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.

Corrigendum: Body composition parameters, immunonutritional indexes, and surgical outcome of pancreatic cancer patients resected after neoadjuvant therapy: a retrospective, multicenter analysis.

[This corrects the article DOI: 10.3389/fnut.2023.1065294.].

Independent effect of fat-to-muscle mass ratio at bioimpedance analysis on long-term survival in patients receiving surgery for pancreatic cancer.

Introduction: Malnutrition and alteration of body composition are early features in pancreatic cancer and appear to be predictors of advanced stages and dismal overall survival. Whether specific patient characteristics measured at the preoperative bioimpedance analysis (BIA) could be associated with long-term outcomes following curative resection has not been yet described. Methods: In a prospective multicenter study, all histologically proven resected pancreatic cancer patients were included in the analysis. BIA was measured for all patients on the day before surgery. Demographics, perioperative data, and postoperative outcomes were prospectively collected. Patients who experienced 90-day mortality were excluded from the analysis. Survival data were obtained through follow-up visits and phone interviews. Bioimpedance variables were analyzed according to the overall survival using the Kaplan-Meier curves and the univariate and multivariate Cox regression model. Results: Overall, 161 pancreatic cancer patients were included. The median age was 66 (60-74) years, and 27.3% received systemic neoadjuvant treatment. There were 23 (14.3%) patients malnourished in the preoperative evaluation. Median OS was 34.0 (25.7-42.3) months. Several bioimpedance variables were associated with OS at the univariate analysis, namely the phase angle [HR 0.85, 95% CI 0.74-0.98)], standardized phase angle [HR 0.91, 95% CI 0.82-0.99)], and an increased ratio between the fat and lean mass (FM/FFM) [HR 4.27, 95% CI 1.10-16.64)]. At the multivariate analysis, the FM/FFM ratio was a confirmed independent predictor of OS following radical resection, together with a positive lymph nodal status. Conclusion: Alteration of body composition at the preoperative bioimpedance vector analysis (BIVA) can predict dismal oncologic outcomes following pancreatic resection for cancer.

Association of chronic statin use, myopenia, myosteatosis and major morbidity in surgical patients with upper gastrointestinal cancer.

Derangements of body composition affect surgical outcomes. Chronic statin use may induce muscle wasting and impair muscle tissue quality. Aim of this study was to evaluate the association of chronic statin use, skeletal muscle area (SMA), myosteatosis and major postoperative morbidity. Between 2011 and 2021, patients undergoing pancreatoduodenectomy or total gastrectomy for cancer, and using statins since at least 1 year, were retrospective studied. SMA and myosteatosis were measured at CT scan. The cut-off for SMA and myosteatosis were determined using ROC curve and considering severe complications as the binary outcome. The presence of myopenia was defined when SMA was lower that the cut-off. A multivariable logistic regression was applied to assess the association between several factors and severe complications. After a matching procedure (1:1) for key baseline risk factors (ASA; age; Charlson comorbidity index; tumor site; intraoperative blood loss), a final sample of 104 patients, of which 52 treated and 52 not treated with statins, was obtained. The median age was 75 years, with an ASA score ≥ 3 in 63% of the cases. SMA (OR 5.119, 95% CI 1.053-24.865) and myosteatosis (OR 4.234, 95% CI 1.511-11.866) below the cut-off values were significantly associated with major morbidity. Statin use was predictive of major complication only in patients with preoperative myopenia (OR 5.449, 95% CI 1.054-28.158). Myopenia and myosteatosis were independently associated with an increased risk of severe complications. Statin use was associated with a higher risk of having major morbidity only in the subgroup of patients with myopenia.

ERAS with or without supplemental artificial nutrition in open pancreatoduodenectomy for cancer. A multicenter, randomized, open labeled trial (RASTA study protocol).

Purpose: The role of supplemental artificial nutrition in patients perioperatively treated according to enhanced recovery programs (ERAS) on surgery-related morbidity is not known. Therefore, there is a need of a clinical trials specifically designed to explore whether given a full nutritional requirement by parenteral feeding after surgery coupled with oral food "at will" compared to oral food "at will" alone, within an established ERAS program, could achieve a reduction of the morbidity burden. Materials and analysis: RASTA will be a multicenter, randomized, parallel-arm, open labeled, superiority trial. The trial will be conducted in five Italian Institutions with proven experience in pancreatic surgery and already applying an established ERAS program. Adult patients (age ≥ 18 and < 90 years of age) candidate to elective open pancreatoduodenectomy (PD) for any periampullary or pancreatic cancer will be randomized to receive a full ERAS protocol that establishes oral food "at will" plus parenteral nutrition (PN) from postoperative day 1 to day 5 (treatment arm), or to ERAS protocol without PN (control arm). The primary endpoint of the trial is the complication burden within 90 days after the day of surgery. The complication burden will be assessed by the Comprehensive Complication Index, that incorporates all complications and their severity as defined by the Clavien-Dindo classification, and summarizes postoperative morbidity with a numerical scale ranging from 0 to 100. The H0 hypothesis tested is that he administration of a parenteral nutrition added to the ERAS protocol will not affect the CCI as compared to standard of care (ERAS). The H1 hypothesis is that the administration of a parenteral nutrition added to the ERAS protocol will positively affect the CCI as compared to standard of care (ERAS). The trial has been registered at ClinicalTrials.gov (number: NCT04438447; date: 18/05/2020). Conclusion: This upcoming trial will permit to establish if early postoperative artificial nutritional support after PD may improve postoperative outcomes compared to oral nutrition alone within an established ERAS program.

Body composition parameters, immunonutritional indexes, and surgical outcome of pancreatic cancer patients resected after neoadjuvant therapy: A retrospective, multicenter analysis.

Background and aims: Body composition parameters and immunonutritional indexes provide useful information on the nutritional and inflammatory status of patients. We sought to investigate whether they predict the postoperative outcome in patients with pancreatic cancer (PC) who received neoadjuvant therapy (NAT) and then pancreaticoduodenectomy. Methods: Data from locally advanced PC patients who underwent NAT followed by pancreaticoduodenectomy between January 2012 and December 2019 in four high-volume institutions were collected retrospectively. Only patients with two available CT scans (before and after NAT) and immunonutritional indexes (before surgery) available were included. Body composition was assessed and immunonutritional indexes collected were: VAT, SAT, SMI, SMA, PLR, NLR, LMR, and PNI. The postoperative outcomes evaluated were overall morbidity (any complication occurring), major complications (Clavien-Dindo ≥ 3), and length of stay. Results: One hundred twenty-one patients met the inclusion criteria and constituted the study population. The median age at the diagnosis was 64 years (IQR16), and the median BMI was 24 kg/m2 (IQR 4.1). The median time between the two CT-scan examined was 188 days (IQR 48). Skeletal muscle index (SMI) decreased after NAT, with a median delta of -7.8 cm2/m2 (p < 0.05). Major complications occurred more frequently in patients with a lower pre-NAT SMI (p = 0.035) and in those who gained in subcutaneous adipose tissue (SAT) compartment during NAT (p = 0.043). Patients with a gain in SMI experienced fewer major postoperative complications (p = 0.002). The presence of Low muscle mass after NAT was associated with a longer hospital stay [Beta 5.1, 95%CI (1.5, 8.7), p = 0.006]. An increase in SMI from 35 to 40 cm2/m2 was a protective factor with respect to overall postoperative complications [OR 0.43, 95% (CI 0.21, 0.86), p < 0.001]. None of the immunonutritional indexes investigated predicted the postoperative outcome. Conclusion: Body composition changes during NAT are associated with surgical outcome in PC patients who receive pancreaticoduodenectomy after NAT. An increase in SMI during NAT should be favored to ameliorate the postoperative outcome. Immunonutritional indexes did not show to be capable of predicting the surgical outcome.

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.

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.

Immunonutrition and prehabilitation in pancreatic cancer surgery: A new concept in the era of ERAS® and neoadjuvant treatment.

Pancreatic cancer (PC) is an aggressive disease, with a growing incidence, and a poor prognosis. Neoadjuvant treatments in PC are highly recommended in borderline resectable and recently in upfront resectable PC. PC is characterized by exocrine insufficiency and nutritional imbalance, leading to malnutrition/sarcopenia. The concept of malnutrition in PC is multifaceted, as the cancer-related alterations create an interplay with adverse effects of anticancer treatments. All these critical factors have a negative impact on the postoperative and oncological outcomes. A series of actions and programs can be implemented to improve resectable and borderline resectable PC in terms of postoperative complications, oncological outcomes and patients' quality of life. A timely nutritional evaluation and the implementation of appropriate evidence-based nutritional interventions in onco-surgical patients should be considered of importance to improve preoperative physical fitness. Unfortunately, nutritional care and its optimization are often neglected in real-world clinical practice. Currently available studies and ERAS® guidelines mostly support the use of pre- or perioperative medical nutrition, including immunonutrition, in order to decrease the rate of postoperative infections and length of hospital stay. Further data also suggest that medical nutrition should be considered proactively in PC patients, to possibly prevent severe malnutrition and its consequences on disease and treatment outcomes. This narrative review summarizes the most recent data related to the role of prehabilitation, ERAS® program, medical nutrition, and the timing of intervention on clinical outcomes of upfront resectable and borderline PC, and their potential implementation within the timeframe of neoadjuvant treatments.

Pharmaconutrition: Which substrates?

With the term "pharmaconutrition" or "immunonutrition" is intended the use of specific nutritional substrates having the ability of modulating specific mechanisms involved in several immune and inflammatory pathways. To achieve these goals, these substrates have to be administered with over physiologic dose. Glutamine and omega-3 polyunsaturated fatty acids, used as single substrate, did not show clear clinical advantages on solid endpoints such as postoperative complications. Despite several multiple substrate enteral feeds are available on the market, very few of them have been tested in randomized clinical trial to prove efficacy. The most extensive investigated formulation is a combination of arginine, omega-3 fatty acids, ribonucleic acid with or without glutamine. Several meta-analyses of randomized clinical trials have been conducted to compare the effects of enteral immunonutrition with control diets on post-surgical morbidity. The results consistently showed that the use of enteral multiple substrate formulas significantly reduced infectious complications and duration of hospitalization. In a more contemporary view, pharmaconutrition should be tested more accurately in the contest of enhanced recovery programs, during neoadjuvant chemotherapy, and in the prehabilitation setting.

Estimating Fatty Pancreas-A Preoperative Bedside Assessment by Bioelectric Impedance Analysis: Implications for Pancreatic Surgery.

OBJECTIVE: The aim of the study was to evaluate whether fatty pancreas could be estimated by fat mass measurement by preoperative bioelectric impedance analysis. Preoperative computed tomography scan and pathologic evaluation were used as validation methods. Moreover, the 3 methodologies were tested for their ability in predicting postoperative pancreatic fistula. METHODS: Seventy-five patients who underwent pancreatic resection were analyzed. Preoperative computed tomography attenuation in Hounsfield unit (CT-HU) was used to assess fatty pancreas. Bioelectric impedance analysis was performed the day before surgery and fat mass index (FMI) was calculated. Pancreatic steatosis was assessed by pathologists at the line of surgical transection. The ability of the methods in predicting postoperative pancreatic fistula was evaluated by the area under the receiver operating characteristics curves. RESULTS: There was a strong correlation between CT-HU values and grade of pancreatic steatosis evaluated at histology ( r = -0.852, P < 0.001) and a moderate correlation between FMI and histologic pancreatic steatosis ( r = 0.612, P < 0.001) and between CT-HU value and FMI ( r = -0.659, P < 0.001) values. The area under the curve (95% confidence interval) was 0.942 (0.879-1) for histology, 0.924 (0.844-1) for CT-HU, and 0.884 (0.778-0.990) for FMI. CONCLUSIONS: Bioelectric impedance analysis represents a valid alternative to assess pancreatic steatosis.

Sporadic nonfunctional pancreatic neuroendocrine tumors: Risk of lymph node metastases and aggressiveness according to tumor size: A multicenter international study.

BACKGROUND: Although the correlation between tumor size and aggressiveness is clearly established in sporadic nonfunctional pancreatic neuroendocrine tumors, the management of tumors ≤2 cm remains debated. In recent guidelines, the cut-off size to operate ranged from 1 to 2 cm. The aim of this retrospective study was to report the rate of lymph nodes metastases in resected sporadic nonfunctional pancreatic neuroendocrine tumors, according to tumor size and, second, to identify risk factors of lymph node metastases and disease-free survival. METHODS: Resected sporadic nonfunctional pancreatic neuroendocrine tumors from 9 international expert centers were included (1999-2017). Functional pancreatic neuroendocrine tumors, genetic syndromes, and R2 resection were excluded. Aggressiveness was defined as microvascular invasion, perineural invasion, lymph node metastases, G3 grading, distant metastases, and/or recurrence. RESULTS: Overall, 495 resected sporadic nonfunctional pancreatic neuroendocrine tumors were included. For tumors up to 5 cm, the risk of lymph node metastases was increased by 1.73 for every 1 cm increase in size (odds ratio = 1.73; 95% confidence interval = 1.46-2.03). Tumor size >2 cm (P < .001), perineural invasion (P = .002), microvascular invasion (P < .001), and distant metastases (P = .008) were independently associated with lymph node metastases. Tumor size >2 cm (P = .003), R1 status (P = .004), lymph node metastases (P < .001), and World Health Organization grade 3 (P = .002) were independently associated with disease-free survival. Aggressiveness rate was 13.1% in tumors ≤1 cm and 29% in tumors between 1.1 and 2 cm. CONCLUSION: In resected sporadic nonfunctional pancreatic neuroendocrine tumors, the risk of lymph node metastases is correlated to tumor size. Considering that sporadic nonfunctional pancreatic neuroendocrine tumors between 1.1 and 2 cm had a higher risk of lymph node metastases and recurrence compared to tumors ≤1 cm, the decision to perform surgery in this subgroup of patients should be individualized in surgically fit patients.

Diversified Effects of Bile Contamination, Postoperative Infections, and Antimicrobial Resistance Level on the Oncologic Prognosis After Pancreatoduodenectomy for Ductal Adenocarcinoma.

BACKGROUND/AIM: Whether the presence of bacteria in the bile or postoperative infections sustained by microorganisms with different levels of drug-resistance are associated with changes in the oncologic prognosis of patients undergoing surgery for pancreatic cancer has not been thoroughly investigated. The aim was to study the association of bile contamination, postoperative infections, and multi-level resistance with long-term outcome. PATIENTS AND METHODS: Prospectively maintained databases were queried for patients who underwent pancreatoduodenectomy (PD). Patients who underwent preoperative biliary stenting prior to PD and an intraoperative bile culture were included. The levels of bacterial resistance of intraoperative bile cultures and of specimens of postoperative infections were stratified into multidrug sensitive (MDS), multidrug-resistant (MDR), and extensive drug-resistant (XDR). RESULTS: A total of 267 patients met the inclusion criteria. The Kaplan-Meier survival curves for overall survival (OS) of patients having no bacteriobilia or positive cultures with MDS versus MDR/XDR bacteria were not statistically different (log-rank=0.9). OS of patients stratified for no postoperative infection or infections by MDS was significantly better than those having MRD/XDR isolates (log-rank=0.04). A Cox multivariate model showed that having MRD/XDR postoperative infections was and independent variable for worse OS (HR=1.227; 95%CI=1.189-1.1918; p=0.036). CONCLUSION: Postoperative drug resistant infections are a significant risk factor for poor OS after pancreatoduodenectomy for ductal adenocarcinoma.

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.

C-reactive protein independently predicts survival in pancreatic neuroendocrine neoplasms.

Pancreatic neuroendocrine neoplasms (pNEN) are highly variable in their postresection survival. Determination of preoperative risk factors is essential for treatment strategies. C-reactive protein (CRP) has been implicated in the pathogenesis of pNEN and shown to be associated with survival in different tumour entities. Patients undergoing surgery for pNEN were retrospectively analysed. Patients were divided into three subgroups according to preoperative CRP serum levels. Clinicopathological features, overall and disease-free survival were assessed. Uni- and multivariable survival analyses were performed. 517 surgically resected pNEN patients were analysed. CRP levels were significantly associated with relevant clinicopathological parameters and prognosis and were able to stratify subgroups with significant and clinically relevant differences in overall and disease-free survival. In univariable sensitivity analyses CRP was confirmed as a prognostic factor for overall survival in subgroups with G2 differentiation, T1/T2 and T3/T4 tumour stages, patients with node positive disease and with and without distant metastases. By multivariable analysis, preoperative CRP was confirmed as an independent predictor of postresection survival together with patient age and the established postoperative pathological predictors grading, T-stage and metastases. Preoperative serum CRP is a strong predictive biomarker for both overall and disease free survival of surgically resected pNEN. CRP is associated with prognosis independently of grading and tumour stage and may be of additional use for treatment decisions.

Evidence Map of Pancreatic Surgery-A living systematic review with meta-analyses by the International Study Group of Pancreatic Surgery (ISGPS).

BACKGROUND: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates. RESULTS: Out of 30,860 articles reviewed, 328 randomized controlled trials on 35,600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%-2%) for partial pancreatoduodenectomy and <1% (99% confidence interval: 0%-1%) for distal pancreatectomy. The benchmark for overall complications was 53% (99%confidence interval: 46%-61%) for partial pancreatoduodenectomy and 59% (99% confidence interval: 44%-80%) for distal pancreatectomy. CONCLUSION: The International Study Group of Pancreatic Surgery Evidence Map of Pancreatic Surgery, which is freely accessible via www.evidencemap.surgery and as a mobile phone app, provides a regularly updated overview of the available literature displayed in an intuitive fashion. Clinical decision making and evidence-based patient information are supported by the primary data provided, as well as by living meta-analyses. Researchers can use the systematic literature search and processed data for their own projects, and funding bodies can base their research priorities on evidence gaps that the map uncovers.

Risk of the Watch-and-Wait Concept in Surgical Treatment of Intraductal Papillary Mucinous Neoplasm.

Importance: The natural history of intraductal papillary mucinous neoplasms (IPMNs) remains uncertain. The inconsistencies among published guidelines preclude accurate decision-making. The outcomes and potential risks of a conservative watch-and-wait approach vs a surgical approach must be compared. Objective: To provide an overview of the surgical management of IPMNs, focusing on the time of resection. Design, Setting, and Participants: This cohort study was conducted in a single referral center; all patients with pathologically proven IPMN who received a pancreatic resection at the institution between October 2001 and December 2019 were analyzed. Preoperatively obtained images and the medical history were scrutinized for signs of progression and/or malignant features. The timeliness of resection was stratified into too early (adenoma and low-grade dysplasia), timely (intermediate-grade dysplasia and in situ carcinoma), and too late (invasive cancer). The perioperative characteristics and outcomes were compared between these groups. Exposures: Timeliness of resection according to the final pathological findings. Main Outcomes and Measures: The risk of malignant transformation at the final pathology. Results: Of 1439 patients, 438 (30.4%) were assigned to the too early group, 504 (35.1%) to the timely group, and 497 (34.5%) to the too late group. Radiological criteria for malignant conditions were detected in 53 of 382 patients (13.9%), 149 of 432 patients (34.5%), and 341 of 385 patients (88.6%) in the too early, timely, and too late groups, respectively (P < .001). Patients in the too early group underwent more parenchyma-sparing resections (too early group, 123 of 438 [28.1%]; timely group, 40 of 504 [7.9%]; too late group, 5 of 497 [1.0%]; P < .001), while morbidity (too early group, 112 of 438 [25.6%]; timely group, 117 of 504 [23.2%]; too late group, 158 of 497 [31.8%]; P = .002) and mortality (too early group, 4 patients [0.9%]; timely, 4 [0.8%]; too late, 13 [2.6%]; P = .03) were highest in the too late group. Of the 497 patients in the too late group, 124 (24.9%) had a previous history of watch-and-wait care. Conclusions and Relevance: Until the biology and progression patterns of IPMN are clarified and accurate guidelines established, a watch-and-wait policy should be applied with caution, especially in IPMN bearing a main-duct component. One-third of IPMNs reach the cancer stage before resection. At specialized referral centers, the risks of surgical morbidity and mortality are justifiable.

Preoperative standardized phase angle at bioimpedance vector analysis predicts the outbreak of antimicrobial-resistant infections after major abdominal oncologic surgery: A prospective trial.

OBJECTIVES: Infectious morbidity is the most common and costly among all surgery-related complications, and infections by multidrug-resistant microorganisms (MDR) are associated with poor outcomes. Derangements of body composition is a recognized risk factor for infections. The aim of this study was to investigate the potential association between specific traits of body composition and the risk of having MDR-related infections. METHODS: This was a prospective study with patients scheduled for major abdominal surgery for gastrointestinal cancer. Bioimpedance vector analysis (BIVA), a reliable tool for body composition assessment, was performed the day before the operation. Postoperative complications were collected focusing on resistance patterns and site of infection. Patterns of resistance were compared with BIVA parameters. RESULTS: Data from 182 patients suffering from pancreatic (n = 76, 41.7%), rectal (n = 38, 20.9%), gastric (n = 31, 17%), or hepatic (n = 37, 20.3%) malignancy were collected. Overall complications occurred in 108 patients (59%), and in 45 patients (28%) bacterial infections were proven at culture. Of these, 15 (8%) were multidrug-sensitive (MDS), 38 MDR, and 2 extended drug-resistant (XDR) infections. The standardized phase angle measured (SPA) at BIVA was significantly lower in the MDR/XDR infections (-0.02 ± 1.20) than for no infection/MDS (0.56 ± 1.53; P = 0.029). A multivariate analysis showed that SPA was the only independent variable for MDR/XDR infections with an odds ratio of 3.057 (95% confidence interval, 1.354-6903; P = 0.007). The predictive ability of SPA revealed an area under the receiver operating characteristic curve of 0.662, with an optimal threshold of -0.3. CONCLUSIONS: In surgical cancer patients, preoperative value of SPA lower than -0.3 is associated with the outbreak of MDR bacterial infections.

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.