Absence of a pancreatic microbiome in intraductal papillary mucinous neoplasm.

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.

Incidence and Risk Factors Associated With Chronic Kidney Disease After Liver Transplantation: A Review of a 20-Year Experience at a Single Center.

BACKGROUND: Chronic kidney disease (CKD) is one of the major complications after liver transplantation (LT), with a significant impact on patient outcomes. This study aims to investigate the incidence and risk factors of CKD in LT recipients at Siriraj Hospital over the past 20 years. METHODS: There were 366 adult patients undergoing LT at Siriraj Hospital between January 2002 and December 2021. After excluding patients with pretransplant CKD stages 4 to 5, simultaneous liver-kidney transplantation, and patients who died after LT within 90 days, we retrospectively reviewed a total of 288 patients. Univariable and multivariable binary logistic regression analyses were used to identify the risk factors of post-transplant CKD. RESULTS: Of the 288 patients, 171 (59.4%) developed CKD after LT. The median time to develop CKD was 5.8 months (IQR, 3.8-15.3). Univariable and multivariable analyses revealed that age ≥55 years (odds ratio [OR] = 2.44; 95% CI, 1.34-4.42; P = .003), pretransplant kidney dysfunction defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 (OR = 2.23; 95% CI, 1.16-4.27; P = .016), and postoperative acute kidney injury (OR = 3.06; 95% CI, 1.73-5.42; P < .001) were significantly associated with post-transplant CKD. Patients with preexisting kidney dysfunction who received delayed calcineurin inhibitor introduction without antibody induction protocol had a significantly lower incidence of post-transplant CKD (OR = 0.28; 95% CI, 0.11-0.70; P = .007). CONCLUSIONS: Advanced age, pre-transplant kidney dysfunction, and postoperative acute kidney injury are risk factors for CKD after LT. Importantly, delayed calcineurin inhibitor introduction can protect patients with pretransplant kidney dysfunction from developing post-transplant CKD. These results may have important clinical implications in reducing the incidence of CKD after LT.

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.

Delayed Calcineurin Inhibitor Introduction Without Antibody Induction in Liver Transplantation Is Safe and Helps Preserve Kidney Function.

INTRODUCTION: Acute kidney injury (AKI) is common after liver transplantation and affects outcome after liver transplantation. Antibody induction is commonly used to reduce dose and/or to delay introduction of calcineurin inhibitor (CNI) but is very expensive. We propose a modified immunosuppressive protocol that delays administration of CNI for 48 to 72 hours without antibody induction. This study evaluates the results of our new protocol. MATERIAL AND METHODS: A retrospective case-control study was performed. Study patients had induction with steroid and mycophenolate mofetil without antibody induction, and CNI administration was delayed for 48 to 72 hours. Control patients received CNI and steroid induction without antibody induction, and CNI was continued posttransplant. AKI was defined as an increase in serum creatinine level of at least 1.5 times the pretransplant baseline within the first postoperative week. RESULTS: Sixty liver transplant recipients from 2013 to 2015 were included in this study (30 in the delayed CNI group and 30 in the control group). The patient characteristics and intraoperative factors were comparable in both groups. AKI developed in 11 patients in the study group and in 20 patients in the control group (37% vs 66.7%; P = .02). There was no acute rejection observed in the first month in either group. CONCLUSION: We have demonstrated that delayed CNI introduction without antibody induction is safe and helps preserve kidney function. Antibody induction can be omitted safely in a delayed CNI introduction protocol to reduce the cost of liver transplantation without increasing the risk of acute rejection.