Prognostic impact of resection margin status on survival after neoadjuvant treatment for pancreatic cancer: systematic review and meta-analysis.

BACKGROUND: A greater than 1 mm tumour-free resection margin (R0 >1 mm) is a prognostic factor in upfront-resected pancreatic ductal adenocarcinoma. After neoadjuvant treatment (NAT); however, the prognostic impact of resection margin (R) status remains controversial. METHODS: Randomised and non-randomised studies assessing the association of R status and survival in resected pancreatic ductal adenocarcinoma after NAT were sought by systematic searches of MEDLINE, Web of Science and CENTRAL. Hazard ratios (HR) and their corresponding 95% CI were collected to generate log HR using the inverse-variance method. Random-effects meta-analyses were performed and the results presented as weighted HR. Sensitivity and meta-regression analyses were conducted to account for different surgical procedures and varying length of follow-up, respectively. RESULTS: Twenty-two studies with a total of 4929 patients were included. Based on univariable data, R0 greater than 1 mm was significantly associated with prolonged overall survival (OS) (HR 1.76, 95% CI 1.57-1.97; P<0.00001) and disease-free survival (DFS) (HR 1.66, 95% CI 1.39-1.97; P<0.00001). Using adjusted data, R0 greater than 1 mm was significantly associated with prolonged OS (HR 1.65, 95% CI 1.39-1.97; P<0.00001) and DFS (HR 1.76, 95% CI 1.30-2.39; P=0.0003). Results for R1 direct were comparable in the entire cohort; however, no prognostic impact was detected in sensitivity analysis including only partial pancreatoduodenectomies. CONCLUSION: After NAT, a tumour-free margin greater than 1 mm is independently associated with improved OS as well as DFS in patients undergoing surgical resection for pancreatic cancer.

The Revised R Status is an Independent Predictor of Postresection Survival in Pancreatic Cancer After Neoadjuvant Treatment.

OBJECTIVE: To investigate the oncological outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) who had an R 0 or R 1 resection based on the revised R status (1 mm) after neoadjuvant therapy (NAT). BACKGROUND: The revised R status is an independent prognostic factor in upfront-resected PDAC; however, the significance of 1 mm margin clearance after NAT remains controversial. METHODS: Patients undergoing pancreatectomy after NAT for PDAC were identified from 2 prospectively maintained databases. Clinicopathological and survival data were analyzed. The primary outcomes were overall survival (OS), recurrence-free survival (RFS), and pattern of recurrence in association with R 0 >1 mm and R 1 ≤1 mm resections. RESULTS: Three hundred fifty-seven patients with PDAC were included after NAT and subsequent pancreatic resection. Two hundred eight patients (58.3%) received FOLFIRINOX, 41 patients (11.5%) received gemcitabine-based regimens, and 299 individuals (83.8%) received additional radiotherapy. R 0 resections were achieved in 272 patients (76.2%) and 85 patients (23.8%) had R 1 resections. Median OS after R 0 was 41.0 months, compared with 20.6 months after R 1 resection ( P = 0.002), and even longer after additional adjuvant chemotherapy ( R 0 44.8 vs R1 20.1 months; P = 0.0032). Median RFS in the R 0 subgroup was 17.5 months versus 9.4 months in the R 1 subgroup ( P < 0.0001). R status was confirmed as an independent predictor for OS ( R 1 hazard ratio: 1.56, 95% CI: 1.07-2.26) and RFS ( R 1 hazard ratio: 1.52; 95% CI: 1.14-2.0). In addition, R 1 resections were significantly associated with local but not distant recurrence ( P < 0.0005). CONCLUSIONS: The revised R status is an independent predictor of postresection survival and local recurrence in PDAC after NAT. Achieving R 0 resection with a margin of at least 1 mm should be a primary goal in the surgical treatment of PDAC after NAT.

Prevalence and long-term implications of preoperative anemia in patients undergoing elective general surgery: a retrospective cohort study at a university hospital.

OBJECTIVE: The aim of this retrospective study was to assess the prevalence of anaemia in a cohort of patients undergoing elective general surgery at a university hospital. Furthermore, the authors investigated the influence of anaemia on short-term and long-term postoperative outcome. BACKGROUND: Awareness of the negative impact of preoperative anaemia on perioperative morbidity and mortality is rising. Anaemia is a potentially modifiable factor, and its therapy might improve patient outcome in elective surgery. Nevertheless, patients with preoperative anaemia frequently undergo elective surgery without receiving adequate preoperative treatment. METHODS: In this single-centre cohort study, the authors analyzed 6908 adult patients who underwent elective general surgery. Patients undergoing day-clinic surgery were excluded. In all patients, preoperative haemoglobin concentration and haematocrit was available. RESULTS: Of all patients analyzed, 32.9% were anaemic (21.0% mild, 11.8% moderate, 1.1% severe). Median time to last follow-up was 5.2 years. During the whole study period, 27.1% of patients died (1.2% died during the hospital stay); median time to death was 1.3 years. Patients with preoperative anaemia had significantly higher mortality rates ( P <0.001) and a higher probability of postoperative complications ( P <0.001). Likewise, receiving blood transfusions was associated with a higher risk of death ( P <0.001). CONCLUSION: This retrospective single-centre analysis confirmed that preoperative anaemia is common, and is a significant risk factor for unfavourable postoperative outcome. As anaemia is a modifiable risk factor, the implementation of a patient blood management concept is crucial to reduce detrimental postoperative events associated with anaemia.

Smoking impairs the effect of neoadjuvant FOLFIRINOX on postresection survival in pancreatic cancer.

INTRODUCTION: Smoking plays an important role in carcinogenesis, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about the association between smoking status and prognosis in resected PDAC. METHODS: All patients who underwent resection for PDAC were identified from two prospective institutional databases. Clinicopathologic data as well as demographics including smoking status were extracted. Survival analysis and multivariable Cox regression modelling was performed. Restricted cubic splines were used for linear data to define cut-off points. RESULTS: Out of 848 patients, 357 (42.1%) received neoadjuvant treatment (NAT), 491 upfront resection (57.9%), and 475 (56%) adjuvant therapy. The median overall survival (OS) was 27.8 months, 36.1 months, and 23.0 months for the entire cohort, after NAT and upfront resection. 464 patients were never smokers (54.7%), 250 former smokers (29.5%), and 134 active smokers (15.8%). In the multivariable model, the interaction of neoadjuvant FOLFIRINOX and active smoking was associated with the highest risk for decreased OS (harzard ratio (HR) 2.35; 95% confidence interval 1.13-4.90) and strongly mitigated the benefit of FOLFIRNOX (HR 0.40; 95% CI 0.25-0.63). Adjusted median OS in NAT patients with FOLFIRINOX was not reached for never and former smokers, compared to 26.2 months in active smokers. Based on the model, a nomogram was generated to illustrate the probability of 5-year survival after PDAC resection. CONCLUSION: The present study confirms that neoadjuvant FOLFIRINOX is associated with excellent survival and demonstrates that active smoking reduces its benefit. The nomogram can assist in daily clinical practice and emphasises the importance of smoking cessation in patients with PDAC, especially prior to NAT with FOLFIRINOX.

Prognostic significance of mean corpuscular volume in patients with pancreatic ductal adenocarcinoma and multimodal treatment.

AIM OF THE STUDY: Mean corpuscular volume (MCV) has shown mounting evidence as a prognostic indicator in a number of malignancies. The aim of this study was to examine the prognostic potential of pretherapeutic MCV among patients with pancreatic ductal adenocarcinoma (PDAC) who underwent upfront resection or resection after neoadjuvant treatment (NT). PATIENTS AND METHODS: Consecutive patients with PDAC who underwent pancreatic resection between 1997 and 2019 were included in this study. Neoadjuvantly treated patients' serum MCV was measured before NT and before surgery. In patients undergoing upfront resection serum MCV was measured before surgery. Median MCV values were used as cut-off to distinguish high from low MCV values. RESULTS: Five hundred and forty-nine (438 upfront resected and 111 neoadjuvantly treated) patients were included in this study. Multivariate analysis revealed, that high MCV before and after NT, were independent negative prognostic factors for overall survival (P<0.01, respectively). Furthermore, the median MCV value from before to after NT increased significantly (P<0.001, Wilcoxon signed-rank test) and was (P=0.03, Wilcoxon rank sum test) associated with tumor response to NT. CONCLUSION: High MCV is an independent adverse prognostic factor in patients with resectable neoadjuvantly treated PDAC and may qualify as useful indicator to help physicians to provide personalized prognostication.

FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

Long-Term Follow-Up after Surgery for Chronic Pancreatitis: A Bicentric Retrospective Experience.

INTRODUCTION: The impact of surgery on nutritional status, pancreatic function, and symptoms of patients affected by chronic pancreatitis (CP) has not been unequivocally determined. This study aimed to evaluate clinical follow-up after surgery for CP in an Italian-Austrian population. MATERIALS AND METHODS: Patients operated for CP at two high-volume centers between 2000 and 2018 were analyzed. The following parameters were compared between the pre- and postoperative period: nutritional status, endocrine and exocrine pancreatic functions, and chronic pain. RESULTS: Overall, 186 patients underwent surgery for CP. Among these, 68 (40%) answered a specific follow-up questionnaire. The body mass index showed a significant increase between pre- and postoperative assessments (21.1 vs. 22.5 p = 0.003). Furthermore, a 60% decrease in the prevalence of chronic pain (81 vs. 21%, p < 0.001) was observed. On the contrary, both exocrine and endocrine pancreatic functions pointed toward a worsening after surgery, with consistent higher rates of patients presenting with diabetes mellitus, as well as patients requiring insulin therapy and oral intake of pancreatic enzymes. The analysis of body composition performed on 40 (24%) patients with a complete imaging pack revealed no significant change in the nutritional status after surgery. DISCUSSION/CONCLUSION: Despite the good results observed in terms of pain relief, the surgical approach led to a consistent worsening of the global pancreatic function. No significant influence of surgery on the nutritional status of patients was detected.

Surgery for chronic pancreatitis: the comparison of two high-volume centers reveals lack of a uniform operative management.

PURPOSE: Many aspects of surgical therapy for chronic pancreatitis (CP), including the correct indication and timing, as well as the most appropriate operative techniques, are still a matter of debate in the surgical community and vary widely across different centers. The aim of the present study was to uncover and analyze these differences by comparing the experiences of two specialized surgical units in Italy and Austria. METHODS: All patients operated for CP between 2000 and 2018 at the two centers involved were included in this retrospective analysis. Data regarding the clinical history and the pre- and perioperative surgical course were analyzed and compared between the two institutions. RESULTS: Our analysis showed a progressive decrease in the annual rate of pancreatic surgical procedures performed for CP in Verona (no. = 91) over the last two decades (from 3% to less than 1%); by contrast, this percentage increased from 3 to 9% in Vienna (no. = 77) during the same time frame. Considerable differences were also detected with regard to the timing of surgery from the first diagnosis of CP - 4 years (IQR 5.5) in the Austrian series vs two (IQR 4.0) in the Italian series -, and of indications for surgery, with a 12% higher prevalence of groove pancreatitis among patients in the Verona cohort. CONCLUSION: The comparison of the surgical attitude towards CP between two surgical centers proved that a consistent approach to this pathology still is lacking. The identification of common guidelines and labels of surgical eligibility is advisable in order to avoid interinstitutional treatment disparities.

[Surgery for periampullary pancreatic cancer]. / Chirurgie periampullärer Pankreaskarzinome.

Periampullary neoplasms are a heterogeneous group of different tumor entities arising from the periampullary region, of which pancreatic ductal adenocarcinoma (PDAC) is the most common subgroup with 60-70%. As typical for pancreatic adenocarcinomas, periampullary pancreatic cancer is characterized by an aggressive growth and early systemic progression. Due to the anatomical location in close relationship to the papilla of Vater symptoms occur at an earlier stage of the disease, so that treatment options and prognosis are overall more favorable compared to pancreatic carcinomas at other locations. Nevertheless, the principles of treatment for periampullary pancreatic cancer are not substantially different from the standards for pancreatic cancer at other locations. A potentially curative approach for non-metastatic periampullary pancreatic cancer is a multimodal therapy concept, which includes partial pancreatoduodenectomy as a radical oncological resection in combination with a systemic adjuvant chemotherapy. As a result, long-term survival can be achieved in patients with favorable prognostic factors. In addition, with the continous development of surgery and systemic treatment potentially curative treatment concepts for advanced initially nonresectable tumors were also established, after completion of neoadjuvant treatment. This article presents the current surgical principles of a radical oncological resection for periampullary pancreatic cancer in the context of a multimodal treatment concept with an outlook for future developments of treatment.

Correction: Sarcopenia and sarcopenic obesity are independent adverse prognostic factors in resectable pancreatic ductal adenocarcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0215915.].

Correction to: The Prognostic Index Independently Predicts Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Resection.

In the original article there are errors in the authors' affiliations.

The Prognostic Index Independently Predicts Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Resection.

BACKGROUND: Cancer-related inflammation is associated with tumour proliferation, maintenance and dissemination. It therefore impacts pancreatic cancer survival. The goal of this study was to examine the Prognostic Index (PI) as a prognostic biomarker for survival in patients with pancreatic ductal adenocarcinoma (PDAC). In addition, we explored factors known to interact with the immune and inflammation cascade that might interfere with the PI's strength for prognostication. METHODS: Patients with PDAC undergoing resection were analysed retrospectively. The PI was calculated from preoperatively derived C-reactive protein levels and white blood count. Data were subject to correlation and survival analysis. RESULTS: Of 357 patients, 235 (65.8%) patients had a PI 0, 108 (30.3%) PI 1, and 14 (3.9%) PI 2. Median (quartiles) survival with a high PI (group 1 + 2) was 13.2 months (7.7-27.0), compared with 18.7 months (10.2-35.4) with a low PI (group 0; p = 0.012). The PI proved to be an independent prognostic factor for cancer-specific survival (p = 0.003) adjusted for conventional prognostic factors. Prognostic strength was influenced by the presence of a bile stent (p = 0.032). CONCLUSIONS: The PI is a strong and solid independent prognostic tool for survival in patients with PDAC undergoing resection. Preoperative survey of inflammatory activity as provided by the use of a biomarker like the PI may help to identify those patients at risk of a poor prognosis.

Systemic Immune-Inflammation Index (SII) Predicts Poor Survival in Pancreatic Cancer Patients Undergoing Resection.

BACKGROUND: The systemic immune-inflammation index based on peripheral neutrophil, lymphocyte, and platelet counts has shown a prognostic impact in several malignancies. The aim of this study was to determine the prognostic role of systemic immune-inflammation index in patients with pancreatic ductal adenocarcinoma undergoing resection. METHODS: Consecutive patients who underwent surgical resection at the department of surgery at the Medical University of Vienna between 1995 and 2014 were included into this study. The systemic immune-inflammation index was calculated by the formula platelet*neutrophil/lymphocyte. Optimal cutoffs were determined using Youden's index. Uni- and multivariate analyses were calculated by the Cox proportional hazard regression model for overall survival. RESULTS: Three hundred twenty-one patients were included in this study. Clinical data was achieved from a prospective patient database. In univariate survival analysis, elevated systemic immune-inflammation index was found to be significantly associated with shortened patients' overall survival (p = 0.007). In multivariate survival analysis, systemic immune-inflammation index remained an independent prognostic factor for overall survival (p = 0.004). No statistical significance could be found for platelet to lymphocyte ratio and neutrophil to lymphocyte ratio in multivariate analysis. Furthermore, area under the curve analysis showed a higher prognostic significance for systemic immune-inflammation index, compared to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio. CONCLUSION: A high systemic immune-inflammation index is an independent, preoperative available prognostic factor in patients with resectable pancreatic ductal adenocarcinoma and is superior to platelet to lymphocyte ratio and neutrophil to lymphocyte ratio for predicting overall survival in pancreatic ductal adenocarcinoma patients.

Sarcopenia and sarcopenic obesity are independent adverse prognostic factors in resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are on the rise. Sarcopenia and sarcopenic obesity have proven to be prognostic factors in different types of cancers. In the context of previous findings, we evaluated the impact of body composition in patients undergoing surgery in a national pancreatic center. METHODS: Patient's body composition (n = 133) was analyzed on diagnostic CT scans and defined as follows: Skeletal muscle index ≤38.5 cm2/m2 (women), ≤52.4 cm2/m2 (men); obesity was classified as BMI ≥25kg/m2. RESULTS: Sarcopenia showed a negative impact on overall survival (OS; 14 vs. 20 months, p = 0.016). Sarcopenic patients suffering from obesity showed poorer OS compared to non-sarcopenic obese patients (14 vs. 23 months, p = 0.007). Both sarcopenia and sarcopenic obesity were associated with sex (p<0.001 and p = 0.006; males vs. females 20% vs. 38% and 12% vs. 38%, respectively); sarcopenia was further associated with neoadjuvant treatment (p = 0.025), tumor grade (p = 0.023), weight loss (p = 0.02) and nutritional depletion (albumin, p = 0.011) as well as low BMI (<25 kg/m2, p = 0.038). Sarcopenic obese patients showed higher incidence of major postoperative complications (p<0.001). In addition, sarcopenia proved as an independent prognostic factor for OS (p = 0.031) in the multivariable Cox Regression model. CONCLUSION: Patients with sarcopenia and sarcopenic obesity undergoing resection for PDAC have a significantly shorter overall survival and a higher complication rate. The assessment of body composition in these patients may provide a broader understanding of patients' individual condition and guide specific supportive strategies in patients at risk.

Long-term Risk of Pancreatic Malignancy in Patients With Branch Duct Intraductal Papillary Mucinous Neoplasm in a Referral Center.

BACKGROUND & AIMS: Little is known about the development of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). We evaluated long-term outcomes of a large cohort of patients with BD-IPMNs to determine risk of malignancy and define a subset of low-risk BD-IPMNs. METHODS: We performed a retrospective analysis of data from 577 patients with suspected or presumed BD-IPMN under surveillance at the Massachusetts General Hospital. Patients underwent cross-sectional imaging analysis at 3 months or later after their initial diagnosis. The diagnosis of BD-IPMN was based on the presence of unilocular or multilocular cysts of the pancreas and a non-dilated main pancreatic duct (<5 mm). We collected demographic, clinical, and pathology data. Cysts were characterized at the time of diagnosis and during the follow-up period. Follow-up duration was time between initial cyst diagnosis and date of last visit or death for patients without development of pancreatic cancer, date of surgery for patients with histologically confirmed malignancy, or date of first discovery of malignancy by imaging analysis for patients with unresectable tumors or who underwent neoadjuvant treatment before surgery. The primary outcome was risk of malignancy, with a focus on patients followed for 5 years or more, compared with that of the US population, based on standardized incidence ratio. RESULTS: Of the 577 patients studied, 479 (83%) were asymptomatic at diagnosis and 363 (63%) underwent endoscopic ultrasound at least once. The median follow-up time was 82 months (range, 6-329 months) for the entire study cohort; 363 patients (63%) underwent surveillance for more than 5 years, and 121 (21%) for more than 10 years. Malignancies (high-grade dysplasia or invasive neoplasm) developed after 5 years in 20 of 363 patients (5.5%), and invasive cancer developed in 16 of 363 patients (4.4%). The standardized incidence ratio for patients with BD-IPMNs without worrisome features of malignancy at 5 years was 18.8 (95% confidence interval, 9.7-32.8; P < .001). One hundred and eight patients had cysts ≤1.5 cm for more than 5 years of follow-up; only 1 of these patients (0.9%) developed a distinct ductal adenocarcinoma. By contrast, among the 255 patients with cysts >1.5 cm, 19 (7.5%) developed malignancy (P = .01). CONCLUSIONS: In a retrospective analysis of patients with BD-IPMNs under surveillance, their overall risk of malignancy, almost 8%, lasted for 10 years or more, supporting continued surveillance after 5 years. Cysts that remain ≤1.5 cm for more than 5 years might be considered low-risk for progression to malignancy.

Discordance Between Perioperative Antibiotic Prophylaxis and Wound Infection Cultures in Patients Undergoing Pancreaticoduodenectomy.

IMPORTANCE: Wound infections after pancreaticoduodenectomy (PD) are common. The standard antibiotic prophylaxis given to prevent the infections is often a cephalosporin. However, this decision is rarely guided by microbiology data pertinent to PD, particularly in patients with biliary stents. OBJECTIVE: To analyze the microbiology of post-PD wound infection cultures and the effectiveness of institution-based perioperative antibiotic protocols. DESIGN, SETTING, AND PARTICIPANTS: The pancreatic resection databases of 3 institutions (designated as institutions A, B, or C) were queried on patients undergoing PD from June 1, 2008, to June 1, 2013, and a total of 1623 patients were identified. Perioperative variables as well as microbiology data for intraoperative bile and postoperative wound cultures were analyzed from June 1, 2008, to June 1, 2013. INTERVENTIONS: Perioperative antibiotic administration. MAIN OUTCOMES AND MEASURES: Wound infection microbiology analysis and resistance patterns. RESULTS: Of the 1623 patients who underwent PD, 133 with wound infections (8.2%) were identified. The wound infection rate did not differ significantly across the 3 institutions. The predominant perioperative antibiotics used at institutions A, B, and C were cefoxitin sodium, cefazolin sodium with metronidazole, and ampicillin sodium-sulbactam sodium, respectively. Of the 133 wound infections, 89 (67.1%) were deep-tissue infection, occurring at a median of 8 (range, 1-57) days after PD. A total of 53 (40.0%) of the wound infections required home visiting nurse services on discharge, and 73 (29.1%) of all PD readmissions were attributed to wound infection. Preoperative biliary stenting was the strongest predictor of postoperative wound infection (odds ratio, 2.5; 95% CI, 1.58-3.88; P = .03). There was marked institutional variation in the type of microorganisms cultured from both the intraoperative bile and wound infection cultures (Streptococcus pneumoniae, 114 cultures [47.9%] in institution A vs 3 [4.5%] in institution B; P = .001) and wound infection cultures (predominant microorganism in institution A: Enterococcus faecalis, 18 cultures [51.4%]; institution B: Staphylococcus aureus, 8 [43.9%]; and institution C: Escherichia coli, 17 [36.2%], P = .001). Similarly, antibiotic resistance patterns varied (resistance pattern in institution A: cefoxitin, 29 cultures [53.1%]; institution B: ampicillin-sulbactam, 9 [69.2%]; and institution C: penicillin, 32 [72.7%], P < .001). Microorganisms isolated in intraoperative bile cultures were similar to those identified in wound cultures in patients with post-PD wound infections. CONCLUSIONS AND RELEVANCE: The findings of this large-scale, multi-institutional study indicate that intraoperative bile cultures should be routinely obtained in patients who underwent preoperative endoscopic retrograde cholangiopancreatography since the isolated microorganisms closely correlate with those identified on postoperative wound cultures. Institution-specific internal reviews should amend current protocols for antibiotic prophylaxis to reduce the incidence of wound infections following PD.

Preoperative biliary drainage does not increase major complications in pancreaticoduodenectomy: a large single center experience from the Massachusetts General Hospital.

BACKGROUND: The impact of preoperative biliary drainage (PBD) on perioperative morbidity and mortality in pancreatic surgery is still under debate. The aim of this study was to investigate outcomes of stented vs. non-stented patients undergoing pancreatoduodenectomy (PD). METHODS: We retrospectively compared 500 consecutive patients who underwent PBD prior to PD with 500 patients who did not. Ninety-day mortality and morbidity were assessed. RESULTS: The overall postoperative morbidity and mortality was 37% and 1.4%, respectively. Major complications (Clavien ≥ III) occurred in 16% of patients. The overall morbidity and mortality was not significantly higher in patients who underwent PBD. However, the rate of wound infection was significantly higher in patients who underwent PBD (19% vs. 9%, P = 0.001). When comparing intraoperative bile cultures of stented patients with and without wound infection, the presence of Enterobacter species (OR 2.4, 95% CI 1.5-4.1, P = 0.001) and Citrobacter species (OR 2.3, 95% CI 1.1-5.2, P = 0.037) in the bile significantly increased the likelihood of wound infection. CONCLUSION: Preoperative biliary drainage is associated with bactobilia and wound infection, but does not affect the overall morbidity and mortality of patients undergoing PD.

Intraductal papillary mucinous neoplasms.

PURPOSE OF REVIEW: Our understanding of intraductal papillary mucinous neoplasm (IPMN) of the pancreas has remarkably grown within the last decade; nonetheless there is still an ongoing controversy if the majority of these potentially malignant neoplasms need to be resected or if observation in a subset is well tolerated. RECENT FINDINGS: Novel cyst fluid biomarkers, like Gnas mutations or mab DAS-1, could play a pivotal role in the distinction of IPMN vs. other cystic lesions, in the sub-classification of IPMN and in the detection of IPMN with high-grade dysplasia or invasive cancer. Other recent studies focused on natural history of minimal- and extensive-mixed IPMN and the safety of the 2012 AIP guidelines. Small series also described that observation can be an option in selected frail patients with MD-IPMN. Further, data from a large European multicenter study analysis indicated that patients with IPMN do not have an increased frequency of extrapancreatic malignancies. SUMMARY: Increasing knowledge about the nature of IPMN and their subtypes has resulted in an individualized approach in diagnosis and treatment. Owing to the availability of accurate diagnostic instruments, timing and indication for pancreatic resection have become more selective, sparing patients with harmless IPMN from major surgery.

Effects of Comorbidities on Outcomes of Patients With Intraductal Papillary Mucinous Neoplasms.

BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas occur mostly in older individuals. Individual life expectancy and risk of death from other factors must be carefully considered in analyzing the risks that IPMNs pose. We investigated whether there is a subset of patients with IPMNs and a high risk of dying from other causes who would not benefit from pancreatic surgery. METHODS: We collected data from 725 patients at Massachusetts General Hospital who underwent resection or have been under observation for IPMNs from 1992 through 2012. Comorbidities were classified according to the age-adjusted Charlson comorbidity index (CACI). Causes of death were recorded, and survival data were analyzed by the Kaplan-Meier method. RESULTS: The patients' median CACI score was 3; 10% of patients had CACI of 7 or more. Of the entire cohort, 55% underwent resection, and the remaining 45% have been under observation. After a median follow-up period of 5 years, 177 patients died (24%, 55% of deaths within 5 years of diagnosis); 78% of deaths were not related to IPMNs. The median survival time for all patients with CACI score of 7 or more was 43 months. Multivariate regression analysis revealed that the chance of non-IPMN-related death within 3 years of diagnosis is 11-fold higher for patients with CACI score of 7 or more than for patients with lower scores. CONCLUSIONS: The CACI can be used to identify patients with a high risk of death from factors other than IPMNs within a few years after diagnosis. These patients are therefore not likely to benefit from further IPMN observation or pancreatic resection.