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.

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.

Development of biotissue training models for anastomotic suturing in pancreatic surgery.

BACKGROUND: Anastomotic suturing is the Achilles heel of pancreatic surgery. Especially in laparoscopic and robotically assisted surgery, the pancreatic anastomosis should first be trained outside the operating room. Realistic training models are therefore needed. METHODS: Models of the pancreas, small bowel, stomach, bile duct, and a realistic training torso were developed for training of anastomoses in pancreatic surgery. Pancreas models with soft and hard textures, small and large ducts were incrementally developed and evaluated. Experienced pancreatic surgeons (n = 44) evaluated haptic realism, rigidity, fragility of tissues, and realism of suturing and knot tying. RESULTS: In the iterative development process the pancreas models showed high haptic realism and highest realism in suturing (4.6 ± 0.7 and 4.9 ± 0.5 on 1-5 Likert scale, soft pancreas). The small bowel model showed highest haptic realism (4.8 ± 0.4) and optimal wall thickness (0.1 ± 0.4 on -2 to +2 Likert scale) and suturing behavior (0.1 ± 0.4). The bile duct models showed optimal wall thickness (0.3 ± 0.8 and 0.4 ± 0.8 on -2 to +2 Likert scale) and optimal tissue fragility (0 ± 0.9 and 0.3 ± 0.7). CONCLUSION: The biotissue training models showed high haptic realism and realistic suturing behavior. They are suitable for realistic training of anastomoses in pancreatic surgery which may improve patient outcomes.

A Combination of Biochemical and Pathological Parameters Improves Prediction of Postresection Survival After Preoperative Chemotherapy in Pancreatic Cancer: The PANAMA-score.

OBJECTIVE: To build a prognostic score for patients with primary chemotherapy undergoing surgery for pancreatic cancer based on pathological parameters and preoperative Carbohydrate antigen 19-9 (CA19-9) levels. BACKGROUND: Prognostic stratification after primary chemotherapy for pancreatic cancer is challenging and prediction models, such as the AJCC staging system, lack validation in the setting of preoperative chemotherapy. METHODS: Patients with primary chemotherapy resected at the Massachusetts General Hospital between 2007 and 2017 were analyzed. Tumor characteristics independently associated with overall survival were identified and weighted by Cox-proportional regression. The pancreatic neoadjuvant Massachusetts-score (PANAMA-score) was computed from these variables and its performance assessed by Harrel concordance index and area under the receiving characteristics curves analysis. Comparisons were made with the AJCC staging system and external validation was performed in an independent cohort with primary chemotherapy from Heidelberg, Germany. RESULTS: A total of 216 patients constituted the training cohort. The multivariate analysis demonstrated tumor size, number of positive lymph-nodes, R-status, and high CA19-9 to be independently associated with overall survival. Kaplan-Meier analysis according to low, intermediate, and high PANAMA-score showed good discriminatory power of the new metrics (P < 0.001). The median overall survival for the three risk-groups was 45, 27, and 12 months, respectively. External validation in 258 patients confirmed the prognostic ability of the score and demonstrated better accuracy compared with the AJCC staging system. CONCLUSION: The proposed PANAMA-score, based on independent predictors of postresection survival, including pathologic variables and CA19-9, not only provides better discrimination compared to the AJCC staging system, but also identifies patients at high-risk for early death.

Timing But Not Patterns of Recurrence Is Different Between Node-negative and Node-positive Resected Pancreatic Cancer.

OBJECTIVE: Our aim was to evaluate recurrence patterns of surgically resected PDAC patients with negative (pN0) or positive (pN1) lymph nodes. SUMMARY BACKGROUND DATA: Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer death by 2030. This is mostly due to early local and distant metastasis, even after surgical resection. Knowledge about patterns of recurrence in different patient populations could offer new therapeutic avenues. METHODS: Clinicopathologic data were collected for 546 patients who underwent resection of their PDAC between 2005 and 2016 from 2 tertiary university centers. Patients were divided into an upfront resection group (n = 394) and a neoadjuvant group (n = 152). RESULTS: Tumor recurrence was significantly less common in pN0 patients as compared with pN1 patients, (upfront surgery: 55% vs. 77%, P < 0.001 and 64% vs. 78%, P = 0.040 in the neoadjuvant group). In addition, time to recurrence was significantly longer in pN0 versus pN1 patients in the upfront resected patients (median 16 mo pN0 vs. 10 mo pN1 P < 0.001), and the neoadjuvant group (pN0 21 mo vs. 11 mo pN1, P < 0.001). Of the patients who recurred, 62% presented with distant metastases (63% of pN0 and 62% of pN1, P = 0.553), 24% with local disease (27% of pN0 and 23% of pN1, P = 0.672) and 14% with synchronous local and distant disease (10% of pN0 and 15% of pN1, P = 0.292). Similarly, there was no difference in recurrence patterns between pN0 and pN1 in the neoadjuvant group, in which 68% recurred with distant metastases (76% of pN0 and 64% of pN1, P = 0.326) and 18% recurred with local disease (pN0: 22% and pN1: 15%, P = 0.435). CONCLUSION: Time to recurrence was significantly longer for pN0 patients. However, patterns of recurrence for pN0 vs. pN1 patients were identical. Lymph node status was predictive of time to recurrence, but not location of recurrence.

Main Pancreatic Duct to Parenchymal Thickness Ratio at Preoperative Imaging is Associated with Overall Survival in Upfront Resected Pancreatic Cancer.

BACKGROUND: Pancreatic cancer induces parenchymal atrophy and duct dilation. The aim of this study was to evaluate whether these radiologic modifications are associated with outcomes. METHODS: Upfront pancreaticoduodenectomy patients with available preoperative contrast enhanced CT scan imaging were retrospectively analyzed. Thickness of the pancreas, size of the main pancreatic duct (MPD), and distance of the tumor from the ampulla were assessed. A training cohort was selected, including short- (3-12 months following surgery) and long-term (≥ 36 months) survivors. Identified survival determinants were validated in the overall cohort. RESULTS: Two-hundred-sixteen patients were analyzed. In the training cohort (N = 118), 68 patients (57.6%) were in the short-term and 50 (42.4%) in the long-term survival group. The short-term survival group had significantly higher CA 19-9 levels (p = 0.027), larger tumors (32.6 ± 12.1 mm vs. 26.5 ± 11.6 mm, p = 0.007), poorer differentiation (p = 0.003), higher rate of R < 1 mm resections (54% vs. 32%, p = 0.008), and reduced receipt of adjuvant chemotherapy (p = 0.020). The MPD-to-pancreatic thickness ratio was significantly lower in the short-term survivors (3.6 ± 6.2 vs. 8.2 ± 12.0, p = 0.016). In the entire cohort, an MPD-to-pancreatic thickness ratio ≥ 3.5 was associated with improved OS [median 33.0 months IQR (19.7-48.1) versus 17 months IQR (14.8-19.2), p = 0.004], and confirmed by a Cox-proportional hazards model independently associated with OS (HR = 0.58; p = 0.009), together with tumor size (HR = 1.02; p =0.012), R1/R2 status (HR = 1.53; p = 0.029), and receipt of adjuvant treatment (HR = 0.61; p = 0.021). CONCLUSIONS: High MPD-to-pancreatic thickness ratio was associated with improved long-term survival in pancreaticoduodenectomy for cancer. Whether these features are related to tumor chronicity, indolent biology, or local growth over metastasis remains to be determined.

Prognostic Impact of Preoperative Nutritional Risk in Patients Who Undergo Surgery for Pancreatic Adenocarcinoma.

BACKGROUND: Nutritional derangements are common hallmarks of pancreatic cancer (PC). Their early detection and management are usually overlooked in routine practice. This study aimed to explore preoperative nutritional status and its prognostic value in patients undergoing surgery for PC. METHODS: Data from 73 patients who underwent surgery for PC from November 2015 to January 2018 at the General and Pancreatic Surgery Unit, The Pancreas Institute, University Hospital of Verona Hospital, Verona, Italy, were retrospectively evaluated. The Nutritional Risk Screening (NRS)-2002 was used to evaluate the preoperative nutritional risk. Body composition was assessed using bioimpedance vectorial analysis (BIVA) on the day prior to surgery. The effect of clinical, pathological, and nutritional characteristics on overall survival (OS) was investigated using a Cox and logistic regression model. Kaplan-Meier curves were compared using the log-rank test. RESULTS: Most patients (80.8%) were at preoperative risk of malnutrition (NRS-2002 ≥ 3) despite a mean BMI of 24.1 kg/m2(± 4.3). Twenty-four patients (32.9%) received neoadjuvant therapy prior to surgery. Preoperative NRS-2002 was significantly higher in this subset of patients (p = 0.026), with a significant difference by chemotherapy regimens (in favor of FOLFIRINOX, p = 0.035). In a multivariate analysis, the only independent prognostic factor for OS was the NRS-2002 score (HR 5.24, p = 0.013). Particularly, the likelihood of 2-year survival was higher in NRS < 3 (p = 0.009). CONCLUSIONS: Our analysis confirms that preoperative malnutrition has a detrimental impact on OS in PC patients undergoing radical surgery for PC. Careful preoperative nutritional evaluation of PC patients should be mandatory, especially in those who are candidates for neoadjuvant therapy.

Microscopic size measurements in post-neoadjuvant therapy resections of pancreatic ductal adenocarcinoma (PDAC) predict patient outcomes.

AIMS: Pancreatic ductal adenocarcinomas (PDACs) are increasingly being treated with neoadjuvant therapy. However, the American Joint Committee on Cancer (AJCC) 8th edition T staging based on tumour size does not reflect treatment effect, which often results in multiple, small foci of residual tumour in a background of mass-forming fibrosis. Thus, we evaluated the performance of AJCC 8th edition T staging in predicting patient outcomes by the use of a microscopic tumour size measurement method. METHODS AND RESULTS: One hundred and six post-neoadjuvant therapy pancreatectomies were reviewed, and all individual tumour foci were measured. T stages based on gross size with microscopic adjustment (GS) and the largest single microscopic focus size (MFS) were examined in association with clinicopathological variables and patient outcomes. Sixty-three of 106 (59%) were locally advanced; 78% received FOLFIRINOX treatment. The average GS and MFS were 25 mm and 11 mm, respectively; nine cases each were classified as T0, 35 and 85 cases as T1, 42 and 12 cases as T2, and 20 and 0 cases as T3, based on the GS and the MFS, respectively. Higher GS-based and MFS-based T stages were significantly associated with higher tumour regression grade, lymphovascular and perineural invasion, and higher N stage. Furthermore, higher MFS-based T stage was significantly associated with shorter disease-free survival (DFS) (P < 0.001) and shorter overall survival (OS) (P = 0.002). GS was significantly associated with OS (P = 0.046), but not with DFS. CONCLUSIONS: In post-neoadjuvant therapy PDAC resections, MFS-based T staging is superior to GS-based T staging for predicting patient outcomes, suggesting that microscopic measurements have clinical utility beyond the conventional use of GS measurements alone.

Preoperative carbohydrates: what is new?

PURPOSE OF REVIEW: The aim of this review is to give an overview of recently published articles covering preoperative carbohydrate loading in surgical patients. RECENT FINDINGS: Between January 1, 2017, and December 31, 2019, 26 publications addressing the effect of carbohydrate load were retrieved through a systematic search. Seventeen were randomized clinical trials, three prospective observational studies and six retrospective series with case-control comparison. Most of the studies were underpowered, addressed surrogate endpoints, and variability among dose and timing of carbohydrate (CHO) treatment was high. The most recent literature endorses preoperative carbohydrate loading up to 2 h before operations as a safe treatment. The new evidence confirm that this strategy is effective in reducing perioperative insulin resistance and the proportion of hyperglycemia episodes, and improving patient well-being and comfort but without affecting surgery-related morbidity. SUMMARY: Further properly designed randomized clinical trials, addressing more clinically relevant endpoints such as length of hospitalization and morbidity rate, are warrant.

Diabetes mellitus is associated with unfavorable pathologic features, increased postoperative mortality, and worse long-term survival in resected pancreatic cancer.

BACKGROUND: The risk of pancreatic ductal adenocarcinoma (PDAC) is increased in patients with diabetes mellitus (DM), particularly in those with new-onset DM. However, the impact of DM on outcomes following pancreatic surgery is not fully understood. We sought to explore the effects of DM on post-resection outcomes in patients undergoing either upfront resection or following neoadjuvant treatment (NAT). METHODS: Resections for PDAC between 2007 and 2016 were identified from a prospectively-maintained database. Data on demographics, pathology, and perioperative outcomes were compared between patients with or without DM. Survival analysis was performed using Kaplan-Meier curves and adjusted for confounders by a Cox-proportional hazards model. RESULTS: 662 patients were identified, of whom 277 (41.8%) had DM. Diabetics were more likely to be male, had higher BMI, and higher ASA-scores. At pathology, DM was associated with larger tumors (30 vs. 26 mm; p = 0.041), higher rates of lymph-node involvement (69% vs. 59%; p = 0.031) and perineural invasion (88% vs. 82%; p = 0.026). Despite having similar rates of complications, diabetics experienced higher 30-day mortality (3.2% vs. 0.8%; p = 0.019). Median overall survival was worse in diabetic patients (18 vs. 34 months; p < 0.001); this effect was more pronounced in patients with NAT (18 vs. 54 months; p < 0.001). At multivariate analysis, DM was confirmed as an independent predictor of post-resection survival. CONCLUSION: DM is a common comorbidity in PDAC and is associated with unfavorable pathology, as well as worse postoperative and oncologic outcomes. The blunted effect on survival is more pronounced in patients who undergo resection following NAT.

Preoperative adiposity at bioimpedance vector analysis improves the ability of Fistula Risk Score (FRS) in predicting pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Anthropometric parameters have been associated with increased risk of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). Nonetheless, conventional metrics to predict POPF do not include the assessment of body composition. We aimed to validate the most used Fistula Risk Score (FRS), and to assess whether the appraisal of adipose compartment at bioimpedance vector analysis (BIVA) improves the accuracy of FRS in CR-POPF prediction. METHOD: PD patients from 3 Italian academic institutions were prospectively included over a 2-year period. Patients with ASA score ≥3, heart failure, chronic kidney disease, or compartmentalized fluid collections were excluded. BIVA was performed on the day prior to surgery. CR-POPF occurrence and severity were classified per the ISGPS classification. RESULTS: Out of 148 PDs, 84 patients (56.8%) had pancreatic cancer, and 29 (19.6%) experienced CR-POPF. FRS elements, namely soft pancreatic texture (p = 0.009), small pancreatic duct diameter (p = 0.029), but not blood loss (p = 0.450), as well as high BMI (p = 0.004) were associated with CR-POPF. Also, the preoperative fat mass (FM) amount measured at BIVA was significantly higher in patients who developed CR-POPF, compared to those who did not (median FM = 19.4 kg/m2 vs. 14.4 kg/m2, respectively; p = 0.005). The predictive ability of a multivariate model adding FM to the FRS, assessed at the receiver operating characteristics curve showed a higher accuracy than the FRS alone (AUC = 0.774 and AUC = 0.738, respectively). CONCLUSIONS: Assessment of preoperative FM at BIVA can improve the accuracy of FRS in predicting CR-POPF following pancreatoduodenectomy.

Adjuvant therapy is associated with improved overall survival in patients with pancreatobiliary or mixed subtype ampullary cancer after pancreatoduodenectomy - A multicenter cohort study.

BACKGROUND/OBJECTIVE: The benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC. METHODS: Patients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated. RESULTS: 214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3-4 82 months median OS, p = 0.002), preoperative serum CEA (CEA <0.5 ng/ml 128 vs. CEA >0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 < 40 IU/ml 147 vs. CA19-9 > 40IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p < 0.001), N stage (N0 159 vs. N+ 110 months, p < 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997-3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904-3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151-0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients. CONCLUSION: Adjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC.

Perioperative Interstitial Fluid Expansion Predicts Major Morbidity Following Pancreatic Surgery: Appraisal by Bioimpedance Vector Analysis.

OBJECTIVE: To evaluate whether perioperative bioimpedance vector analysis (BIVA) predicts the occurrence of surgery-related morbidity. SUMMARY BACKGROUND DATA: BIVA is a reliable tool to assess hydration status and compartimentalized fluid distribution. METHODS: The BIVA of patients undergoing resection for pancreatic malignancies was prospectively measured on the day prior to surgery and on postoperative day (POD)1. Postoperative morbidity was scored per the Clavien-Dindo classification (CDC), and the Comprehensive Complication Index (CCI). RESULTS: Out of 249 patients, the overall and major complication rates were 61% and 16.5% respectively. The median CCI was 24 (IQR 0.0-24.2), and 24 patients (9.6%) had a complication burden with CCI≥40. At baseline the impedance vectors of severe complicated patients were shorter compared to the vectors of uncomplicated patients only for the female subgroup (P=0.016). The preoperative extracellular water (ECW) was significantly higher in patients who experienced severe morbidity according to the CDC or not [19.4L (17.5-22.0) vs. 18.2L (15.6-20.6), P=0.009, respectively] and CCI≥40, or not [20.3L (18.5-22.7) vs. 18.3L (15.6-20.6), P=0.002, respectively]. The hydration index on POD1 was significantly higher in patients who experienced major complications than in uncomplicated patients (P=0.020 and P=0.025 for CDC and CCI, respectively).At a linear regression model, age (ß=0.14, P=0.035), sex female (ß=0.40, P<0.001), BMI (ß=0.30, P<0.001), and malnutrition (ß=0.14, P=0.037) were independent predictors of postoperative ECW. CONCLUSION: The amount of extracellular fluid accumulation predicts major morbidity after pancreatic surgery. Female, obese and malnourished patients were at high risk of extracellular fluid accumulation.

Association Between Compliance to an Enhanced Recovery Protocol and Outcome After Elective Surgery for Gastric Cancer. Results from a Western Population-Based Prospective Multicenter Study.

BACKGROUND: The association between compliance to an enhanced recovery protocol (ERAS) and outcome after surgery for gastric cancer has been poorly investigated, particularly in Western patients. The aim of the study was to evaluate whether the rate of adherence to the ERAS program was correlated with outcome and time of discharge. METHODS: A prospective, observational, multicenter study was designed to be performed at Italian referral centers for gastric surgery. The protocol was discussed and approved by the Italian Research Group on Gastric Cancer. Twenty-three ERAS domains were applied. A multivariate logistic regression was used to assess the association between ERAS compliance and overall and major complication rates. The Poisson regression model (measured as mean ratios) was used to assess the association of ERAS compliance rate and length of stay (LOS). RESULTS: Eight centers participated and 290 subjects with a median age of 73 years were enrolled. The overall rates of adherence to pre-, intra-, and postoperative ERAS items were 69.8%, 60.3%, and 82.5%, respectively. At the multivariate model, there was an association between overall rate of morbidity and an overall ERAS compliance rate greater than 70% (OR 0.413; 95% CI 0.235-0.7240; P 0.002). A similar association was found for major complications (OR 0.328; 95% CI 0.151-0.709; P 0.005). The Poisson regression showed that in patients with ERAS compliance rate >70%, LOS was reduced of approximately 20% (mean ratio 0.812; 95% CI 0.694-0.950; P 0.009). CONCLUSIONS: These results suggest a moderate compliance to an ERAS program and a significant association between adherence and outcomes.

Preoperative Oral Carbohydrate Load Versus Placebo in Major Elective Abdominal Surgery (PROCY): A Randomized, Placebo-controlled, Multicenter, Phase III Trial.

OBJECTIVE: To explore whether preoperative oral carbohydrate (CHO) loading could achieve a reduction in the occurrence of postoperative infections. BACKGROUND: Hyperglycemia may increase the risk of infection. Preoperative CHO loading can achieve postoperative glycemic control. METHODS: This was a randomized, controlled, multicenter, open-label trial. Nondiabetic adult patients who were candidates for elective major abdominal operation were randomized (1:1) to a CHO (preoperative oral intake of 800 mL of water containing 100 g of CHO) or placebo group (intake of 800 mL of water). The blood glucose level was measured every 4 hours for 4 days. Insulin was administered when the blood glucose level was >180 mg/dL. The primary endpoint was the occurrence of postoperative infection. The secondary endpoint was the number of patients needing insulin. RESULTS: From January 2011 through December 2015, 880 patients were randomly allocated to the CHO (n = 438) or placebo (n = 442) group. From each group, 331 patients were available for the analysis. Postoperative infection occurred in 16.3% (54/331) of CHO group patients and 16.0% (53/331) of placebo group patients (relative risk 1.019, 95% confidence interval 0.720-1.442, P = 1.00). Insulin was needed in 8 (2.4%) CHO group patients and 53 (16.0%) placebo group patients (relative risk 0.15, 95% confidence interval 0.07-0.31, P < 0.001). CONCLUSIONS: Oral preoperative CHO load is effective for avoiding a blood glucose level >180 mg/dL, but without affecting the risk of postoperative infectious complication.

Preoperative Biliary Stenting and Major Morbidity After Pancreatoduodenectomy: Does Elapsed Time Matter?: The FRAGERITA Study Group.

OBJECTIVE: To analyze possible associations between the duration of stent placement before surgery and the occurrence and severity of postoperative complications after pancreatoduodenectomy (PD). BACKGROUND: The effect of preoperative stent duration on postoperative outcomes after PD has not been investigated. METHODS: From 2013 to 2016, patients who underwent PD for any reasons after biliary stent placement at 5 European academic centers were analyzed from prospectively maintained databases. The primary aim was to investigate the association between the duration of preoperative biliary stenting and postoperative morbidity. Patients were stratified by stent duration into 3 groups: short (<4 weeks), intermediate (4-8 weeks), and long (≥8 weeks). RESULTS: In all, 312 patients were analyzed. The median time from stent placement to surgery was 37 days (2-559 days), and most operations were performed for pancreatic cancer (67.6%). Morbidity and mortality rates were 56.0% and 2.6%, respectively. Patients in the short group (n = 106) experienced a higher rate of major morbidity (43.4% vs 20.0% vs 24.2%; P < 0.001), biliary fistulae (13.2% vs 4.3% vs 5.5%; P = 0.031), and length of hospital stay [16 (10-52) days vs 12 (8-35) days vs 12 (8-43) days; P = 0.025]. A multivariate adjusted model identified the short stent duration as an independent risk factor for major complications (odds ratio 2.64, 95% confidence interval 1.23-5.67, P = 0.013). CONCLUSIONS: When jaundice treatment cannot be avoided, delaying surgery up to 1 month after biliary stenting may reduce major morbidity, procedure-related complications, and length of hospital stay.

Neoadjuvant Therapy Versus Upfront Resection for Pancreatic Cancer: The Actual Spectrum and Clinical Burden of Postoperative Complications.

BACKGROUND: Neoadjuvant therapy (NAT) is used for borderline-resectable or locally advanced pancreatic cancer (PDAC) and exhibits promising results in terms of pathological outcomes. However, little is known about its effect on surgical complications. METHODS: We analyzed 445 pancreatic resections for PDAC from 2014 to 2016 at The Pancreas Institute, Verona University Hospital. The Modified Accordion Severity Grading System and average complication burden (ACB) were used to compare patients treated with NAT with patients who underwent upfront surgery (UFS). RESULTS: Of 305 pancreaticoduodenectomies (PD), patients treated with NAT (n = 99) had less pancreatic fistula (POPF, 9.1% vs. 15.6%, p = 0.05) without grade C cases, but grade B ACB was increased (0.28 for NAT vs. 0.24 for UFS, p = 0.05). The postpancreatectomy hemorrhage (PPH) rate was lower in the NAT group (9.1% vs. 14.6%, p = 0.02), but ACB grades B (0.37 for NAT vs. 0.26 for UFS, p = 0.03) and C (0.43 for NAT vs. 0.29 for UFS, p = 0.05) were increased. Delayed gastric emptying (DGE) was increased in NAT cases (15.2% vs. 8.3%, p = 0.04), with higher grade C ACB (0.43 for NAT vs. 0.29 for UFS, p = 0.03). Of 94 distal pancreatectomies (DP), NAT patients (n = 26) developed more grade C POPF (11.5% vs. 1.5%, p = 0.04) and DGE (11.5% vs. 2.9%, p = 0.01) without differences in ACB. CONCLUSIONS: Patients undergoing PD for PDAC after NAT exhibited reduced incidence of POPF and PPH but increased incidence of DGE compared with patients treated with UFS. Among patients developing postoperative complications after PD, those receiving NAT were associated with increased clinical burden.

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.

Recurrence Patterns After Anatomic or Parenchyma-Sparing Liver Resection for Hepatocarcinoma in a Western Population of Cirrhotic Patients.

BACKGROUND: The optimal surgical strategy to lessen the risk of hepatocarcinoma (HCC) recurrence is debated. This study aimed to investigate the role of anatomic resection (AR) and parenchyma-sparing resection (PSR) in HCC recurrence patterns. METHODS: The study analyzed 384 cirrhotic patients with a first diagnosis of HCC. Of these patients, 142 underwent AR, and 242 underwent PSR. The two groups were unbalanced at the univariate analysis. To minimize this bias, a 1:1 propensity score-matching analysis (PSA) was used. Disease-free survival (DFS) curves were analyzed by the Kaplan-Maier method. RESULTS: The PSA allowed pairing of 200 patients (100 for AR and 100 for PSR). In this study, 59 patients (62.8%) had recurrence after AR compared with 58 patients (63.7%) after PSR (p = 0.891). The rates of local recurrence were respectively 15.3% and 15.5% (p = 0.968). When microvascular invasion was considered, the median DFS was 10.7 months for AR and 9.4 months for PSR (p = 0.607). In comparisons of AR and PSR, DFS did not differ significantly between subgroups with high histologic grading (p = 0.520), multiple nodules (p = 0.307), and Child-Pugh B (p = 0.679). CONCLUSION: Excision of the anatomic segment did not seem to reduce the rate of relapse or recurrence patterns significantly, even in high-risk subgroups.