GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

Textbook Oncological Outcome in European GASTRODATA.

OBJECTIVE: To assess the rate of textbook outcome (TO) and textbook oncological outcome (TOO) in the European population based on the GASTRODATA registry. BACKGROUND: TO is a composite parameter assessing surgical quality and strongly correlates with improved overall survival. Following the standard of treatment for locally advanced gastric cancer, TOO was proposed as a quality and optimal multimodal treatment parameter. METHODS: TO was achieved when all the following criteria were met: no intraoperative complications, radical resection according to the surgeon, pR0 resection, retrieval of at least 15 lymph nodes, no severe postoperative complications, no reintervention, no admission to the intensive care unit, no prolonged length of stay, no postoperative mortality and no hospital readmission. TOO was defined as TO with the addition of perioperative chemotherapy compliance. RESULTS: Of the 2558 patients, 1700 were included in the analysis. TO was achieved in 1164 (68.5%) patients. The use of neoadjuvant chemotherapy [odds ratio (OR) = 1.33, 95% CI: 1.04-1.70] and D2 or D2+ lymphadenectomy (OR = 1.55, 95% CI: 1.15-2.10) had a positive impact on TO achievement. Older age (OR = 0.73, 95% CI: 0.54-0.94), pT3/4 (OR = 0.79, 95% CI: 0.63-0.99), ASA 3/4 (OR = 0.68, 95% CI: 0.54-0.86) and total gastrectomy (OR = 0.56, 95% CI: 0.45-0.70), had a negative impact on TO achievement. TOO was achieved in 388 (22.8%) patients. Older age (OR = 0.37, 95% CI: 0.27-0.53), pT3 or pT4 (OR = 0.52, 95% CI: 0.39-0.69), and ASA 3 or 4 (OR = 0.58, 95% CI: 0.43-0.79) had a negative impact on TOO achievement. CONCLUSIONS: Despite successively improved surgical outcomes, stage-appropriate chemotherapy in adherence to the current guidelines for multimodal treatment of gastric cancer remains poor. Further implementation of oncologic quality metrics should include greater emphasis on perioperative chemotherapy and adequate lymphadenectomy.

The impact of prior endoscopic or surgical therapy on open Zenker's diverticulum surgery: analysis on a large single center cohort : Comparison of primary and revisional open surgery for Zenker's diverticulum.

BACKGROUND: Endoscopic treatment of Zenker's diverticulum is an attractive minimally invasive alternative compared to the classic open approach. However, increased recurrence rate were reported. In case of relapse, endoscopic therapy might be repeated, or alternatively open surgery is performed. This study aimed to identify potential differences in the outcomes between primary or secondary surgical treatment in Zenker's diverticulum. METHODS: From January 2003 to April 2019, 227 subsequent patients underwent surgical diverticulectomy and cervical myotomy at the surgical department of TUM. 41 of 227 patients had received previous therapy, either open or endoscopic. Perioperative parameters in priorly untreated patients were retrospectively compared to those after previous therapy (mostly endoscopic) with special regard to perioperative data and postoperative complications. Univariate and multivariate regression analyses were performed to identify predictors for postoperative complications. RESULTS: We could show that the number of complications (p = 0.047) in pretreated patients is significant higher as well as the severity after Clavien-Dindo (p = 0.025). Stapler line leakage, wound infections, and operative revision rate was higher also pretreated group. Pretreatment and surgery time showed a significant association with postoperative complications in univariate analysis. In multivariate analysis, pretreatment remained a significant independent predictor of complications. CONCLUSION: The present data indicate that endoscopic therapy might represent a risk factor for postoperative complications in case of relapse surgery. Therefore primary open surgery should be debated in patients with an increased high risk of relapse.

Open vs robotic gastrectomy with D2 lymphadenectomy: a propensity score-matched analysis on 1469 patients from the IMIGASTRIC prospective database.

BACKGROUND: Comparative data on D2-robotic gastrectomy (RG) vs D2-open gastrectomy (OG) are lacking in the Literature. Aim of this paper is to compare RG to OG with a focus on D2-lymphadenectomy. STUDY DESIGN: Data of patients undergoing D2-OG or RG for gastric cancer were retrieved from the international IMIGASTRIC prospective database and compared. RESULTS: A total of 1469 patients were selected for inclusion in the study. After 1:1 propensity score matching, a total of 580 patients were matched and included in the final analysis, 290 in each group, RG vs OG. RG had longer operation time (210 vs 330 min, p < 0.0001), reduced intraoperative blood loss (155 vs 119.7 ml, p < 0.0001), time to liquid diet (4.4 vs 3 days, p < 0.0001) and to peristalsis (2.4 vs 2 days, p < 0.0001), and length of postoperative stay (11 vs 8 days, p < 0.0001). Morbidity rate was higher in OG (24.1% vs 16.2%, p = 0.017). CONCLUSION: RG significantly expedites recovery and reduces the risk of complications compared to OG. However, long-term survival is similar.

A multi-center post-market clinical study to confirm safety and performance of PuraStat® in the management of bleeding during open liver resection.

BACKGROUND: PuraStat® is a non-bioactive haemostatic agent that has demonstrated efficacy in a number of different surgical procedures. We performed a prospective multi-centre post-market study to evaluate the efficacy and safety of PuraStat® in liver resections performed for metastatic tumors. METHODS: This was a prospective cohort study. Patients undergoing liver resection for metastatic tumor were screened for eligibility, and included if they were ≥18 years old, undergoing open liver resection, had normal liver function, and required application of PuraStat® for haemostasis where standard haemostatic techniques were either insufficient or impractical. The primary endpoint was "time to haemostasis" (TTH). Secondary endpoints included blood loss, total postoperative drainage volume, transfusion of blood products, and ease of use. RESULTS: Eighty patients were included for analysis in the intention to treat population. 207 bleeding sites were treated with PuraStat. Of these, 190 (91.7%) bleeding sites reached haemostasis after PuraStat® application. Mean TTH (mm:ss) was 1:01 (SD 1:06, range 0:09-6:55). Ease of use of the product was described as either "excellent" or "good" in 78 (98.8%) patients. No serious adverse events were identified. CONCLUSION: This study confirms the safety, efficacy and ease of use of PuraStat® in the management of bleeding in liver surgery.

Pancreatoduodenectomy with or without prophylactic falciform ligament wrap around the hepatic artery for prevention of postpancreatectomy haemorrhage: randomized clinical trial (PANDA trial).

BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels. METHODS: In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH. RESULTS: Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively). CONCLUSION: A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy. REGISTRATION NUMBER: NCT02588066 (http://www.clinicaltrials.gov).

Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma - the phase III "PREVENT"- (FLOT9) trial of the AIO /CAOGI /ACO.

BACKGROUND: The main reason for treatment failure after curative surgical resection of gastric cancer is intra-abdominal spread, with 40-50% peritoneal seeding as primary localization of recurrence. Peritoneal relapse is seen in 60-70% of tumors of diffuse type, compared to only 20-30% of intestinal type. Hyperthermic IntraPEritoneal Chemoperfusion (HIPEC) is an increasingly used therapy method for patients with peritoneal metastases. The preventive use of HIPEC could represent an elegant approach for patients (pts) before macroscopic peritoneal seeding, since pts. with operable disease are fit and may have potential risk of microscopic involvement, thus having a theoretical chance of cure with HIPEC even without the need for cytoreduction. No results from a PCRT from the Western hemisphere have yet been published. METHODS: This is a multicenter, randomized, controlled, open-label study including a total of 200 pts. with localized and locally advanced diffuse or mixed type (Laurens's classification) adenocarcinoma of the stomach and Type II/III GEJ. All enrolled pts. will have received 3-6 pre-operative cycles of biweekly FLOT (Docetaxel 50 mg/m2; Oxaliplatin 85 mg/m2; Leucovorin 200 mg/m2; 5-FU 2600 mg/m2, q2wk). Pts will be randomized 1:1 to receive surgery only and postoperative FLOT (control arm) or surgery + intraoperative HIPEC (cisplatin 75 mg/m2 solution administered at a temperature of 42 °C for 90 min) and postoperative FLOT (experimental arm). Surgery is carried out as gastrectomy or transhiatal extended gastrectomy. Primary endpoint is PFS/DFS, major secondary endpoints are OS, rate of pts. with peritoneal relapse at 2 and 3 years, perioperative morbidity/mortality and quality of life. The trial starts with a safety run-in phase. After 20 pts. had curatively intended resection in Arm B, an interim safety analysis is performed. Recruitment has already started and first patient in was on January 18th, 2021. DISCUSSION: If the PREVENT concept proves to be effective, this could potentially lead to a new standard of therapy. On the contrary, if the outcome is negative, pts. with gastric cancer and no peritoneal involvement will not be treated with HIPEC during surgery. TRIAL REGISTRATION: The study is registered on June 25th, 2020 under ClinicalTrials.gov Identifier: NCT04447352 ; EudraCT: 2017-003832-35 .

Incidence and Grading of Complications After Gastrectomy for Cancer Using the GASTRODATA Registry: A European Retrospective Observational Study.

OBJECTIVE: Utilizing a standardized dataset based on a newly developed list of 27 univocally defined complications, this study analyzed data to assess the incidence and grading of complications and evaluate outcomes associated with gastrectomy for cancer in Europe. SUMMARY BACKGROUND DATA: The absence of a standardized system for recording gastrectomy-associated complications makes it difficult to compare results from different hospitals and countries. METHODS: Using a secure online platform (www.gastrodata.org), referral centers for gastric cancer in 11 European countries belonging to the Gastrectomy Complications Consensus Group recorded clinical, oncological, and surgical data, and outcome measures at hospital discharge and at 30 and 90 days postoperatively. This retrospective observational study included all consecutive resections over a 2-year period. RESULTS: A total of 1349 gastrectomies performed between January 2017 and December 2018 were entered into the database. Neoadjuvant chemotherapy was administered to 577 patients (42.8%). Total (46.1%) and subtotal (46.4%) gastrectomy were the predominant resections. D2 or D2+ lymphadenectomy was performed in almost 80% of operations. The overall complications' incidence was 29.8%; 402 patients developed 625 complications, with the most frequent being nonsurgical infections (23%), anastomotic leak (9.8%), other postoperative abnormal fluid from drainage and/or abdominal collections (9.3%), pleural effusion (8.3%), postoperative bleeding (5.6%), and other major complications requiring invasive treatment (5.6%). The median Clavien-Dindo score and Comprehensive Complications Index were IIIa and 26.2, respectively. In-hospital, 30-day, and 90-day mortality were 3.2%, 3.6%, and 4.5%, respectively. CONCLUSIONS: The use of a standardized platform to collect European data on perioperative complications revealed that gastrectomy for gastric cancer is still associated with heavy morbidity and mortality. Actions are needed to limit the incidence of, and to effectively treat, the most frequent and most lethal complications.

Meta-analysis and single-center experience on the protective effect of negative suction drains on wound healing after stoma reversal.

BACKGROUND: Compromised wound healing following stoma reversal is a frequent problem. The use of negative suction drainage for reduction of complications remains controversial. METHODS: The patient database of our center was reviewed for patients with ileostomy reversal between 2007 and 2017. Risk factors for wound complications were analyzed using multivariate regression analysis. Systematic review and meta-analysis was performed. Ultimately, results of this study were integrated into meta-analysis to assess the effect of drainage placement on wound healing. RESULTS: In our institutional analysis, a total of 406 patients with ileostomy reversal were included (n = 240 (59.1%) with drainage vs. n = 166 (40.8%) without drainage). In multivariate analysis, body mass index (BMI) was a risk factor for wound complications (odds ratio (95% CI) 1.06 (1.02-1.12)). Patients with drainage needed significantly fewer interventions than those without drainage (17.1% vs. 28.9%, p = 0.005). Placement of drainage significantly reduced the risk of wound complications even in the group with elevated BMI (odds ratio (95% CI) 0.462 (0.28-0.76), p = 0.003). Meta-analysis identified 6 studies with a total of 1180 patients eligible for further analysis (2 prospectively randomized trials; 4 retrospective cohort studies). Overall analysis revealed a significantly beneficial effect of wound drainage following ileostomy reversal (RR (95% CI) 0.47 (0.34, 0.66); p < 0.0001). CONCLUSION: In our institutional analysis as well as meta-analysis, the use of subcutaneous suction drains was beneficial for prevention of wound healing complications following ostomy reversal. Drainage placement is especially valuable in high-risk situations such as in obese patients.

[Clinical Manifestations and Therapeutic Implications of Peritonitis]. / Klinische Manifestationen und therapeutische Implikationen der Peritonitis.

Clinical Manifestations and Therapeutic Implications of Peritonitis Abstract. Peritonitis is a heterogenous disease, commonly classified into three types. Primary peritonitis, defined by the absence of another directly related intraabdominal abnormality, can often be treated conservatively and is thus distinguished from secondary peritonitis, which results from an independent diagnosis like the perforation or necrosis of an intraabdominal organ and usually requires surgical therapy. The more recently defined tertiary peritonitis is a form of secondary peritonitis that relapses or persists after 48 hours of adequate therapy with no surgically removable focus. This article addresses three important clinical manifestations of peritonitis and their therapeutic implications: spontaneous bacterial peritonitis as the mayor manifestation of primary peritonitis; postoperative peritonitis as a severe subform of secondary peritonitis; and peritoneal dialysis-associated peritonitis as a distinctive clinical picture.

The optimal extent of lymph node dissection in gastroesophageal junctional cancer: retrospective case control study.

BACKGROUND: Recently, the incidence of gastroesophageal junction (GEJ) cancer has been increasing in Eastern countries. Mediastinal lymph node (MLN) metastasis rates among patients with GEJ cancer are reported to be 5-25%. However, survival benefits associated with MLN dissection in GEJ cancer has been a controversial issue, especially in Eastern countries, due to its rarity and potential morbidity. METHODS: We retrospectively reviewed 290 patients who underwent surgery for GEJ cancer at the National Cancer Center in Korea from June 2001 to December 2015. Clinicopathologic characteristics and surgical outcomes were compared between patients without MLN dissection (Group A) and patients with MLN dissection (Group B). Prognostic factors associated with the survival rate were identified in a multivariate analysis. RESULTS: Twenty-nine (10%) patients underwent MLN dissection (Group B). Three of 29 patients (10.3%) showed a metastatic MLN in Group B. For abdominal LNs, the 5-year disease-free survival rate was 79.5% in Group A and 33.9% in Group B (P < 0.001). The multivariate analysis revealed that abdominal LN dissection, pT category, and pN category were statistically significant prognostic factors. LNs were the most common site for recurrence in both groups. CONCLUSION: Abdominal LN dissection and pathologic stage are the important prognostic factors for type II and III GEJ cancer rather than mediastinal lymph node dissection.

International consensus on a complications list after gastrectomy for cancer.

BACKGROUND: Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus. METHODS: The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications. RESULTS: A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet. CONCLUSION: The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.

Mortality and postoperative complications after different types of surgical reconstruction following pancreaticoduodenectomy-a systematic review with meta-analysis.

BACKGROUND: Pancreaticoduodenectomy/PD is a technically demanding pancreatic resection. Options of surgical reconstruction include (1) the child reconstruction defined as pancreatojejunostomy/PJ followed by hepaticojejunostomy/HJ and the gastrojejunostomy/GJ "the standard/s-Child," (2) the s-child reconstruction with an additional Braun enteroenterostomy "BE-Child," or (3) Isolated-Roux-En-Y-pancreaticojejunostomy "Iso-Roux-En-Y," in which the pancreas anastomosis is reconstructed in a separate loop after the GJ. Yet, the impact of these reconstruction methods on patients' outcome has not been sufficiently compared in a systematic manner. METHODS: A systematic review and meta-analysis were conducted according to the Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines by screening Pubmed/Medline, Scopus, Cochrane Library and Web-of-Science. Articles meeting predefined criteria were extracted and meta-analysis was performed. RESULTS: Nineteen studies were identified comparing BE-Child or Isolated-Roux-En-Y vs. s-Child. Compared to s-Child neither BE-Child (p = 0.43) nor Iso-Roux-En-Y (p = 0.94) displayed an impact on postoperative mortality, whereas BE-Child showed less postoperative complications (p = 0.02). BE-Child (p = 0.15) and Iso-Roux-En-Y (p = 0.61) did not affect postoperative pancreatic fistula/POPF in general, but BE-Child was associated with a decrease of clinically relevant POPF (p = 0.005), clinically relevant delayed gastric emptying/DGE B/C (p = 0.004), bile leaks (p = 0.01), and hospital stay (p = 0.06). BE-Child entailed also an increased operation time (p = 0.0002) with no impact on DGE A/B/C, hemorrhage, surgical site infections and pulmonary complications. CONCLUSION: BE-Child is associated with a decreased risk for postoperative complications, particularly a decreased risk for clinically relevant DGE, POPF, and bile leaks, whereas Iso-Roux-En-Y does not seem to affect the clinical course after PD. Therefore, BE seems to be a valuable surgical method to improve patients' outcome after PD.

Role of robot-assisted distal gastrectomy compared to laparoscopy-assisted distal gastrectomy in suprapancreatic nodal dissection for gastric cancer.

PURPOSE: Despite theoretical advantages, no clear benefit was proven for initial application of robotic surgery for gastric cancer so far. The aim of this analysis was to examine the role of robotic surgery regarding nodal dissection technically demanding areas compared to conventional laparoscopic surgery. METHODS: This analysis included 87 patients who underwent robot-assisted distal gastrectomy (RADG) and 288 patients who underwent laparoscopy-assisted distal gastrectomy (LADG) at the National Cancer Center, Korea, between February 2009 and September 2011. Clinicopathologic data, surgery-related data, postoperative morbidity, and pathologic data for each nodal station were analyzed. RESULTS: Time to flatulence was 3.5 ± 0.8 days for RADG and 3.8 ± 0.8 days for LADG (P = 0.01). Postoperative hospital stay was 6.7 ± 1.0 days in RADG and 7.4 ± 2.4 days in LADG (P < 0.001).The number of dissected lymph nodes was 37.1 ± 12.9 in the RADG group and 34.1 ± 12.1 in the LADG group (P = 0.044). In patients undergoing D2 gastrectomy, the number of dissected lymph nodes in the N2 area was 16.3 ± 7.7 for RADG and 13.2 ± 5.3 for LADG (P = 0.001). The number of dissected lymph nodes around the splenic artery area was 2.9 ± 2.9 in RADG and 2.2 ± 2.0 in LADG (P = 0.04). Regarding postoperative complications, there was no statistically significant difference [five patients (5.7%) in RADG and 26 patients (9%) in LADG) (P = 0.330)]. CONCLUSION: RADG could provide an advantage over LADG in the dissection of the N2 area lymph nodes, especially around the splenic artery area.

Procalcitonin ratio and on-demand relaparotomy for septic peritonitis: validation of the focus index (FI).

PURPOSE: Secondary peritonitis remains challenging to manage and some recent evidence suggests that on-demand relaparotomy is more appropriate than planned relaparotomy. This study was designed to validate the predictive power of postoperative procalcitonin (PCT) changes in relation to elimination of the septic abdominal focus. METHODS: In this prospective trial, postoperative PCT serum levels were monitored in 234 surgical patients with secondary peritonitis. The PCT ratio on postoperative days (PODs) 1 and 2 (focus index; FI) was calculated and correlated with the success of the operation. RESULTS: A cutoff value of 1.1 was calculated for the FI. Values below 1.1 indicated insufficient elimination of the focus and values above 1.1 correlated with effective treatment. The optimal time for first PCT sampling was found to be 12-24 h after the index operation. After the respective data cleanup, successful elimination of the intraabdominal focus could be confirmed, with a sensitivity of 93 % and a specificity of 71 %. CONCLUSIONS: The FI is a single parameter-based reliable predictor of successful surgical eradication and strengthens the on-demand relaparotomy concept as the method of choice to treat secondary peritonitis.

Robot-assisted gastrectomy for early gastric cancer: is it beneficial in viscerally obese patients compared to laparoscopic gastrectomy?

BACKGROUND: The adoption of robotic systems for gastric cancer surgery has been proven feasible and safe; however, a benefit over the laparoscopic approach has not yet been well-documented. We aimed to investigate the surgical outcomes of robotic versus laparoscopic gastrectomy for gastric cancer, according to the extent of surgery and patients' obesity status. METHODS: Between January 2009 and July 2011, 770 patients were enrolled in this retrospective analysis. All had stage IA/IB gastric cancer preoperatively and underwent either laparoscopic (n = 622) or robotic (n = 148) gastrectomy. Patients were classified into obese and non-obese groups on the basis of visceral fat area (VFA). The extent of surgery was defined by whether patients underwent distal or total gastrectomy. RESULTS: The surgical outcomes following distal gastrectomy were similar between the robotic and laparoscopic groups regardless of the obesity status. After total gastrectomy, the number of total and N2-area lymph nodes were significantly higher in the robotic group than in the laparoscopic group in non-obese patients with VFA < 100 cm(2) (total, 38.8 vs. 46.5; p = 0.018; N2 area, 9.0 vs. 12.4; p = 0.041), but no significant differences were observed in obese population. Robotic group developed less severe complications after total gastrectomy compared to laparoscopic group in non-obese patients (p = 0.036). CONCLUSION: Robotic assistance did not improve surgical outcomes over the laparoscopic approach in obese patients undergoing distal gastrectomy. However, non-obese patients with low VFA may benefit from robotic assistance during total gastrectomy in terms of radical D2 lymphadenectomy with fewer serious complications.

The impact of neural invasion severity in gastrointestinal malignancies: a clinicopathological study.

OBJECTIVES: Because neural invasion (NI) is still inconsistently reported and not well characterized within gastrointestinal malignancies (GIMs), our aim was to determine the exact prevalence and severity of NI and to elucidate the true impact of NI on patient's prognosis. BACKGROUND: The union internationale contre le cancer (UICC) recently added NI as a novel parameter in the current TNM classification. However, there are only a few existing studies with specific focus on NI, so that the distinct role of NI in GIMs is still uncertain. MATERIALS AND METHODS: NI was characterized in approximately 16,000 hematoxylin and eosin tissue sections from 2050 patients with adenocarcinoma of the esophagogastric junction (AEG)-I-III, squamous cell carcinoma (SCC) of the esophagus, gastric cancer (GC), colon cancer (CC), rectal cancer (RC), cholangiocellular cancer (CCC), hepatocellular cancer (HCC), and pancreatic cancer (PC). NI prevalence and severity was determined and related to patient's prognosis and survival. RESULTS: NI prevalence largely varied between HCC/6%, CC/28%, RC/34%, AEG-I/36% and AEG-II/36%, SCC/37%, GC/38%, CCC/58%, and AEG-III/65% to PC/100%. NI severity score was uppermost in PC (24.9±1.9) and lowest in AEG-I (0.8±0.3). Multivariable analyses including age, sex, TNM stage, and grading revealed that the prevalence of NI was significantly associated with diminished survival in AEG-II/III, GC, and RC. However, increasing NI severity impaired survival in AEG-II/III and PC only. CONCLUSIONS: NI prevalence and NI severity strongly vary within GIMs. Determination of NI severity in GIMs is a more precise tool than solely recording the presence of NI and revealed dismal prognostic impact on patients with AEG-II/III and PC. Evidently, NI is not a concomitant side feature in GIMs and, therefore, deserves special attention for improved patient stratification and individualized therapy after surgery.

Cutting edge: Divergent cell-specific functions of MyD88 for inflammatory responses and organ injury in septic peritonitis.

Although global MyD88 deficiency attenuates lethal inflammation in sepsis, cell-specific functions of MyD88 remain largely unknown. Using mice with selective expression of MyD88 in myeloid cells (Myd88(MYEL)), we show that, during polymicrobial septic peritonitis, both myeloid and nonmyeloid cells contribute to systemic inflammation, whereas myeloid cell MyD88 was sufficient to fully establish the peritoneal cytokine response. Importantly, Myd88(MYEL) mice developed markedly aggravated liver injury that was linked to impaired upregulation of cellular inhibitor of apoptosis protein 2 and an excessive production of TNF-α. Upregulation of inducible cAMP early repressor (ICER), a known transcriptional repressor of the Tnfa gene, was impaired in Myd88(MYEL) mice. Moreover, Myd88(MYEL) mice showed enhanced transcription of the Tnfa gene and an excessive production of CCL3, which is also negatively regulated by ICER, but they had normal levels of CXCL1, which is expressed in an ICER-independent manner. Together, these findings suggest a novel protective role for nonmyeloid cell MyD88 in attenuating liver injury during septic peritonitis.

Secondary gastrectomy for stage IV gastroesophageal adenocarcinoma after induction-chemotherapy.

PURPOSE: With improved chemotherapeutic regimens, metastasized gastric cancer may show a good response rendering an initially unresectable tumor resectable. We performed a retrospective analysis on the outcome of stage IV gastric cancer patients treated by chemotherapy followed by oncologic resection in a western institution. METHODS: From August 1988 to December 2010, a total number of 1,817 patients underwent surgery for gastric cancer at the Department of Surgery, Technical University of Munich. A retrospective analysis of our prospective gastric cancer database identified 58 patients with stage IV gastric cancer having undergone induction chemotherapy followed by surgery in an individualized treatment concept. After induction chemotherapy usually consisting of 2 cycles of PLF (cisplatin, 5-fluorouracil, leucovorin), resection was performed with or without removal of metastases in patients without disease progression. Patients were followed up until death or loss to follow up. RESULTS: The three most common metastatic locations were liver (27.6 %), distant lymph nodes (22.4 %), and peritoneum (19.0 %). Of patients, 13.8 % had metastases in more than one location. Thirty-day mortality was 5.2 %, 90-day mortality was 13.8 %, while overall postoperative morbidity accounted for 24 %. In 19 (32.8 %) patients, a complete resection without any macroscopic tumor residues was achieved. In 39 (67.2 %) patients, tumors could not be completely removed with either local residual disease or residual disease at distant sites. Overall median survival was 20 months, while patients without residual tumor survived significantly longer (72 months) than patients with residual disease (12 months, p = 0.001). CONCLUSION: Secondary surgery of metastasized gastric cancer may be justified in selected cases without progression under induction chemotherapy. An achievable complete removal of the primary tumor and metastases appears the main selection criterion for patients benefitting from this approach.