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Objective: To develop a prediction model for major morbidity and endocrine dysfunction after central pancreatectomy (CP) which could help in tailoring the use of this procedure., Background: CP is a parenchyma-sparing alternative to distal pancreatectomy for symptomatic benign and premalignant tumors in the body and neck of the pancreas CP lowers the risk of new-onset diabetes and exocrine pancreatic insufficiency compared with distal pancreatectomy but it is thought to increase the risk of short-term complications, including postoperative pancreatic fistula (POPF)., Methods: International multicenter retrospective cohort study including patients from 51 centers in 19 countries (2010-2021). The primary endpoint was major morbidity. Secondary endpoints included POPF grade B/C, endocrine dysfunction, and the use of pancreatic enzymes. Two risk models were designed for major morbidity and endocrine dysfunction utilizing multivariable logistic regression and internal and external validation., Results: A total of 838 patients after CP were included [301 (36%) minimally invasive] and major morbidity occurred in 248 (30%) patients, POPF B/C in 365 (44%), and 30-day mortality in 4 (1%). Endocrine dysfunction in 91 patients (11%) and use of pancreatic enzymes in 108 (12%). The risk model for major morbidity included male sex, age, Body Mass Index, and American Society of Anesthesiologists score ≥3. The model performed acceptably with an area under the curve of 0.72 (CI: 0.68-0.76). The risk model for endocrine dysfunction included higher Body Mass Index and male sex and performed well [area under the curve: 0.83 (CI: 0.77-0.89)]., Conclusions: The proposed risk models help in tailoring the use of CP in patients with symptomatic benign and premalignant lesions in the body and neck of the pancreas (readily available through www.pancreascalculator.com )., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Little is known about the prognostic significance of pancreatic duct (PD) dilation following pancreatoduodenectomy for intraductal papillary mucinous neoplasms (IPMN). Although PD dilation is typically the hallmark radiographic feature of IPMN, other causes of PD dilation exist, including anastomotic stricture, pancreatitis, senescence, and postsurgical passive dilation. Therefore, PD dilation after pancreatoduodenectomy for IPMN represents a diagnostic and management dilemma. The purpose of this study was to evaluate the significance of PD dilation after pancreatoduodenectomy for noninvasive IPMN., Methods: All patients who underwent pancreatoduodenectomy for noninvasive IPMN at nine pancreatic academic centers between 2013 and 2018 were included. Variables were entered prospectively into institutional databases and retrospectively reviewed for the purpose of this study. Dilation of the PD remnant was defined as a duct diameter of ≥5 mm, according to international guidelines., Results: Four-hundred and eighty-one patients were included in this study. The mean age of the patients was 66 years (range 30-90). Patients were surveilled for a median of 4.5 (+/-2.3; max 10.6) years. During follow-up, 132 patients (27.4%) developed PD dilation in the remnant tissue after a median of 3.3 years. Multivariable analysis demonstrated that older age at the time of pancreatoduodenectomy (P=0.01) and longer surveillance duration (P=0.002) were predictors of PD dilation. Interestingly, neither the pathological IPMN subtype (branch-duct vs. main duct/mixed, P=0.96) nor the preoperative PD diameter (P=0.14) was associated with an increased risk of PD dilation in the remnant. During follow-up, IPMN recurrence was suspected in the remaining 72 patients (18.4%), solely because of ductal dilation on cross-sectional imaging in 97% (70/72). Completion pancreatectomy was performed in only 16 patients (3.3%), of whom only four (0.8%) had invasive carcinoma. Three of these four patients had high-grade dysplasia in the original pancreatoduodenectomy specimen, whereas only one had a low-grade dysplastic lesion initially. On multivariable analysis, no variable was predictive of IPMN recurrence in the remnant., Conclusions: New main duct dilation in the pancreatic remnant after pancreatoduodenectomy for IPMN is common, occurring in 27% of the patients. The duration of surveillance is the main factor associated with remnant PD dilation, suggesting that this is likely a physiologic phenomenon. Although recurrence of IPMN in the remnant is often suspected, only 0.8% of patients develop an invasive carcinoma in the pancreatic remnant requiring completion pancreatectomy., Competing Interests: Disclosures and conflicts of interest: None reported., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Small invasive carcinomas arising in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas can present as multiple, small foci. In such cases, there is no clear optimal measurement method for determining the invasive size for tumour staging and prognostication., Methods: In all, 117 small invasive IPMNs (size of largest invasive component ≤2 cm) from seven institutions (2000-2016) were reviewed, and all individual foci of invasive carcinoma were measured. T stages (AJCC 8th edition) based on the largest single focus size (LS), average size of all foci (AS), and total sum of all foci (TS) were examined in association with clinicopathologic parameters and patient outcomes., Results: The cohort comprised IPMNs with invasive tubular-type (n = 82, 70%) and colloid-type (n = 35, 30%) carcinomas. The mean LS, AS, and TS were 0.86, 0.71, and 1.32 cm, respectively. Based on the LS, AS, and TS, respectively, 48, 65, and 39 cases were classified as pT1a; 22, 18, and 11 cases as pT1b; and 47, 34, and 50 cases as pT1c. Higher pT stages based on all measurements were significantly associated with small vessel, large vessel, and perineural invasion (P < 0.05). LS-, AS-, and TS-based pT stages were not significantly associated with recurrence-free survival (RFS) or overall survival (OS) by univariate or multivariate analyses. However, among tubular-type carcinomas, higher LS-, AS-, and TS-based pT stages trended with lower RFS (based on 1-, 3-, and 5-year survival rates). All microscopic measurement methods were most predictive of RFS and OS using a 1.5-cm cutoff, with LS significantly associated with both RFS and OS by univariate and multivariate analysis., Conclusions: For invasive tubular-type carcinomas arising in IPMN, microscopic size-based AJCC pT stages were not significant predictors of patient outcomes. However, for LS, a size threshold of 1.5 cm was optimal for stratifying both RFS and OS. The AJCC 8th ed. may not be applicable for stratifying small invasive IPMNs with colloid-type histology that generally portend a more favourable prognosis., (© 2024 John Wiley & Sons Ltd.)

Objective: To determine if lymph node yield (LNY) is associated with improved overall survival (OS) and time to recurrence (TTR) in patients with node-negative pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant therapy (NAT)., Background: Lymph node yield has been associated with survival in solid gastrointestinal cancers, including PDAC., Methods: Patients with pathological T stage I-III, node-negative (N0), PDAC treated with NAT followed by pancreatoduodenectomy were identified in the Massachusetts General Hospital (MGH) pancreatectomy database and the National Cancer Database (NCDB). A cutoff point of 22 nodes was identified in the NCDB using the point with the optimal (log-rank test) split. Overall survival and TTR were evaluated using univariate and multivariable analyses., Results: In the MGH cohort, 233 node-negative patients following NAT were included. A LNY ≥ 22 was associated with prolonged median OS (59 months vs. 25 months, P<0.001) and prolonged TTR (32 months vs. 14 months, P=0.019). On multivariable analysis, LNY was an independent predictor of survival (HR 0.97, 95% CI 0.95-0.99, P=0.034) per sampled node. In the NCDB, 2,029 node-negative patients following NAT were included. A LNY ≥ 22 was associated with prolonged median OS (49 months vs. 33 months, P<0.001). On multivariable analysis, LNY was an independent predictor of survival (HR 0.99, 95% CI 0.98-0.99, P<0.001) per sampled node., Conclusion: Lymph node yield was associated with improved oncologic outcomes in patients treated with NAT followed by pancreatoduodenectomy in two independent datasets. Responsible mechanisms by which LNY impacts the outcomes of node-negative patients following NAT warrant further exploration., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aims to validate the existence of a microbiome within intraductal papillary mucinous neoplasm (IPMN) that can be differentiated from the taxonomically diverse DNA background of next-generation sequencing procedures., Design: We generated 16S rRNA amplicon sequencing data to analyse 338 cyst fluid samples from 190 patients and 19 negative controls, the latter collected directly from sterile syringes in the operating room. A subset of samples (n=20) and blanks (n=5) were spiked with known concentrations of bacterial cells alien to the human microbiome to infer absolute abundances of microbial traces. All cyst fluid samples were obtained intraoperatively and included IPMNs with various degrees of dysplasia as well as other cystic neoplasms. Follow-up culturing experiments were conducted to assess bacterial growth for microbiologically significant signals., Results: Microbiome signatures of cyst fluid samples were inseparable from those of negative controls, with no difference in taxonomic diversity, and microbial community composition. In a patient subgroup that had recently undergone invasive procedures, a bacterial signal was evident. This outlier signal was not characterised by higher taxonomic diversity but by an increased dominance index of a gut-associated microbe, leading to lower taxonomic evenness compared with the background signal., Conclusion: The 'microbiome' of IPMNs and other pancreatic cystic neoplasms does not deviate from the background signature of negative controls, supporting the concept of a sterile environment. Outlier signals may appear in a small fraction of patients following recent invasive endoscopic procedures. No associations between microbial patterns and clinical or cyst parameters were apparent., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Changes in tumor size and serum carbohydrate antigen 19-9 are commonly reported markers used to assess response to neoadjuvant therapy in pancreatic ductal adenocarcinoma. We evaluated the impact of the percentual tumor size reduction and carbohydrate antigen 19-9 kinetics on resectability and response to neoadjuvant FOLFIRINOX., Methods: This was an institutional analysis of patients with non-metastatic (upfront resectable, borderline resectable, and locally advanced) pancreatic ductal adenocarcinoma who underwent neoadjuvant FOLFIRINOX. Resectability, pathologic response, disease recurrence, and overall survival were evaluated., Results: Among 193 patients who completed FOLFIRINOX, 60% underwent resection, and 91% were R0. Pathologically, complete, and near-complete responses were achieved in 4% and 40% of patients, respectively. Tumor size reduction (odds ratio 1.02 per 1%, P = .024) and normalization of carbohydrate antigen 19-9 (odds ratio 2.61, P = .035) were associated with increased odds of resectability. Concerning pathologic response, tumor size reduction (odds ratio 1.03 per 1%, P = .018) was associated with increased odds of a complete and near-complete response. Lastly, in resected patients, a postoperative increase in carbohydrate antigen 19-9 after prior normalization after neoadjuvant therapy were at an increased risk of recurrence (hazard ratio 9.58, P < .001) and worse survival (hazard ratio 10.4, P < .001) compared to patients who maintained normalization., Conclusion: In patients with non-metastatic pancreatic ductal adenocarcinoma who underwent neoadjuvant therapy, tumor size reduction was a significant predictor of resectability and pathologic response, including complete and near complete responses, whereas serum carbohydrate antigen 19-9 normalization predicted resectability, disease recurrence, and survival. Patients with a postoperative carbohydrate antigen 19-9 rise after prior normalization after administration of neoadjuvant therapy were at an increased risk of recurrence and worse overall survival., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background & Aims: Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance., Methods: International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer., Results: Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WFs and 68 (1.8%) HRS after a median surveillance of 53 (interquartile range 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WFs or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95% CI, 0.23-3.39), and in patients 65 years or older with stable lesions smaller than 15 mm in diameter after 5 years, the SIR was 0.95 (95% CI, 0.11-3.42). The all-cause mortality for patients who did not develop WFs or HRS for at least 5 years was 4.9% (n = 79), and the disease-specific mortality was 0.3% (n = 5)., Conclusions: The risk of developing pancreatic malignancy in presumed BD-IPMN without WFs or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts <30 mm, and in patients 65 years or older who have cysts ≤15 mm., (Copyright © 2023 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Mucinous cystic neoplasms of the pancreas are uncommon tumors that have the potential of becoming cancer. There is no consensus regarding the high-risk features of these tumors. Our study aimed to identify the preoperative demographic, clinical, or radiologic factors that can predict the presence of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas., Methods: We identified 157 patients who underwent resection and fulfilled the pathologic criteria for mucinous cystic neoplasms of the pancreas in a prospectively maintained database spanning 3 decades (1990-2020). Multivariable logistic regression was used to identify predictors of high-grade dysplasia or invasive carcinoma in mucinous cystic neoplasms of the pancreas., Results: The rate of high-grade dysplasia or invasive carcinoma was 11%. Tumor size ≥4 cm (P < .001), mural nodularity (P = .04), and a serum CA 19-9 level >37 U/mL (P < .001) were associated with high-grade dysplasia or invasive carcinoma. In the multivariable analysis, tumor size ≥4 cm (odds ratio 16.9, 95% confidence interval 2.04-140, P = .009) and a CA 19-9 level >37 U/mL (odds ratio 5.68, 95% confidence interval 1.52-21.3, P = .010) were predictors of high-grade dysplasia or invasive carcinoma. There were no tumors with high-grade dysplasia or invasive carcinoma in patients with tumor size <4 cm in the absence of an elevated CA 19-9 or mural nodularity., Conclusion: Tumors with a size ≥4 cm and/or a high CA 19-9 level should be considered for prompt surgical resection. Conversely, tumors <4 cm with no other high-risk features have a negligible risk for high-grade dysplasia or invasive carcinoma and may benefit from nonoperative surveillance. Mural nodularity is an additional suspicious feature. These findings may contribute to future guidelines., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The World Health Organization guidelines did not make a recommendation on use of remdesivir based on disease severity. Little is known regarding effectiveness of remdesivir in critically ill coronavirus disease 2019 (COVID-19) patients. This has led to a state of dilemma for doctors leaving them skeptical of whether they should continue to recommend the drug or not., Materials and Methods: A systematic search adhering to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines was conducted from inception until February 20, 2020. Electronic bibliographic databases (PubMed, Cochrane database, Scopus, Embase) were included. Using dichotomous data for select values, the unadjusted odds ratios (ORs) were calculated applying Mantel Haenszel (M-H) using random-effects model. The primary outcome of interest was all-cause mortality in ventilated and non-ventilated patients., Results: The Remdesivir arm was associated with similar rates of 28-day all-cause mortality (OR: 0.93, 95% confidence interval [CI]: 0.80 - 1.08; P = 0.33). Remdesivir was not found to be favorable for ventilated patients. Non ventilated COVID-19 patients showed a significant lower in-hospital mortality rate as compared with patients requiring mechanical ventilatory support (OR: 6.86, 95% CI: 5.39 - 268.74; P <0.0001)., Conclusion: Non-ventilated patients were associated with significant lower all-cause mortality rates. Prudent use of remdesivir is recommended in critically ill COVID-19 patients., Competing Interests: No conflicts of interest., (Copyright © 2021 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, and The Korean Society for AIDS.)