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Press review
Journal of Visceral Surgery (2015) 152, 125—132
Available online at
ScienceDirect www.sciencedirect.com
Press review C. Mariette a,∗, S. Benoist b a
Service de chirurgie digestive et générale, hôpital C.-Huriez, CHRU, place de Verdun, 59037 Lille cedex, France b Service de chirurgie digestive, hôpital du Kremlin-Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France Available online 6 March 2015 䊏
Chau A, Maggiori L, Debove C, Kanso F, Hennequin C, Panis Y. Toward the end of abdominoperineal resection for rectal cancer? An 8-year experience in 189 consecutive patients with low rectal cancer. Ann Surg 2014;260:801—5. doi: 10.1097/SLA.0000000000000979
Objectives To assess whether recent advances, such as intersphincteric resection (ISR) or local excision (LE) if a suspicion of complete tumor response after radiochemotherapy (RCT), could have modified the rate of end stoma (ES) in low rectal cancer treatment. Background ES rate remains around 30% to 50% in patients with low rectal cancer. Method From 2005 to 2013, all patients with low rectal cancer undergoing laparoscopic total mesorectal excision, with or without neoadjuvant RCT, and patients undergoing LE after RCT were included. Results A total of 189 patients presented a low rectal cancer; 162 (86%) underwent RCT; total mesorectal excision was performed in 172 (90%), followed by stapled colorectal anastomosis (n = 26; 15%), manual coloanal anastomosis with partial (n = 92; 53%) or total ISR (n = 32; 19%), or ES that included abdominoperineal resection (n = 21; 12%) and low Hartmann procedure (n = 1; 1%). LE after RCT was performed in 19 of 189 (10%) patients with a suspicion of complete tumor response. Among them, 2 of 19 (11%) underwent immediate secondary total mesorectal excision (1 abdominoperineal resection and 1 coloanal anastomosis with total ISR) because of poor pathological criteria.
∗
Corresponding author. E-mail address: [email protected] (C. Mariette).
1878-7886/$ — see front matter http://dx.doi.org/10.1016/j.jviscsurg.2015.02.009
Conclusions Management of rectal cancer with colorectal anastomosis and coloanal anastomosis with partial ISR allowed to obtain a 38% ES rate (71/189); the additional use of total ISR decreased this rate to 22% (39/189). Selective use of LE reduced this rate to only 12% (22/189). Nowadays, recent advances lead to a paradigm shift, with only 12% ES rate in low rectal cancer. Comments 1. These excellent results should be compared with those of the literature and in particular with the 25% and 27% definitive stoma rates found in the two largest randomized studies comparing laparoscopic vs. open surgery [1,2], and the 35% in the Dutch study [3]. This rate reaches 51% in two recent population studies [4,5]. 2. Of note, the authors’ R1 resection rate is high: 17%, even taking into consideration that recent studies suggest that R1 in expert centers is more often related to tumor aggressiveness than to surgical inadequacy? [6]. 3. The results reported here are immediate outcomes that do not take into account the long-term functional consequences and especially those patients who had a definitive stoma secondarily, leading to poor quality of life References [1] Surg Endosc 2012;27:295—302. [2] Lancet Oncol 2013;14:210—8. [3] Lancet Oncol 2011;12:575—82. [4] Dis Colon Rectum 2013;56:704—10. [5] Dis Colon Rectum 2011;54:1205—10. [6] Ann Surg 2014; 260:794—9. 䊏
Regimbeau JM, Fuks D, Pautrat K, et al. FRENCH Study Group. Effect of postoperative antibiotic administration on postoperative infection following cholecystectomy for acute calculous cholecystitis: A randomized clinical trial. JAMA 2014;312:145—54. doi:10.1001/jama.2014.7586
126 Importance Ninety percent of cases of acute calculous cholecystitis are of mild (grade I) or moderate (grade II) severity. Although the preoperative and intraoperative antibiotic management of acute calculous cholecystitis has been standardized, few data exist on the utility of postoperative antibiotic treatment. Objectives To determine the effect of postoperative amoxicillin plus clavulanic acid on infection rates after cholecystectomy. Design, setting, and patients A total of 414 patients treated at 17 medical centers for grade I or II acute calculous cholecystitis and who received 2 g of amoxicillin plus clavulanic acid 3 times a day while in the hospital before and once at the time of surgery were randomized after surgery to an open-label, non-inferiority, randomized clinical trial between May 2010 and August 2012. Interventions After surgery, no antibiotics or continue with the preoperative antibiotic regimen 3 times daily for 5 days. Main outcomes and measures The proportion of postoperative surgical site or distant infections recorded before or at the 4-week follow-up visit. Results An imputed intention-to-treat analysis of 414 patients showed that the postoperative infection rates were 17% (35 of 207) in the non-treatment group and 15% (31 of 207) in the antibiotic group (absolute difference, 1.93%; 95% CI, —8.98% to 5.12%). In the per-protocol analysis, which involved 338 patients, the corresponding rates were both 13% (absolute difference, 0.3%; 95% CI, —5.0% to 6.3%). Based on a non-inferiority margin of 11%, the lack of postoperative antibiotic treatment was not associated with worse outcomes than antibiotic treatment. Bile cultures showed that 60.9% were pathogen free. Both groups had similar Clavien complication severity outcomes: 195 patients (94.2%) in the non-treatment group had a score of 0 to I and 2 patients (0.97%) had a score of III to V, and 182 patients (87.8%) in the antibiotic group had a score of 0 to I and 4 patients (1.93%) had a score of III to V. Conclusions and relevance Among patients with mild or moderate calculous cholecystitis who received preoperative and intraoperative antibiotics, lack of postoperative treatment with amoxicillin plus clavulanic acid did not result in a greater incidence of postoperative infections. Comments 1. Cholecystectomy for acute calculous cholecystitis represents the third most frequent surgical emergency; most patients receive postoperative therapeutic antibiotics with the intention of reducing the infective complication rates, based on the idea that bile is infected in 40 to 60% of patients [1]. This trial shows that routine postoperative antibiotics are not needed. 2. Interestingly, bile was found to be sterile in 60.9% of patients. In patients with infected bile, the pathogens identified (n = 206) varied widely, with 28% being resistant to the prescribed antimicrobials. In this subgroup, no difference in outcome was found between the two groups. 3. This new publication with a high level of evidence highlights the dynamism of French multicenter clinical research and the prominent role played by the
C. Mariette, S. Benoist French research working party (Fédération franc¸aise de recherche en chirurgie digestive). Reference [1] J Infect 2005:51:128—34.
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Adam MA, Pura J, Gu L, et al. Extent of surgery for papillary thyroid cancer is not associated with survival: An analysis of 61,775 patients. Ann Surg 2014;260:601—5. doi:10.1097/SLA.0000000000000925.
Objective To examine the association between the extent of surgery and overall survival in a large contemporary cohort of patients with papillary thyroid cancer (PTC). Background Guidelines recommend total thyroidectomy for PTC tumors > 1 cm, based on older data demonstrating an overall survival advantage for total thyroidectomy over lobectomy. Methods Adult patients with PTC tumors 1.0—4.0 cm undergoing thyroidectomy in the National Cancer Database, 1998—2006, were included. Cox proportional hazards models were applied to measure the association between the extent of surgery and overall survival while adjusting for patient demographic and clinical factors, including comorbidities, extrathyroidal extension, multifocality, nodal and distant metastases, and radioactive iodine treatment. Results Among 61,775 PTC patients, 54,926 underwent total thyroidectomy and 6849 lobectomy. Compared with lobectomy, patients undergoing total thyroidectomy had more nodal (7% vs 27%), extrathyroidal (5% vs 16%), and multifocal disease (29% vs 44%) (all P < 0.001). Median follow-up was 82 months (range, 60—179 months). After multivariable adjustment, overall survival was similar in patients undergoing total thyroidectomy versus lobectomy for tumors 1.0—4.0 cm [hazard ratio (HR) = 0.96; 95% confidence interval (CI), 0.84—1.09; P = 0.54] and when stratified by tumor size: 1.0—2.0 cm [HR = 1.05; 95% CI, 0.88—1.26; P = 0.61] and 2.1—4.0 cm [HR = 0.89; 95% CI, 0.73—1.07; P = 0.21]. Older age, male sex, black race, lower income, tumor size, and presence of nodal or distant metastases were independently associated with compromised survival (P < 0.0001). Conclusions Current guidelines suggest total thyroidectomy for PTC tumors > 1 cm. However, we did not observe a survival advantage associated with total thyroidectomy compared with lobectomy. These findings call into question whether tumor size should be an absolute indication for total thyroidectomy. Comments 1. Survival after optimally treated papillary thyroid cancer (PTC) is close to 90% at 20 years. While the current recommendations suggest total or subtotal thyroidectomy for PTC > 1 cm [1], the authors did not find any benefit for totalization for tumors between 1 to 4 cm, after adjusting for confounding factors, such as comorbidities, multifocality, lymph node or metastatic involvement as well as the complete character of resection. 2. The theoretic advantage of total thyroidectomy is to treat potential multifocal contra-lateral lesions;
Press review however, this is counterbalanced by increased morbidity (hypocalcemia and recurrent nerve paralysis), making its value debatable in a cancer with such a good prognosis. 3. These data confirm recent information emanating from the American SEER database containing data on 22,724 analyzed patients [2]. 4. Of note, for a cancer with such good prognosis, this study is limited by the lack of information on recurrence and cancer-specific survival, which could have helped define the risk profiles for individual patients and then lead to selective proposal of totalization. References [1] Thyroid 2009;19:1167—1214. [2] Arch Otolaryngol Head Neck Surg 2010;136:1055—61. 䊏
Sauvanet A, Gaujoux S, Blanc B, et al. Parenchyma-sparing pancreatectomy for presumed noninvasive intraductal papillary mucinous neoplasms of the pancreas. Ann Surg 2014;260:364—71. doi:10.1097/SLA.0000000000000601
Objective To assess the feasibility and outcomes of parenchymasparing pancreatectomy (PSP), including enucleation (EN), resection of uncinate process (RUP), and central pancreatectomy (CP), as an alternative to standard pancreatectomy for presumed non-invasive intraductal papillary and mucinous neoplasms (IPMNs). Background Pancreaticoduodenectomy and distal pancreatectomy are associated with significant perioperative morbidity, a substantial risk of pancreatic insufficiency, and may overtreat non-invasive IPMNs. Methods From 1999 to 2011, PSP was attempted in 91 patients with presumed non-invasive IPMNs, after complete preoperative work-up, including computed tomography, magnetic resonance imaging, and endoscopic ultrasonography. Intraoperative frozen section examination was routinely performed to assess surgical margins and rule out invasive malignancy. Follow-up included clinical, biochemical, and radiological assessments. Results Overall PSP was achieved with a feasibility rate of 89% (n = 81), including 44 ENs, 5 RUPs, and 32 CPs. Postoperative mortality rate was 1.3% (n = 1), and overall morbidity was noteworthy (61%; n = 47). Definitive pathological examination confirmed IPMN diagnosis in 95% of patients (n = 77), all except 2 (3%), without invasive component. After a median follow-up of 50 months, both pancreatic endocrine/exocrine functions were preserved in 92% of patients. Ten-year progression-free survival was 76%, and reoperation for recurrence was required in 4% of patients (n = 3). Conclusions In selected patients, PSP for presumed non-invasive IPMN in experienced hands is highly feasible and avoids inappropriate standard resections for IPMN-mimicking lesions. Early morbidity is greater than that after standard resections but counterbalanced by preservation of pancreatic endocrine/exocrine functions and a low rate of reoperation for tumor recurrence. Comments 1. With expanding use of imaging, the diagnosis of IPMN is made more and more frequently; surgical management
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should be proposed to patients with symptoms and/or risk factors of malignant degeneration. Because standard pancreatic resections, such as pancreatoduodenectomy or distal pancreatectomy, are associated with high morbidity and above all, frequent degradation of exocrine and endocrine functions, it is most pertinent to evaluate the feasibility and results of limited parenchymal-sparing resections. Of note, as these limited resection procedures are not carcinologic, they should be reserved for patients with IPMN considered to be benign; therefore, modern multimodal, high-quality imaging is essential. While the quality of these results is laudable, questions arise as to their reproducibility, the selection of eligible patients, and the techniques to be used. The goal is to avoid a non-carcinologic procedure for patients with benign lesions; however, if the lesion proves to be malignant, this could have dramatic negative consequences. Of note, these limited procedures are possible only when the diseased portion of the pancreas is anatomically accessible, that is, for lesions that are superficial and easy to enucleate. This management modality questions the pan-canalar involvement concept of IPMN and consequently, the theoretical routine indication for total pancreatectomy. 䊏
Boleslawski E, Vibert E, Pruvot FR, et al. Relevance of postoperative peak transaminase after elective hepatectomy. Ann Surg 2014;260:815—20. doi:10.1097/SLA.0000000000000942.
Objectives Determine whether inflow occlusion is correlated with peak postoperative serum transaminases (PSTs) and whether PST is predictive of outcome after liver resections. Background PST is used as the surrogate of ischemia-reperfusion and as the main endpoint in prospective trials of inflow occlusion. This assumption has, however, not been validated. Furthermore, the impact of PST on the postoperative course is unknown. Methods This prospectively designed registered study included consecutive adult patients undergoing elective hepatectomy in 9 HPB centers. Primary outcome was PST of aspartate amino transferase (AST) and alanine amino transferase (ALT). Secondary outcome was 90-day morbidity (Dindo—Clavien grades) and length of stay. Explanatory variables were preoperative (including age, sex, body mass index, comorbidities, cirrhosis, and chemotherapy), and intraoperative variables (including procedure performed, inflow occlusion and its duration, length of surgery, vasoactive drugs used, blood loss, and transfusion) were collected prospectively on a dedicated Web site. Multivariable regression models were used to identify independent predictors of PST and of morbidity. Results Between January 2013 and September 2013, 651 hepatectomies were included. Inflow occlusion was performed in 58% (intermittent in 32%, continuous in 24%) and was not performed in 42%. PST-AST (336 IU/L; interquartile range: 204—573) and PST-ALT (336 IU/L; interquartile range: 205—557) occurred on postoperative day 1. PST was not correlated with the duration of inflow occlusion (-AST = 0.20, P < 0.01; -ALT = 0.18, P < 0.01). PST was not independently
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associated with morbidity. Receiver operating characteristic curve identified a cut-off of 450 IU/L but this prediction’s accuracy was low: area under the receiver operating characteristic curve for PST-AST: 0.61, confidence interval: 0.56—0.66, P < 0.01, and area under the receiver operating characteristic curve for PST-ALT: 0.57, confidence interval: 0.52—0.62, P = 0.01. Conclusions PST is not correlated with ischemia time and should not be used as a surrogate of postoperative outcome. Comments 1. While peak cytolysis is often used as a marker for hepatocellular alterations related to ischemia-reperfusion secondary to clamping maneuvers, the authors suggest that there is no correlation between peak cytolysis markers and duration of pedicular clamping and postoperative follow-up. 2. This study topples a dogma, since peak cytolysis has been widely used as an endpoint in several studies in hepatic surgery [1—3]. 3. One of the main limitations in this study is that 42% of the patients did not undergo clamping and when performed, clamping was often intermittent, the ideal method to prevent ischemia-perfusion phenomena. Moreover, it is probable that additional measures were taken in these expert centers to avoid the ischemia-reperfusion lesions. 4. A relationship was identified between the operative duration and morbidity, most likely reflecting the complexity of the operation. The relationship between cytolysis peak and duration of operation more likely reflects liver mobilization and longer overall and hepatic hypoperfusion. 5. It is interesting to note that the threshold transaminase values of 500 and 1000 IU/L were associated with higher overall morbidity and severity of morbidity postoperatively; clinical significance, however, remains to be shown. 6. It is important to understand the phenomena behind increased morbidity associated with pedicular clamping. References [1] J Am Coll Surg 02006;202:203—21. [2] Br J Surg 2006;93:685—9. [3] Ann Surg 2003;238:843—52. 䊏
Caiazzo R, Lassailly G, Leteurtre E, et al. Roux-en-Y gastric bypass versus adjustable gastric banding to reduce non-alcoholic fatty liver disease: A 5-year controlled longitudinal study. Ann Surg 2014;260:893—8. doi:10.1097/SLA.0000000000000945
Objectives To compare the long-term benefit of gastric bypass [Roux-en-Y gastric bypass (RYGB)] versus adjustable gastric banding (AGB) on non-alcoholic fatty liver disease (NAFLD) in severely obese patients. Background NAFLD improves after weight loss surgery, but no histological study has compared the effects of the various bariatric interventions. Methods Participants consisted of 1236 obese patients (body mass index = 48.4 ± 7.6 kg/m2 ), enrolled in a prospective longitudinal study for up to 5 years after RYGB (n = 681) or AGB (n = 555). Liver biopsy samples were available for 1201
patients (97.2% of those at risk) at baseline, 578 patients (47.2%) at 1 year, and 413 patients (68.9%) at 5 years. Results At baseline, NAFLD was present in 86% patients and categorized as severe [NAFLD activity score (NAS) ≥ 3] in 22% patients. RYGB patients had a higher body mass index (49.8 ± 8.2 vs 46.8 ± 6.5 kg/m2 , P < 0.001) and more severe NAFLD (NAS: 2.0 ± 1.5 vs 1.7 ± 1.4, P = 0.004) than AGB patients. Weight loss at 5 years was 25.5% ± 11.8% after RYGB versus 21.4% ± 12.7% after AGB (P < 0.001). When analyzed with a mixed model, all NAFLD parameters improved after surgery (P < 0.001) and improved significantly more after RYGB than after AGB [steatosis (%): 1 year, 7.9 ± 13.7 vs 17.9 ± 21.5, P < 0.001/5 years, 8.7 ± 7.1 vs 14.5 ± 20.8, P < 0.05; NAS: 1 year, 0.7 ± 1.0 vs 1.1 ± 1.2, P < 0.001/5 years, 0.7 ± 1.2 vs 1.0 ± 1.3, P < 0.05]. In multivariate analysis, the superiority of RYGB was primarily but not entirely explained by weight loss. Conclusions The improvement of NAFLD was superior after RYGB than after AGB. Comments 1. Even though other papers have already shown that surgery improve non-alcoholic fatty liver disease [1,2], this study is the first to compare different surgical procedures and show the superiority of RYGB in this respect. 2. As most of the parameters were more severe in the bypass group, the fact that the two groups were not strictly comparable at inclusion does not change the conclusions of the study. 3. Of interest, the liver histologic improvements after RYGB were related to quicker and more marked weight loss. 4. Future studies should compare other surgical procedures, such as sleeve gastrectomy and also evaluate the impact of bariatric surgery on the reduction of the risk of hepatocellular carcinoma. References [1] J Hepatol 2012;56:234—40. [2] J Hepatol 2004;40:578—4. 䊏
Radé F, Bretagnol F, Auguste M, et al. Determinants of outcome following laparoscopic peritoneal lavage for perforated diverticulitis. Br J Surg 2014;101:1602—6. doi:10.1002/bjs.9621
Background Laparoscopic peritoneal lavage has been proposed for generalized peritonitis from perforated diverticulitis to avoid a stoma. Reports of its feasibility and safety are promising. This study aimed to establish determinants of failure to enable improved selection of patients for this approach. Methods The study included all patients with perforated sigmoid diverticulitis who underwent emergency laparoscopic peritoneal lavage from January 2000 to December 2013. Factors predicting failure of laparoscopic treatment were analysed from data collected retrospectively. Results For patients undergoing emergency sigmoid resection (72 of 361), mortality and morbidity rates were 13 and 35%, respectively. In all, 71 patients had laparoscopic lavage, with mortality and morbidity rates of 6 and 28%, respectively. Reintervention was necessary in 11 patients (15%) for unresolved sepsis. Age 80 years or more, American Society of
Press review Anesthesiologists grade III or above, and immunosuppression were associated with reintervention. Conclusion Elderly patients and those with immunosuppression or severe systemic co-morbidity are at risk of reintervention after laparoscopic lavage. Comments 1. In this series, patients were highly selected as this technique was performed in slightly more than 50% of patients. Moreover, a third of the patients had a perisigmoid abscess that was non-accessible to percutaneous drainage or failed to resolve thereafter. In this setting, the 28% morbidity and 6% mortality rates are acceptable, but remain high, as recognized by the authors, compared to their initial experience, which was more favorable [1]. 2. The risk factors for failure outlined here are somewhat disappointing as they correspond to common 3. place risk factors in surgery, and not specifically to diverticular disease. It is not certain that a different approach would have been less morbid in elderly patients with high co-morbidity. 4. It might have been interesting to know the long-term colostomy rate, since one of the putative advantages of this lavage-drainage technique is avoidance of colostomy [2]. 5. The results of two ongoing controlled trails on laparoscopic lavage for diverticular disease perforation are eagerly awaited [3,4]. References [1] J Am Coll Surg 2008;206:654—7. [2] Dis Colon Rectum 2009;52:609—15. [3] BMC Surg 2010;10:29. [4] Trials 2011;12:186. Further reading Dis Colon Rectum 2012;55:932—8. Br J Surg 2013;100:704—10. 䊏
Faitot F, Faron M, Adam R, et al. Two-stage hepatectomy versus 1-stage resection combined with radiofrequency for bilobar colorectal metastases: A case-matched analysis of surgical and oncological outcomes. Ann Surg 2014;260:822—7. doi:10.1097/SLA.0000000000000976
Objectives The aim of this study was to compare the long-term results of 2 surgical strategies for patients with bilobar colorectal liver metastases (bCRLM). Background Two-stage hepatectomy is the surgical strategy mostly chosen for treating extensive BCLM with the pitfall of dropout after the first stage. One-stage strategy combining limited resections and radiofrequency ablation could be proposed as an option in this population. Pateints and methods Between 2000 and 2010, 272 patients were consecutively operated in 2 expert centers practicing 1- or 2-stage hepatectomy for bCRLM. A case-match study (1:1) was conducted using number and size of nodules, synchronous presentation, primary node status, and extrahepatic disease as matching variables to compare overall survival (OS) and disease-free survival (DFS). The analysis was performed in intention-totreat, including patients who did not undergo the second stage.
129 Results In the case-match analysis (156 matched patients), median OS and DFS did not differ significantly between patients in 1- and 2-stage hepatectomy, respectively: 37.2 and 34.5 months (P = 0.6), 9.4 and 7.5 months (P = 0.25). Multivariate analysis confirmed the absence of impact of strategy on OS and DFS. Primary advanced T stage and synchronous presentation were predictors of poor OS (HR = 3.67 and 1.92); CEA more than 200 ng/mL, absence of postoperative chemotherapy, and extrahepatic disease were predictive of recurrence (HR = 2.77, 1.85 and 1.69, respectively). Conclusions This first case-match study demonstrates that on an intention-to-treat analysis 1- and 2-stage hepatectomy in patients with bCRLM achieve comparable OS and DFS, despite the high dropout of the 2-stage strategy. Comments 1. Whatever strategy was used, aggressive therapy resulted in satisfactory long-term outcome in 36% of patients, in spite of initial non-resectability of bilobar colorectal liver metastases (bCRLM). 2. The selection process of patients, particularly in the case-control portion of the study, is not provided: specifically, it is unclear how the 78 patients in the 1S group were chosen. 3. The major problem in this retrospective study is that the two groups are not comparable, even after pairing. Patients in the 2S group had tumors that were more locally advanced, voluminous and deep-seated, probably more often responsible for vascular involvement. This hypothesis is supported by the fact that more patients required additional chemotherapy cycles with targeted therapies in the 2S group. Moreover, in patients at very high risk of recurrence, intra-arterial chemotherapy was used more often in the 1S group, as this has been shown to increase overall survival and decrease the rate of intra-hepatic recurrence [1,2]. Within this setting, oncologic results in the 2S group are finally remarkable in some respects. 4. However, it is likely that these two therapeutic approaches should not be compared, as they are in fact complementary. There exists in fact three categories of patients with bCRLM: one in which most lesions are superficial or subcapsular, where the 1S approach is best; a second in which lesions are deeper and bigger (> 3 cm) or with clear involvement of the vascular pedicles for which radiofrequence ablation appears difficult (these patients should undergo a 2S liver resection); and a third category of patients for whom either of the two strategies are possible and therapy should be discussed based on other criteria, such as non-tumoral parenchymal volume, risk of biliary injury or general patient condition. It would have been more interesting to compare the patients undergoing the 2S technique for whom the 1S technique would also have been possible, with those in the 1S group. References [1] J Gastrointest Surg 2011;15:336—44. [2] Ann Surg 2013;257:114—120. Further reading Ann Surg 2008;248:994—1005. J Clin Oncol 2011;29:1083—90. Ann Surg Oncol 2014;21:815—21.
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Tilly C, Lefèvre JH, Svrcek M, et al. R1 rectal resection: look up and don’t look down. Ann Surg 2014;260:794—9. doi:10.1097/SLA.0000000000000988
Background After rectal resection for adenocarcinoma, pathological examination may reveal invasion of the distal margin (DM) and/or a circumferential resection margin of the tumor (CRM-T) or of involved nodes (CRM-N) less than or equal to 1 mm. Such findings transform a planned R0 resection to R1. Aim The aim was to analyze the impact of an R1 resection on prognosis, recurrence rate, and choice of adjuvant treatment. Pateints and methods All R1 resections observed between 2006 and 2011 were retrospectively collected. Patients were matched with 80 patients with R0 resections according to age, body mass index, gender, neoadjuvant treatment, type of resection, ypT/pT stages, and N stage. Results Among 472 rectal resections performed, 40 (8.5%) were R1 (CRM-T = 34; CRM-N = 11; invaded DM = 4). Among the 4 patients with invaded DM, 3 underwent salvage abdominoperineal resection. Of the 12 patients who had not received neoadjuvant treatment, 5 received adjuvant radiotherapy. Mean follow-up was 49.3 ± 29.3 months for the 120 patients; 5-year overall survival (OS) and disease-free survival (DFS) were 72% and 56%. Comparison between R0 and R1 resections showed a trend toward worse OS in R1 resections: 62% versus 79% (P = 0.0954), a significantly worse DFS: 41% versus 65% (P = 0.0267). Local recurrence rates were similar: 12% versus 13% (P = 0.9177), whereas distant recurrence was significantly more frequent after R1 resection: 56% versus 26% (P = 0.0040). Conclusions R1 resection is associated with a worse prognosis, but local recurrence rate does not differ significantly from matched R0 resections. The difference was observed for distant recurrences, especially lung, favoring the use of chemotherapy and close surveillance of the thorax. Comments 1. It would have been interesting to analyze all R1 patients whether they had received preoperative radiation therapy or not: patients who had R1 resections despite preoperative RCT would be those for whom no response was obtained. The only postoperative treatment possible for these patients is chemotherapy alone. 2. This study does not tell us what to do when the distal margin is involved: this concerned only four patients. Moreover, the fact that no tumor was found in two of the three abdominoperineal salvage operations does not allow the conclusion that APA should be proposed in this setting. Of note, however, this was what most experts recommended in the last French language congress of digestive and hepato-biliary surgery for this situation. 3. The conclusions of this article are based on the results of a case-controlled comparison showing no difference in local recurrence between R1 and R0 resections. The problem is that, unlike R0 patients, nine of 40 patients (22%) in the R1 group had some form of postoperative therapy, chemo-radiation or salvage APR: none of these patients developed local recurrence. It would therefore have been more judicious to eliminate them from the calculation of the local recurrence rate.
4. Finally, the main message of this article is to show that R1 is a poor prognostic factor and a major risk factor for distant metastases, particularly pulmonary metastases. For these patients, it appears justified that postoperative treatment should include systemic chemotherapy. 䊏
Collin Å, Jung B, Nilsson E, et al. Impact of mechanical bowel preparation on survival after colonic cancer resection. Br J Surg 2014;101:1594—1600. doi:10.1002/bjs.9629
Background A randomized study in 1999—2005 of mechanical bowel preparation (MBP) preceding colonic resection found no decrease in postoperative complications. The aim of the present study was to evaluate the long-term effect of MBP regarding cancer recurrence and survival after colonic resections. Methods The cohort of patients with colonic cancer in the MBP study was followed up for 10 years. Data were collected from registers run by the National Board of Health and Welfare. Register data were validated against information in patient charts. Cox proportional hazards model was used for multivariable analysis of factors predictive of cancer-specific survival. Results Register analysis showed significantly fewer recurrences, and better cancer-specific and overall survival in the MBP group. After validation, 839 of 1343 patients remained for analysis (448 MBP, 391 no MBP). Eighty (17.9%) of 448 patients in the MBP group and 88 (22.5%) of 391 in the no MBP group developed a cancer recurrence (P = 0.093). The 10-year cancer-specific survival rate was 84.1% in the MBP group and 78.0% in the no MBP group (P = 0.019). Overall survival rates were 58.8 and 56.0%, respectively (P = 0.186). Conclusion Patients receiving MBP before elective colonic cancer surgery had significantly better cancer-specific survival after 10 years. Comments 1. There are not many possible explanations for this surprising result. Can mechanical preparation eliminate circulating tumor cells in the gastrointestinal tract? This hypothesis is indirectly supported by the results of two meta-analyses that showed that intraoperative lavage of the rectal stump decreased the risk of local recurrence in patients with rectal cancer [1,2]. 2. Results must be interpreted with prudence, however, because several other factors could have possibly influenced the carcinologic outcome. In particular, the use of adjuvant chemotherapy was not indicated. 3. Nonetheless, this study revives the debate about mechanical bowel preparation and its oncologic impact, opening the door for further controlled studies on this topic. References [1] Ann Surg Oncol 2013;20:856—63. [2] Colorectal Dis 2012;14:1313—21. Further reading Ann Surg 2009;249:203—9. Cochrane Database Syst Rev 2011;(9):CD001544. Br J Surg 2007;94:689—95.
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Loupakis F, Cremolini C, Masi G, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 2014;371:1609—18. doi:10.1056/NEJMoa1403108
Background A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard firstline treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects. Methods We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival. Results The median progression-free survival was 12.1 months in the experimental group, as compared with 9.7 months in the control group (hazard ratio for progression, 0.75; 95% confidence interval [CI], 0.62—0.90; P = 0.003). The objective response rate was 65% in the experimental group and 53% in the control group (P = 0.006). Overall survival was longer, but not significantly so, in the experimental group (31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63—1.00; P = 0.054). The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group. Conclusions FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. Comments 1. The 31-month overall survival rate after Folfoxiri—bevacizumab is quite remarquable in that the population in this trial was particularly severely involved, 80% with synchronous colorectal liver metastases (CRLM) and 79% with extrahepatic metastatic disease. 2. This trial confirms the results of the phase II Olivera controlled trial suggesting that Folfoxiri—bevacizumab would increase the response rate and progression-free survival compared to Folfox—bevacizumab [1]. 3. The problem with this maximalist strategy is to know what to propose as second-line treatment after tumor progression since it already uses three of the five drugs currently available for the treatment of CRLM. This chemotherapy should now be tested in strategies evaluating overall survival after second- or third-line chemotherapy. 4. Toxicity is increased with this combination chemotherapy. In the Folfoxiri—bev group, 16% of patients had to increase the interval between two consecutive cycles and 21% underwent cycles with reduced doses. Moreover, evaluation of quality of life would have been pertinent.
131 Reference [1] Ann Oncol 2014. pii: mdu580. Further reading Lancet Oncol 2014;15:1065—75. N Engl J Med 2004;350:2335—42. Lancet Oncol 2010;11:845—52. 䊏
Gronnier C, Tréchot B, Duhamel A, et al. Impact of neoadjuvant chemoradiotherapy on postoperative outcomes after esophageal cancer resection: Results of a European multicenter study. Ann Surg 2014;260:764—70. doi:10.1097/SLA.0000000000000955
Objectives To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection. Background Conflicting data have emerged from randomized studies regarding the impact of NCRT on AL. Methods Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n = 593) were compared with those treated by primary surgery (n = 1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics. Results Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P = 0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P = 0.110) and 33.4% versus 32.1% (P = 0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P = 0.291), whereas chylothorax (2.5% vs 1.2%; P = 0.020), cardiovascular complications (8.6% vs 0.1%; P = 0.037), and thromboembolic events (8.6% vs 6.0%; P = 0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P = 0.228), with more chylothorax (2.5% vs 0.7%; P = 0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P = 0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT. Conclusions Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection. Comments 1. Even though retrospective, this study constitutes one of the largest cohorts on the topic and, moreover, is relatively homogeneous as concerns the operative technique. The message is fairly clear: if chemoradiotherapy is needed for oncologic reasons, it should be done. 2. It would have been interesting to separate the clinically symptomatic anastomotic leaks from leaks evidenced only by radiology, for which the clinical consequences are not the same. 3. It would also have been interesting to evaluate the risk of AL according to the dose of radiotherapy, even if the
132 doses recommended in France, between 45 and 50 Gy, are relatively homogeneous. 4. There was no information available about how anastomotic fistula were managed. As expert centers were involved, it is probable that management was early and well codified, which partly explains why complications
C. Mariette, S. Benoist of anastomotic leakage were not more severe in the RCT group. Further reading J Clin Oncol 2008;26:1086—92. N Engl J Med 2012;366:2074—84. J Clin Oncol 2014;23:2416—22.
Available online at
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Press review C. Mariette a,∗, S. Benoist b a
Service de chirurgie digestive et générale, hôpital C.-Huriez, CHRU, place de Verdun, 59037 Lille cedex, France b Service de chirurgie digestive, hôpital du Kremlin-Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France Available online 6 March 2015 䊏
Chau A, Maggiori L, Debove C, Kanso F, Hennequin C, Panis Y. Toward the end of abdominoperineal resection for rectal cancer? An 8-year experience in 189 consecutive patients with low rectal cancer. Ann Surg 2014;260:801—5. doi: 10.1097/SLA.0000000000000979
Objectives To assess whether recent advances, such as intersphincteric resection (ISR) or local excision (LE) if a suspicion of complete tumor response after radiochemotherapy (RCT), could have modified the rate of end stoma (ES) in low rectal cancer treatment. Background ES rate remains around 30% to 50% in patients with low rectal cancer. Method From 2005 to 2013, all patients with low rectal cancer undergoing laparoscopic total mesorectal excision, with or without neoadjuvant RCT, and patients undergoing LE after RCT were included. Results A total of 189 patients presented a low rectal cancer; 162 (86%) underwent RCT; total mesorectal excision was performed in 172 (90%), followed by stapled colorectal anastomosis (n = 26; 15%), manual coloanal anastomosis with partial (n = 92; 53%) or total ISR (n = 32; 19%), or ES that included abdominoperineal resection (n = 21; 12%) and low Hartmann procedure (n = 1; 1%). LE after RCT was performed in 19 of 189 (10%) patients with a suspicion of complete tumor response. Among them, 2 of 19 (11%) underwent immediate secondary total mesorectal excision (1 abdominoperineal resection and 1 coloanal anastomosis with total ISR) because of poor pathological criteria.
∗
Corresponding author. E-mail address: [email protected] (C. Mariette).
1878-7886/$ — see front matter http://dx.doi.org/10.1016/j.jviscsurg.2015.02.009
Conclusions Management of rectal cancer with colorectal anastomosis and coloanal anastomosis with partial ISR allowed to obtain a 38% ES rate (71/189); the additional use of total ISR decreased this rate to 22% (39/189). Selective use of LE reduced this rate to only 12% (22/189). Nowadays, recent advances lead to a paradigm shift, with only 12% ES rate in low rectal cancer. Comments 1. These excellent results should be compared with those of the literature and in particular with the 25% and 27% definitive stoma rates found in the two largest randomized studies comparing laparoscopic vs. open surgery [1,2], and the 35% in the Dutch study [3]. This rate reaches 51% in two recent population studies [4,5]. 2. Of note, the authors’ R1 resection rate is high: 17%, even taking into consideration that recent studies suggest that R1 in expert centers is more often related to tumor aggressiveness than to surgical inadequacy? [6]. 3. The results reported here are immediate outcomes that do not take into account the long-term functional consequences and especially those patients who had a definitive stoma secondarily, leading to poor quality of life References [1] Surg Endosc 2012;27:295—302. [2] Lancet Oncol 2013;14:210—8. [3] Lancet Oncol 2011;12:575—82. [4] Dis Colon Rectum 2013;56:704—10. [5] Dis Colon Rectum 2011;54:1205—10. [6] Ann Surg 2014; 260:794—9. 䊏
Regimbeau JM, Fuks D, Pautrat K, et al. FRENCH Study Group. Effect of postoperative antibiotic administration on postoperative infection following cholecystectomy for acute calculous cholecystitis: A randomized clinical trial. JAMA 2014;312:145—54. doi:10.1001/jama.2014.7586
126 Importance Ninety percent of cases of acute calculous cholecystitis are of mild (grade I) or moderate (grade II) severity. Although the preoperative and intraoperative antibiotic management of acute calculous cholecystitis has been standardized, few data exist on the utility of postoperative antibiotic treatment. Objectives To determine the effect of postoperative amoxicillin plus clavulanic acid on infection rates after cholecystectomy. Design, setting, and patients A total of 414 patients treated at 17 medical centers for grade I or II acute calculous cholecystitis and who received 2 g of amoxicillin plus clavulanic acid 3 times a day while in the hospital before and once at the time of surgery were randomized after surgery to an open-label, non-inferiority, randomized clinical trial between May 2010 and August 2012. Interventions After surgery, no antibiotics or continue with the preoperative antibiotic regimen 3 times daily for 5 days. Main outcomes and measures The proportion of postoperative surgical site or distant infections recorded before or at the 4-week follow-up visit. Results An imputed intention-to-treat analysis of 414 patients showed that the postoperative infection rates were 17% (35 of 207) in the non-treatment group and 15% (31 of 207) in the antibiotic group (absolute difference, 1.93%; 95% CI, —8.98% to 5.12%). In the per-protocol analysis, which involved 338 patients, the corresponding rates were both 13% (absolute difference, 0.3%; 95% CI, —5.0% to 6.3%). Based on a non-inferiority margin of 11%, the lack of postoperative antibiotic treatment was not associated with worse outcomes than antibiotic treatment. Bile cultures showed that 60.9% were pathogen free. Both groups had similar Clavien complication severity outcomes: 195 patients (94.2%) in the non-treatment group had a score of 0 to I and 2 patients (0.97%) had a score of III to V, and 182 patients (87.8%) in the antibiotic group had a score of 0 to I and 4 patients (1.93%) had a score of III to V. Conclusions and relevance Among patients with mild or moderate calculous cholecystitis who received preoperative and intraoperative antibiotics, lack of postoperative treatment with amoxicillin plus clavulanic acid did not result in a greater incidence of postoperative infections. Comments 1. Cholecystectomy for acute calculous cholecystitis represents the third most frequent surgical emergency; most patients receive postoperative therapeutic antibiotics with the intention of reducing the infective complication rates, based on the idea that bile is infected in 40 to 60% of patients [1]. This trial shows that routine postoperative antibiotics are not needed. 2. Interestingly, bile was found to be sterile in 60.9% of patients. In patients with infected bile, the pathogens identified (n = 206) varied widely, with 28% being resistant to the prescribed antimicrobials. In this subgroup, no difference in outcome was found between the two groups. 3. This new publication with a high level of evidence highlights the dynamism of French multicenter clinical research and the prominent role played by the
C. Mariette, S. Benoist French research working party (Fédération franc¸aise de recherche en chirurgie digestive). Reference [1] J Infect 2005:51:128—34.
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Adam MA, Pura J, Gu L, et al. Extent of surgery for papillary thyroid cancer is not associated with survival: An analysis of 61,775 patients. Ann Surg 2014;260:601—5. doi:10.1097/SLA.0000000000000925.
Objective To examine the association between the extent of surgery and overall survival in a large contemporary cohort of patients with papillary thyroid cancer (PTC). Background Guidelines recommend total thyroidectomy for PTC tumors > 1 cm, based on older data demonstrating an overall survival advantage for total thyroidectomy over lobectomy. Methods Adult patients with PTC tumors 1.0—4.0 cm undergoing thyroidectomy in the National Cancer Database, 1998—2006, were included. Cox proportional hazards models were applied to measure the association between the extent of surgery and overall survival while adjusting for patient demographic and clinical factors, including comorbidities, extrathyroidal extension, multifocality, nodal and distant metastases, and radioactive iodine treatment. Results Among 61,775 PTC patients, 54,926 underwent total thyroidectomy and 6849 lobectomy. Compared with lobectomy, patients undergoing total thyroidectomy had more nodal (7% vs 27%), extrathyroidal (5% vs 16%), and multifocal disease (29% vs 44%) (all P < 0.001). Median follow-up was 82 months (range, 60—179 months). After multivariable adjustment, overall survival was similar in patients undergoing total thyroidectomy versus lobectomy for tumors 1.0—4.0 cm [hazard ratio (HR) = 0.96; 95% confidence interval (CI), 0.84—1.09; P = 0.54] and when stratified by tumor size: 1.0—2.0 cm [HR = 1.05; 95% CI, 0.88—1.26; P = 0.61] and 2.1—4.0 cm [HR = 0.89; 95% CI, 0.73—1.07; P = 0.21]. Older age, male sex, black race, lower income, tumor size, and presence of nodal or distant metastases were independently associated with compromised survival (P < 0.0001). Conclusions Current guidelines suggest total thyroidectomy for PTC tumors > 1 cm. However, we did not observe a survival advantage associated with total thyroidectomy compared with lobectomy. These findings call into question whether tumor size should be an absolute indication for total thyroidectomy. Comments 1. Survival after optimally treated papillary thyroid cancer (PTC) is close to 90% at 20 years. While the current recommendations suggest total or subtotal thyroidectomy for PTC > 1 cm [1], the authors did not find any benefit for totalization for tumors between 1 to 4 cm, after adjusting for confounding factors, such as comorbidities, multifocality, lymph node or metastatic involvement as well as the complete character of resection. 2. The theoretic advantage of total thyroidectomy is to treat potential multifocal contra-lateral lesions;
Press review however, this is counterbalanced by increased morbidity (hypocalcemia and recurrent nerve paralysis), making its value debatable in a cancer with such a good prognosis. 3. These data confirm recent information emanating from the American SEER database containing data on 22,724 analyzed patients [2]. 4. Of note, for a cancer with such good prognosis, this study is limited by the lack of information on recurrence and cancer-specific survival, which could have helped define the risk profiles for individual patients and then lead to selective proposal of totalization. References [1] Thyroid 2009;19:1167—1214. [2] Arch Otolaryngol Head Neck Surg 2010;136:1055—61. 䊏
Sauvanet A, Gaujoux S, Blanc B, et al. Parenchyma-sparing pancreatectomy for presumed noninvasive intraductal papillary mucinous neoplasms of the pancreas. Ann Surg 2014;260:364—71. doi:10.1097/SLA.0000000000000601
Objective To assess the feasibility and outcomes of parenchymasparing pancreatectomy (PSP), including enucleation (EN), resection of uncinate process (RUP), and central pancreatectomy (CP), as an alternative to standard pancreatectomy for presumed non-invasive intraductal papillary and mucinous neoplasms (IPMNs). Background Pancreaticoduodenectomy and distal pancreatectomy are associated with significant perioperative morbidity, a substantial risk of pancreatic insufficiency, and may overtreat non-invasive IPMNs. Methods From 1999 to 2011, PSP was attempted in 91 patients with presumed non-invasive IPMNs, after complete preoperative work-up, including computed tomography, magnetic resonance imaging, and endoscopic ultrasonography. Intraoperative frozen section examination was routinely performed to assess surgical margins and rule out invasive malignancy. Follow-up included clinical, biochemical, and radiological assessments. Results Overall PSP was achieved with a feasibility rate of 89% (n = 81), including 44 ENs, 5 RUPs, and 32 CPs. Postoperative mortality rate was 1.3% (n = 1), and overall morbidity was noteworthy (61%; n = 47). Definitive pathological examination confirmed IPMN diagnosis in 95% of patients (n = 77), all except 2 (3%), without invasive component. After a median follow-up of 50 months, both pancreatic endocrine/exocrine functions were preserved in 92% of patients. Ten-year progression-free survival was 76%, and reoperation for recurrence was required in 4% of patients (n = 3). Conclusions In selected patients, PSP for presumed non-invasive IPMN in experienced hands is highly feasible and avoids inappropriate standard resections for IPMN-mimicking lesions. Early morbidity is greater than that after standard resections but counterbalanced by preservation of pancreatic endocrine/exocrine functions and a low rate of reoperation for tumor recurrence. Comments 1. With expanding use of imaging, the diagnosis of IPMN is made more and more frequently; surgical management
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should be proposed to patients with symptoms and/or risk factors of malignant degeneration. Because standard pancreatic resections, such as pancreatoduodenectomy or distal pancreatectomy, are associated with high morbidity and above all, frequent degradation of exocrine and endocrine functions, it is most pertinent to evaluate the feasibility and results of limited parenchymal-sparing resections. Of note, as these limited resection procedures are not carcinologic, they should be reserved for patients with IPMN considered to be benign; therefore, modern multimodal, high-quality imaging is essential. While the quality of these results is laudable, questions arise as to their reproducibility, the selection of eligible patients, and the techniques to be used. The goal is to avoid a non-carcinologic procedure for patients with benign lesions; however, if the lesion proves to be malignant, this could have dramatic negative consequences. Of note, these limited procedures are possible only when the diseased portion of the pancreas is anatomically accessible, that is, for lesions that are superficial and easy to enucleate. This management modality questions the pan-canalar involvement concept of IPMN and consequently, the theoretical routine indication for total pancreatectomy. 䊏
Boleslawski E, Vibert E, Pruvot FR, et al. Relevance of postoperative peak transaminase after elective hepatectomy. Ann Surg 2014;260:815—20. doi:10.1097/SLA.0000000000000942.
Objectives Determine whether inflow occlusion is correlated with peak postoperative serum transaminases (PSTs) and whether PST is predictive of outcome after liver resections. Background PST is used as the surrogate of ischemia-reperfusion and as the main endpoint in prospective trials of inflow occlusion. This assumption has, however, not been validated. Furthermore, the impact of PST on the postoperative course is unknown. Methods This prospectively designed registered study included consecutive adult patients undergoing elective hepatectomy in 9 HPB centers. Primary outcome was PST of aspartate amino transferase (AST) and alanine amino transferase (ALT). Secondary outcome was 90-day morbidity (Dindo—Clavien grades) and length of stay. Explanatory variables were preoperative (including age, sex, body mass index, comorbidities, cirrhosis, and chemotherapy), and intraoperative variables (including procedure performed, inflow occlusion and its duration, length of surgery, vasoactive drugs used, blood loss, and transfusion) were collected prospectively on a dedicated Web site. Multivariable regression models were used to identify independent predictors of PST and of morbidity. Results Between January 2013 and September 2013, 651 hepatectomies were included. Inflow occlusion was performed in 58% (intermittent in 32%, continuous in 24%) and was not performed in 42%. PST-AST (336 IU/L; interquartile range: 204—573) and PST-ALT (336 IU/L; interquartile range: 205—557) occurred on postoperative day 1. PST was not correlated with the duration of inflow occlusion (-AST = 0.20, P < 0.01; -ALT = 0.18, P < 0.01). PST was not independently
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associated with morbidity. Receiver operating characteristic curve identified a cut-off of 450 IU/L but this prediction’s accuracy was low: area under the receiver operating characteristic curve for PST-AST: 0.61, confidence interval: 0.56—0.66, P < 0.01, and area under the receiver operating characteristic curve for PST-ALT: 0.57, confidence interval: 0.52—0.62, P = 0.01. Conclusions PST is not correlated with ischemia time and should not be used as a surrogate of postoperative outcome. Comments 1. While peak cytolysis is often used as a marker for hepatocellular alterations related to ischemia-reperfusion secondary to clamping maneuvers, the authors suggest that there is no correlation between peak cytolysis markers and duration of pedicular clamping and postoperative follow-up. 2. This study topples a dogma, since peak cytolysis has been widely used as an endpoint in several studies in hepatic surgery [1—3]. 3. One of the main limitations in this study is that 42% of the patients did not undergo clamping and when performed, clamping was often intermittent, the ideal method to prevent ischemia-perfusion phenomena. Moreover, it is probable that additional measures were taken in these expert centers to avoid the ischemia-reperfusion lesions. 4. A relationship was identified between the operative duration and morbidity, most likely reflecting the complexity of the operation. The relationship between cytolysis peak and duration of operation more likely reflects liver mobilization and longer overall and hepatic hypoperfusion. 5. It is interesting to note that the threshold transaminase values of 500 and 1000 IU/L were associated with higher overall morbidity and severity of morbidity postoperatively; clinical significance, however, remains to be shown. 6. It is important to understand the phenomena behind increased morbidity associated with pedicular clamping. References [1] J Am Coll Surg 02006;202:203—21. [2] Br J Surg 2006;93:685—9. [3] Ann Surg 2003;238:843—52. 䊏
Caiazzo R, Lassailly G, Leteurtre E, et al. Roux-en-Y gastric bypass versus adjustable gastric banding to reduce non-alcoholic fatty liver disease: A 5-year controlled longitudinal study. Ann Surg 2014;260:893—8. doi:10.1097/SLA.0000000000000945
Objectives To compare the long-term benefit of gastric bypass [Roux-en-Y gastric bypass (RYGB)] versus adjustable gastric banding (AGB) on non-alcoholic fatty liver disease (NAFLD) in severely obese patients. Background NAFLD improves after weight loss surgery, but no histological study has compared the effects of the various bariatric interventions. Methods Participants consisted of 1236 obese patients (body mass index = 48.4 ± 7.6 kg/m2 ), enrolled in a prospective longitudinal study for up to 5 years after RYGB (n = 681) or AGB (n = 555). Liver biopsy samples were available for 1201
patients (97.2% of those at risk) at baseline, 578 patients (47.2%) at 1 year, and 413 patients (68.9%) at 5 years. Results At baseline, NAFLD was present in 86% patients and categorized as severe [NAFLD activity score (NAS) ≥ 3] in 22% patients. RYGB patients had a higher body mass index (49.8 ± 8.2 vs 46.8 ± 6.5 kg/m2 , P < 0.001) and more severe NAFLD (NAS: 2.0 ± 1.5 vs 1.7 ± 1.4, P = 0.004) than AGB patients. Weight loss at 5 years was 25.5% ± 11.8% after RYGB versus 21.4% ± 12.7% after AGB (P < 0.001). When analyzed with a mixed model, all NAFLD parameters improved after surgery (P < 0.001) and improved significantly more after RYGB than after AGB [steatosis (%): 1 year, 7.9 ± 13.7 vs 17.9 ± 21.5, P < 0.001/5 years, 8.7 ± 7.1 vs 14.5 ± 20.8, P < 0.05; NAS: 1 year, 0.7 ± 1.0 vs 1.1 ± 1.2, P < 0.001/5 years, 0.7 ± 1.2 vs 1.0 ± 1.3, P < 0.05]. In multivariate analysis, the superiority of RYGB was primarily but not entirely explained by weight loss. Conclusions The improvement of NAFLD was superior after RYGB than after AGB. Comments 1. Even though other papers have already shown that surgery improve non-alcoholic fatty liver disease [1,2], this study is the first to compare different surgical procedures and show the superiority of RYGB in this respect. 2. As most of the parameters were more severe in the bypass group, the fact that the two groups were not strictly comparable at inclusion does not change the conclusions of the study. 3. Of interest, the liver histologic improvements after RYGB were related to quicker and more marked weight loss. 4. Future studies should compare other surgical procedures, such as sleeve gastrectomy and also evaluate the impact of bariatric surgery on the reduction of the risk of hepatocellular carcinoma. References [1] J Hepatol 2012;56:234—40. [2] J Hepatol 2004;40:578—4. 䊏
Radé F, Bretagnol F, Auguste M, et al. Determinants of outcome following laparoscopic peritoneal lavage for perforated diverticulitis. Br J Surg 2014;101:1602—6. doi:10.1002/bjs.9621
Background Laparoscopic peritoneal lavage has been proposed for generalized peritonitis from perforated diverticulitis to avoid a stoma. Reports of its feasibility and safety are promising. This study aimed to establish determinants of failure to enable improved selection of patients for this approach. Methods The study included all patients with perforated sigmoid diverticulitis who underwent emergency laparoscopic peritoneal lavage from January 2000 to December 2013. Factors predicting failure of laparoscopic treatment were analysed from data collected retrospectively. Results For patients undergoing emergency sigmoid resection (72 of 361), mortality and morbidity rates were 13 and 35%, respectively. In all, 71 patients had laparoscopic lavage, with mortality and morbidity rates of 6 and 28%, respectively. Reintervention was necessary in 11 patients (15%) for unresolved sepsis. Age 80 years or more, American Society of
Press review Anesthesiologists grade III or above, and immunosuppression were associated with reintervention. Conclusion Elderly patients and those with immunosuppression or severe systemic co-morbidity are at risk of reintervention after laparoscopic lavage. Comments 1. In this series, patients were highly selected as this technique was performed in slightly more than 50% of patients. Moreover, a third of the patients had a perisigmoid abscess that was non-accessible to percutaneous drainage or failed to resolve thereafter. In this setting, the 28% morbidity and 6% mortality rates are acceptable, but remain high, as recognized by the authors, compared to their initial experience, which was more favorable [1]. 2. The risk factors for failure outlined here are somewhat disappointing as they correspond to common 3. place risk factors in surgery, and not specifically to diverticular disease. It is not certain that a different approach would have been less morbid in elderly patients with high co-morbidity. 4. It might have been interesting to know the long-term colostomy rate, since one of the putative advantages of this lavage-drainage technique is avoidance of colostomy [2]. 5. The results of two ongoing controlled trails on laparoscopic lavage for diverticular disease perforation are eagerly awaited [3,4]. References [1] J Am Coll Surg 2008;206:654—7. [2] Dis Colon Rectum 2009;52:609—15. [3] BMC Surg 2010;10:29. [4] Trials 2011;12:186. Further reading Dis Colon Rectum 2012;55:932—8. Br J Surg 2013;100:704—10. 䊏
Faitot F, Faron M, Adam R, et al. Two-stage hepatectomy versus 1-stage resection combined with radiofrequency for bilobar colorectal metastases: A case-matched analysis of surgical and oncological outcomes. Ann Surg 2014;260:822—7. doi:10.1097/SLA.0000000000000976
Objectives The aim of this study was to compare the long-term results of 2 surgical strategies for patients with bilobar colorectal liver metastases (bCRLM). Background Two-stage hepatectomy is the surgical strategy mostly chosen for treating extensive BCLM with the pitfall of dropout after the first stage. One-stage strategy combining limited resections and radiofrequency ablation could be proposed as an option in this population. Pateints and methods Between 2000 and 2010, 272 patients were consecutively operated in 2 expert centers practicing 1- or 2-stage hepatectomy for bCRLM. A case-match study (1:1) was conducted using number and size of nodules, synchronous presentation, primary node status, and extrahepatic disease as matching variables to compare overall survival (OS) and disease-free survival (DFS). The analysis was performed in intention-totreat, including patients who did not undergo the second stage.
129 Results In the case-match analysis (156 matched patients), median OS and DFS did not differ significantly between patients in 1- and 2-stage hepatectomy, respectively: 37.2 and 34.5 months (P = 0.6), 9.4 and 7.5 months (P = 0.25). Multivariate analysis confirmed the absence of impact of strategy on OS and DFS. Primary advanced T stage and synchronous presentation were predictors of poor OS (HR = 3.67 and 1.92); CEA more than 200 ng/mL, absence of postoperative chemotherapy, and extrahepatic disease were predictive of recurrence (HR = 2.77, 1.85 and 1.69, respectively). Conclusions This first case-match study demonstrates that on an intention-to-treat analysis 1- and 2-stage hepatectomy in patients with bCRLM achieve comparable OS and DFS, despite the high dropout of the 2-stage strategy. Comments 1. Whatever strategy was used, aggressive therapy resulted in satisfactory long-term outcome in 36% of patients, in spite of initial non-resectability of bilobar colorectal liver metastases (bCRLM). 2. The selection process of patients, particularly in the case-control portion of the study, is not provided: specifically, it is unclear how the 78 patients in the 1S group were chosen. 3. The major problem in this retrospective study is that the two groups are not comparable, even after pairing. Patients in the 2S group had tumors that were more locally advanced, voluminous and deep-seated, probably more often responsible for vascular involvement. This hypothesis is supported by the fact that more patients required additional chemotherapy cycles with targeted therapies in the 2S group. Moreover, in patients at very high risk of recurrence, intra-arterial chemotherapy was used more often in the 1S group, as this has been shown to increase overall survival and decrease the rate of intra-hepatic recurrence [1,2]. Within this setting, oncologic results in the 2S group are finally remarkable in some respects. 4. However, it is likely that these two therapeutic approaches should not be compared, as they are in fact complementary. There exists in fact three categories of patients with bCRLM: one in which most lesions are superficial or subcapsular, where the 1S approach is best; a second in which lesions are deeper and bigger (> 3 cm) or with clear involvement of the vascular pedicles for which radiofrequence ablation appears difficult (these patients should undergo a 2S liver resection); and a third category of patients for whom either of the two strategies are possible and therapy should be discussed based on other criteria, such as non-tumoral parenchymal volume, risk of biliary injury or general patient condition. It would have been more interesting to compare the patients undergoing the 2S technique for whom the 1S technique would also have been possible, with those in the 1S group. References [1] J Gastrointest Surg 2011;15:336—44. [2] Ann Surg 2013;257:114—120. Further reading Ann Surg 2008;248:994—1005. J Clin Oncol 2011;29:1083—90. Ann Surg Oncol 2014;21:815—21.
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C. Mariette, S. Benoist 䊏
Tilly C, Lefèvre JH, Svrcek M, et al. R1 rectal resection: look up and don’t look down. Ann Surg 2014;260:794—9. doi:10.1097/SLA.0000000000000988
Background After rectal resection for adenocarcinoma, pathological examination may reveal invasion of the distal margin (DM) and/or a circumferential resection margin of the tumor (CRM-T) or of involved nodes (CRM-N) less than or equal to 1 mm. Such findings transform a planned R0 resection to R1. Aim The aim was to analyze the impact of an R1 resection on prognosis, recurrence rate, and choice of adjuvant treatment. Pateints and methods All R1 resections observed between 2006 and 2011 were retrospectively collected. Patients were matched with 80 patients with R0 resections according to age, body mass index, gender, neoadjuvant treatment, type of resection, ypT/pT stages, and N stage. Results Among 472 rectal resections performed, 40 (8.5%) were R1 (CRM-T = 34; CRM-N = 11; invaded DM = 4). Among the 4 patients with invaded DM, 3 underwent salvage abdominoperineal resection. Of the 12 patients who had not received neoadjuvant treatment, 5 received adjuvant radiotherapy. Mean follow-up was 49.3 ± 29.3 months for the 120 patients; 5-year overall survival (OS) and disease-free survival (DFS) were 72% and 56%. Comparison between R0 and R1 resections showed a trend toward worse OS in R1 resections: 62% versus 79% (P = 0.0954), a significantly worse DFS: 41% versus 65% (P = 0.0267). Local recurrence rates were similar: 12% versus 13% (P = 0.9177), whereas distant recurrence was significantly more frequent after R1 resection: 56% versus 26% (P = 0.0040). Conclusions R1 resection is associated with a worse prognosis, but local recurrence rate does not differ significantly from matched R0 resections. The difference was observed for distant recurrences, especially lung, favoring the use of chemotherapy and close surveillance of the thorax. Comments 1. It would have been interesting to analyze all R1 patients whether they had received preoperative radiation therapy or not: patients who had R1 resections despite preoperative RCT would be those for whom no response was obtained. The only postoperative treatment possible for these patients is chemotherapy alone. 2. This study does not tell us what to do when the distal margin is involved: this concerned only four patients. Moreover, the fact that no tumor was found in two of the three abdominoperineal salvage operations does not allow the conclusion that APA should be proposed in this setting. Of note, however, this was what most experts recommended in the last French language congress of digestive and hepato-biliary surgery for this situation. 3. The conclusions of this article are based on the results of a case-controlled comparison showing no difference in local recurrence between R1 and R0 resections. The problem is that, unlike R0 patients, nine of 40 patients (22%) in the R1 group had some form of postoperative therapy, chemo-radiation or salvage APR: none of these patients developed local recurrence. It would therefore have been more judicious to eliminate them from the calculation of the local recurrence rate.
4. Finally, the main message of this article is to show that R1 is a poor prognostic factor and a major risk factor for distant metastases, particularly pulmonary metastases. For these patients, it appears justified that postoperative treatment should include systemic chemotherapy. 䊏
Collin Å, Jung B, Nilsson E, et al. Impact of mechanical bowel preparation on survival after colonic cancer resection. Br J Surg 2014;101:1594—1600. doi:10.1002/bjs.9629
Background A randomized study in 1999—2005 of mechanical bowel preparation (MBP) preceding colonic resection found no decrease in postoperative complications. The aim of the present study was to evaluate the long-term effect of MBP regarding cancer recurrence and survival after colonic resections. Methods The cohort of patients with colonic cancer in the MBP study was followed up for 10 years. Data were collected from registers run by the National Board of Health and Welfare. Register data were validated against information in patient charts. Cox proportional hazards model was used for multivariable analysis of factors predictive of cancer-specific survival. Results Register analysis showed significantly fewer recurrences, and better cancer-specific and overall survival in the MBP group. After validation, 839 of 1343 patients remained for analysis (448 MBP, 391 no MBP). Eighty (17.9%) of 448 patients in the MBP group and 88 (22.5%) of 391 in the no MBP group developed a cancer recurrence (P = 0.093). The 10-year cancer-specific survival rate was 84.1% in the MBP group and 78.0% in the no MBP group (P = 0.019). Overall survival rates were 58.8 and 56.0%, respectively (P = 0.186). Conclusion Patients receiving MBP before elective colonic cancer surgery had significantly better cancer-specific survival after 10 years. Comments 1. There are not many possible explanations for this surprising result. Can mechanical preparation eliminate circulating tumor cells in the gastrointestinal tract? This hypothesis is indirectly supported by the results of two meta-analyses that showed that intraoperative lavage of the rectal stump decreased the risk of local recurrence in patients with rectal cancer [1,2]. 2. Results must be interpreted with prudence, however, because several other factors could have possibly influenced the carcinologic outcome. In particular, the use of adjuvant chemotherapy was not indicated. 3. Nonetheless, this study revives the debate about mechanical bowel preparation and its oncologic impact, opening the door for further controlled studies on this topic. References [1] Ann Surg Oncol 2013;20:856—63. [2] Colorectal Dis 2012;14:1313—21. Further reading Ann Surg 2009;249:203—9. Cochrane Database Syst Rev 2011;(9):CD001544. Br J Surg 2007;94:689—95.
Press review 䊏
Loupakis F, Cremolini C, Masi G, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med 2014;371:1609—18. doi:10.1056/NEJMoa1403108
Background A fluoropyrimidine plus irinotecan or oxaliplatin, combined with bevacizumab (a monoclonal antibody against vascular endothelial growth factor), is standard firstline treatment for metastatic colorectal cancer. Before the introduction of bevacizumab, chemotherapy with fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) showed superior efficacy as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI). In a phase 2 study, FOLFOXIRI plus bevacizumab showed promising activity and an acceptable rate of adverse effects. Methods We randomly assigned 508 patients with untreated metastatic colorectal cancer to receive either FOLFIRI plus bevacizumab (control group) or FOLFOXIRI plus bevacizumab (experimental group). Up to 12 cycles of treatment were administered, followed by fluorouracil plus bevacizumab until disease progression. The primary end point was progression-free survival. Results The median progression-free survival was 12.1 months in the experimental group, as compared with 9.7 months in the control group (hazard ratio for progression, 0.75; 95% confidence interval [CI], 0.62—0.90; P = 0.003). The objective response rate was 65% in the experimental group and 53% in the control group (P = 0.006). Overall survival was longer, but not significantly so, in the experimental group (31.0 vs. 25.8 months; hazard ratio for death, 0.79; 95% CI, 0.63—1.00; P = 0.054). The incidences of grade 3 or 4 neurotoxicity, stomatitis, diarrhea, and neutropenia were significantly higher in the experimental group. Conclusions FOLFOXIRI plus bevacizumab, as compared with FOLFIRI plus bevacizumab, improved the outcome in patients with metastatic colorectal cancer and increased the incidence of some adverse events. Comments 1. The 31-month overall survival rate after Folfoxiri—bevacizumab is quite remarquable in that the population in this trial was particularly severely involved, 80% with synchronous colorectal liver metastases (CRLM) and 79% with extrahepatic metastatic disease. 2. This trial confirms the results of the phase II Olivera controlled trial suggesting that Folfoxiri—bevacizumab would increase the response rate and progression-free survival compared to Folfox—bevacizumab [1]. 3. The problem with this maximalist strategy is to know what to propose as second-line treatment after tumor progression since it already uses three of the five drugs currently available for the treatment of CRLM. This chemotherapy should now be tested in strategies evaluating overall survival after second- or third-line chemotherapy. 4. Toxicity is increased with this combination chemotherapy. In the Folfoxiri—bev group, 16% of patients had to increase the interval between two consecutive cycles and 21% underwent cycles with reduced doses. Moreover, evaluation of quality of life would have been pertinent.
131 Reference [1] Ann Oncol 2014. pii: mdu580. Further reading Lancet Oncol 2014;15:1065—75. N Engl J Med 2004;350:2335—42. Lancet Oncol 2010;11:845—52. 䊏
Gronnier C, Tréchot B, Duhamel A, et al. Impact of neoadjuvant chemoradiotherapy on postoperative outcomes after esophageal cancer resection: Results of a European multicenter study. Ann Surg 2014;260:764—70. doi:10.1097/SLA.0000000000000955
Objectives To assess the impact of neoadjuvant chemoradiotherapy (NCRT) on anastomotic leakage (AL) and other postoperative outcomes after esophageal cancer (EC) resection. Background Conflicting data have emerged from randomized studies regarding the impact of NCRT on AL. Methods Among 2944 consecutive patients operated on for EC between 2000 and 2010 in 30 European centers, patients treated by NCRT after surgery (n = 593) were compared with those treated by primary surgery (n = 1487). Multivariable analyses and propensity score matching were used to compensate for the differences in some baseline characteristics. Results Patients in the NCRT group were younger, with a higher prevalence of male sex, malnutrition, advanced tumor stage, squamous cell carcinoma, and surgery after 2005 when compared with the primary surgery group. Postoperative AL rates were 8.8% versus 10.6% (P = 0.220), and 90-day postoperative mortality and morbidity rates were 9.3% versus 7.2% (P = 0.110) and 33.4% versus 32.1% (P = 0.564), respectively. Pulmonary complication rates did not differ between groups (24.6% vs 22.5%; P = 0.291), whereas chylothorax (2.5% vs 1.2%; P = 0.020), cardiovascular complications (8.6% vs 0.1%; P = 0.037), and thromboembolic events (8.6% vs 6.0%; P = 0.037) were higher in the NCRT group. After propensity score matching, AL rates were 8.8% versus 11.3% (P = 0.228), with more chylothorax (2.5% vs 0.7%; P = 0.030) and trend toward more cardiovascular and thromboembolic events in the NCRT group (P = 0.069). Predictors of AL were high American Society of Anesthesiologists scores, supracarinal tumoral location, and cervical anastomosis, but not NCRT. Conclusions Neoadjuvant chemoradiotherapy does not have an impact on the AL rate after EC resection. Comments 1. Even though retrospective, this study constitutes one of the largest cohorts on the topic and, moreover, is relatively homogeneous as concerns the operative technique. The message is fairly clear: if chemoradiotherapy is needed for oncologic reasons, it should be done. 2. It would have been interesting to separate the clinically symptomatic anastomotic leaks from leaks evidenced only by radiology, for which the clinical consequences are not the same. 3. It would also have been interesting to evaluate the risk of AL according to the dose of radiotherapy, even if the
132 doses recommended in France, between 45 and 50 Gy, are relatively homogeneous. 4. There was no information available about how anastomotic fistula were managed. As expert centers were involved, it is probable that management was early and well codified, which partly explains why complications
C. Mariette, S. Benoist of anastomotic leakage were not more severe in the RCT group. Further reading J Clin Oncol 2008;26:1086—92. N Engl J Med 2012;366:2074—84. J Clin Oncol 2014;23:2416—22.