Cho E, Curhan G, Hankinson SE, et al. Prospective evaluation of analgesic use and risk of renal cell cancer. Arch Intern Med 2011; 171:1487-93. 21. Choueiri TK, Je Y, Cho E. Analgesic use and the risk of kidney cancer: a metaanalysis of epidemiologic studies. Int J Cancer 2014; 134:384-96. 22. Kabat GC, Silvera SAN, Miller AB, Rohan TE. A cohort study of reproductive and hormonal factors and renal cell cancer risk in women. Br J Cancer 2007; 96:845-9. 23. Abdul KS, Jayasinghe SS, Chandana EP, Jayasumana C, De Silva PM. Arsenic and human health effects: a review. Environ Toxicol Pharmacol 2015; 4 0:828-46. 24. Song JK, Luo H, Yin XH, et al. Association between cadmium exposure and renal cancer risk: a meta-analysis of observational studies. Sci Rep 2015; 5:17976. 25. Chien C-C, Han M-M, Chiu Y-H, et al. Epidemiology of cancer in end-stage renal disease dialysis patients: a national cohort study in Taiwan. J Cancer 2017; 8:9-18. 26. Hidayat K, Du X, Zou S-Y, Shi B-M. Blood pressure and kidney cancer risk. J Hypertens 2017; 35:1333-44. 27. Mazzucotelli V, Piselli P, Verdirosi D, et al. De novo cancer in patients on dialysis and after renal transplantation: north-western Italy, 1997e2012. J Nephrol 2017; 30:851-7. 28. Pialoux V, Brown AD, Leigh R, Friedenreich CM, Poulin MJ. Effect of cardiorespiratory fitness on vascular regulation and oxidative stress in postmenopausal women. Hypertension 2009; 54:1014-20. 29. Pearson-Stuttard J, Zhou B, Kontis V, Bentham J, Gunter MJ, Ezzati M. Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment. Lancet Diabetes Endocrinol 2018; 6:e6-15. 30. Joh H-K, Willett WC, Cho E. Type 2 diabetes and the risk of renal cell cancer in women. Diabetes Care 2011; 34:1552-6. 31. Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med 2009; 166:1871-7. 32. Lowrance WT, Ordoñez J, Udaltsova N, Russo P, Go AS. CKD and the risk of incident cancer. J Am Soc Nephrol 2014; 25:2327-34. 33. Lee JE, Hankinson SE, Cho E. Reproductive factors and risk of renal cell cancer: the Nurses’ Health Study. Am J Epidemiol 2009; 169:1243-50. 34. Louglin KR. The management of urological malignancies during pregnancy. Br J Urol 1995; 76:639-44. 35. Pearson GA, Eckford SD. Renal cell carcinoma in pregnancy. J Obstet Gynaecol 2009; 29:53-4. 36. Binbay M, Yuruk E, Ucpinar B, Binbay Z, Colakerol A, Muslumanoglu AY. Laparoscopic partial nephrectomy for renal-cell carcinoma during pregnancy. J Endourol Case Rep 2016; 2:18-20. 37. Lisowska J, Gronostaj K, Golabek T, et al. Transperitoneal laparoscopic radical nephrectomy for renal cell carcinoma during pregnancy. Eur Urol Suppl 2014; 13: e1394. 38. Bovio IM, Allan RW, Oliai BR, Hampton T, Rush DS. Xp11.2 translocation renal carcinoma with placental metastasis: a case report. Int J Surg Pathol 2011; 19:80-3. 39. Van der Veldt AA, Van Wouwe M, Van den Eertwegh AJ, Van Moorselaar RJ, Van Geijn HP. Metastatic renal cell cancer in a 20-year-old pregnant woman. Urology 2008; 72:775, discussion: 776-7. 40. Committee on Obstetric Practice. Committee Opinion No. 723: guidelines for diagnostic imaging during pregnancy and lactation. Obstet Gynecol 2017; 130: e210-6. 41. Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol 2008; 112:333-40. 42. American Institute of Ultrasound in Medicine. AIUM standard for the performance of an ultrasound examination of the abdomen or retroperitoneum. J Ultrasound Med 2002; 21:1182-7. 43. Paspulati RM, Bhatt S. Sonography in benign and malignant renal masses. Radiol Clin North Am 2006; 44:787-803. 44. Tolcher MC, Fisher WE, Clark SL. Nonobstetric surgery during pregnancy. Obstet Gynecol 2018; 132:395-403. 45. Swartz MA, Lydon-Rochelle MT, Simon D, Wright JL, Porter MP. Admission for nephrolithiasis in pregnancy and risk of adverse birth outcomes. Obstet Gynecol 2007; 109:1099-104. 46. Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL. Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA 2016; 316:952-61.
Lucio Dell’Atti et al 47. Telischak NA, Yeh BM, Joe BN, Westphalen AC, Poder L, Coakley FV. MRI of adnexal masses in pregnancy. AJR Am J Roentgenol 2008; 191:364-70. 48. Morice P, Uzan C, Gouy S, Verschraegen C, Haie-Meder C. Gynaecological cancers in pregnancy. Lancet 2012; 379:558-69. 49. Schiavina R, Borghesi M, Dababneh H, et al. Small renal masses managed with active surveillance: predictors of tumor growth rate after long-term follow-up. Clin Genitourin Cancer 2015; 13:e87-92. 50. Kutikov A, Fossett LK, Ramchandani P, et al. Incidence of benign pathologic findings at partial nephrectomy for solitary renal mass presumed to be renal cell carcinoma on preoperative imaging. Urology 2006; 68:737-40. 51. Ristau BT, Kutikov A, Uzzo RG, Smaldone MC. Active surveillance for small renal masses: when less is more. Eur Urol Focus 2016; 2:660-8. 52. Richard PO, Jewett MA, Bhatt JR, et al. Renal tumor biopsy for small renal masses: a single-center 13-year experience. Eur Urol 2015; 68:1007-13. 53. Lee JY, Kim CK, Choi D, Park BK. Volume doubling time and growth rate of renal cell carcinoma determined by helical CT: a single-institution experience. Eur Radiol 2008; 18:731-7. 54. Chawla SN, Crispen PL, Hanlon AL, Greenberg RE, Chen DY, Uzzo RG. The natural history of observed enhancing renal masses: meta-analysis and review of the world literature. J Urol 2006; 175:425-31. 55. Gordetsky J, Eich ML, Garapati M, et al. Active Surveillance of Small Renal Masses. Urology 2019; 123:157-66. 56. Abou Youssif T, Kassouf W, Steinberg J, Aprikian AG, Laplante MP, Tanguay S. Active surveillance for selected patients with renal masses: updated results with long-term follow-up. Cancer 2007; 110:1010-4. 57. Yilmaz E, Oguz F, Tuncay G, et al. Renal cell carcinoma diagnosed during pregnancy: a case report and literature review. J Int Med Res 2018; 46:3422-6. 58. Hwang CK, Ogan K, Pattaras J, Master VA. Estimated volume growth characteristics of renal tumors undergoing active surveillance. Can J Urol 2010; 17: 5459-64. 59. Lee D, Abraham N. Laparoscopic radical nephrectomy during pregnancy: case report and review of the literature. J Endourol 2008; 22:517-8. 60. Stroup SP, Altamar HO, L’Esperance JO, Auge BK. Retroperitoneoscopic radical nephrectomy for renal-cell carcinoma during twin pregnancy. J Endourol 2007; 21: 735-7. 61. Khaled H, Al Lahloubi N, Rashad N. Review on renal cell carcinoma and pregnancy. A challenging situation. J Adv Res 2016; 7:575-80. 62. Sainsbury DC, Dorkin TJ, MacPhail S, Soomro NA. Laparoscopic radical nephrectomy in first-trimester pregnancy. Urology 2004; 64:1231.e7-8. 63. Bettez M, Carmel M, Temmar R, et al. Fatal fast-growing renal cell carcinoma during pregnancy. J Obstet Gynaecol Can 2011; 33:258-61. 64. Pertia A, Gagua D, Managadze L, Chkhotua A. Treatment of renal cell carcinoma in pregnancy: simultaneous nephron-sparing surgery and Caesarian section (case report). Georgian Med News 2011; 201:7-10. 65. Lambe M, Lindblad P, Wuu J, Remler R, Hsieh CC. Pregnancy and risk of renal cell cancer: a population-based study in Sweden. Br J Cancer 2002; 86: 1425-9. 66. Tupikowski K, Dembowski J, Zdrojowy R, et al. Renal-cell carcinoma in pregnancy. Cent Eur J Urol 2009; 62:107-8.
67. Amant F, Halaska MJ, Fumagalli M, et al, ESGO task force ‘Cancer in Pregnancy’. Gynecologic cancers in pregnancy: guidelines of a second international consensus meeting. Int J Gynecol Cancer 2014; 24:394-403. 68. Bamias A, Tzannis K, Papatsoris A, et al. Prognostic significance of cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma treated with first-line sunitinib: a European multiinstitutional study. Clin Genitourin Cancer 2014; 12:373-83. 69. Greco F, Autorino R, Altieri V, et al. Ischemia techniques in nephron-sparing surgery: a systematic review and meta-analysis of surgical, oncological, and functional outcomes. Eur Urol 2019; 75:477-91. 70. Akin Y, Ciftci H, Karahan MA, Incebiyik A. Laparoscopic retroperitoneal radical nephrectomy in a pregnant woman with retrocaval artery. Int Urol Nephrol 2015; 47:469-71. 71. O’Connor JP, Biyani CS, Taylor J, Agarwal V, Curley PJ, Browning AJ. Laparoscopic nephrectomy for renal-cell carcinoma during pregnancy. J Endourol 2004; 18:871-4. 72. Ljungberg B, Bensalah K, Canfield S, et al. EAU Guidelines on renal cell carcinoma: 2014 update. Eur Urol 2015; 67:913-24. 73. Petrut B, Hogea M, Tat T, Buse M, Schitcu V, Sparchez Z. Literature review on the feasibility of laparoscopic partial nephrectomy for renal cancer during pregnancy: a propos of a case. J BUON 2018; 23:872-6. 74. Fan X, Xu K, Lin T, et al. Comparison of transperitoneal and retroperitoneal laparoscopic nephrectomy for renal cell carcinoma: a systematic review and metaanalysis. BJU Int 2013; 111:611-21. 75. Ren T, Liu Y, Zhao X, et al. Transperitoneal approach versus retroperitoneal approach: a meta-analysis of laparoscopic partial nephrectomy for renal cell carcinoma. PLoS One 2014; 9:e91978. 76. Caruso RP, Phillips CK, Kau E, Taneja SS, Stifelman MD. Robot assisted laparoscopic partial nephrectomy: initial experience. J Urol 2006; 176:36-9. 77. Park S, Ham W, Jung H, Jeong W, Kim WT, Rha KH. Robot-assisted laparoscopic partial nephrectomy during pregnancy. J Rob Surg 2008; 2:193-5. 78. Reedy MB, Kallen B, Kuehl TJ. Laparoscopy during pregnancy: a study of five fetal outcome parameters with use of the Swedish Health Registry. Am J Obstet Gynecol 1997; 177:673-9. 79. Committee on Obstetric Practice and the American Society of Anesthesiologists. Committee Opinion No. 696: nonobstetric surgery during pregnancy. Obstet Gynecol 2017; 129:777-8. 80. Pearl JP, Price RR, Tonkin AE, Richardson WS, Stefanidis D. SAGES guidelines for the use of laparoscopy during pregnancy. Surg Endosc 2017; 31:3767-82. 81. Nasioudis D, Tsilimigras D, Economopoulos KP. Laparoscopic cholecystectomy during pregnancy: a systematic review of 590 patients. Int J Surg 2016; 27:165-75. 82. Bedson R, Riccoboni A. Physiology of pregnancy: clinical anaesthetic implications. Cont Educ Anaesth Crit Care Pain 2014; 14:69-72. 83. Hunter JG, Swanstrom L, Thornburg K. Carbon dioxide pneumoperitoneum induces fetal acidosis in a pregnant ewe model. Surg Endosc 1995; 9:272-9. 84. Nejdlova M, Johnson T. Anesthesia for non-obstetric procedures during pregnancy. Cont Educ Anaesth Crit Care Pain 2012; 12:203-6. 85. Curet MJ, Allen D, Josloff RK, et al. Laparoscopy during pregnancy. Arch Surg 1996; 131:546-50.
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Laparoscopic Approach in Management of Renal Cell Carcinoma During Pregnancy: State of the Art Lucio Dell’Atti,1 Chiara Borghi,2 Andrea Benedetto Galosi1 Abstract Renal cell carcinoma (RCC) is extremely rare in pregnant women. However, this is one of the most reported urologic tumors during pregnancy. The aim of this review was to evaluate RCC during pregnancy in terms of epidemiology, risk factors, diagnosis, natural history of disease, and the safety of laparoscopic approach in the management of this tumor. RCC presentation is frequently made incidentally during an ultrasonography performed for other reasons, such as hydronephrosis owing to non-neoplastic causes. The optimal time for surgery during pregnancy and the consequences of surgery on the maternal and fetal well-being are major considerations. Risks for adverse pregnancy outcomes should be explained, and the patient’s decision about pregnancy termination should be considered. Ultrasound is good in diagnosing renal masses, with a sensitivity comparable to that of computed tomography only for exophytic masses larger than 3 cm. Magnetic resonance imaging is reproducible and a good, though expensive, alternative to computed tomography scans for the evaluation of renal lesions in pregnant women. Radical nephrectomy or nephron-sparing surgery are essential treatments for management of RCC. Laparoscopic surgery has historically been considered dangerous during pregnancy and avoided whenever possible, because of concerns regarding surgery-related risks, such as uterine injury, miscarriage, teratogenesis, preterm birth, and hypercapnia. The laparoscopic treatment during pregnancy is becoming increasingly accepted where feasible with low morbidity. However, the combination of a multidisciplinary approach, multi-specialty communication, and skilled surgeons can give the best possible outcomes for mother and fetus. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2019 Elsevier Inc. All rights reserved. Keywords: Diagnosis, Laparoscopy, Renal cancer, Surgery, Treatment
Introduction Even experienced laparoscopic surgeons may not decide on the management of cancer during pregnancy, which represents a medical dilemma.1 Renal cell carcinoma (RCC) diagnosis is extremely rare during gestation.2 However, this is one of the most reported urologic tumors in pregnant women.3 This pathologic condition is emotionally devastating for young patients and their family, overshadowing the joyfulness of pregnancy.4 1 Department of Urology, University Hospital “Ospedali Riuniti” and Polythecnic University of Marche Region, Ancona, Italy 2 Unit of Obstetrics and Gynecology, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara and S. Anna Hospital of Ferrara, Ferrara, Italy
Submitted: Apr 6, 2019; Revised: May 19, 2019; Accepted: May 20, 2019 Address for correspondence: Lucio Dell’Atti, MD, PhD, Department of Urology, Marche Polytechnic University, University Hospital “Ospedali Riuniti”, 71 Conca St, 60126 Torrette, Ancona, Italy E-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2019 Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.clgc.2019.05.025
If renal cancer is diagnosed during the first trimester, concerns about surgery and further adjuvant therapies during pregnancy should be discussed.2,3 Risks for adverse pregnancy outcomes should be explained, and the patient’s decision about pregnancy termination should be considered.3,4 On the other hand, if the renal mass is diagnosed during the second or the third trimester, surgery could be safely performed without compromising fetal outcome but still, if possible, it is preferred to postpone it until postpartum.5 The aim of this review was to evaluate RCC during pregnancy in terms of epidemiology, risk factors, diagnosis, natural history of disease, and the safety of a laparoscopic approach in the management of this tumor. A MEDLINE search of the peer reviewed literature on diagnosis and case reports of RCC during pregnancy, published in English, was done through March 1, 2019 using the words: “renal cancer,” “pregnancy,” “gestation,” “diagnosis,” “treatment,” “laparoscopy,” and “management.” Given the rarity of this cancer, articles were not limited by design or number of reported patients. A total of 109
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Laparoscopy and Renal Carcinoma During Pregnancy documented cases of all renal malignancies during pregnancy, including 91 reported cases of RCCs, were evaluated for this review (Figure 1).
Epidemiology RCC represents the 10th most frequently diagnosed cancer in women, accounting for 3% of all oncologic diagnoses.6 Although most detected lesions are small tumors, locally advanced disease continues to be diagnosed in a notable proportion of patients, with up to 17% of patients harboring distant metastases at the time of diagnosis.7 RCC incidence rates vary substantially worldwide.8 Rates are generally higher in Europe and North America than in Asia and South America. Within a continent, rates also differ by country.9 Rates among females are generally about one-half of those among males and also vary geographically. In the United States, RCC incidence rates differ among racial/ethnic populations. Rates are lower among Asian/Pacific Islanders (4.7 per 100,000), mirroring rates of their countries of origin. However, incidence rates for white Hispanics (9.7 per 100,000) are much higher than rates reported in Latin America (6.7 per 100,000), suggesting the potential role of environmental exposures.10 The estimated incidence of cancer diagnosed in pregnant women in developed societies is 1 per 1000 pregnancies.11 The most common tumors diagnosed during pregnancy are breast cancer, melanoma, cervical cancer, and lymphomas. Lung, ovarian, gastrointestinal, urologic, and other malignancies are rarely observed.9-11 Although RCC accounts for 3% of all adult malignancies, and the mean age at diagnosis is 56 years, it is rare in gestation, despite the current tendency of women to bear children at more advanced ages.9,10 A meta-analysis of 14 studies, published in 2013, concluded that parity was associated
with an increased risk of RCC. As an example, women with a history of at least 1 pregnancy showed an increased risk up to 40% to 90% if compared with nulliparous women. Risk was higher with higher number of pregnancies.3 Moreover, RCC rates seem to be increased during pregnancy, because of the incidental detection of renal masses, owing to more frequent abdominal ultrasound imaging.3 As a matter of fact, urinary tract ultrasound is often performed at any gestational age, mainly because of ureter mechanical compression between the gravid uterus and iliopsoas muscle or ascending urinary tract infections.4
Etiology Obesity, smoking, analgesics, environmental factors, hypertension, diabetes, chronic kidney diseases, and reproductive and hormonal factors are established risk factors for RCC.12,13 Translational studies demonstrated that RCC could be induced by prolonged intake of fat.12 This is confirmed by pathologic changes observed through histologic sectioning. Macleod et al observed, on a prospective cohort of 77,260 residents of Washington, that obesity was significantly associated with RCC (body mass index 35 kg/m2 vs. < 25 kg/m2: hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.06-2.79).14 The relative risk estimates that every 5 kg of body weight gained increases the risk of RCC by 35% in women.14 The biological reasons behind this association are unclear, although recent evidence shows that the effects of circulating hormones such as estrogens, insulin-like growth factors, and adipokines might play a role. Adipose tissue in obese women is a source of estrogens that may play a role in the pathogenesis of RCC.15 Physical activity may reduce RCC risk by decreasing obesity, insulin resistance, blood pressure, and lipid peroxidation.16 A recent meta-analysis reported
Figure 1 Treatment of Patients Who Were Diagnosed With Renal Cell Carcinoma During Pregnancy
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Abbreviations: Lap ¼ Laparoscopic; N/A ¼ not available; NSS ¼ nephron sparing surgery; RN ¼ radical nephrectomy.
Clinical Genitourinary Cancer Month 2019
Lucio Dell’Atti et al an inverse association between physical activity and RCC risk (relative risk [RR], 0.88; 95% CI, 0.79-0.97).17 Smoking has been associated with a number of common cancers, including RCC.18 Tobacco smoke includes a mix of carcinogens involved in the etiology of RCC. In the VITamin And Lifestyle (VITAL) study, smoking was independently linked with renal cancers (> 37.5 pack-years vs. never: HR, 1.58; 95% CI, 1.092.29).14 Similarly, in the PLCO trial, the number of cigarettes per day was confirmed to be significantly associated with a higher risk of developing RCC and with a higher risk of high-grade RCC.19 Epidemiological data suggest that analgesic use increases the risk of RCC. Cho et al demonstrated the relationship between analgesics and nonsteroidal anti-inflammatory drug consumption and an increased risk of RCC (pooled multivariate RR, 1.51; 95% CI, 1.12-2.04).20 A meta-analysis by Choueiri et al observed that the use of acetaminophen and nonsteroidal anti-inflammatory drugs was associated with an increased risk of RCC (pooled RR, 1.28; 95% CI, 1.15-1.44 and pooled RR, 1.25; 95% CI, 1.06-1.46, respectively).21 In terms of occupational exposure, more robust studies are needed to confirm the relation between industrial agents and risk of RCC.22 However, despite the limited evidence, exposure to x-radiation and industrial agents, such as inorganic arsenic agents, perfluorooctanoic acid, cadmium, nitrate, and radon in drinking water, may be considered as potential RCC risk factors.23,24 Hypertension is another independent risk factor for RCC. About 18% of cases diagnosed with RCC during pregnancy presented with hypertension. A number of prospective studies investigated the association between blood pressure and the risk of RCC.25 In the VITAL study, hypertension was independently associated with RCC risk (HR, 1.70; 95% CI, 1.30-2.22).14 A recent meta-analysis of 18 prospective studies further encourages an association between hypertension and RCC risk.26 A history of hypertension was associated with a 67% increased risk of RCC, and each 10-mm Hg increase in blood pressure was associated with a 10% to 22% increased risk of RCC. The biological reasons behind this relationship remain unclear, but some authors have hypothesized the involvement of chronic renal hypoxia and lipid peroxidation with formation of reactive oxygen species.27 Moreover, women with hypertensive disorders may also be more likely to get a renal imaging and therefore identify incidental renal cancers.28 Diabetes is associated with an increased risk of several types of tumors.29 However, its relationship with RCC remains unclear. In the VITAL study, there was no observed relationship between type 2 diabetes and RCC after accounting for multiple factors.14 This association was consistent across different strata of body mass indexes, smoking habit, and blood pressure values.30 Moreover, RCC risk increased with an increasing number of comorbidities, including obesity, hypertension, and type 2 diabetes. Specifically, women who had all 3 of these conditions had 4-fold higher probability of RCC development compared with women without comorbidities.31 RCC of native end-stage kidney disease or acquired cystic kidney disease are found in about 4% of patients.32 In the VITAL study, the presence of a kidney disease (HR, 2.58; 95% CI, 1.21-5.50) was independently related to RCC.14
A possible correlation between hormonal factors and RCC development exists, although the underlying mechanism is not fully understood. An increased risk of RCC has been associated with parity among women in several cohort studies.22,33 Associations with other reproductive factors, including the use of oral contraceptives and hormone replacement therapy, are not consistently seen.10
Clinical Presentation The presentation of RCC in pregnant women is frequently made incidentally during an ultrasonography performed for other reasons, such as hydronephrosis owing to non-neoplastic causes (calculi or mechanical compression of the ureter), or ascending urinary tract infection.34,35 The main reported presenting symptoms are: pain (50%), hematuria (47%), hypertension (18%), and the classical triad of hematuria, pain, and palpable mass (26%).36 Hematuria in pregnancy is usually owing to non-neoplastic causes such as infection, calculi, bladder varicosities, and glomerulonephritis. The classical triad of pain, palpable mass, and hematuria may present a diagnostic dilemma because hypertension is often seen in pregnancy and may mimic preeclampsia, causing a delay in diagnosis.37 Fever (21%), weight loss (9%), and oligemic shock from hemorrhage into the tumor (3%) also can occur. Other less frequent presentations are hemolytic anemia, hypercalcemia, or rupture of tumoral cyst.36,37 Five cases were reported with metastatic disease during pregnancy, and the remaining were diagnosed with less advanced disease, usually during the second and third trimesters of pregnancy.36,38 Few cases were reported during the first trimester.36,39
Diagnosis and Imaging In general, the use of diagnostic imaging during pregnancy is limited, because ionizing radiation used for standard radiology and computed tomography are potentially related to biological effects causing congenital malformations, central nervous system injury, mental retardation, intrauterine growth restriction, or stillbirth.40 The safest diagnostic imaging studies during all stages of gestation are ultrasound and magnetic resonance imaging (MRI), with no teratogenic effects.40,41 RCC is frequently diagnosed as an incidental finding during a routine ultrasound examination for antepartum care.36 Ultrasound is good in diagnosing renal masses, with a sensitivity comparable to that of computed tomography (CT) only for exophytic masses larger than 3 cm.42 Ultrasonography, CT, and MRI have variable sensitivity in detecting and staging RCC. Ultrasonography is less sensitive in detecting small renal lesions, especially those that do not deform the contour of the kidney.43 The sensitivity of CT and ultrasonography for detection of lesions 3 cm and less is 94% and 79%, respectively. CT and MRI have nearly 100% accuracy in the diagnosis of RCC.42,43 CT scan is the imaging modality of choice for the diagnosis of renal tumors.43 A CT scan not including the gravid uterus in the field-of-view results in negligible fetal doses and may be performed in pregnancy without risks to the fetus. A standard single CT scan through the gravid uterus results in a fetal dose of 25 mGy or less. A CT of the abdomen/pelvis exposes the uterus to 18 to 25 mGy and should be avoided, unless a medical emergency warrants it.41 Exposure to high doses of radiation (greater than 50-100 mGy)
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Laparoscopy and Renal Carcinoma During Pregnancy during the first 2 weeks after conception is thought to be an all or none phenomenon, resulting in either fetal death or no effect. Because most organogenesis takes place between weeks 2 and 8 after conception, fetal anomalies would be potentially affected by very high doses of radiation (greater than 200 mGy) during this time frame. Severe intellectual disability may occur at lower doses (greater than 60 mGy) early in pregnancy (8-15 weeks of gestation), and microcephaly may occur with doses greater than 200 mGy during this timeframe. A 10- to 20-mGy exposure may also increase the lifetime risk of leukemia 2-fold (background risk of 1:3000). Fetal gonad and thyroid injury are other areas of theoretical concern, with certain types and doses of radiation exposure generally unrelated to preoperative surgical diagnostic tests.44,45 MRI is reproducible and a good, although expensive, alternative to CT scan for the evaluation of renal lesions in pregnant women. It accurately evaluates the local tumor size and location, the involvement of the adjacent structures, and the possible development of cancer thrombus in the renal vein and inferior vena cava.46 Gadolinium, the contrast agent utilized during MRI examination, crosses the placenta barrier, but no adverse effect on the fetus has been recorded. However, it may induce fetal hypothyroidism.47 Whole body MRI is an emerging method for malignant cancer staging; its sensitivity is comparable to skeletal scintigraphy for assessment of skeletal metastasis.48 However, its sensitivity in detecting pulmonary lesions in comparison with chest CT remains unknown.49 The European Society of Radiology guideline has approved its use in all stages of pregnancy.40 The differential diagnosis of renal masses includes inflammatory, cystic, benign, and malignant lesions other than renal cell carcinoma.50
Prognosis
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Active surveillance (AS) presents a unique opportunity to observe the natural history of RCC, as most tumors are treated with a surgical approach soon after diagnosis.51 Many authors showed that small renal tumors grew slowly and seldom metastasized.51-53 Most renal neoplasms are slow-growing, with an average volume doubling time of more than 500 days.53 A meta-analysis of 234 renal tumors showed a mean growth rate of 0.28 cm/y; the tumors pathologically confirmed as RCC had a higher growth rate, up to 0.4 cm/y.54 However, RCC may have relatively aggressive growth potential compared with other benign renal tumors. Contemporary selection for AS remains a process of shared decision-making, considering patient age, pregnancy status, renal function, tumor size and complexity, and interventional risk, along with judicious renal mass biopsy use.55 To fully understand the growth kinetics of RCC, few studies have demonstrated the correlation between the immunohistochemical biomarkers and the growth rate of RCCs.56 For renal masses, AS with delayed treatment until progression is now gradually accepted especially for patients during pregnancy.57 The growth rate of renal tumors under AS is various and not wellpredicted by clinical and radiographic factors.49 On the other hand, immunohistochemistry can define the nature of tumor growth through assessment of the expression of biomarkers that reflect cell proliferation, apoptosis, and angiogenesis.58 In the case of RCC during pregnancy, timely diagnosis and management is crucial in predicting maternal-fetal prognosis. However, the timing of surgery for renal tumors during pregnancy
Clinical Genitourinary Cancer Month 2019
is controversial.59 The surgical resection from open to laparoscopic technique remains the mainstay of treatment.60 Recommendations regarding surgery are determined by time of diagnosis, size and stage of tumor, risk of malignancy, general health of the mother, and probability of survival of the fetus.61 Therefore, it may be rational to await fetal delivery prior to treatment if the neoplasm is discovered during late stages of pregnancy.60,61 If there are suspicions of malignant renal mass in the first trimester, surgery is often not delayed despite the small increased risk of miscarriage.62 However, surgical treatment during the second trimester will need to balance the maternal and fetal risks related to invasive procedures with the risks of delaying surgery.63 Surgery-related mechanisms causing increased morbidity during abdominal surgery include direct uterine trauma, decreased uteroplacental blood flow, teratogenic effect of anesthetic agents, adverse effects of anesthesia on maternal hemodynamics and acidbase balance, enhancement of impaired ventilatory mechanics, increased thromboembolic risk, and adverse effects of postoperative medications.64 Concerns about teratogenic effects and an increased risk of abortion have been discussed widely in the literature, and an indication to postpone laparoscopic or laparotomic surgery at the second trimester if possible has been proposed.65 Actually, evidence shows that the rates of early pregnancy loss are not significantly increased by surgery itself during the first trimester of pregnancy.66 Surgical procedures performed during the second or the third trimester could predispose to uterine contractions, stillbirth, or early preterm labor.67 Nevertheless, no clear benefit from routine preoperative tocolysis has been demonstrated.66,67 If a renal tumor is discovered close to the expected date of labor, then the surgery may be postponed until that date. Resection of a tumor discovered in the third trimester is usually recommended together with a caesarean section.64 If surgery during pregnancy is essential and cannot be postponed, careful perioperative precautions are required owing to the physiological changes of cardiovascular, respiratory, and gastrointestinal systems of pregnant patients, and a multidisciplinary team including anesthesiologists, surgeons, and obstetricians should be involved in the management.65-67 In pregnancy, the kidney biopsy is not mandatory for diagnosis, as radiologic studies usually provide sufficient results for diagnosis prior to treatment.40 The timing of the biopsy can range from early pregnancy to 40 gestational weeks.50 Core biopsy is prescribed in selected cases, mainly in patients with small masses who are candidates for an AS, local ablative therapies (ie, cryosurgery or radiofrequency ablation), patients with a solitary kidney, and patients with metastatic disease before initiating targeted treatments.49,50
Laparoscopic Management in RCC Approximately 1 in 500 women will require non-obstetrical abdominal surgery during pregnancy.66,67 The most common non-obstetrical surgical emergencies complicating pregnancy are acute appendicitis and cholecystitis.44 Other diseases that may require surgical treatments during pregnancy comprise ovarian masses or torsion, symptomatic cholelithiasis, adrenal tumors, renal masses, splenic disorders, symptomatic hernias, complications of inflammatory bowel diseases, and other rare conditions.44,48
Lucio Dell’Atti et al Once the decision for a surgical treatment has been made, the modality (laparotomy vs. laparoscopy) should be offered based on the skills of the surgeon and the availability of the appropriate equipment.59,61 Benefits of laparoscopy during pregnancy appear similar to those benefits in non-pregnant patients including less postoperative ileus, less postoperative pain, decreased length of hospital stays, and faster return to work.5,36 Radical nephrectomy (RN) or nephron-sparing surgery (NSS) are essential treatments for management of RCC. Even in metastatic disease, RN is done before a systemic therapy.68 NSS is recommended in patients with T1 stage tumors.69 The laparoscopic treatment during pregnancy is becoming increasingly accepted where feasible.70 O’Connor and colleagues were the first authors to report successful laparoscopic RN during pregnancy.71 Since then, many other cases have been described. In patients with renal masses not treatable by NSS, Ljungberg et al, on behalf of the European Association of Urology, recommended laparoscopic RN as the new standard.72 Thus, the relatively little amount of data published on pregnant patients and renal tumors gets to even fewer cases in which NSS treatment has been applied. Binbay et al36 reported the case of laparoscopic partial nephrectomy observed during pregnancy for a right-sided renal tumor. Early unclamping technique was preferred. Renorraphy was completed with a barbed suture, application of Floseal, and completed with a glyconate suture. They also placed a double J catheter. The pregnancy, delivery, and oncologic follow-up was declared as uneventful and with no tumor recurrence or metastasis at 22 months after surgery. More recently (in 2018), Petrut et al73 reported a trans-peritoneal laparoscopic partial nephrectomy, using 3 trocars, performed during the 16th week of pregnancy. The patient was discharged on the 4th postoperative day. During the 36 months of follow-up, the CT and ultrasonography scan did not reveal any tumor recurrence. Laparoscopic RN can be performed via the transperitoneal or retroperitoneal approach, each providing specific advantages and disadvantages.69 The choice of the laparoscopic approach depends on the surgeon and his laparoscopic experience. Selected tumors may be approached by either route or the other, according to the surgeons’ preference, the location, and technical complexity of the renal mass. The transperitoneal approach was usually utilized for anterior or lateral masses. The retroperitoneoscopic approach was usually utilized for posterior, posteromedial, or posterolateral renal tumors.69,74 Factors in favor of the transperitoneal route are the lager working space, allowing for wider angulation and maneuverability with laparoscopic instruments, and the more accustomed orientation by anatomic landmarks. However, it requires bowel mobilization to expose the kidney.74 The retroperitoneoscopic approach, by avoiding bowel mobilization, seems to provide a more direct access to the kidney and the renal vessels. Drawbacks of the technique are the spatial limitations of the narrow retroperitoneal working space and the lack of view.75,76 However, Akin et al70 performed RN using the retroperitoneal laparoscopic approach for a renal mass with 10-cm diameter. The operation time was 46 minutes, and the estimated blood loss was 20 cc. They used only 3 trocars during the laparoscopic
retroperitoneal procedure. The patient was discharged on postoperative day 3. There is evidence observed in the literature that shows the successful implementation of robotic-assisted laparoscopic partial nephrectomy.76 Park et al have even described one case of robot-assisted partial nephrectomy in 2008 done during pregnancy and without complications reported during or after the treatment.77 This supports the notion that the laparoscopic NSS technique is a safe and feasible option during pregnancy (Table 1).
Discussion Laparoscopic surgery has historically been considered dangerous during pregnancy and avoided whenever possible because of concerns regarding surgery-related risks, such as uterine injury, miscarriage, teratogenesis, preterm birth, and hypercapnia.70,71 These concerns have proven to be false as surgical skills have increased, more experience has been gained, and the envelope has continued to be pushed with ever more elegant instrumentation.74,76 Currently, laparoscopic urologic surgical modalities are performed with increasing numbers even during pregnancy, and developing minimally invasive surgery has enabled us to improve results.77 There is a growing body of evidence that this formidable tool can be performed safely during pregnancy for gynecologic, gastrointestinal, and urologic indications.76-78 The landmark survey by Reedy et al, including 413 laparoscopic procedures performed during pregnancy for general surgical and gynecologic indications, appeared to result in no higher fetal or maternal complications rates in comparison to laparotomy.78,79 Traditionally, the recommendations for non-emergent surgical treatments during pregnancy have been to avoid surgery during the first and third trimester to minimize the risks of spontaneous abortion and preterm labor, respectively.80 This has led some authors to suggest delaying surgery until the second trimester and that the gestational age limit for successful completion of laparoscopic surgery during pregnancy should be 26 to 28 weeks. When the pregnant patient is placed in a supine position, the gravid uterus places pressure on the inferior vena cava, resulting in decreased venous return to the heart.80,81 This decrease in venous return leads to reduction in cardiac output with concomitant maternal hypotension and decreased placental perfusion during surgery. For the right kidney masses, placing the patient in a left lateral decubitus position will shift the uterus off the vena cava, improving venous return and cardiac output.80-82 Clearly, safe laparoscopic access is paramount, and we feel that the open (Hasson) technique is appropriate. If the uterus is < 18 weeks, the initial trocar placement is in the umbilicus, not subumbilical (Figure 2). CO2 pneumoperitoneum is obtained with open placement of the laparoscopic trocar that ranges from a 10-mm to 3-mm diagnostic laparoscope.67 As our technology has advanced, in the past few years, we almost exclusively have been using only the 5-mm laparoscope, even if we place a 10-mm Hasson trocar in the navel. This gives one the flexibility to move the laparoscope to virtually any other port if the pathology warrants superior visualization from another trocar site (one
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1 31 8th w T1b 25th w iNS SD 1 34 14th w T1b 16th w iNS SD
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Abbreviations: CS ¼ Cesarean section; i ¼ intraperitoneal; N/A ¼ not available; NS ¼ nephron sparing; r ¼ retroperitoneal; RN ¼ radical nephrectomy; SD ¼ spontaneous delivery; trim ¼ trimester; w ¼ week.
1 41 16th w T2b N/A eRN N/A 1 36 16th w T3a N/A iRN CS 1 32 16th w T1b 20th w iRN SD 1 32 21st w T1a 22th w eRN N/A 1 28 21st w T3b 33rd w iRN CS 1 36 14th w T1a 14th w iNS N/A 1 39 12th w T2b 19th w iRN SD 1 52 20th w T1b 25th w eRN CS 1 30 8th w T1b 16th w eRN SD 1 30 11th w T1b 13th w iRN SD 1 34 11th w T1a 19th w iRN SD Patients Age, y Age of gestation at diagnosis Pathologic stage Age of gestation at treatment Treatment Pregnancy outcomes
Domjàn et al5 Yin et al1 Bettez et al63 Park et al77 Lee et al59 Stroup et al60 Sainsbury Van Basten et al62 et al4 O’Connor et al71 Study
Table 1 Outcomes in Patients Affected by Renal Cell Carcinoma During Pregnancy and Treated With a Laparoscopic Approach
Lisowska et al37
Akin et al70
Binbay et al36
Petrut et al73
Laparoscopy and Renal Carcinoma During Pregnancy could use the 10-mm laparoscope at the Hasson port and then change to the 5-mm laparoscope for the smaller trocar sites). In pregnancies associated with a uterine size 18 weeks, the initial trocar is placed above the navel with the lateral ports being placed under direct visualization. Some authors suggested ultrasound-guided first trocar insertion to avoid enlarged uterus damage.67,80,81 Minimizing CO2 insufflation to maximize both cardiac output and maternal hepatic flow, and to minimize fetal acidosis is best accomplished by keeping intraperitoneal pressures < 12 mm Hg.82,83 Surgery during pregnancy requires an adequate anesthesia for both mother and child. Safety of the fetus implies avoidance of potentially harmful drugs at critical times of fetal development, maintenance of stable maternal hemodynamic parameters to provide adequate uteroplacental circulation, and avoidance of preterm labor.84 All general anesthetic drugs cross the placenta, and there is no optimal general anesthetic technique. Any drug given during pregnancy could potentially negatively affect the development of the fetus depending on the dosage, the route, and the time of administration.83,84 The opening of the peritoneal cavity in the intraperitoneal approach may theoretically be associated with less uterine irritation and, in turn, fewer obstetric complications, including preterm labor.78,80 However, these benefits must be weighed against the risks of laparoscopic surgery. Such risks include injury to the pregnant uterus and the technical difficulties owing to the increasing size of the gravid uterus. In addition, CO2 pneumoperitoneum causes a decrease in cardiac index, an increase in mean arterial pressure, and an increase in systemic vascular resistance. The increased intraabdominal pressure decreases venous return and cardiac output, which may lead to decreased uterine blood flow, increased intrauterine pressure, and possibly decreased fetal perfusion. Significantly, the decreased venous return seen during laparoscopic surgery owing to increased intra-abdominal pressure is volume-dependent, and in adequately resuscitated pregnant women, increased intraabdominal pressure should not lead to decreased CO2 and fetal blood flow. The low pressure of 8 mm Hg to 12 mm Hg should be used, if possible, to minimize any adverse effect on fetal perfusion. This pressure was elicited by Hunter et al when they studied pregnant ewes.83 It may lead to maternal hypercapnia, tachycardia, and hypertension, but it was only a transient effect. Though Hunter felt that CO2 was the detrimental agent in pregnant ewes, no abnormal organogenesis has been observed in laparoscopic appendectomies performed in humans in the first trimester with CO2 as the insufflation agent.78,83 A risk of hypercapnia certainly does exist with a CO2 pneumoperitoneum. Case series recommend monitoring the end-tidal CO2, with a goal of < 35 mm Hg. It is also recommended to hyperventilate the mother to keep end-tidal CO2 concentration in expired air less than 35 mm Hg.83,84 If the procedure is related to a high risk of maternal hypotension or hypoxia and the continuous fetal heart rate monitoring during surgery is technically feasible, this monitoring is generally warranted in potentially viable pregnancies. Continuous fetal monitoring is not usually necessary during abdominal surgery. If intraoperative signs of fetal distress owing to hypoxia are detected, non-surgical
Lucio Dell’Atti et al Figure 2 Laparoscopic Ports Position in Pregnancy: If the Uterus is < 18 Weeks, the Initial Trocar (Red Star) Placement is the Umbilicus. In Pregnancies Associated With a Uterine Size ‡ 18 Weeks, the Initial Trocar is Placed Above the Navel With the Lateral Ports (Blue Stars) Being Placed Under Direct Visualization
manipulation, change of patient’s position, and conservative techniques for intrauterine fetal resuscitation should be performed. Maternal oxygenation or hemodynamic support systems can be helpful in such cases and avoids indication for immediate delivery.44,83
Some authors have compared laparoscopic procedures with open procedures in the pregnant patient, comparing various outcomes, such as hospital length of stay, use of tocolytics, need for postoperative analgesia, and the time of return to a regular diet and mobilization. Curet et al85 compared 16 pregnant patients
Figure 3 Management of Small Renal Masses (cT1a) During Pregnancy
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Laparoscopy and Renal Carcinoma During Pregnancy undergoing laparoscopic procedures with 18 pregnant patients undergoing open procedures (both groups were comparable in age, trimester, intraoperative oxygenation, and end-tidal CO2) and found that gestational age at delivery, birth weight, and Apgar scores were not statistically different in the 2 groups. In addition, the laparoscopic group had a shorter hospital stay, fewer days of postoperative narcotic use, and resumed a regular diet sooner postoperatively than the open surgery group did. These differences were statistically significant. Surgical outcomes of laparoscopic procedures in pregnant patients are similar to outcomes in non-pregnant ones.44,82,85
Conclusions Laparoscopic surgery associated with pregnancy is feasible with low morbidity. Although the operative times are longer, pregnant women undergoing operative laparoscopy with the appropriately skilled laparoscopist benefit from the minimally invasive procedures with brief hospital stays, rapid postoperative recoveries, and earlier return to normal gastrointestinal function and ambulation compared with pregnant women undergoing laparotomy. We feel that less manipulation of the uterus and a decrease in delay of the diagnosis can decrease maternal and fetal/ infant mortality with subsequent successful pregnancy outcomes with fewer complications. It must be emphasized that the laparoscopic procedures should not be undertaken without a surgeon having the proper skills, constantly in communication with am anesthesiologist monitoring CO2 and arterial blood gases, as well as dedicated obstetricians and an operating room team properly skilled, knowledgeable, and comfortable with advanced minimally invasive surgery. The combination of multidisciplinary approach, multi-specialty communication, and skilled surgeons will surely give the best possible outcomes for mother and fetus (Figure 3).
Disclosure The authors have stated that they have no conflicts of interest.
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