Press review

Journal of Visceral Surgery (2015) 152, 189—196

Available online at

ScienceDirect www.sciencedirect.com

Press review C. Mariette a,∗, S. Benoist b a

Service de chirurgie digestive et générale, hôpital Claude-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 28 May 2015

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Robb WB, Bruyere E, Amielh D, Vinatier E, Mabrut JY, Perniceni T, et al. Esophageal gastrointestinal stromal tumor: is tumoral enucleation a viable therapeutic option? Ann Surg 2015;261:117—24. doi:10.1097/SLA.0000000000000505

Objective The primary objective was to evaluate the feasibility of surgical enucleation of esophageal gastrointestinal stromal tumors (E-GISTs). Secondary objectives evaluated: (i) the impact of tumor enucleation on oncological outcomes; (ii) the effect of pre-therapeutic biopsy on the feasibility of EGIST enucleation; and (iii) the impact of mucosal ulceration on outcomes. Background E-GISTs are very rare tumors and esophageal resection has been the recommended approach. The feasibility and impact on outcomes of tumor enucleation are unknown. Methods Through a large national multicenter retrospective study, 19 patients with E-GISTs were identified between 2001 and 2010. Patients who underwent either enucleation or esophagectomy were compared. Results Of 19 patients identified with E-GISTs, curative treatment was surgical for 16 patients, with enucleation in 8 and esophagectomy in 8. In the enucleation group, median tumoral diameter was 40 mm (18—65 mm), without any mucosal ulceration, preoperative capsular ruptures, or incomplete resections. In the esophagectomy group, the median tumoral diameter was 85 mm (55—250 mm), with mucosal ulceration in 4 patients, preoperative capsular rupture in 1, and no incomplete resections. Severe post-

∗

Corresponding author. E-mail address: [email protected] (C. Mariette).

1878-7886/$ — see front matter http://dx.doi.org/10.1016/j.jviscsurg.2015.04.005

operative complication rates were 50% and 25% in the esophagectomy and enucleation groups, respectively, with 2 postoperative deaths after esophagectomy. After a median follow-up of 6.4 years, 2 recurrences were observed after esophagectomy versus 0 after enucleation. Endoscopic biopsies did not expose patients to complications or local recurrence after enucleation. Endoscopic mucosal ulceration was associated with more aggressive tumors. Conclusion E-GIST enucleation seems safe for tumors of less than 65 mm in diameter. Comments 1. This study has small samples, but represents by far the largest series reported to date for these very rare tumors; esophageal GIST represent 0.7% of all GIST, already a category of rare tumors. 2. The authors suggest that enucleation is feasible without impacting the risk of tumor capsular rupture or incomplete resection, nor long-term oncologic outcomes. Enucleation is performed most often by minimal access surgery, i.e. thoracoscopy, if the lesion is less than 65 mm in diameter, thus decreasing postoperative morbidity. 3. While removal of gastric GIST should be performed by wedge resection, it would seem that the surgical approach to GIST tumors is organ-dependent. 4. This study opens interesting perspectives, notably the unresolved management question of what to do for GIST tumors less than 20 mm in diameter. Because of the minimally invasive character of enucleation, surgical management could be an alternative to simple surveillance. 5. Finally, the dogma that intraoperative biopsies are necessary fades, as enucleation was not associated with an increased risk of intra- or postoperative complications.

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Barczy´ nski M, Konturek A, Nowak W. Randomized clinical trial of posterior retroperitoneoscopic adrenalectomy versus lateral transperitoneal laparoscopic adrenalectomy with a 5-year follow-up. Ann Surg 2014;260:740—7. doi:10.1097/SLA.0000000000000982

Objective To test if posterior retroperitoneoscopic adrenalectomy (PRA) is superior to lateral transperitoneal laparoscopic adrenalectomy (LTLA). Background Most popular LTLA has been recently challenged by an increasing popularity of PRA, which is believed by many surgeons (not evidence-based) as superior to LTLA in the treatment of small and benign adrenal tumors. Methods Participants were assigned randomly to PRA or LTLA and followed for 5 years after surgery. The primary endpoint was the duration of surgery. Secondary endpoints were blood loss, conversion rate, postoperative recovery, morbidity, and costs. Results Sixty-five patients were included, of whom 61 (PRA 30, LTLA 31) completed the 5-year follow-up. The following differences were identified in favor of PRA vs LTLA: shorter duration of surgery (50.8 vs 77.3 minutes), lower intraoperative blood loss (52.7 vs 97.8 mL), diminished pain intensity within 48 hours postoperatively, lower prevalence of shoulder-tip pain (3.0% vs 37.5%), shorter time to oral intake (4.4 vs 7.3 hours), shorter time to ambulation (6.1 vs 11.5 hours), shorter length of hospital stay, and lower cost (1728 D vs 2315 D), respectively (P < 0.001 for all). No differences were noted in conversion rate or morbidity except for herniation occurring more often after LTLA than PRA (16.1% vs 0%, P = 0.022) and need for hernia repair (12.9% vs 0%, P = 0.050), respectively. Conclusions Both approaches were equally safe. However, outcomes of PRA operations were superior to LTLA in terms of shorter surgery duration, lower blood loss, lower postoperative pain, faster recovery, improved cost-effectiveness, and abolished risk of surgical access site herniation. Comments 1. Three other randomized trials, with small samples, did not find any difference between the two approaches, other than a shorter convalescence period for two, and a shorter time to oral intake for the third [1—3]. This study is the first, however, where PRA was performed in the prone position. 2. The authors found clear postoperative advantages in favor of PRA, essentially because of the shorter operative time and the absence of pneumoperitoneum with its impact on nausea and pain. 3. Of note, the main objective was not very robust nor as medically pertinent as morbidity would have been, and there was no evaluation of patient perceptions, such as quality of life. All the studied objectives were secondary endpoints, and not very convincing for practitioners. 4. Once again, we find the ambivalence that characterizes too many surgical trials whose design is to overrate the positive results and enhance their publication rather than to evaluate robust and medically pertinent endpoints (usually not influenced by practice). Thus, the 26 minute difference in duration of operation is far from a pertinent

endpoint, and above all, an endpoint whose evaluation escapes blinding, by definition. References [1] Ann Surg 1996;224:727—34. [2] J Laparoendosc Adv Surg Tech A 2013;23:362—6. [3] J Urol 2005;174:442—5. 䊏

Mehrabi A, Hafezi M, Arvin J, Esmaeilzadeh M, Garoussi C, Emami G, et al. A systematic review and meta-analysis of laparoscopic versus open distal pancreatectomy for benign and malignant lesions of the pancreas: it’s time to randomize. Surgery 2015;157:45—55. doi:10.1016/j.surg.2014.06.081

Background Laparoscopic distal pancreatectomy is regarded as a feasible and safe surgical alternative to open distal pancreatectomy for lesions of the pancreatic tail and body. The aim of the present systematic review was to provide recommendations for clinical practice and research on the basis of surgical morbidity, such as pancreas fistula, delayed gastric empting, safety, and clinical significance of laparoscopic versus open distal pancreatectomy for malignant and nonmalignant diseases of the pancreas. Methods A systematic literature search (MEDLINE) was performed to identify all types of studies comparing laparoscopic distal pancreatectomy and open distal pancreatectomy. Random effects meta-analyses were calculated after critical appraisal of the included studies and presented as odds ratios or mean differences each with corresponding 95% confidence intervals. Results A total of 4148 citations were retrieved initially; available data of 29 observational studies (3701 patients overall) were included in the meta-analyses. Five systematic reviews on the same topic were found and critically appraised. Meta-analyses showed superiority of laparoscopic distal pancreatectomy in terms of blood loss, time to first oral intake, and hospital stay. All other parameters of operative morbidity and safety showed no difference. Data on oncologic radicality and effectiveness are limited. Conclusions Laparoscopic distal pancreatectomy seems to be a safe and effective alternative to open distal pancreatectomy. No more non-randomized trials are needed within this context. A large, randomized trial is warranted and should focus on oncologic effectiveness, defined endpoints, and costeffectiveness. Comments 1. The results of this type of meta-analysis, based on non-randomized comparative studies, warrant caution, mainly because of the very absence of randomized studies. 2. The following elements limit the extrapolation of results in terms of clinical practice: (i) absence of contact with authors; (ii) absence of standardized definition of complications; (iii) absence of oncologic data allowing evaluation of carcinologic safety; (iv) absence of randomization which led to comparison of groups that were not comparable, with more favorable patient status or tumors in the laparoscopic group; (v) bias in evaluation in favor of the more innovative procedure.

Press review 3. The message is that, after 29 non-randomized comparative studies, it is high time that someone initiates a multicenter randomized trial comparing laparoscopy to laparotomy with a robust main endpoint, such as morbidity or survival and including at least one objective evaluated by the patient, such as quality of life. 4. The choice could be a randomized superiority trial aiming to show the benefits of laparoscopy, for example, on morbidity. But since the feasibility has been established, and the technique is already fairly widespread, a non-inferiority study with survival as the main objective would equally be pertinent. 䊏

Schoenberg MB, Marx S, Kersten JF, Rösch T, Belle S, Kähler G, et al. Laparoscopic Heller myotomy versus endoscopic balloon dilatation for the treatment of achalasia: a network meta-analysis. Ann Surg 2013;258:943—52. doi:10.1097/SLA.0000000000000212

Objective Comparison of short- and long-term effects after laparoscopic Heller myotomy (LHM) and endoscopic balloon dilation (EBD) considering the need for retreatment. Background Previously published studies have indicated that LHM is the most effective treatment for Achalasia [1,2]. In contrast to that, a recent randomized trial found EBD equivalent to LHM 2 years after initial treatment [3]. Methods A search in Medline, PubMed, and Cochrane Central Register of Controlled Trials was conducted for prospective studies on interventional achalasia therapy with predefined exclusion criteria. Data on success rates after the initial and repeated treatment were extracted. An adjusted network meta-analysis and meta-regression analysis was used, combined with a head-to-head comparison, for follow-up at 12, 24, and 60 months. Results Sixteen studies including results of 590 LHM and EBD patients were identified. Odds ratio (OR) was 2.20 at 12 months (95% confidence interval: 1.18—4.09; P = 0.01); 5.06 at 24 months (2.61—9.80; P < 0.00001) and 29.83 at 60 months (3.96—224.68; P = 0.001). LHM was also significantly superior for all time points when therapy included re-treatments [OR = 4.83 (1.87—12.50), 19.61 (5.34—71.95), and 17.90 (2.17—147.98); P ≤ 0.01 for all comparisons] Complication rates were not significantly different. Metaregression analysis showed that amount of dilations had a significant impact on treatment effects (P = 0.009). Every dilation (up to 3) improved treatment effect by 11.9% (2.8—21.8%). Conclusions In this network meta-analysis, LHM demonstrated superior short- and long-term efficacy and should be considered first-line treatment of esophageal achalasia. Comments 1. This meta-analysis should please the surgeons since it shows that surgery by LHM is superior to endoscopic treatment. 2. These results are similar to what can be found in a previous meta-analysis but which did not take into account the results of the multicenter study by Boeckxtaens et al. published in the New England Journal of Medicine [3], which showed that up to five iterative EBD could be

191 performed during the first six months without considering that this was a failure of the procedure. 3. The limits of this meta-analysis are inclusion of nonrandomized studies but also that only two of the studies actually compared LHM to EBD, leading to indirect comparisons or what is called a ‘‘network meta-analysis’’. 4. While the results of the Boeckxtaens et al. [3] analysis showed that LHM and EBD were comparable in terms of control of reflux, it remains to be shown by a future meta-analysis that the two approaches procure similar results as concerns the symptoms of reflux. References [1] Ann Surg 2009;249:45—7. [2] Dig Dis Sci 2009;54:2303—11. [3] N Engl J Med 2011;364:1807—16. 䊏

Nafteux PR, Lerut TE, Villeneuve PJ, Dhaenens JM, De Hertogh G, Moons J, et al. Signet ring cells in esophageal and gastroesophageal junction carcinomas have a more aggressive biological behavior. Ann Surg 2014;260:1023—9. doi:10.1097/SLA.0000000000000689

Objective To clarify the biologic behavior of esophageal signet ring cell (SRC) carcinomas of the esophagus and gastroesophageal junction (GEJ). To evaluate the accuracy of pretreatment biopsies in diagnosing true SRC carcinoma. Background In contrast with gastric cancer, little is known about the biologic behavior and prognosis of SRC. Methods All adenocarcinomas (ADC) of the esophagus and GEJ patients undergoing primary resection between 1990 and 2009 were included (n = 920). Specimens containing SRCs (n = 114) were classified according to World Health Organization criteria (> 50% SRC or < 50% SRC). Results Thirty-two patients showed more than 50% SRC and 71 patients showed less than 50% SRC. Overall cancer-specific 5-year survival was worse for SRC (22.4%, P < 0.0001) and for SRC > 50% (13.6%, P = 0.0001) compared with ADC. Complete resection was achieved in 86.5% of patients (n = 697) in ADC, 69.5% (n = 57) in SRC < 50%, and 78.1% (n = 25) in SRC > 50% (vs ADC, respectively, P < 0.0001 and P = 0.1801). In 379 pN + R0 patients, the median number of positive lymph nodes was comparable between ADC and SRC < 50% (4 vs 5, P = 0.207) or SRC > 50% (4 vs 8, P = 0.077). Compared with ADC, SRC > 50% showed more pN3’s (30% vs 61%, P = 0.006), higher recurrence (56% vs 42% for ADC, P = 0.003), and localregional recurrences (29% vs 16%, P = 0.002). Pretreatment biopsies were unreliable to define the presence of SRC > 50% (sensitivity = 56.3%, positive predictive value = 43.9%). Conclusions SRCs are aggressive neoplasms associated with poorer prognosis than other ADCs after primary esophagectomy. Because our data suggest that pretreatment biopsies failed to reliably define presence of SRC > 50%, presence of SRCs in pretreatment biopsies seems to be of no use to define treatment strategy or prognosis. Comments 1. While the incidence of esophageal SRC is rare, the present study confirms the poor prognosis of SRC in this localization compared to adenocarcinoma [1].

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2. Likewise, the value of this study resides in the fact that the impact of SRC was analyzed. While the WHO definition of SRC is based on a > 50% percentage of SRC, the present study suggests that even below this threshold, the presence of SRC is associated with poorer prognosis, albeit to a lesser degree. 3. Poor prognosis is related essentially to a lower R0 resection rate and a higher recurrence rate in the form of carcinomatosis, correlated either to increased aggressiveness of disease, or to delay in diagnosis linked to the infiltrating pattern of the disease. 4. The limits of diagnosis of ADC on pre-therapeutic biopsies must be interpreted with caution because of the absence of a standardized method of biopsy, the absence of double blind re-reading of pathology specimens, the limited number of patients with a > 50% component of SRC who underwent complete resection, exclusion of patients having received neo-adjuvant therapy, and especially with large tumors. The high diagnostic effectiveness was recently underscored in a cohort of gastric cancer [2], leading to the idea of testing the value of neo-adjuvant chemotherapy in this type of cancer [3]. References [1] Ann Surg 2009;250:878—87. [2] World J Surg 2012;36:346—354. [3] BMC Cancer 2013;13:281.

Comments 1. While mortality is low after distal pancreatectomy, morbidity remains high, ranging from 35% to 60%, and consisting mainly of POPF [1,2]. 2. POPF can in itself also be a source of morbidity, in the form of abscess, sepsis, gastroparesis and bleeding, enhancing recurrence and decreasing survival [3], underscoring therefore the value of prevention. 3. Even if the conclusion of the value of mechanical suture closure is robust, that of the benefit of pancreaticojejunostomy is less strong because of the three-fold smaller number of patients in this subset. 4. The main limits of this meta-analysis are: (i) the inhomogeneous definition of POPF; (ii) absence of subgroup analysis between the laparoscopic and laparotomy approaches; (iii) the variable endpoints reported, also leading to inhomogeneity; (iv) potential missing or nonpublished studies. 5. Of note, no other device, adhesive agent or biological glue has been shown to be of any value in the prevention of POPF after distal pancreatectomy. References [1] World J Gastrointest Surg 2012;4:114—20. [2] Ann Surg 2007;245:573—82. [3] Ann Surg Oncol 2011;18:2329—37. 䊏

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Zhang H, Zhu F, Shen M, Tian R, Shi CJ, Wang X, et al. Systematic review and meta-analysis comparing three techniques for pancreatic remnant closure following distal pancreatectomy. Br J Surg 2015;102:4—15. doi:10.1002/bjs.9653

Background Established closure techniques for the pancreatic remnant after distal pancreatectomy include stapler, suture and anastomotic closure. However, controversy remains regarding the ideal technique; therefore, the aim of this study was to compare closure techniques and risk of postoperative pancreatic fistula (POPF). Methods A systematic review was carried out according to PRISMA guidelines for studies published before January 2014 that compared at least two closure techniques for the pancreatic remnant in distal pancreatectomy. A random effects model was constructed using weighted odds ratios (ORs). Results Thirty-seven eligible studies matched the inclusion criteria and 5252 patients who underwent distal pancreatectomy were included. The primary outcome measure, the POPF rate, ranged 0 from to 70%. Meta-analysis of the 31 studies comparing stapler versus suture closure showed that the stapler technique had a significantly lower rate of POPF, with a combined OR of 0.77 (95% CI 0.61 to 0.98; P = 0.031). Anastomotic closure was associated with a significantly lower POPF rate than suture closure (OR 0.55, 0.31—0.98; P = 0.042). Combined stapler and suture closure had significantly lower POPF rates than suture closure alone, but no significant difference compared with stapler closure alone. Conclusions The use of stapler closure or anastomotic closure for the pancreatic remnant after distal pancreatectomy significantly reduces POPF rates compared with suture closure. The combination of stapler and suture closure shows superiority over suture closure alone.

Denost Q, Adam JP, Pontallier A, Celerier B, Laurent C, Rullier E. Laparoscopic total mesorectal excision with coloanal anastomosis for rectal cancer. Ann Surg 2015;261:138—43. doi:10.1097/SLA.0000000000000855

Objective Oncologic and functional outcomes were compared between transanal and transabdominal specimen extraction after laparoscopic coloanal anastomosis for rectal cancer. Background Laparoscopic coloanal anastomosis is an attractive new surgical option in patients with low rectal cancer because laparotomy is not necessary due to transanal specimen extraction. Risks of tumor spillage and fecal incontinence induced by transanal extraction are not known. Methods Between 2000 and 2010, 220 patients with low rectal cancer underwent laparoscopic rectal excision with hand-sewn coloanal anastomosis. The rectal specimen was extracted transanally in 122 patients and transabdominally in 98 patients. Endpoints were circumferential resection margin, mesorectal grade, local recurrence, survival, and functional outcome. Results The mortality rate was 0.5% and surgical morbidity rate was 17%. The rate of positive circumferential resection margin was 9% and the mesorectum was graded complete in 79%, subcomplete in 12%, and incomplete in 9%. After a follow-up of 51 months (range, 1—151), the local recurrence rate was 4% and overall survival and disease-free survival rates were 83% and 70% at 5 years, respectively. The continence score was 6 (range, 0—20). There was no difference of mortality rate, morbidity rate, circumferential resection margin, mesorectal grade, local recurrence (4% vs 5%, P = 0.98), and disease-free survival rate (72% vs 68%, P = 0.63) between transanal and transabdominal extraction groups. Continence score was also similar (6 vs 6, P = 0.92).

Press review Conclusions Transanal extraction of the rectal specimen did not compromise oncologic and functional outcome after laparoscopic surgery for low rectal cancer and seems as a safe option to preserve the abdominal wall. Comments 1. This study shows that results of laparoscopic resection for low rectal cancer are excellent in an expert center. These results are comparable, and slightly superior to those reported in controlled trials in which patients with high and mid rectal cancers were included [1—4]. 2. There is, however, a bias related to the retrospective nature of this study. As there were more transanal extractions, it is probable that there was a reason for abdominal extraction for the patients who had this extraction modality. This seems to be the case as the patients in this group were more often obese, masculine, with larger tumors, giving rise to more R1 resections. It is even possible that the transanal extraction was not possible in these patients. For these same reasons, patients undergoing transanal extraction should have had better oncologic and functional outcomes. As this was not the case, a doubt persists as the absence of oncologic and functional consequences of transanal extraction. 3. The authors indicated that 151 patients (69%) had a Jpouch. In patients undergoing transanal extraction, this means that the reservoir, once constructed, had to be reintegrated into the perineal cavity, a potential source of sphincteric trauma. It therefore seems more judicious to perform a side-to-end coloanal anastomosis rather than a J-pouch in patients undergoing a transanal extraction. References [1] Br J 2010;97:1638—45. [2] Br J Surg 2009;96:982—9. [3] Lancet Oncol 2014;15:767—74 [4] Colorectal Dis 2012;14:705—13

193 encountered. There was no postoperative mortality, and the morbidity rate was 26%. The mesorectum was complete in 47 cases (84%) and nearly complete in 9 cases (16%). The median number of lymph nodes retrieved was 12 (range, 7—29) per patient. The median radial and distal margins were 8 mm (0—20) and 10 mm (3—40), respectively. R0 resection was achieved in 53 patients (94.6%). The median Wexner score was 4 (3—12). Thirteen (28%) patients reported stool fragmentation and difficult evacuation. Conclusions ETAP is a feasible alternative surgical option to conventional laparoscopy for rectal resection and may represent a promising step toward rectal natural orifice transluminal endoscopic surgery (NOTES). Comments 1. This series included the largest number of patients to date evaluating this innovative technique. The oncologic and functional outcomes are comparable to those reported for traditional laparoscopic rectal cancer resection [1]. 2. The technique seems particularly useful in the narrow pelvis of the obese male, for whom the laparoscopic abdominal dissection is especially difficult as concerns the horizontal portion of the sub-peritoneal rectum. For this portion of the rectum, transanal dissection can be performed more easily, and has the advantage of being in the axis of the rectum. 3. This multicenter evaluation was the indispensable step before setting up a controlled study comparing this innovative technique to classical laparoscopy for excision of cancer of the lower rectum. A multicenter phase III trial (Greccar 11) comparing these two approaches should open in the near future. Reference [1] Surg Endosc 2013;27:1485—502. 䊏

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Tuech JJ, Karoui M, Lelong B, De Chaisemartin C, Bridoux V, Manceau G, et al. A step toward NOTES total mesorectal excision for rectal cancer: endoscopic transanal proctectomy. Ann Surg 2015;261:228—33. doi:10.1097/SLA.0000000000000994

Background Previous publications have suggested that endoscopic transanal proctectomy (ETAP) is a promising technique and may be an alternative to conventional low anterior resection for rectal cancer. The aim of this study was to evaluate the technical feasibility of ETAP, with a particular focus on postoperative and oncological results and on functional outcomes. Methods This study was a multicenter prospective study of unselected consecutive patients with low rectal cancer requiring proctectomy and coloanal anastomosis. All patients underwent a standardized procedure. The study endpoints were the safety and adequacy of the oncological resection criteria. All patients were evaluated with the Wexner Fecal Incontinence Questionnaire after stoma closure. Results Fifty-six consecutive patients (41 men) underwent ETAP between February 2010 and June 2012. The median age was 65 years (39—83), and the median body mass index was 27 (20—42). No intraoperative complications were

Park EJ, Cho MS, Baek SJ, Hur H, Min BS, Baik SH, et al. Long-term oncologic outcomes of robotic low anterior resection for rectal cancer: a comparative study with laparoscopic surgery. Ann Surg 2015;261:129—37. doi:10.1097/SLA.0000000000000613

Objectif The aim of this study is to evaluate long-term oncologic outcomes of robotic surgery for rectal cancer compared with laparoscopic surgery at a single institution. Background Robotic surgery is regarded as a new modality to surpass the technical limitations of conventional surgery. Short-term outcomes of robotic surgery for rectal cancer were acceptable in previous reports. However, evidence of long-term feasibility and oncologic safety is required. Methods Between April 2006 and August 2011, 217 patients who underwent minimally invasive surgery for rectal cancer with stage I—III disease were enrolled prospectively (robot, n = 133; laparoscopy, n = 84). Median follow-up period was 58 months (range, 4—80 months). Perioperative clinicopathologic outcomes, morbidities, 5-year survival rates, prognostic factors, and cost were evaluated. Results Perioperative clinicopathologic outcomes demonstrated no significant differences, except for the conversion rate and length of hospital stay. The 5-year overall survival

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rate was 92.8% in robotic, and 93.5% in laparoscopic surgical procedures (P = 0.829). The 5-year disease-free survival rate was 81.9% and 78.7%, respectively (P = 0.547). Local recurrence was similar: 2.3% and 1.2% (P = 0.649). According to the univariate analysis, this type of surgical approach was not a prognostic factor for long-term survival. The patient’s mean payment for robotic surgery was approximately 2.34 times higher than laparoscopic surgery. Conclusions No significant differences were found in the 5-year overall, disease-free survival and local recurrence rates between robotic and laparoscopic surgical procedures. We concluded that robotic surgery for rectal cancer failed to offer any oncologic or clinical benefits as compared with laparoscopy despite an increased cost. Comments 1. The 93% 5-year survival rate is particularly high, and can probably be explained by a highly selected population. Effectively, only 11% of the patients in this series had preoperative radiation chemotherapy and pathology reports showed that most patients had stage I or II tumors. 2. The principal advantage of the robot is to facilitate the dissection of the lower rectum, particularly in delicate situations such as the narrow pelvis of the obese male with a large tumor [1]. However, in this series, patients were not particularly obese (mean BMI of 23 kg/m2 ) with small stage II or stage III tumors. This population was therefore not well adapted to show any benefit of the robot. 3. Because of the associated higher costs, the robot should be used only if better oncologic or even functional outcomes can be obtained. This means we must await the results of several phase III trials currently underway in several countries. Reference [1] Ann Surg Oncol 2010;17:1614—20. 䊏

Fleshman JW, Beck DE, Hyman N, Wexner SD, Bauer J, George V et al. A prospective, multicenter, randomized, controlled study of non-crosslinked porcine acellular dermal matrix fascial sublay for parastomal reinforcement in patients undergoing surgery for permanent abdominal wall ostomies. Dis Colon Rectum 2014;57:623—31. doi: 10.1097/DCR.0000000000000106

Background A large proportion of patients with a colostomy or an ileostomy develop parastomal hernias. The placement of a reinforcing material at the stoma site may reduce parastomal hernia incidence. Objective We aimed to assess the safety and efficacy of stoma reinforcement with sublay placement of non-cross-linked porcine-derived acellular dermal matrix at the time of stoma construction. Design This is a randomized, patient- and third-party assessorblind, controlled trial. Settings This study took place in colorectal/general surgery institutions. Interventions

Patients were prospectively randomly assigned to undergo standard end-stoma construction with or without porcine-derived acellular dermal matrix reinforcement. Patients Patients undergoing construction of a permanent stoma were eligible. A total of 113 patients (59 men, 54 women; mean age, 60 years; mean BMI, 25.4 kg/m2 ) participated: 58 controls and 55 with reinforcement. Main outcomes measures The incidence of parastomal hernia, safety, and stomarelated quality-of life were assessed. Results Intraoperative complications and blood loss were similar between groups. Quality-of-life scores were similar through 24 months of follow-up. At 24 months of follow-up, the incidence of parastomal hernias was similar for both groups (12.2% of the porcine-derived acellular dermal matrix group and 13.2% of controls). Limitations Study limitations include the inclusion of ileostomy and colostomy patients, open and laparoscopic techniques, and small numbers of patients at follow-up. Conclusions Safety and quality-of-life data from this randomized control trial show similar outcomes in both groups. Prosthetic reinforcement of stomas was safe, but it did not significantly reduce the incidence of parastomal hernia formation. Comments 1. The methodology used in this study is for the least surprising. Initially, the hypothesis was that they needed 220 patients to show a 50% reduction in parastomal hernia. Then, without any further justification, they decided to randomize only 110 patients. Finally, only 102 patients were included. Moreover, while the main endpoint was the rate of parastomal hernia at 24 months, only 75 patients were followed for two years, and no intermediate analysis was planned. 2. The overall parastomal hernia rate was low in this study, 11.7%. This may be explained by the specific population under scrutiny, since nearly one-third of patients underwent definitive ileostomy for which parastomal hernia is seen much less than for colostomy. It would have been interesting to analyse the results according to the type of stoma performed. 3. A medico-economic study would have been of interest, since one of the major disadvantages of bio-prostheses is the high direct costs. 4. The results of a French phase III study (GRECCAR 07) are awaited, evaluating the value of synthetic prosthesis to prevent the risk of parastomal hernia. 䊏

Marthey L, Sa-Cunha A, Blanc JF, Gauthier M, Cueff A, Francois E, et al. FOLFIRINOX for locally advanced pancreatic adenocarcinoma: results of an AGEO multicenter prospective observational cohort. Ann Surg Oncol 2015;22:295—301. doi:10.1245/s10434-014-3898-9

Background First-line treatment with FOLFIRINOX significantly increases overall survival (OS) in patients with metastatic pancreatic adenocarcinoma (PA) compared with gemcitabine. The aim of this observational cohort was to evaluate the tolerability and efficacy of this regimen in unresectable locally advanced PA (LAPA).

Press review Patients and methods From February 2010 to February 2012, all consecutive patients from 11 French centers treated by FOLFIRINOX for a histologically proven LAPA were prospectively enrolled. Unresectability was defined independently by each center’s multidisciplinary staff at diagnosis. Absence of metastatic disease was confirmed by chest-abdomen-pelvis computed tomography scan. FOLFIRINOX was delivered every 2 weeks as previously reported until progressive disease, major toxicity, or consolidation treatment by radiotherapy and/or surgery. Results Seventy-seven patients were enrolled. They received a median number of five cycles (1—30). Grade 3—4 toxicities were neutropenia (11%), nausea (9%), diarrhea (6%), fatigue (6%), and anemia (1%). Grade 2—3 sensory neuropathy occurred in 25% of patients. No toxic death was reported and only 6% of patients had to stop treatment because of toxicity. Disease control rate was 84 with 28% of objective response (Response Evaluation Criteria in Solid Tumors). Seventy-five percent of patients received a consolidation therapy: 70% had radiotherapy and 36% underwent a surgical resection, with a curative intent. Within the whole cohort, 1-year OS rate was 77% (95% CI 65—86) and 1-year progression-free survival rate was 59% (95% CI 46—70). Conclusions First-line FOLFIRINOX for LAPA seems to be effective and have a manageable toxicity profile. These promising results will have to be confirmed in a phase III randomized trial. Comments 1. This study represents the largest cohort of patients treated by Folfirinox for locally advanced pancreatic adenocarcinoma and should serve as a reference for future therapeutic trials in this population. The oncologic outcomes observed are superior to those usually reported in this situation with Gemzar [3,4]. 2. The toxicity rate of Folfirinox in this study is lower than that usually reported [1,2]. This can probably be explained by increased experience with this chemotherapy with notably a reduction in the doses in two-thirds of patients as well as use of growth factor G-CSF in 82% of them. 3. There are several biases in this study. First, the criteria of non-resectability were not determined in advance, and these varied from one center to another. Because of this, it would have been judicious to propose a second, centralized analysis of imaging studies to check that the tumors were not resectable, particularly for cases with isolated venous involvement. Moreover, even though the cohort was prospective, the oncologic outcome was not analyzed with intention to treat. Effectively, only the patients who could receive Folfirinox were included. As an example, patients who had a severe complication related to their preoperative biliary drainage that prevented them from receiving the initially planned Folfirinox chemotherapy were not included. 4. The 32% secondary R0 resection rate is particulary remarkable in patients with locally advanced pancreatic cancer at initial diagnosis. As 25 of 28 patients undergoing operation also had intraoperative radiation therapy, it is difficult to affirm that this secondary resection rate was directly related to Folfirinox. 5. Following these promising results, two French controlled trials are about to start to evaluate the value of Folfirinox not only for non-resectable locally advanced pancreatic

195 cancer (NEOPAN trial) but also for pancreatic cancer immediately resectable (PANACHE trial). References [1] N Engl J Med 2011;364:1817—25. [2] BMC Cancer;2012;12:199. [3] J Clin Oncol 2011;29:4015—112. [4] J Clin Oncol 2007;25:326—31. 䊏

Elias D, Faron M, Iuga BS, Honoré C, Dumont F, Bourgain JL, et al. Prognostic similarities and differences in optimally resected liver metastases and peritoneal metastases from colorectal cancers. Ann Surg 2015;261:157—63. doi:10.1097/SLA.0000000000000582

Purpose To analyze and compare survival in patients operated for colorectal liver metastases (LM) with that in patients optimally resected for peritoneal metastases (PM). Patients and methods This study concerns 287 patients with LM and 119 patients with PM treated with surgery plus chemotherapy between 1993 and 2009, excluding patients presenting both LM and PM. Results Mortality (respectively, 2.7% and 4.2%), morbidity (respectively, 11% and 17%), and 5-year overall survival (OS) rates (respectively, 38.5% and 36.5%) were not statistically different between the LM group and the PM group. Multivariate analysis showed that the extent of the disease was the main prognostic factor, which led us to divide the population into 5 subgroups. The best 5-year OS rate (72.4%) was obtained in patients with minimal peritoneal disease [peritoneal cancer index (PCI) ≤ 5]. OS was similar for the patients with less than 10 LM and those with a PCI between 6 and 15 (respectively, 39.4% and 38.7%). Five-year OS was lower in patients with more than 10 LM (18.1%), and dramatically low for patients with a PCI > 15 (11.8%). Conclusions This study underlines the prognostic impact of the tumor burden in metastatic colorectal disease. In selected patients, similar survival rates can be obtained after optimal treatment of LM and PM. As the role of optimal surgical resection of LM is widely accepted, our results confirm that an optimal attitude should also be adopted to treat PM with a PCI < 16, particularly in patients with very low PCI (< 5) where survival could be better than LM. Comments 1. The concept of this study is somewhat strange. The justification of an aggressive therapeutic approach for PM based the fact that prognosis is comparable to that of LM is not convincing. All the more since this study comes from a team that has shown that surgery for PM associated with intra-pertioneal chemotherapy was more effective than chemotherapy alone [1] and that the combination leads to long-term survival [2]. 2. The comparison of prognosis between PM and LM in this series introduces several biases that warrant caution when interpreting the results. First of all, in this highly specialized center, the two populations were selected in very different manners. For logistical reasons, patients undergoing cytoreductive surgery for PM were those for whom disease remained stable or responded favorably to long-term chemotherapy and who therefore had a better prognosis. On the other hand, the prognosis of most patients treated for LM, because of accrual, were

196 those who had extensive and non-resectable LM and were referred to this specialized center with the hope that their disease might become resectable. Moreover, it is somewhat surprising that the patients with LM were not divided into three groups, as was done for carcinomatosis. In this manner, patients in the most favorable group

C. Mariette, S. Benoist LM, that is LM < 10, had a less favorable prognosis than the best prognostic group PM, that is with PCI < 5. It would have been better to include a group with LM < 5. References [1] J Clin Oncol 2009;27:681—5. [2] Ann Surg 2013;257:1065—71.