Predicting the Risk of Morbidity by GLIM-Based Nutritional Assessment and Body Composition Analysis in Oncologic Abdominal Surgery in the Context of Enhanced Recovery Programs : The PHase Angle Value in Abdominal Surgery (PHAVAS) Study.

BACKGROUND: Preoperative nutritional status and body structure affect short-term prognosis in patients undergoing major oncologic surgery. Bioimpedance vectorial analysis (BIVA) is a reliable tool to assess body composition. Low BIVA-derived phase angle (PA) indicates a decline of cell membrane integrity and function. The aim was to study the association between perioperative PA variations and postoperative morbidity following major oncologic upper-GI surgery. PATIENTS AND METHODS: Between 2019 and 2022 we prospectively performed BIVA in patients undergoing surgical resection for pancreatic, hepatic, and gastric malignancies on the day before surgery and on postoperative day (POD) 1. Malnutrition was defined as per the Global Leadership Initiative on Malnutrition criteria. The PA variation (ΔPA) between POD1 and preoperatively was considered as a marker for morbidity. Uni and multivariable logistic regression models were applied. RESULTS: Overall, 542 patients with a mean age of 64.6 years were analyzed, 279 (51.5%) underwent pancreatic, 201 (37.1%) underwent hepatobiliary, and 62 (11.4%) underwent gastric resections. The prevalence of preoperative malnutrition was 16.6%. The overall morbidity rate was 53.3%, 59% in those with ΔPA < -0.5 versus 46% when ΔPA ≥ -0.5. Age [odds ratio (OR) 1.11; 95% confidence interval (CI) (1.00; 1.22)], pancreatic resections [OR 2.27; 95% CI (1.24; 4.18)], estimated blood loss (OR 1.20; 95% CI (1.03; 1.39)], malnutrition [OR 1.77; 95% CI (1.27; 2.45)], and ΔPA [OR 1.59; 95% CI (1.54; 1.65)] were independently associated with postoperative complications in the multivariate analysis. CONCLUSIONS: Patients with preoperative malnutrition were significantly more likely to develop postoperative morbidity. Moreover, a decrease in PA on POD1 was independently associated with a 13% increase in the absolute risk of complications. Whether proactive interventions may reduce the downward shift of PA and the complication rate need further investigation.

External validation of scores predicting postoperative fistula after pancreatogastrostomy for pancreatoduodenectomy reconstruction. A single center experience.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is the most frequent complication of pancreatic surgery and can be fatal. Selection and stratification of patients according to the risk of POPF are important for the perioperative management. Predictive metrics have been developed and validated in pancreatojejunostomy. Aim of this study is to assess whether the most used prognostic scores can be predictive of fistula following Wirsung-pancreaticogastrostomy (WPG) for pancreatoduodenectomy (PD)reconstruction. METHOD: This single-center prospective observational study included 212 PDs between January 2008 and October 2022 with a standardized WPG. All component variables of the six scores were separately validated in our cohort. The overall predictive ability of the six fistula scores was measured and compared with the receiver operating characteristics curves (ROC) method and expressed by the area under the ROC-curve (AUC). Univariate and multivariate logistic regression analyses were performed considering all risk factors in the scores in order to identify variables independently correlated with POPF in the WPG. RESULTS: CR-POPF occurred in 36 of 212 (17 %) patients. All scores showed poor prognostic stratification for the development of CR-POPF. The occurrence of CR-POPF was associated with nine factors: male gender (p = 0.003); BMI (kg/m2) (p = 0.005); ASA (%) (p = 0.003); Soft pancreatic texture (%) (p = 0.003), Pathology (p = 0.008); MPD (p = 0.011); EBL (mL) (p = 0.021); Preop. Bilirubin (mg/dl) (p = 0.038); Preop. Glucose (mg/dl) (p = 0.0369). Male gender (OR: 5.54, CI 1.41-21.3) and soft consistency of the remnant pancreas (OR: 3.83, CI 1.14-12.8) were the only independent prognostic factors on multivariate analysis. CONCLUSIONS: Our study including exclusively pancreatogastrostomies failed to validate the most used predictive scores for POPF. We found that only male gender and soft pancreatic texture are associated with POPF. Specific predictive scores following pancreatogasgtrostomy are needed.

Implementing Enhanced Perioperative Care in Emergency General Surgery: A Prospective Multicenter Observational Study.

INTRODUCTION: ERAS pathway has been proposed as the standard of care in elective abdominal surgery. Guidelines on ERAS in emergency surgery have been recently published; however, few evidences are still available in the literature. The aim of this study was to evaluate the feasibility of an enhanced recovery protocol in a large cohort of patients undergoing emergency surgery and to identify possible factors impacting postoperative protocol compliance. METHODS: This is a prospective multicenter observational study including patients who underwent major emergency general surgery for either intra-abdominal infection or intestinal obstruction. The primary endpoint of the study is the adherence to ERAS postoperative protocol. Secondary endpoints are 30-day mortality and morbidity rates, and length of hospital stay. RESULTS: A total of 589 patients were enrolled in the study, 256 (43.5%) of them underwent intestinal resection with anastomosis. Major complications occurred in 92 (15.6%) patients and 30-day mortality was 6.3%. Median adherence occurred on postoperative day (POD) 1 for naso-gastric tube removal, on POD 2 for mobilization and urinary catheter removal, and on POD 3 for oral intake and i.v. fluid suspension. Laparoscopy was significantly associated with adherence to postoperative protocol, whereas operative fluid infusion > 12 mL/Kg/h, preoperative hyperglycemia, presence of a drain, duration of surgery and major complications showed a negative association. CONCLUSIONS: The present study supports that an enhanced recovery protocol in emergency surgery is feasible and safe. Laparoscopy was associated with an earlier recovery, whereas preoperative hyperglycemia, fluid overload, and abdominal drain were associated with a delayed recovery.

Outpatient Non-operative Management of Uncomplicated Acute Appendicitis: A Non-inferiority Study.

INTRODUCTION: Non-operative management (NOM) of uncomplicated acute appendicitis is a well-established alternative to upfront surgery. The administration of intravenous broad-spectrum antibiotics is usually performed in hospital, and only one study described outpatient NOM. The aim of this multicentre retrospective non-inferiority study was to evaluate both safety and non-inferiority of outpatient compared to inpatient NOM in uncomplicated acute appendicitis. METHODS: The study included 668 consecutive patients with uncomplicated acute appendicitis. Patients were treated according to the surgeon's preference: 364 upfront appendectomy, 157 inpatient NOM (inNOM), and 147 outpatient NOM (outNOM). The primary endpoint was the 30-day appendectomy rate, with a non-inferiority limit of 5%. Secondary endpoints were negative appendectomy rate, 30-day unplanned emergency department (ED) visits, and length of stay. RESULTS: 30-day appendectomies were 16 (10.9%) in the outNOM group and 23 (14.6%) in the inNOM group (p = 0.327). OutNOM was non-inferior to inNOM with a risk difference of-3.80% 97.5% CI (- 12.57; 4.97). No difference was found between inNOM and outNOM groups for the number of complicated appendicitis (3 vs. 5) and negative appendectomy (1 vs. 0). Twenty-six (17.7%) outNOM patients required an unplanned ED visit after a median of 1 (1-4) days. In the outNOM group, the mean cumulative in-hospital stay was 0.89 (1.94) days compared with 3.94 (2.17) days in the inNOM group (p < 0.001). CONCLUSIONS: Outpatient NOM was non-inferior to inpatient NOM with regard to the 30-day appendectomy rate, while a shorter hospital stay was found in the outNOM group. Further, studies are required to confirm these findings.

Association of indirect measurement of cell function by bioimpedance analysis with complications in oncologic hepatic surgery.

BACKGROUND: Bioelectric impedance vector analysis (BIVA) is a reliable tool to assess body composition. The aim was to study the association of BIVA-derived phase angle (PA) and standardized PA (SPA) values and the occurrence of surgery-related morbidity. METHODS: Patients undergoing hepatectomy for cancer in two Italian centers were prospectively enrolled. BIVA was performed the morning of surgery. Patients were then stratified for the occurrence or not of postoperative morbidity. RESULTS: Out of 190 enrolled patients, 76 (40%) experienced postoperative complications. Patients with morbidity had a significant lower PA, SPA, body cell mass, and skeletal muscle mass, and higher extracellular water and fat mass. At the multivariate analysis, presence of cirrhosis (OR 7.145, 95% CI:2.712-18.822, p < 0.001), the Charlson comorbidity index (OR 1.236, 95% CI: 1.009-1.515, p = 0.041), the duration of surgery (OR 1.004, 95% CI:1.001-1.008, p = 0.018), blood loss (OR 1.002. 95% CI: 1.001-1.004, p = 0.004), dehydration (OR 10.182, 95% CI: 1.244-83.314, p = 0.030) and SPA < -1.65 (OR 3.954, 95% CI: 1.699-9.202, p = 0.001) were significantly and independently associated with the risk of complications. CONCLUSION: Introducing BIVA before hepatic resections may add valuable and independent information on the risk of morbidity.

Impact of enhanced recovery protocols after pancreatoduodenectomy: meta-analysis.

BACKGROUND: This individual-patient data meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared with conventional care on postoperative outcomes in patients undergoing pancreatoduodenectomy. METHODS: The Cochrane Library, MEDLINE, Embase, Scopus, and Web of Science were searched systematically for articles reporting outcomes of ERAS after pancreatoduodenectomy published up to August 2020. Comparative studies were included. Main outcomes were postoperative functional recovery elements, postoperative morbidity, duration of hospital stay, and readmission. RESULTS: Individual-patient data were obtained from 17 of 31 eligible studies comprising 3108 patients. Time to liquid (mean difference (MD) -3.23 (95 per cent c.i. -4.62 to -1.85) days; P < 0.001) and solid (-3.84 (-5.09 to -2.60) days; P < 0.001) intake, time to passage of first stool (MD -1.38 (-1.82 to -0.94) days; P < 0.001) and time to removal of the nasogastric tube (3.03 (-4.87 to -1.18) days; P = 0.001) were reduced with ERAS. ERAS was associated with lower overall morbidity (risk difference (RD) -0.04, 95 per cent c.i. -0.08 to -0.01; P = 0.015), less delayed gastric emptying (RD -0.11, -0.22 to -0.01; P = 0.039) and a shorter duration of hospital stay (MD -2.33 (-2.98 to -1.69) days; P < 0.001) without a higher readmission rate. CONCLUSION: ERAS improved postoperative outcome after pancreatoduodenectomy. Implementation should be encouraged.

Enhanced recovery protocols consist of interdisciplinary interventions aimed at standardizing care and reducing the impact of surgical stress. They often include a short period of preoperative fasting during the night before surgery, early removal of lines and surgical drains, early food intake and mobilization out of bed on the day of surgery. This study gives a summary of reports assessing such care protocols in patients undergoing pancreatic head surgery, and assesses the impact of these protocols on functional recovery in an analysis of individual-patient data. The study revealed the true benefits of enhanced recovery protocols, including shorter time to food intake, earlier bowel activity, fewer complications after surgery, and a shorter hospital stay compared with conventional care.

Skeletal muscle wasting and long-term prognosis in patients undergoing rectal cancer surgery without neoadjuvant therapy.

BACKGROUND: Derangement of body composition has been associated with dismal long-term survival in several gastrointestinal cancers including rectal tumors treated with neoadjuvant therapies. The role of specific preoperative anthropometric indexes on the oncologic outcomes of patients undergoing upfront surgery for rectal cancer has not been investigated. The aim of the study is to evaluate the association of body composition and overall survival in this specific cohort. METHODS: Lumbar computed tomography images, obtained within the 30 days previous to surgery, between January 2009 and December 2016, were used to calculate population-specific thresholds of muscle mass (sarcopenia), subcutaneous and visceral adiposity, visceral obesity, sarcopenic obesity, and myosteatosis. These body composition variables were related with overall survival (OS), tumor-specific survival (TSS), and disease-free survival (DFS). OS, TSS, and DFS were evaluated by the Kaplan-Meier method. Cox regression analysis was used to identify independent predictors of mortality, tumor-specific mortality, and recurrence, and data were presented as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: During the study period, 411 patients underwent rectal resection for cancer, and among these, 129 were without neoadjuvant chemoradiation. The median follow-up was 96.7 months. At the end of the follow-up, 41 patients (31.8%) had died; of these, 26 (20.1%) died for tumor-related reasons, and 36 (27.1%) experienced disease recurrence. One-, three-, and five-year OS was 95.7%, 86.0%, and 76.8% for non-sarcopenic patients versus 82.4%, 58.8%, and 40.0% for sarcopenic ones respectively (p < 0.001). Kaplan-Meier survival curves comparing sarcopenic and non-sarcopenic patients showed a significant difference in terms of OS (log-rank < 0.0001). Through multivariate Cox regression, overall mortality risk was associated only with sarcopenia (HR 1.96; 95%CI 1.03-3.74; p = 0.041). Disease stage IV and III (HR 13.75; 95% CI 2.89-65.6; p < 0.001 and HR 4.72; 95% CI 1.06-21.1; p = 0.043, respectively) and sarcopenia (HR 2.62; 95% CI 1.22-5.6; p = 0.013) were independently associated with TSS. The other body composition indexes investigated showed no significant association with prognosis. CONCLUSIONS: These results support the inclusion of body composition assessment for prognostic stratification of rectal cancer patients undergoing upfront resection.

HPV 16 and 18 contribute to development of anal dysplasia in HIV infection irrespective of gender and sexual orientation.

OBJECTIVES: The aim of the present study was too investigate prevalence and persistence of human papilloma virus (HPV) and cytological abnormalities (CAs) in the anal swabs of people living with HIV (PLWH): men who have sex with men (MSM), men who have sex with women (MSW) and women (W). METHODS: Between March 2010 and January 2019, an anal swab for cytological and HPV genotyping tests was offered to all PLWH attending our clinic. Logistic regression analysis was conducted to identify predictors of infection. RESULTS: In all, 354 PLWH were screened: 174 MSM, 90 MSW and 61 W. Prevalence of at least one high-risk (HR) HPV was higher in MSM (91%) and W (85%) than in MSW (77%) (P < 0.05). Cytological abnormalities were found in 21.1% of the entire population. At multivariable regression analysis a lower risk for HPV infection was found for W than for MSM [odds ratio = 0.24 (95% confidence interval: 0.115-0.513)] and for MSW than for MSM [0.37 (0.180-0.773)] and there was a significantly higher risk of CAs in PLWH with HPV 16 and 18 [3.3 (1.04-10.49)]. A total of 175 PLWH (103 MSM, 33 MSW and 26 W) had at least one follow-up visit (T1) after a median (interquartile range) follow-up of 3.6 (2.1-5.7) years. The acquisition rate of HR-HPV was high, with 66.7% of PLWH negative for HR-HPV at T0 who became positive at T1 (P < 0.001). The prevalence of CAs was stable (20.6%). A significant association between CAs at T1 and persistence of HPV-16 and/or 18 was found (P < 0.05). CONCLUSIONS: HPV 16 and 18 are associated with the presence and development of CAs irrespective of sexual orientation.

Studying Enhanced Recovery After Surgery (ERAS®) Core Items in Colorectal Surgery: A Causal Model with Latent Variables.

BACKGROUND: Previous Enhanced Recovery After Surgery (ERAS®) studies have not always taken into account that ERAS interventions depend on baseline covariates and that several confounding variables affect the composite outcomes. METHOD: A causal latent variable model is proposed to analyze data obtained prospectively concerning 1261 patients undergoing elective colorectal surgery within the ERAS protocol. Primary outcomes (composite of any complication, surgical site infection, medical complications, early ready for discharge (TRD), early actual discharge) and secondary outcomes (composite of late bowel function recovery, IV fluid resumption, nasogastric tube replacement, postoperative nausea and vomiting, re-intervention, re-admission, death) are considered along with their multiple dimensions. RESULTS: Concerning the primary outcomes, our results evidence three subpopulations of patients: one with probable good outcome, one with possibly prolonged TRD and discharge without complications, and the other one with probable complications and prolonged TRD and discharge. Epidural anesthesia, waiving surgical drainage, and early ambulation, IV fluid stop and urinary catheter removal act favorably, while preoperative hospital stay and blood transfusion act negatively. Concerning the secondary outcomes our results evidence two subpopulations of patients: one with high probability of good outcome and one with high probability of complications. Epidural anesthesia, waiving surgical drainage, early ambulation and IV fluid stop act favorably, while blood transfusion acts negatively also with respect to these secondary outcomes. CONCLUSION: The multivariate causal latent class two-parameter logistic model, a modern statistical method overcoming drawbacks of traditional models to estimate the average causal effects on the treated, allows us to disentangle subpopulations of patients and to evaluate ERAS interventions.

Is BMI a Factor in Compliance to Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

Background: Compliance to adjuvant chemotherapy (AC) for patients undergoing rectal surgery ranges from 43% to 73.6%. Reasons reported for not initiating or completing AC include onset of postoperative complications, drug toxicity, disease progression and/or patient preferences. Little is known regarding the impact of obesity on the compliance to AC in this setting. Methods: This multicenter, retrospective study analyzed compliance to AC and treatment-related morbidity in 511 patients having undergone surgery with curative intent for rectal cancer in six Italian colorectal centers between January 2013 and December 2017. Results: 70 patients were obese (BMI 30 kg/m2). The proportion of open procedures (22.9% vs. 13.4%) and conversions (14.3% vs. 4.8%) was greater in obese compared to non-obese patients (p 0.001). Median hospital stay was one day longer for obese patients (9 days vs. 10 days, p=0.038) while there was no statistically significant difference in the complication rate, whether overall (58.6% in obese vs. 52.3% in non-obese) or with a Clavien-Dindo score 3 (17.1% vs 10.9%). AC was offered to 49/70 (70%) patients in the obese group and 306/441 (69.4%) in the non-obese group (p=0.43). There was no statistically significant difference in AC compliance: 18.4% and 22.9% did not start AC, while 36.7% and 34.6%, started AC but did not complete the scheduled treatment (p=0.79) in the obese and non-obese group, respectively. Overall, 55% of patients who started AC successfully completed their adjuvant treatment. Conclusions: Obesity did not impact compliance to AC for locally advanced rectal cancer: compliance was poor in obese and non-obese patients with no statistically significant difference between the two groups. Major complication rate was not statistically significantly affected by increased BMI.

Quasi-elective left colectomy after endoscopic colon stenting for obstructive cancer yields comparable oncologic outcome to full-elective operation.

PURPOSE: Whether deferring surgery after endoscopic self-expandable metal stent (SEMS) placement for neoplastic stricture, and operating patients in a quasi-elective situation, may result in similar oncologic outcomes to elective operations is unclear. This study aimed to evaluate the disease-free survival (DFS) rates of patients who underwent an interval colon resection after SEMS placement or an elective operation with comparable cancer stages. METHODS: From a prospective dataset, we retrospectively selected patients with the following characteristics: (1) left-sided colon cancer and (2) cancer stage I to III. Exclusion criteria were as follows: (1) palliative surgery and (2) emergency operation. Then we stratified patients into two groups: (A) full-elective left colon resection and (B) quasi-elective left colon resection, defined as surgery performed after SEMS placement for obstructive colon cancer. DFS function was studied by the Kaplan-Meier method. RESULTS: After 1:2 matching based on cancer stage, 106 patients of the group A were compared with 53 patients of group B. In each group, there were 9.4% of stage I, 39.4% of stage II, and 50.9% of stage III patients. The rate of technical failure in SEMS placement was 3.8%. After a mean follow-up of 54 months, 16 (15.1%) patients in the full-elective groups and 10 (18.9%) in the quasi-elective group experience cancer recurrence (log rank = 0.588). DFS curve did not reach the median value. CONCLUSIONS: SEMS placement with interval colon resection for obstructive neoplastic strictures seems to provide similar long-term oncologic outcomes to operations performed in an elective setting when a low rate of technical failure is achieved.

Open Abdomen in Obese Patients: Pay Attention! New Evidences from IROA, the International Register of Open Abdomen.

BACKGROUND: Open abdomen is the cornerstone of damage control strategies in acute care and trauma surgery. The role of BMI has not been well investigated. The aim of the study was to assess the role of BMI in determining outcomes after open abdomen. METHODS: This is an analysis of patients recorded into the International Register of Open Abdomen; patients were classified in two groups according to BMI using a cutoff of 30 kg/m2. The primary outcome was in-hospital mortality; secondary outcomes were primary fascia closure rate, length of treatment, complication rate, entero-atmospheric fistula rate and length of ICU stay. RESULTS: A total of 591 patients were enrolled from 57 centers, and obese patients were 127 (21.5%). There was no difference in mortality between the two groups; complications developed during the open treatment were higher in obese patients (63.8% vs. 53.4%, p = 0.038) while post-closure complications rate was similar. Obese patients had a significantly longer duration of the open treatment (9.1 ± 11.5 days vs. 6.3 ± 7.5 days; p = 0,002) and lower primary fascia closure rate (75.5% vs. 89.5%; p < 0,001). No differences in fistula rate were found. There was a linear correlation between the duration of open abdomen and the BMI (Pearson's linear correlation coefficient = 0,201; p < 0,001). CONCLUSIONS: Open abdomen in obese patients seems to be safe as in non-obese patients with similar mortality; however, in obese patients the length of open abdomen is significantly higher with higher complication rate, longer ICU length of stay and lower primary fascia closure rate. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, Identifier: NCT02382770.

Treatment of hepatocellular carcinoma beyond the Milan criteria. A weighted comparative study of surgical resection versus chemoembolization.

BACKGROUND: Optimal treatment of hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) is debated. The aim of the study was to assess overall-survival (OS) and disease-free-survival (DFS) for HCC beyond MC when treated by trans-arterial-chemoembolization (TACE) or surgical resection (SR). METHOD: between 2005 and 2015, all patients with a first diagnosis of HCC beyond MC(1 nodule>5 cm, or 3 nodules>3 cm without macrovascular invasion) were evaluated. Analyses were carried out through Kaplan-Meier, Cox models and the inverse probability weighting (IPW) method to reduce allocation bias. Sub-analyses have been performed for multinodular and single large tumors compared with a MC-IN cohort. RESULTS: 226 consecutive patients were evaluated: 118 in SR group and 108 in TACE group. After IPW, the two pseudo-populations were comparable for tumor burden and liver function. In the SR group, 1-5 years OS rates were 72.3% and 35% respectively and 92.7% and 39.3% for TACE (p = 0.500). The median DFS was 8 months (95%CI:8-9) for TACE, and 11 months (95%CI:9-12) for SR (p < 0.001). TACE was an independent predictor for recurrence (HR 1.5; 95%CI: 1.1-2.1; p = 0.015). Solitary tumors > 5 cm and multinodular disease had comparable OS and DFS as Milan-IN group (p > 0.05). CONCLUSION: Surgery allowed a better control than TACE in patient bearing HCC beyond MC. This translated into a significant benefit in terms of DFS but not OS.

Epidural analgesia vs systemic opioids in patients undergoing laparoscopic colorectal surgery.

PURPOSE: A well-controlled pain is one of the most important targets of enhanced recovery after surgery (ERAS) protocols. Recent studies questioned the role of TEA (thoracic epidural analgesia) in support of less invasive techniques, in particular in laparoscopic mini-invasive surgery. The aim of this study is to compare patients undergoing laparoscopic mini-invasive colorectal surgery and receiving different analgesic techniques. METHODS: Prospectively collected data entered in the electronic registry of POIS (Perioperative Italian Society) specifically designed for ERAS were reviewed. Patients undergoing colorectal laparoscopic surgery were divided in two groups according to TEA or parenteral opioid administration. In comparing TEA and opioid groups, propensity score weights were obtained. Postoperative pain control and time to readiness for discharge (TRD) were considered as primary endpoints of the study. Secondary endpoints were postoperative morbidity, PONV (postoperative nausea and vomiting), hours of mobilization, length of hospital stay (LOS), timing of fluid and solid re-assumption, and recovery of bowel function. RESULTS: Fourteen Italian hospitals reported data on 560 patients (283 TEA, 277 opioid group). Patients of the opioid group were able to mobilize for a longer period than TEA group patients but presented a higher incidence of PONV. Pain intensity and TRD were similar in both groups. LOS was significantly reduced in TEA patients; also, this result was clinically irrelevant (5.7 ± 3.21 days TEA group vs 5.8 ± 2.92 opioid group). CONCLUSION: In patients undergoing laparoscopic colorectal surgery, TEA was not associated to a better pain control or to an improvement in postoperative outcome compared with opioid administration.

Impact of Sarcopenic Obesity on Failure to Rescue from Major Complications Following Pancreaticoduodenectomy for Cancer: Results from a Multicenter Study.

BACKGROUND: Failure to rescue (FTR) is a quality-of-care indicator in pancreatic surgery, but may also identify patients who may not tolerate major postoperative complications despite being treated with best available care. Previous studies found that high visceral adipose tissue-to-skeletal muscle ratio is associated with poor outcomes following pancreaticoduodenectomy (PD). The aim of the study is to assess the impact of sarcopenic obesity on occurrence of FTR from major complications in cancer patients undergoing PD. METHODS: Prospectively collected data from three high-volume hospitals were reviewed. Total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed at preoperative staging computed tomography scan. Sarcopenic obesity was defined as high VFA/TAMA ratio. FTR was defined as postoperative mortality following major complication. RESULTS: 120 patients with major complications were included. FTR occurred in 23 (19.2%) patients. The "seminal" complications leading to FTR were pancreatic or biliary fistula-related sepsis (n = 14), postoperative pancreatic fistula (POPF)-related hemorrhage (n = 5), and duodenojejunal anastomosis leak-related sepsis (n = 1). On univariate analysis, older age [odds ratio (OR) 3.5, p = 0.034], American Society of Anesthesiologists (ASA) score 3+ (OR 4.2, p = 0.005), cardiovascular disease (OR 3.3, p = 0.013), low serum albumin (OR 2.6, p = 0.042), sarcopenic obesity (OR 4.2, p = 0.009), POPF (OR 3.1, p = 0.027), and cardiorespiratory complications (OR 3.7, p = 0.011) were significantly associated with FTR. On multivariate analysis, sarcopenic obesity [OR 5.7, 95% confidence interval (CI) 1.6-20.7, p = 0.008], ASA score 3+ (OR 4.1, 95% CI 1.2-14.3, p = 0.025), and pancreatic fistula (OR 3.2, 95% CI 1.0-10.2, p = 0.045) were independently associated with FTR. CONCLUSION: Sarcopenic obesity, low preoperative physical status, and occurrence of pancreatic fistula are associated with significantly higher risk of FTR from major complications after PD.

Management and Outcomes of Pancreatic Resections Performed in High-Volume Referral and Low-Volume Community Hospitals Lead by Surgeons Who Shared the Same Mentor: The Importance of Training.

BACKGROUND: High hospital volume improves outcomes after pancreatic resection. The aim of this study was to assess if practice and outcomes differed between high- and low-volume centers across which chief surgeons shared a similar training and mentoring. METHODS: Data on patients undergoing standard pancreatic resections (2010-2013) at 7 Italian hospitals were collected. Chiefs of pancreatic surgery at each hospital had received the same training, with the same mentor. Two centers were high-volume referral hospitals for pancreatic disease, while 5 were low-volume hospitals. RESULTS: A total of 856 patients were included, with median annual volume of resections 82 at high-volume referral hospitals and 11 at low-volume hospitals. Patients at low-volume hospitals were older, had more comorbidities, and were more often referred from the emergency room. Intraoperative techniques and reconstruction methods were similar. Comparable rates of major postoperative complications (18 vs. 22%; p = 0.236) and pancreatic fistula (29 vs. 32%; p = 0.287) were achieved in both groups, with no significant increases in failure to rescue from grade B-C fistula (6.2 vs. 15.0%; p = 0.108) and mortality (2.4 vs. 4.1%; p = 0.233) in low-volume hospitals. Postoperative length of stay was shorter in high-volume referral hospitals (10 vs. 15 days; p < 0.001). CONCLUSION: Similar postoperative outcomes can be achieved across high- and low-volume centers where chief surgeons shared a similar training and mentoring. However, multidisciplinary postoperative provision more often associated with high-volume centers may also affect outcomes.

T cell neoepitope discovery in colorectal cancer by high throughput profiling of somatic mutations in expressed genes.

OBJECTIVE: Patient-specific (unique) tumour antigens, encoded by somatically mutated cancer genes, generate neoepitopes that are implicated in the induction of tumour-controlling T cell responses. Recent advancements in massive DNA sequencing combined with robust T cell epitope predictions have allowed their systematic identification in several malignancies. DESIGN: We undertook the identification of unique neoepitopes in colorectal cancers (CRCs) by using high-throughput sequencing of cDNAs expressed by standard cancer cell cultures, and by related cancer stem/initiating cells (CSCs) cultures, coupled with a reverse immunology approach not requiring human leukocyte antigen (HLA) allele-specific epitope predictions. RESULTS: Several unique mutated antigens of CRC, shared by standard cancer and related CSC cultures, were identified by this strategy. CD8+ and CD4+ T cells, either autologous to the patient or derived from HLA-matched healthy donors, were readily expanded in vitro by peptides spanning different cancer mutations and specifically recognised differentiated cancer cells and CSC cultures, expressing the mutations. Neoepitope-specific CD8+ T cell frequency was also increased in a patient, compared with healthy donors, supporting the occurrence of clonal expansion in vivo. CONCLUSIONS: These results provide a proof-of-concept approach for the identification of unique neoepitopes that are immunogenic in patients with CRC and can also target T cells against the most aggressive CSC component.

Small bowel obstruction and incisional hernia after laparoscopic and open colorectal surgery: a meta-analysis of comparative trials.

INTRODUCTION: Recent studies show contrasting data on the impact of laparoscopy on long-term complications such as the occurrence of small bowel obstruction (SBO) and incisional hernia (IH). The objective of the study was to assess the impact of the laparoscopic approach on the occurrence of SBO and IH after colorectal resection. METHODS: Two trained investigators independently searched MEDLINE, Embase, PubMed, and the Cochrane Central Register of clinical trials for studies comparing laparoscopy to open surgery for mid- to long-term outcomes after colorectal surgery. No language restriction was set. Sensitivity analyses for study design and quality, conversion rate, type of procedure (colon or rectal surgery), and length of follow-up were performed. RESULTS: Eleven RCTs and 14 non-RCT comparative studies for a total of 6540 patients were included in the analysis. Laparoscopy was associated with a significant reduction in the occurrence of SBO (RR 0.57, [95 %CI 0.42-0.76], 16 trials) and IH (RR 0.60, [95 %CI 0.50-0.72], 19 trials). Sensitivity analysis including only RCTs confirmed the reduction in SBO (RR 0.58, [95 %CI 0.39-0.87], 8 trials), while the difference was close to significance for IH (RR 0.76, [95 %CI 0.56-1.03], 7 trials). Sensitivity analysis including only studies with conversion rate lower than 15 % showed a significant protective effect of laparoscopy for both SBO (RR 0.53, [95 %CI 0.37-0.77], 11 trials) and IH (RR 0.58, [95 %CI 0.47-0.72], 12 trials). No significant difference between laparoscopy and open surgery was found when the analysis was limited to studies with conversion rate >15 % (SBO: RR 0.60 [0.32-1.12], IH: RR 0.70 [0.46-1.06]). Length of follow-up did not substantially impact on results. CONCLUSION: Laparoscopic surgery is associated with a significant reduction in both SBO and IH compared to the open approach. A low conversion rate in the laparoscopic group plays a key role for reduction in both SBO and IH.

Impact of laparoscopy on adherence to an enhanced recovery pathway and readiness for discharge in elective colorectal surgery: Results from the PeriOperative Italian Society registry.

INTRODUCTION: Previous studies reported that laparoscopic surgery (LPS) improved postoperative outcomes in patients undergoing colorectal surgery within an enhanced recovery program (ERP). However, the effect of minimally invasive surgery on each ERP item has not been clarified, yet. The aim of this study is to assess the impact of LPS on adherence to ERP items and recovery as measured by time to readiness for discharge (TRD). METHODS: Prospectively collected data entered in an electronic Italian registry specifically designed for ERP were reviewed. Patients undergoing elective colorectal surgery were divided into three groups: successful laparoscopy, conversion to open surgery, primary open surgery. Adherence to 19 ERP elements and postoperative outcomes were compared among groups. Multivariate regression analysis was used to identify whether LPS had an independent role to improve ERP adherence and postoperative outcomes. RESULTS: 714 patients (successful LPS 531, converted 42, open 141) underwent elective colorectal surgery within an ERP. Epidural analgesia was used in the 75.1% of open group patients versus 49.9% of LPS group patients (p = 0.012). After surgery, oral feeding recovery, i.v. fluids suspension, removal of both urinary and epidural catheters occurred earlier in the LPS group both in the overall series and in uneventful patients only. Mean TRD and length of hospital stay were significantly shorter in the LPS group (p < 0.001 for both). Overall morbidity rate was 18.7% in the LPS group versus 32.6% in the open group (p = 0.001). At multivariate analysis, LPS was significantly associated to an increased adherence to postoperative ERP items, a shorter TRD, and a reduced overall morbidity, whereas rectal surgery and new stoma formation impaired postoperative recovery. CONCLUSIONS: The present study showed that a successful laparoscopic procedure had an independent role to increase the adherence to postoperative ERP and to improve short-term postoperative outcome.

Laparoscopic surgery for pancreatic neoplasms: the European association for endoscopic surgery clinical consensus conference.

BACKGROUND: Introduced more than 20 years ago, laparoscopic pancreatic surgery (LAPS) has not reached a uniform acceptance among HPB surgeons. As a result, there is no consensus regarding its use in patients with pancreatic neoplasms. This study, organized by the European Association for Endoscopic Surgery (EAES), aimed to develop consensus statements and clinical recommendations on the application of LAPS in these patients. METHODS: An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreatic surgery. Each panelist performed a critical appraisal of the literature and prepared evidence-based statements assessed by other panelists during Delphi process. The statements were further discussed during a one-day face-to-face meeting followed by the second round of Delphi. Modified statements were presented at the plenary session of the 24th International Congress of the EAES in Amsterdam and in a web-based survey. RESULTS: LAPS included laparoscopic distal pancreatectomy (LDP), pancreatoduodenectomy (LPD), enucleation, central pancreatectomy, and ultrasound. In general, LAPS was found to be safe, especially in experienced hands, and also advantageous over an open approach in terms of intraoperative blood loss, postoperative recovery, and quality of life. Eighty-five percent or higher proportion of responders agreed with the majority (69.5%) of statements. However, the evidence is predominantly based on retrospective case-control studies and systematic reviews of these studies, clearly affected by selection bias. Furthermore, no randomized controlled trials (RCTs) have been published to date, although four RCTs are currently underway in Europe. CONCLUSIONS: LAPS is currently in its development and exploration stages, as defined by the international IDEAL framework for surgical innovation. LDP is feasible and safe, performed in many centers, while LPD is limited to few centers. RCTs and registry studies are essential to proceed with the assessment of LAPS.