- Email: [email protected]
Laparoscopic right hepatectomy combined with partial diaphragmatic resection for colorectal liver metastases: Is it feasible and reasonable?
Laparoscopic right hepatectomy combined with partial diaphragmatic resection for colorectal liver metastases: Is it feasible and reasonable? Panagiotis Lainas, MD, PhD,a Antoine Camerlo, MD,a Claudius Conrad, MD, PhD,a,b Nayruthia Shivathirthan, MD,a David Fuks, MD, PhD,a and Brice Gayet, MD, PhD,a Paris, France, and Boston, MA
Background. The impact of diaphragmatic invasion in patients with colorectal liver metastases (CRLMs) remains poorly evaluated. We aimed to evaluate feasibility and safety of laparoscopic right hepatectomy (LRH) with or without diaphragmatic resection for CRLM. Methods. From 2002 to 2012, 52 patients underwent LRH for CRLM. Of them, 7 patients had combined laparoscopic partial diaphragmatic resection (‘‘diaphragm’’ group). Data were retrospectively collected and short and long-term outcomes analyzed. Results. Operative time was lower in the control group (272 vs 345 min, P = .06). Six patients required conversion to open surgery. Blood loss and transfusion rate were similar. Portal triad clamping was used more frequently in the ‘‘diaphragm’’ group (42.8% vs 6.6%, P = .02). Maximum tumor size was greater in the ‘‘diaphragm’’ group (74.5 vs 37.1 mm, P = .002). Resection margin was negative in all cases. Mortality was nil and general morbidity similar in the 2 groups. Specific liver-related complications occurred in 2 patients in the ‘‘diaphragm’’ group and 17 in the control group (P = .69). Mean hospital stay was similar (P = 56). Twenty-two (42.3%) patients experienced recurrence. One-, 3-, and 5-year overall survival after surgery in ‘‘diaphragm’’ and control groups were 69%, 34%, 34%, and 97%, 83%, 59%, respectively (P = .103). One- and 3-year disease-free survival after surgery in ‘‘diaphragm’’ and control groups were 57%, 47% and 75%, 54%, respectively (P = .310). Conclusion. LRH with en-bloc diaphragmatic resection could be reasonably performed for selected patients in expert centers. Technical difficulties related to diaphragmatic invasion must be circumvented. Further experience must be gained to confirm our results. (Surgery 2015;158:128-34.) From the Department of Digestive Pathology,a Institut Mutualiste Montsouris, Paris Descartes University, Paris, France; and Department of Surgery,b Massachusetts General Hospital, Harvard Medical School, Boston, MA
DURING THE LAST 20 YEARS, laparoscopic liver surgery has seen an incredible proliferation worldwide. The feasibility and safety of laparoscopy for liver resections have been demonstrated and the indications are expanding.1-5 Benefits of reduced blood loss, lesser hospital stay, less postoperative pain, and lower general morbidity have been reported Accepted for publication February 1, 2015. Reprint requests: Brice Gayet, MD, PhD, Department of Digestive Disease, Institut Mutualiste Montsouris, Universit e Paris Descartes, 42 Boulevard Jourdan, 75014 Paris, France. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2015.02.003
128 SURGERY
for the laparoscopic approach compared to open surgery in recent retrospective studies.6-11 This minimally invasive approach, however, is mostly performed in highly specialized centers.12-15 Furthermore, the technical difficulties for the correct oncologic resection of liver tumors that extend to adjacent organs have been considered until recently as a contraindication for a laparoscopic approach. Hence, large peripherally located tumors of the liver present a major challenge to surgeons. In such cases, the anatomic location of the tumor may grossly involve the diaphragm by dense adhesion or direct histologic invasion of the latter. To achieve negative surgical margins in these patients, hepatectomy with simultaneous en-bloc diaphragmatic
Surgery Volume 158, Number 1
resection may be necessary. Combined hepatectomy and diaphragmatic resection has been reported in open surgery, but mainly single cases and few series are available with controversial results regarding postoperative and oncological course.16-21 Our established experience with laparoscopic major hepatectomy and laparoscopic diaphragmatic hernia repair surgery as well as the encouraging literature results of open surgery for liver tumors invading the diaphragm, have led us to selectively expand our indications for minimally invasive liver resection in cases of concomitant diaphragmatic involvement. In this series, we report our preliminary short and long-term results on the feasibility and safety of laparoscopic liver resection (LLR) for colorectal liver metastases (CRLMs) involving the diaphragm. METHODS Study population. This retrospective analysis was carried out using a prospectively collected database of all patients who underwent elective LLR between January 2002 and December 2012 at the Institut Mutualiste Montsouris, Paris, France. All patients undergoing laparoscopic right hepatectomy for CRLM were selected. Patients with combined diaphragmatic resection were compared with patients without diaphragmatic resection in terms of demographic data, intraoperative factors, tumor pathology, short-and long-term outcomes. This study was approved by the institutional review board. Operative procedures. All procedures were performed mainly by a single surgeon (B.G.). The operative technique of laparoscopic right hepatectomy, including the positioning of the trocars, has been previously described.22,23 In brief, all resections were performed with curative intent. Laparoscopic ultrasonography was performed routinely to confirm the number of lesions, their size, and their relationship with the intrahepatic vascular structures and hepatic vein anatomy. Liver parenchyma transection was performed by the ultrasonic dissector, primarily SonoSurg or Harmonic (Ethicon Endo-Surgery, Inc, Cincinnati, OH) and more recently Thunderbeat (Olympus Co, Tokyo). The Gayet bipolar forceps (MicroFrance BG-CEV134, Medtronic, Minneapolis, MN) provided retraction and rescue hemostasis. Portal triad clamping was not used routinely except in case of failure of bleeding control. The final step of the operations included resection of the involved diaphragm en-bloc with the involved liver. During each hepatectomy, the diaphragm was opened with ultrasonic shears. A transthoracic
Lainas et al 129
small catheter was then introduced into the pleural cavity to avoid diaphragmatic cupping. Then the involved portion of diaphragm was resected en-bloc with the tumor and repaired with a nonabsorbable running suture. At the end of the diaphragmatic closure, the anesthesiologist ventilated the patient manually with defined pressure settings to evacuate the carbon dioxide pneumothorax. A pleural drainage was not inserted routinely after diaphragmatic resection. Operative and postoperative outcomes. Primary clinical outcomes included operative time, blood loss, conversion rate, intraoperative complications, characteristics of the underlying liver parenchyma, and postoperative morbidity and mortality. All cases of conversion to laparotomy were noted, and results were analyzed on an intention-to-treat basis. Postoperative complications were graded according to the modified Clavien-Dindo classification24 and major complications were defined as Clavien-Dindo $3. Liver specific complications included: liver failure defined according to the ‘‘50–50 criteria’’ on postoperative day 525; hemorrhage was defined as a decrease of hemoglobin levels >3 g/dL after the end of surgery compared with postoperative baseline levels and/or any postoperative transfusion of packed red blood cell units for a decreasing hemoglobin and/or the need for invasive reintervention; ascites was defined as an abdominal drainage output of more than 10 mL per kg per day after the third postoperative day; and biliary leakage was defined by a bilirubin concentration in the drainage fluid more than 3-fold greater than that in the serum. Both complications and operative mortality were events that occurred within 90 days of surgery or at any time during the postoperative hospital stay. Pathologic resection margin was classified into R0 (microscopically more than 1 mm from resection margin) and R1 (microscopically less than 1 mm from resection margin). During follow-up, patients were seen at the outpatient clinic for a clinical examination, a biologic markers control (carcinoembryonic antigen, carbohydrate antigen 19-9), and a morphologic evaluation (computed tomography or magnetic resonance imaging) 1 month after discharge, every 3 months for the first 2 years and every 6 months until the 5th postoperative year. Thereafter, patients were seen yearly. Followup is discontinued in the absence of recurrence after the 10th year following intervention. Statistical analysis. The patients’ baseline characteristics were expressed as a mean ± SEM for continuous data and as numbers with percentages
130 Lainas et al
Surgery July 2015
Table I. Demographic preoperative characteristics
Patients Sex, F/M Age, y ASA, 1/2/3 BMI Underlying liver, n (%) Normal/steatosis Chemotherapy lesions Cirrhosis Preoperative comorbidities, n (%) Diabetes mellitus Hypertension HBV/HCV infection Dyslipidemia COPD Previous abdominal surgery, n (%) Previous liver surgery, n (%)
Right hepatectomy group (n = 45)
Right hepatectomy + diaphragm resection group (n = 7)
P
17/28 64.1 ± 1.7 6/32/7 24.9 ± 0.7
3/4 63.4 ± 4.8 0/6/1 27.1 ± 2.5
1.00 .77 .57 .52
28 (62.2) 17 (37.8) 0
4 (57.1) 3 (42.9) 0
1.00 1.00 —
3 (6.6) 11 (24.4) 0 8 (17.7) 6 (13.3) 41 (91.1) 10 (22.2)
0 1 (14.3) 0 0 0 5 (71.4) 2 (28.5)
1.00 1.00 — .58 1.00 .18 .65
ASA, American Society of Anesthesiologists physical status score; BMI, body mass index; COPD, chronic obstructive pulmonary disease; HBV, hepatitis B virus; HCV, hepatitis C virus.
for categorical data. Preoperative, operative, and postoperative characteristics, as well as long-term survival of patients, were compared according to the procedure (LLR with diaphragm resection versus no diaphragm resection). The Fisher exact test or v2 test was used to compare differences in categorical variables, and the Wilcoxon rank sum test was used for continuous variables. Overall survival was defined as time from surgery to death (all causes). Cumulative overall survival rates were determined using the Kaplan–Meier method and compared with the log rank test. All statistical analyses were performed using the SPSS for Windows version 20.0 (SPSS, IBM, Armonk, NY). RESULTS Preoperative characteristics. Among selected patients, 7 underwent combined laparoscopic right hepatectomy with partial diaphragmatic resection (‘‘diaphragm’’ group), and 45 other patients underwent laparoscopic right hepatectomy without diaphragmatic resection (control group). All lesions in the ‘‘diaphragm’’ group were located in posterior or posterosuperior segments. As detailed in Table I, the 2 groups were comparable regarding sex, age, American Society of Anesthesiologists physical status score, underlying liver status, comorbidities, and previous abdominal and liver surgery. Thirty (57.6%) patients had neoadjuvant chemotherapy (median number of cycles n = 6) with no difference in the 2 groups (60 vs 45%, P = .96).
Intraoperative and pathologic results. The intraoperative results are shown in Table II. Operative time was lower in the control group but the difference did not reach statistical significance (272 vs 345 minutes, P = .06). Six patients required conversion to open surgery and were analyzed with the laparoscopic groups on an intention-to-treat basis. One ‘‘diaphragm’’ group patient (14.3%) required conversion through a pre-existing cholecystectomy incision, at the end of laparoscopic liver and diaphragmatic resection, because laparoscopic repair of the diaphragm was not possible by laparoscopy because of the absence of pneumoperitoneum after the diaphragm was opened. In the control group, 5 (11.1%) patients required conversion to open surgery because of intraoperative bleeding during parenchymal transection (>900 mL). Intraoperative blood loss and transfusion rate were similar in both groups but portal triad clamping was used more frequently in the ‘‘diaphragm’’ group (42.8% vs 6.6%, P = .02). Histopathologic analysis confirmed diaphragmatic invasion in all 7 patients in the ‘‘diaphragm’’ group (Table III). The maximum tumor size was significantly greater in the ‘‘diaphragm’’ group (74.5 vs 37.1 mm, P = .002). Resection margin was negative in all cases. None of the patients had lymph node involvement. Postoperative outcomes. Mortality was nil and general morbidity was similar in the 2 groups (28.6% vs 28.9%, P = 1.00), as shown in Table IV. Severity of complications was similar in the two
Lainas et al 131
Surgery Volume 158, Number 1
Table II. Intraoperative results
Duration of surgery, min Blood loss, mL Transfusion, n (%) Use of portal triad clamping, n (%) Conversion to open surgery, n (%)
Right hepatectomy group (n = 45)
Right hepatectomy + diaphragm resection group (n = 7)
P value
272.3 ± 12.4 480.7 ± 92.6 8 (17.7) 3 (6.6) 5 (11.1)
345.0 ± 34.1 440.0 ± 124.8 1 (14.3) 3 (42.8) 1 (14.3)
.06 .69 1.00 .02 1.00
Table III. Oncologic results
Maximum tumor size, mm Tumor size >5 cm, n (%) Single/multiple lesions Diaphragmatic invasion, n (%) Operative margin, mm
Right hepatectomy group (n = 45)
Right hepatectomy + diaphragm resection group (n = 7)
P value
37.1 ± 4.8 7 (15.5) 16/29 0 12.7 ± 3.2
74.5 ± 14.2 4 (57.1) 5/2 7 (100) 8.0 ± 1.5
.0024 .029 .10 <.001 .97
All P values in bold are significant.
Table IV. Postoperative morbidity and mortality Right hepatectomy group (n = 45) Mortality, n (%) Reoperation, n (%) Specific morbidity, n (%) Hemorrhage Liver failure/encephalopathy Biliary collection General morbidity, n (%) Pulmonary Renal Cardiovascular Parietal Other Severity of complications according to Clavien classification Grade I, II, III, IV, V Hospital stay, d
0 1 (2.2) 17 (37.7) 0 13 (28.9) 4 (8.9) 13 (28.9) 4 (8.8) 2 (4.4) 1 (2.2) 1 (2.2) 5 (11.1)
9, 12, 8, 1, 0 12.2 ± 1.7
groups according to the Clavien classification. In the ‘‘diaphragm’’ group, general morbidity consisted in pulmonary complications (n = 2); one patient experienced a pulmonary infection and the second one developed pleural empyema secondary to biliary intra-abdominal collection on postoperative day 9. This latter patient was treated with biliary stenting and pulmonary drainage for almost 3 months. Specific liver-related postoperative complications occurred in two (28.6%) patients in the ‘‘diaphragm’’ group and in 17 (37.7%) control group patients (P = .69). One patient required
Right hepatectomy + diaphragm resection group (n = 7)
2 1 1 2 2
0 0 (28.6) 0 (14.3) (14.3) (28.6) (28.6) 0 0 0 0
1, 2, 1, 0, 0 12.4 ± 3.3
P value — 1.00 .69 — .66 .53 1.00 .18 1.00 1.00 1.00 1.00
— .56
emergent reoperation on postoperative day 3 for small bowel perforation, probably to the result of injury by forceps manipulation during the initial intervention. The mean hospital stay after surgery was similar for both groups (12.2 vs. 12.4 days, P = .56). During follow-up, no ‘‘diaphragm’’ group patient experienced postoperative diaphragmatic hernia or some other important technical mishap specific to diaphragm resection. Survival and recurrence. The mean follow-up period was 36 months (range, 6–106 months). Two (28.6%) patients had adjuvant chemotherapy in
132 Lainas et al
the ‘‘diaphragm’’ group and 11 (24.4%) in the control group (P = 1.00). Twenty-two (42.3%) patients experienced recurrence during follow up, with no significant difference between the 2 groups (42.8 vs 42.2%, P = 1.00). In the ‘‘diaphragm’’ group, recurrence occurred in 3 patients: 2 patients had diffuse peritoneal carcinomatosis 1 and 3 months after resection and a third patient presented with simultaneous multiple liver and lung recurrence, which were distant to the site of primary resection (successfully treated by chemotherapy and liver radiofrequency twice). None of these recurrences was located in the diaphragm. The 1-, 3-, and 5-year overall survival after surgery in the ‘‘diaphragm’’ and control groups were 69%, 34%, and 34% and 97%, 83%, and 59%, respectively (P = .103) (Fig). The 1- and 3-year disease-free survival after surgery in the ‘‘diaphragm’’ and control groups were 57%, 47% and 75%, and 54%, respectively (P = .310). DISCUSSION LLR is an accepted alternative to open resection and might even have improved outcome in selected patients.12 Several recent comparative studies and meta-analysis have described advantages for LLR in terms of reduced blood loss and lower general morbidity with equivalent oncologic outcomes.5-10,26,27 Nevertheless, LLR usually is limited to small tumors (<4 cm) in the anterolateral segments (segments II-III-IVb-V and VI), and most studies are dominated by wedge resection.28 As experience with minimal access liver surgery grows, the indications for more complex procedures are expanding. Here, we have reported the first case series of laparoscopic right hepatectomy with en-bloc resection of the diaphragm. In the present series, we have showed the technical feasibility and safety of laparoscopic diaphragmatic resection in combination with right hepatectomy for CRLM without compromising the long-term survival. Regardless the operative approach, the impact of diaphragm invasion is poorly studied; since 1995, few surgical series evaluated specifically the surgical results of en-bloc liver and diaphragm resection.17,19,29 In a recent study by Li et al,21 in which they compared 192 patients who underwent concomitant liver and diaphragmatic resection with 192 patients who underwent only liver resection by open surgery, they concluded that the need for diaphragm resection at the time of hepatectomy increases postoperative morbidity but not mortality. However, Li et al21 did not assess longterm survival and oncological outcomes. Most
Surgery July 2015
Fig. Overall survival after surgery in the ‘‘diaphragm’’ (green line) and control (blue line) groups.
series described only resection of hepatocellular carcinoma (HCC) and rate of tumoral diaphragmatic involvement ranged from 3 to 8% of patients resected for HCC. Retrospective analysis showed no difference of postoperative mortality and morbidity between resected patients with or without en-bloc diaphragmatic resection, and authors then conclude that it is safe to combine diaphragmatic and liver resection. As to the oncologic outcomes, all 3 authors have shown similar survival rates between patients with HCC extended to diaphragm and control group, which justified surgical resection of HCC with diaphragmatic involvement. In the literature, no substantial data are available on the safety and the oncologic benefits of resection of CRLM extended to diaphragm. In the present series, the nonsignificant trend toward lower overall survival in the ‘‘diaphragm’’ group may be explained by the larger diameter of tumor and extended resection; however, diaphragmatic resection can be required each time a liver tumor has dense adhesion to the diaphragm in order to obtain free margin resection. Moreover, pleural opening facilitates mobilization of liver and avoids bleeding parenchymal tear or tumoral rupture. Nevertheless, some authors have suggested blunt dissection to avoid unnecessary combined resection of diaphragm29,30 based on the fact that the truly histological invasion of HCC to adjacent diaphragm has been reported between 7.1 and 50%.17,31 This attitude, however, can seriously compromise oncologic safety. In our study, all patients with diaphragmatic resection demonstrated
Lainas et al 133
Surgery Volume 158, Number 1
invasion as proven by histologic analysis. This result leads us to resect the diaphragm in cases of adhesion between diaphragm and tumor. Historically, liver tumors involving the diaphragm are a contraindication for a laparoscopic approach. The challenges are 3-fold: the first one that the location of such tumors in posterosuperior segments (IVa-VII-VIII) poses a major technical challenge. In this study, all lesions in the ‘‘diaphragm’’ group were located in posterior or posterosuperior segments. Exposure of deeply and posterior located lesions is intricate and bleeding control can be difficult due to the proximity of the hepatic veins. To address these difficulties, we performed major hepatectomy by anterior approach for lesions close to suprahepatic major branches. Interestingly, the Pringle maneuver was used more frequently in the ‘‘diaphragm’’ group, the reason being that tumors in this group were much larger and located in posterosuperior segments with difficult exposure and control of the hepatic veins major branches. In this complex situation, we advocated for a careful dissection, using the Pringle maneuver electively. The second technical limiting point is the pneumothorax disturbing the operative exposure. We were able to overcome this challenge in this series, with a transthoracic catheter used to evacuate pleural air and permitting to keep the diaphragm in a concave position. Chest radiography was systematically performed at postoperative day 1 and each time a patient reported pulmonary symptoms. The third difficulty is the diaphragmatic reconstruction: the right lobe blocks the view on the operative field during diaphragmatic repair. To avoid this problem, diaphragm was resected en-bloc at the end of the parenchymal transection and then sutured after removal of the specimen. In our experience, we always repair the diaphragm with running suture even in large defects, which is consistent with data reported by others surgical series (98% of primary repair).19,29 Insertion of a diaphragm prosthesis could be applied for very large defects (>10 cm diameter) and, although not necessary in our series, should be technically feasible by laparoscopy. The current study has several limitations. First, this study is a retrospective analysis from a prospectively maintained database that included a very limited sample size of patients undergoing right hepatectomy with en-bloc diaphragmatic resection. Second, all laparoscopy patients were operated in an expert center, which limits the reproducibility of these results. In that sense, we cannot yet recommend systematic use of laparoscopy for major
hepatectomy with concomitant diaphragmatic resection in nonexpert hands. As a conclusion, laparoscopic right hepatectomy associated with en-bloc diaphragmatic resection reasonably could be performed for selected patients in expert centers. Some technical difficulties specific to the diaphragmatic invasion have to be circumvented to achieve resection in a difficult operative site. Nevertheless, further experience must be gained to confirm the results of this case series. REFERENCES 1. Gagner M, Rogula T, Selzer D. Laparoscopic liver resection: benefits and controversies. Surg Clin North Am 2004;84: 451-62. 2. Gumbs AA, Gayet B. Video: the lateral laparoscopic approach to lesions in the posterior segments. J Gastrointest Surg 2008; 12:1154. 3. Buell JF, Cherqui D, Geller DA, et al. The international position on laparoscopic liver surgery: The Louisville Statement, 2008. Ann Surg 2009;250:825-30. 4. Nguyen KT, Laurent A, Dagher I, et al. Minimally invasive liver resection for metastatic colorectal cancer: a multiinstitutional, international report of safety, feasibility, and early outcomes. Ann Surg 2009;250:842-8. 5. Tzanis D, Shivathirthan N, Laurent A, et al. European experience of laparoscopic major hepatectomy. J Hepatobiliary Pancreat Sci 2013;20:120-4. 6. Dagher I, Di Giuro G, Dubrez J, et al. Laparoscopic versus open right hepatectomy: a comparative study. Am J Surg 2009;198:173-7. 7. Fancellu A, Rosman AS, Sanna V, et al. Meta-analysis of trials comparing minimally-invasive and open liver resections for hepatocellular carcinoma. J Surg Res 2011;171:e33-45. 8. Hu BS, Chen K, Tan HM, et al. Comparison of laparoscopic vs open liver lobectomy (segmentectomy) for hepatocellular carcinoma. World J Gastroenterol 2011;17:4725-8. 9. Lee KF, Chong CN, Wong J, et al. Long-term results of laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma: a case-matched analysis. World J Surg 2011;35:2268-74. 10. Gustafson JD, Fox JP, Ouellette JR, et al. Open versus laparoscopic liver resection: looking beyond the immediate postoperative period. Surg Endosc 2012;26:468-72. 11. Yin Z, Fan X, Ye H, et al. Short- and long-term outcomes after laparoscopic and open hepatectomy for hepatocellular carcinoma: a global systematic review and meta-analysis. Ann Surg Oncol 2013;20:1203-15. 12. Buell JF, Thomas MT, Rudich S, et al. Experience with more than 500 minimally invasive hepatic procedures. Ann Surg 2008;248:475-86. 13. Castaing D, Vibert E, Ricca L, et al. Oncologic results of laparoscopic versus open hepatectomy for colorectal liver metastases in two specialized centers. Ann Surg 2009;250:849-55. 14. Dagher I, O’Rourke N, Geller DA, et al. Laparoscopic major hepatectomy: an evolution in standard of care. Ann Surg 2009;250:856-60. 15. Gumbs AA, Gayet B. Adopting Gayet’s Techniques of totally laparoscopic liver surgery in the United States. Liver Cancer 2013;2:5-15. 16. Scudamore CH, Shackleton CR, Fache JS, et al. Diaphragmatic resection in association with right hepatectomy. Can J Surg 1990;33:21-4.
134 Lainas et al
17. Lau WY, Leung KL, Leung TW, et al. Resection of hepatocellular carcinoma with diaphragmatic invasion. Br J Surg 1995;82:264-6. 18. Leung KF, Chui AK, Leung KL, et al. Clinicopathological study of hepatocellular carcinoma with diaphragmatic involvement. Br J Surg 2001;88:681-2. 19. Lin MC, Wu CC, Chen JT, et al. Surgical results of hepatic resection for hepatocellular carcinoma with gross diaphragmatic invasion. Hepatogastroenterology 2005;52:1497-501. 20. Lordan JT, Riga A, Worthington TR, et al. Early and longterm outcomes of patients undergoing liver resection and diaphragm excision for advanced colorectal liver metastases. Ann R Coll Surg Engl 2009;91:483-8. 21. Li GZ, Sloane JL, Lidsky ME, et al. Simultaneous diaphragm and liver resection: a propensity-matched analysis of postoperative morbidity. J Am Coll Surg 2013;216:402-11. 22. Gayet B, Cavaliere D, Vibert E, et al. Totally laparoscopic right hepatectomy. Am J Surg 2007;194:685-9. 23. Gumbs AA, Gayet B. Multimedia article. Totally laparoscopic extended right hepatectomy. Surg Endosc 2008;22: 2076-7. 24. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205-13.
Surgery July 2015
25. Balzan S, Belghiti J, Farges O, et al. The ‘‘50-50 criteria’’ on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg 2005;242:824-8; discussion 828-9. 26. Mirnezami R, Mirnezami AH, Chandrakumaran K, et al. Short- and long-term outcomes after laparoscopic and open hepatic resection: systematic review and meta-analysis. HPB (Oxford) 2011;13:295-308. 27. Nguyen KT, Marsh JW, Tsung A, et al. Comparative benefits of laparoscopic vs open hepatic resection: a critical appraisal. Arch Surg 2011;146:348-56. 28. Vigano L, Tayar C, Laurent A, et al. Laparoscopic liver resection: a systematic review. J Hepatobiliary Pancreat Surg 2009;16:410-21. 29. Yamashita Y, Morita K, Iguchi T, et al. Surgical impacts of an en bloc resection of the diaphragm for hepatocellular carcinoma with gross diaphragmatic involvement. Surg Today 2011;41:101-6. 30. Ezaki T, Koyanagi N, Toyomasu T, et al. Appraisal of a manual blunt dissection for an intraoperative diagnosis of extrahepatic cancer invasion. Hepatogastroenterology 1998;45:1837-41. 31. Tung WY, Chau GY, Loong CC, et al. Surgical resection of primary hepatocellular carcinoma extending to adjacent organ(s). Eur J Surg Oncol 1996;22:516-20.
Background. The impact of diaphragmatic invasion in patients with colorectal liver metastases (CRLMs) remains poorly evaluated. We aimed to evaluate feasibility and safety of laparoscopic right hepatectomy (LRH) with or without diaphragmatic resection for CRLM. Methods. From 2002 to 2012, 52 patients underwent LRH for CRLM. Of them, 7 patients had combined laparoscopic partial diaphragmatic resection (‘‘diaphragm’’ group). Data were retrospectively collected and short and long-term outcomes analyzed. Results. Operative time was lower in the control group (272 vs 345 min, P = .06). Six patients required conversion to open surgery. Blood loss and transfusion rate were similar. Portal triad clamping was used more frequently in the ‘‘diaphragm’’ group (42.8% vs 6.6%, P = .02). Maximum tumor size was greater in the ‘‘diaphragm’’ group (74.5 vs 37.1 mm, P = .002). Resection margin was negative in all cases. Mortality was nil and general morbidity similar in the 2 groups. Specific liver-related complications occurred in 2 patients in the ‘‘diaphragm’’ group and 17 in the control group (P = .69). Mean hospital stay was similar (P = 56). Twenty-two (42.3%) patients experienced recurrence. One-, 3-, and 5-year overall survival after surgery in ‘‘diaphragm’’ and control groups were 69%, 34%, 34%, and 97%, 83%, 59%, respectively (P = .103). One- and 3-year disease-free survival after surgery in ‘‘diaphragm’’ and control groups were 57%, 47% and 75%, 54%, respectively (P = .310). Conclusion. LRH with en-bloc diaphragmatic resection could be reasonably performed for selected patients in expert centers. Technical difficulties related to diaphragmatic invasion must be circumvented. Further experience must be gained to confirm our results. (Surgery 2015;158:128-34.) From the Department of Digestive Pathology,a Institut Mutualiste Montsouris, Paris Descartes University, Paris, France; and Department of Surgery,b Massachusetts General Hospital, Harvard Medical School, Boston, MA
DURING THE LAST 20 YEARS, laparoscopic liver surgery has seen an incredible proliferation worldwide. The feasibility and safety of laparoscopy for liver resections have been demonstrated and the indications are expanding.1-5 Benefits of reduced blood loss, lesser hospital stay, less postoperative pain, and lower general morbidity have been reported Accepted for publication February 1, 2015. Reprint requests: Brice Gayet, MD, PhD, Department of Digestive Disease, Institut Mutualiste Montsouris, Universit e Paris Descartes, 42 Boulevard Jourdan, 75014 Paris, France. E-mail: [email protected]. 0039-6060/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2015.02.003
128 SURGERY
for the laparoscopic approach compared to open surgery in recent retrospective studies.6-11 This minimally invasive approach, however, is mostly performed in highly specialized centers.12-15 Furthermore, the technical difficulties for the correct oncologic resection of liver tumors that extend to adjacent organs have been considered until recently as a contraindication for a laparoscopic approach. Hence, large peripherally located tumors of the liver present a major challenge to surgeons. In such cases, the anatomic location of the tumor may grossly involve the diaphragm by dense adhesion or direct histologic invasion of the latter. To achieve negative surgical margins in these patients, hepatectomy with simultaneous en-bloc diaphragmatic
Surgery Volume 158, Number 1
resection may be necessary. Combined hepatectomy and diaphragmatic resection has been reported in open surgery, but mainly single cases and few series are available with controversial results regarding postoperative and oncological course.16-21 Our established experience with laparoscopic major hepatectomy and laparoscopic diaphragmatic hernia repair surgery as well as the encouraging literature results of open surgery for liver tumors invading the diaphragm, have led us to selectively expand our indications for minimally invasive liver resection in cases of concomitant diaphragmatic involvement. In this series, we report our preliminary short and long-term results on the feasibility and safety of laparoscopic liver resection (LLR) for colorectal liver metastases (CRLMs) involving the diaphragm. METHODS Study population. This retrospective analysis was carried out using a prospectively collected database of all patients who underwent elective LLR between January 2002 and December 2012 at the Institut Mutualiste Montsouris, Paris, France. All patients undergoing laparoscopic right hepatectomy for CRLM were selected. Patients with combined diaphragmatic resection were compared with patients without diaphragmatic resection in terms of demographic data, intraoperative factors, tumor pathology, short-and long-term outcomes. This study was approved by the institutional review board. Operative procedures. All procedures were performed mainly by a single surgeon (B.G.). The operative technique of laparoscopic right hepatectomy, including the positioning of the trocars, has been previously described.22,23 In brief, all resections were performed with curative intent. Laparoscopic ultrasonography was performed routinely to confirm the number of lesions, their size, and their relationship with the intrahepatic vascular structures and hepatic vein anatomy. Liver parenchyma transection was performed by the ultrasonic dissector, primarily SonoSurg or Harmonic (Ethicon Endo-Surgery, Inc, Cincinnati, OH) and more recently Thunderbeat (Olympus Co, Tokyo). The Gayet bipolar forceps (MicroFrance BG-CEV134, Medtronic, Minneapolis, MN) provided retraction and rescue hemostasis. Portal triad clamping was not used routinely except in case of failure of bleeding control. The final step of the operations included resection of the involved diaphragm en-bloc with the involved liver. During each hepatectomy, the diaphragm was opened with ultrasonic shears. A transthoracic
Lainas et al 129
small catheter was then introduced into the pleural cavity to avoid diaphragmatic cupping. Then the involved portion of diaphragm was resected en-bloc with the tumor and repaired with a nonabsorbable running suture. At the end of the diaphragmatic closure, the anesthesiologist ventilated the patient manually with defined pressure settings to evacuate the carbon dioxide pneumothorax. A pleural drainage was not inserted routinely after diaphragmatic resection. Operative and postoperative outcomes. Primary clinical outcomes included operative time, blood loss, conversion rate, intraoperative complications, characteristics of the underlying liver parenchyma, and postoperative morbidity and mortality. All cases of conversion to laparotomy were noted, and results were analyzed on an intention-to-treat basis. Postoperative complications were graded according to the modified Clavien-Dindo classification24 and major complications were defined as Clavien-Dindo $3. Liver specific complications included: liver failure defined according to the ‘‘50–50 criteria’’ on postoperative day 525; hemorrhage was defined as a decrease of hemoglobin levels >3 g/dL after the end of surgery compared with postoperative baseline levels and/or any postoperative transfusion of packed red blood cell units for a decreasing hemoglobin and/or the need for invasive reintervention; ascites was defined as an abdominal drainage output of more than 10 mL per kg per day after the third postoperative day; and biliary leakage was defined by a bilirubin concentration in the drainage fluid more than 3-fold greater than that in the serum. Both complications and operative mortality were events that occurred within 90 days of surgery or at any time during the postoperative hospital stay. Pathologic resection margin was classified into R0 (microscopically more than 1 mm from resection margin) and R1 (microscopically less than 1 mm from resection margin). During follow-up, patients were seen at the outpatient clinic for a clinical examination, a biologic markers control (carcinoembryonic antigen, carbohydrate antigen 19-9), and a morphologic evaluation (computed tomography or magnetic resonance imaging) 1 month after discharge, every 3 months for the first 2 years and every 6 months until the 5th postoperative year. Thereafter, patients were seen yearly. Followup is discontinued in the absence of recurrence after the 10th year following intervention. Statistical analysis. The patients’ baseline characteristics were expressed as a mean ± SEM for continuous data and as numbers with percentages
130 Lainas et al
Surgery July 2015
Table I. Demographic preoperative characteristics
Patients Sex, F/M Age, y ASA, 1/2/3 BMI Underlying liver, n (%) Normal/steatosis Chemotherapy lesions Cirrhosis Preoperative comorbidities, n (%) Diabetes mellitus Hypertension HBV/HCV infection Dyslipidemia COPD Previous abdominal surgery, n (%) Previous liver surgery, n (%)
Right hepatectomy group (n = 45)
Right hepatectomy + diaphragm resection group (n = 7)
P
17/28 64.1 ± 1.7 6/32/7 24.9 ± 0.7
3/4 63.4 ± 4.8 0/6/1 27.1 ± 2.5
1.00 .77 .57 .52
28 (62.2) 17 (37.8) 0
4 (57.1) 3 (42.9) 0
1.00 1.00 —
3 (6.6) 11 (24.4) 0 8 (17.7) 6 (13.3) 41 (91.1) 10 (22.2)
0 1 (14.3) 0 0 0 5 (71.4) 2 (28.5)
1.00 1.00 — .58 1.00 .18 .65
ASA, American Society of Anesthesiologists physical status score; BMI, body mass index; COPD, chronic obstructive pulmonary disease; HBV, hepatitis B virus; HCV, hepatitis C virus.
for categorical data. Preoperative, operative, and postoperative characteristics, as well as long-term survival of patients, were compared according to the procedure (LLR with diaphragm resection versus no diaphragm resection). The Fisher exact test or v2 test was used to compare differences in categorical variables, and the Wilcoxon rank sum test was used for continuous variables. Overall survival was defined as time from surgery to death (all causes). Cumulative overall survival rates were determined using the Kaplan–Meier method and compared with the log rank test. All statistical analyses were performed using the SPSS for Windows version 20.0 (SPSS, IBM, Armonk, NY). RESULTS Preoperative characteristics. Among selected patients, 7 underwent combined laparoscopic right hepatectomy with partial diaphragmatic resection (‘‘diaphragm’’ group), and 45 other patients underwent laparoscopic right hepatectomy without diaphragmatic resection (control group). All lesions in the ‘‘diaphragm’’ group were located in posterior or posterosuperior segments. As detailed in Table I, the 2 groups were comparable regarding sex, age, American Society of Anesthesiologists physical status score, underlying liver status, comorbidities, and previous abdominal and liver surgery. Thirty (57.6%) patients had neoadjuvant chemotherapy (median number of cycles n = 6) with no difference in the 2 groups (60 vs 45%, P = .96).
Intraoperative and pathologic results. The intraoperative results are shown in Table II. Operative time was lower in the control group but the difference did not reach statistical significance (272 vs 345 minutes, P = .06). Six patients required conversion to open surgery and were analyzed with the laparoscopic groups on an intention-to-treat basis. One ‘‘diaphragm’’ group patient (14.3%) required conversion through a pre-existing cholecystectomy incision, at the end of laparoscopic liver and diaphragmatic resection, because laparoscopic repair of the diaphragm was not possible by laparoscopy because of the absence of pneumoperitoneum after the diaphragm was opened. In the control group, 5 (11.1%) patients required conversion to open surgery because of intraoperative bleeding during parenchymal transection (>900 mL). Intraoperative blood loss and transfusion rate were similar in both groups but portal triad clamping was used more frequently in the ‘‘diaphragm’’ group (42.8% vs 6.6%, P = .02). Histopathologic analysis confirmed diaphragmatic invasion in all 7 patients in the ‘‘diaphragm’’ group (Table III). The maximum tumor size was significantly greater in the ‘‘diaphragm’’ group (74.5 vs 37.1 mm, P = .002). Resection margin was negative in all cases. None of the patients had lymph node involvement. Postoperative outcomes. Mortality was nil and general morbidity was similar in the 2 groups (28.6% vs 28.9%, P = 1.00), as shown in Table IV. Severity of complications was similar in the two
Lainas et al 131
Surgery Volume 158, Number 1
Table II. Intraoperative results
Duration of surgery, min Blood loss, mL Transfusion, n (%) Use of portal triad clamping, n (%) Conversion to open surgery, n (%)
Right hepatectomy group (n = 45)
Right hepatectomy + diaphragm resection group (n = 7)
P value
272.3 ± 12.4 480.7 ± 92.6 8 (17.7) 3 (6.6) 5 (11.1)
345.0 ± 34.1 440.0 ± 124.8 1 (14.3) 3 (42.8) 1 (14.3)
.06 .69 1.00 .02 1.00
Table III. Oncologic results
Maximum tumor size, mm Tumor size >5 cm, n (%) Single/multiple lesions Diaphragmatic invasion, n (%) Operative margin, mm
Right hepatectomy group (n = 45)
Right hepatectomy + diaphragm resection group (n = 7)
P value
37.1 ± 4.8 7 (15.5) 16/29 0 12.7 ± 3.2
74.5 ± 14.2 4 (57.1) 5/2 7 (100) 8.0 ± 1.5
.0024 .029 .10 <.001 .97
All P values in bold are significant.
Table IV. Postoperative morbidity and mortality Right hepatectomy group (n = 45) Mortality, n (%) Reoperation, n (%) Specific morbidity, n (%) Hemorrhage Liver failure/encephalopathy Biliary collection General morbidity, n (%) Pulmonary Renal Cardiovascular Parietal Other Severity of complications according to Clavien classification Grade I, II, III, IV, V Hospital stay, d
0 1 (2.2) 17 (37.7) 0 13 (28.9) 4 (8.9) 13 (28.9) 4 (8.8) 2 (4.4) 1 (2.2) 1 (2.2) 5 (11.1)
9, 12, 8, 1, 0 12.2 ± 1.7
groups according to the Clavien classification. In the ‘‘diaphragm’’ group, general morbidity consisted in pulmonary complications (n = 2); one patient experienced a pulmonary infection and the second one developed pleural empyema secondary to biliary intra-abdominal collection on postoperative day 9. This latter patient was treated with biliary stenting and pulmonary drainage for almost 3 months. Specific liver-related postoperative complications occurred in two (28.6%) patients in the ‘‘diaphragm’’ group and in 17 (37.7%) control group patients (P = .69). One patient required
Right hepatectomy + diaphragm resection group (n = 7)
2 1 1 2 2
0 0 (28.6) 0 (14.3) (14.3) (28.6) (28.6) 0 0 0 0
1, 2, 1, 0, 0 12.4 ± 3.3
P value — 1.00 .69 — .66 .53 1.00 .18 1.00 1.00 1.00 1.00
— .56
emergent reoperation on postoperative day 3 for small bowel perforation, probably to the result of injury by forceps manipulation during the initial intervention. The mean hospital stay after surgery was similar for both groups (12.2 vs. 12.4 days, P = .56). During follow-up, no ‘‘diaphragm’’ group patient experienced postoperative diaphragmatic hernia or some other important technical mishap specific to diaphragm resection. Survival and recurrence. The mean follow-up period was 36 months (range, 6–106 months). Two (28.6%) patients had adjuvant chemotherapy in
132 Lainas et al
the ‘‘diaphragm’’ group and 11 (24.4%) in the control group (P = 1.00). Twenty-two (42.3%) patients experienced recurrence during follow up, with no significant difference between the 2 groups (42.8 vs 42.2%, P = 1.00). In the ‘‘diaphragm’’ group, recurrence occurred in 3 patients: 2 patients had diffuse peritoneal carcinomatosis 1 and 3 months after resection and a third patient presented with simultaneous multiple liver and lung recurrence, which were distant to the site of primary resection (successfully treated by chemotherapy and liver radiofrequency twice). None of these recurrences was located in the diaphragm. The 1-, 3-, and 5-year overall survival after surgery in the ‘‘diaphragm’’ and control groups were 69%, 34%, and 34% and 97%, 83%, and 59%, respectively (P = .103) (Fig). The 1- and 3-year disease-free survival after surgery in the ‘‘diaphragm’’ and control groups were 57%, 47% and 75%, and 54%, respectively (P = .310). DISCUSSION LLR is an accepted alternative to open resection and might even have improved outcome in selected patients.12 Several recent comparative studies and meta-analysis have described advantages for LLR in terms of reduced blood loss and lower general morbidity with equivalent oncologic outcomes.5-10,26,27 Nevertheless, LLR usually is limited to small tumors (<4 cm) in the anterolateral segments (segments II-III-IVb-V and VI), and most studies are dominated by wedge resection.28 As experience with minimal access liver surgery grows, the indications for more complex procedures are expanding. Here, we have reported the first case series of laparoscopic right hepatectomy with en-bloc resection of the diaphragm. In the present series, we have showed the technical feasibility and safety of laparoscopic diaphragmatic resection in combination with right hepatectomy for CRLM without compromising the long-term survival. Regardless the operative approach, the impact of diaphragm invasion is poorly studied; since 1995, few surgical series evaluated specifically the surgical results of en-bloc liver and diaphragm resection.17,19,29 In a recent study by Li et al,21 in which they compared 192 patients who underwent concomitant liver and diaphragmatic resection with 192 patients who underwent only liver resection by open surgery, they concluded that the need for diaphragm resection at the time of hepatectomy increases postoperative morbidity but not mortality. However, Li et al21 did not assess longterm survival and oncological outcomes. Most
Surgery July 2015
Fig. Overall survival after surgery in the ‘‘diaphragm’’ (green line) and control (blue line) groups.
series described only resection of hepatocellular carcinoma (HCC) and rate of tumoral diaphragmatic involvement ranged from 3 to 8% of patients resected for HCC. Retrospective analysis showed no difference of postoperative mortality and morbidity between resected patients with or without en-bloc diaphragmatic resection, and authors then conclude that it is safe to combine diaphragmatic and liver resection. As to the oncologic outcomes, all 3 authors have shown similar survival rates between patients with HCC extended to diaphragm and control group, which justified surgical resection of HCC with diaphragmatic involvement. In the literature, no substantial data are available on the safety and the oncologic benefits of resection of CRLM extended to diaphragm. In the present series, the nonsignificant trend toward lower overall survival in the ‘‘diaphragm’’ group may be explained by the larger diameter of tumor and extended resection; however, diaphragmatic resection can be required each time a liver tumor has dense adhesion to the diaphragm in order to obtain free margin resection. Moreover, pleural opening facilitates mobilization of liver and avoids bleeding parenchymal tear or tumoral rupture. Nevertheless, some authors have suggested blunt dissection to avoid unnecessary combined resection of diaphragm29,30 based on the fact that the truly histological invasion of HCC to adjacent diaphragm has been reported between 7.1 and 50%.17,31 This attitude, however, can seriously compromise oncologic safety. In our study, all patients with diaphragmatic resection demonstrated
Lainas et al 133
Surgery Volume 158, Number 1
invasion as proven by histologic analysis. This result leads us to resect the diaphragm in cases of adhesion between diaphragm and tumor. Historically, liver tumors involving the diaphragm are a contraindication for a laparoscopic approach. The challenges are 3-fold: the first one that the location of such tumors in posterosuperior segments (IVa-VII-VIII) poses a major technical challenge. In this study, all lesions in the ‘‘diaphragm’’ group were located in posterior or posterosuperior segments. Exposure of deeply and posterior located lesions is intricate and bleeding control can be difficult due to the proximity of the hepatic veins. To address these difficulties, we performed major hepatectomy by anterior approach for lesions close to suprahepatic major branches. Interestingly, the Pringle maneuver was used more frequently in the ‘‘diaphragm’’ group, the reason being that tumors in this group were much larger and located in posterosuperior segments with difficult exposure and control of the hepatic veins major branches. In this complex situation, we advocated for a careful dissection, using the Pringle maneuver electively. The second technical limiting point is the pneumothorax disturbing the operative exposure. We were able to overcome this challenge in this series, with a transthoracic catheter used to evacuate pleural air and permitting to keep the diaphragm in a concave position. Chest radiography was systematically performed at postoperative day 1 and each time a patient reported pulmonary symptoms. The third difficulty is the diaphragmatic reconstruction: the right lobe blocks the view on the operative field during diaphragmatic repair. To avoid this problem, diaphragm was resected en-bloc at the end of the parenchymal transection and then sutured after removal of the specimen. In our experience, we always repair the diaphragm with running suture even in large defects, which is consistent with data reported by others surgical series (98% of primary repair).19,29 Insertion of a diaphragm prosthesis could be applied for very large defects (>10 cm diameter) and, although not necessary in our series, should be technically feasible by laparoscopy. The current study has several limitations. First, this study is a retrospective analysis from a prospectively maintained database that included a very limited sample size of patients undergoing right hepatectomy with en-bloc diaphragmatic resection. Second, all laparoscopy patients were operated in an expert center, which limits the reproducibility of these results. In that sense, we cannot yet recommend systematic use of laparoscopy for major
hepatectomy with concomitant diaphragmatic resection in nonexpert hands. As a conclusion, laparoscopic right hepatectomy associated with en-bloc diaphragmatic resection reasonably could be performed for selected patients in expert centers. Some technical difficulties specific to the diaphragmatic invasion have to be circumvented to achieve resection in a difficult operative site. Nevertheless, further experience must be gained to confirm the results of this case series. REFERENCES 1. Gagner M, Rogula T, Selzer D. Laparoscopic liver resection: benefits and controversies. Surg Clin North Am 2004;84: 451-62. 2. Gumbs AA, Gayet B. Video: the lateral laparoscopic approach to lesions in the posterior segments. J Gastrointest Surg 2008; 12:1154. 3. Buell JF, Cherqui D, Geller DA, et al. The international position on laparoscopic liver surgery: The Louisville Statement, 2008. Ann Surg 2009;250:825-30. 4. Nguyen KT, Laurent A, Dagher I, et al. Minimally invasive liver resection for metastatic colorectal cancer: a multiinstitutional, international report of safety, feasibility, and early outcomes. Ann Surg 2009;250:842-8. 5. Tzanis D, Shivathirthan N, Laurent A, et al. European experience of laparoscopic major hepatectomy. J Hepatobiliary Pancreat Sci 2013;20:120-4. 6. Dagher I, Di Giuro G, Dubrez J, et al. Laparoscopic versus open right hepatectomy: a comparative study. Am J Surg 2009;198:173-7. 7. Fancellu A, Rosman AS, Sanna V, et al. Meta-analysis of trials comparing minimally-invasive and open liver resections for hepatocellular carcinoma. J Surg Res 2011;171:e33-45. 8. Hu BS, Chen K, Tan HM, et al. Comparison of laparoscopic vs open liver lobectomy (segmentectomy) for hepatocellular carcinoma. World J Gastroenterol 2011;17:4725-8. 9. Lee KF, Chong CN, Wong J, et al. Long-term results of laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma: a case-matched analysis. World J Surg 2011;35:2268-74. 10. Gustafson JD, Fox JP, Ouellette JR, et al. Open versus laparoscopic liver resection: looking beyond the immediate postoperative period. Surg Endosc 2012;26:468-72. 11. Yin Z, Fan X, Ye H, et al. Short- and long-term outcomes after laparoscopic and open hepatectomy for hepatocellular carcinoma: a global systematic review and meta-analysis. Ann Surg Oncol 2013;20:1203-15. 12. Buell JF, Thomas MT, Rudich S, et al. Experience with more than 500 minimally invasive hepatic procedures. Ann Surg 2008;248:475-86. 13. Castaing D, Vibert E, Ricca L, et al. Oncologic results of laparoscopic versus open hepatectomy for colorectal liver metastases in two specialized centers. Ann Surg 2009;250:849-55. 14. Dagher I, O’Rourke N, Geller DA, et al. Laparoscopic major hepatectomy: an evolution in standard of care. Ann Surg 2009;250:856-60. 15. Gumbs AA, Gayet B. Adopting Gayet’s Techniques of totally laparoscopic liver surgery in the United States. Liver Cancer 2013;2:5-15. 16. Scudamore CH, Shackleton CR, Fache JS, et al. Diaphragmatic resection in association with right hepatectomy. Can J Surg 1990;33:21-4.
134 Lainas et al
17. Lau WY, Leung KL, Leung TW, et al. Resection of hepatocellular carcinoma with diaphragmatic invasion. Br J Surg 1995;82:264-6. 18. Leung KF, Chui AK, Leung KL, et al. Clinicopathological study of hepatocellular carcinoma with diaphragmatic involvement. Br J Surg 2001;88:681-2. 19. Lin MC, Wu CC, Chen JT, et al. Surgical results of hepatic resection for hepatocellular carcinoma with gross diaphragmatic invasion. Hepatogastroenterology 2005;52:1497-501. 20. Lordan JT, Riga A, Worthington TR, et al. Early and longterm outcomes of patients undergoing liver resection and diaphragm excision for advanced colorectal liver metastases. Ann R Coll Surg Engl 2009;91:483-8. 21. Li GZ, Sloane JL, Lidsky ME, et al. Simultaneous diaphragm and liver resection: a propensity-matched analysis of postoperative morbidity. J Am Coll Surg 2013;216:402-11. 22. Gayet B, Cavaliere D, Vibert E, et al. Totally laparoscopic right hepatectomy. Am J Surg 2007;194:685-9. 23. Gumbs AA, Gayet B. Multimedia article. Totally laparoscopic extended right hepatectomy. Surg Endosc 2008;22: 2076-7. 24. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205-13.
Surgery July 2015
25. Balzan S, Belghiti J, Farges O, et al. The ‘‘50-50 criteria’’ on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy. Ann Surg 2005;242:824-8; discussion 828-9. 26. Mirnezami R, Mirnezami AH, Chandrakumaran K, et al. Short- and long-term outcomes after laparoscopic and open hepatic resection: systematic review and meta-analysis. HPB (Oxford) 2011;13:295-308. 27. Nguyen KT, Marsh JW, Tsung A, et al. Comparative benefits of laparoscopic vs open hepatic resection: a critical appraisal. Arch Surg 2011;146:348-56. 28. Vigano L, Tayar C, Laurent A, et al. Laparoscopic liver resection: a systematic review. J Hepatobiliary Pancreat Surg 2009;16:410-21. 29. Yamashita Y, Morita K, Iguchi T, et al. Surgical impacts of an en bloc resection of the diaphragm for hepatocellular carcinoma with gross diaphragmatic involvement. Surg Today 2011;41:101-6. 30. Ezaki T, Koyanagi N, Toyomasu T, et al. Appraisal of a manual blunt dissection for an intraoperative diagnosis of extrahepatic cancer invasion. Hepatogastroenterology 1998;45:1837-41. 31. Tung WY, Chau GY, Loong CC, et al. Surgical resection of primary hepatocellular carcinoma extending to adjacent organ(s). Eur J Surg Oncol 1996;22:516-20.