Indications, Techniques, and Barriers for Pancreas Transplant Biopsy: A Consensus Perspective From a Survey of US Centers.

BACKGROUND: Pancreas transplant biopsy practices for the diagnosis of rejection or other pathologies are not well described. METHODS: We conducted a survey of staff at US pancreas transplant programs (March 22, 2022, to August 22, 2022) to assess current program practices and perceptions about the utility and challenges in the performance and interpretation of pancreas allograft biopsies. RESULTS: Respondents represented 65% (76/117) of active adult pancreas transplant programs, capturing 66% of recent pancreas transplant volume in the United States. Participants were most often nephrologists (52%), followed by surgeons (46%), and other staff (4%). Pancreas allograft biopsies were performed mostly by interventional radiologists (74%), followed by surgeons (11%), nephrologists (8%), and gastroenterologists (1%). Limitations in the radiologist's or biopsy performer's comfort level or expertise to safely perform a biopsy, or to obtain sufficient/adequate samples were the two most common challenges with pancreas transplant biopsies. Pancreas transplant biopsies were read by local pathologists at a majority (86%) of centers. Challenges reported with pancreas biopsy interpretation included poor reliability, lack of reporting of C4d staining, lack of reporting of rejection grading, and inconclusive interpretation of the biopsy. Staff at a third of responding programs (34%) stated that they rarely or never perform pancreas allograft biopsies and treat presumed rejection empirically. CONCLUSIONS: This national survey identified significant variation in clinical practices related to pancreas allograft biopsies and potential barriers to pancreas transplant utilization across the United States. Consideration of strategies to improve program experience with percutaneous pancreas biopsy and to support optimal management of pancreas allograft rejection informed by histology is warranted.

Intraductal papillary mucinous neoplasm of the intrahepatic bile duct: a review of literature and a rare case report.

Background: Intraductal papillary neoplasm of the bile duct is a rare variant of bile duct tumors, which is characterized by papillary or villous growth inside the bile duct. Having papillary and mucinous features such as those found in pancreatic intraductal papillary mucinous neoplasm (IPMN) is extremely rare. We report a rare case of intraductal papillary mucinous neoplasm of the intrahepatic bile duct. Case report: A 65-year-old male Caucasian with multiple comorbidities presented to the emergency room with moderate constant pain at the right upper quadrant (RUQ) abdomen for the last several hours. On physical examination, he was found to have normal vital signs, with icteric sclera and pain on deep palpation at the RUQ region. His laboratory results were significant for jaundice, elevated liver function tests and creatinine, hyperglycemia, and leukocytosis. Multiple imaging studies revealed a 5 cm heterogeneous mass in the left hepatic lobe that demonstrated areas of internal enhancement, mild gall bladder wall edema, dilated gall bladder with mild sludge, and 9 mm common bile duct (CBD) dilatation without evidence of choledocholithiasis. He underwent a CT-guided biopsy of this mass, which revealed intrahepatic papillary mucinous neoplasm. This case was discussed at the hepatobiliary multidisciplinary conference, and the patient underwent an uneventful robotic left partial liver resection, cholecystectomy, and lymphadenectomy. Conclusion: IPMN of the biliary tract may represent a carcinogenesis pathway different from that of CBD carcinoma arising from flat dysplasia. Complete surgical resection should be performed whenever possible because of its significant risk of harboring invasive carcinoma.

Role of Serum (1,3)-Β-D-Glucan to Screen for Pneumocystis Pneumonia in Kidney Transplant Recipients.

BACKGROUND: Pneumocystis pneumonia is a common opportunistic infection in kidney transplant recipients caused by the ascomycetous fungi Pneumocystis jirovecii. Its clinical presentation of a progressive nonproductive cough, shortness of breath, and fever is nonspecific and often delays diagnosis and appropriate treatment. Moreover, the plain radiograph may show a spectrum of findings from normal to bilateral diffuse infiltrates. Detection of serum (1,3)-ß-D-glucan along with consistent clinical findings can be used as early screening tools to diagnose and initiate treatment for Pneumocystis pneumonia pending confirmation by bronchoscopy. METHODS: This case series describes 6 kidney transplant recipients who were diagnosed as having Pneumocystis pneumonia. The baseline demographic variables, presenting symptoms, radiographic findings, laboratory findings including lactate dehydrogenase and serum (1,3)-ß-D-glucan levels, bronchoscopy findings, and its timing in relation to a positive serum (1,3)-ß-D-glucan test, and response to treatment were collected. RESULTS: All 6 patients who completed the first 3 months of prophylaxis against Pneumocystis pneumonia with sulfamethoxazole-trimethoprim were diagnosed as having Pneumocystis pneumonia between 2 to 24 years post transplant. They initiated treatment early based on a positive serum (1,3)-ß-D-glucan and negative Histoplasma antigen and serum galactomannan test with a presumptive diagnosis of Pneumocystis pneumonia, which was later confirmed with a positive polymerase chain reaction on bronchoalveolar lavage fluid. CONCLUSIONS: Pneumocystis pneumonia is a common opportunistic fungal infection in immunosuppressed kidney transplant recipients, and use of serum (1,3)-ß-D-glucan can be used as an initial screening test for its early diagnosis and treatment.

Cholestatic liver diseases: An era of emerging therapies.

Recently the field of cholestasis has expanded enormously reflecting an improved understanding of the molecular mechanisms underlying bile secretion and its perturbation in chronic cholestatic disease. Novel anti-cholestatic therapeutic options have been developed for patients not favorably responding to ursodeoxycholic acid (UDCA), the current standard treatment for cholestatic liver disease. Important novel treatment targets now also include nuclear receptors involved in bile acid (BA) homoeostasis like farnesoid X receptor and G protein-coupled receptors e.g., the G-protein-coupled BA receptor "transmembrane G coupled receptor 5". Fibroblast growth factor-19 and enterohepatic BA transporters also deserve attention as additional drug targets as does the potential treatment agent norUDCA. In this review, we discuss recent and future promising therapeutic agents and their potential molecular mechanisms in cholestatic liver disorders.

Incidental liver metastasis in pancreatic adenocarcinoma.

Exocrine cancer of pancreas is the fourth leading cause of death in the USA among both men and women. Contrast enhanced multidetector-row computer tomography (MDCT) is the current modality of choice for the detection of distant metastasis in pancreatic cancer as a part of pre-operative workup, which helps decide on resectability. Authors present a first ever reported case of an incidental liver metastasis found on intra-operative wedge hepatic biopsy during Whipple's procedure for pancreatic cancer. This pancreatic cancer was initially thought to be resectable based on MDCT staging per guidelines. The case highlights the importance of diagnostic staging laparoscopy and neoadjuvant chemotherapy before resecting pancreatic adenocarcinoma.

Influence of facility type on survival outcomes after pancreatectomy for pancreatic adenocarcinoma.

INTRODUCTION: Although a volume-outcome relationship has been well established for pancreatectomy, little is known about differences in mortality by facility type. The objective of this study is to evaluate the impact of facility type on short-term and long-term survival outcomes for patients with pancreatic adenocarcinoma who underwent pancreatectomy and identify determinants of overall survival (OS). METHODS: A cohort of 33,382 patients with Stage I-III pancreatic adenocarcinoma diagnosed between 1998 and 2011 were evaluated from the National Cancer Data Base. Clinicopathological, sociodemographic and treatment variables were compared among three facility types where patients received resection: (i) community cancer program (CCP), (ii) comprehensive community cancer program (CCCP), and (iii) academic research program (ARP). 5-year OS was calculated using the Kaplan-Meier method. RESULTS: Despite ARP having significantly higher percentage of poorly differentiated tumors, higher T-stage tumors, more positive lymph nodes, and greater circle distance compared to the other facilities, it had the highest 5-yr OS. The 5-yr OS for CCP, CCCP, and ARP was 11.2%, 13.2%, and 16.6%, respectively (P < 0.0001) and the median survival time (months) was 12.4, 15.6 and 19.1, respectively. CONCLUSION: Patients receiving pancreatic resection at an ARP yielded a higher 5-year OS compared to CCP or CCCP.

Kidney outcomes in patients with liver cirrhosis and chronic kidney disease receiving an orthotopic liver transplant alone.

Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD-6 estimated glomerular filtration rate (e-GFR) <40 mL/min/1.73 m2 for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver-kidney transplant (SLKT; n=5). Pretransplant, patients with LTA compared with SLKT had lower serum creatinine (2.5±0.73 vs 4.6±0.52 mg/dL, P=.001), higher MDRD-6 e-GFR (21.0±7.2 vs 10.3±2.0 mL/min/1.73 m2 , P=.002), higher 24-hour urine creatinine clearance (34.2±8.8 vs 18.0±2.2 mL/min, P=.002), lower proteinuria (133.2±117.7 vs 663±268.2 mg/24 h, P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post-LTA, the e-GFR (mL/min/1.73 m2 ) increased in all nine patients, with mean e-GFR at 1 month (49.8±8.4), 3 months (49.6±8.7), 6 months (49.8±8.1), 12 months (47.6±9.2), 24 months (47.9±9.1), and 36 months (45.1±7.3) significantly higher compared to pre-LTA e-GFR (P≤.005 at all time points). One patient developed end-stage renal disease 9 years post-LTA and another patient expired 7 years post-LTA. The low e-GFR alone in the absence of other markers or risk factors of CKD should not be an absolute criterion for SLKT in patients with liver cirrhosis.

Torsed hepaticoileostomy-an unusual complication of Bile Duct injury repair.

We present a 42-year-old male with strictured bilioenteric anastomosis after bile duct injury repair. The patient improved after percutaneous biliary drainage and balloon dilation of the stricture. Persistent bile reflux around the catheter insertion site prompted a cholangiogram that suggested an error in the enteric limb. Surgical exploration revealed that a torsed ileal loop was used for bilioenteric anastomosis. This error was repaired surgically. The patient had immediate and long-term resolution of symptoms.

Aberrant left main bile duct draining directly into the cystic duct or gallbladder: an unreported anatomical variation and cause of bile duct injury during laparoscopic cholecystectomy.

Despite recent advances, iatrogenic bile duct injury remains one of the most common complications of laparoscopic cholecystectomy. Aberrant biliary tract anatomy is one of the major risk factors for iatrogenic bile duct injury. In this case report, for the first time, we report a case of aberrant left main bile duct draining directly into the cystic duct or gallbladder that presented with bile duct injury after laparoscopic cholecystectomy. We hope that the diagnostic and management approach used in this case will help physicians to identify and manage their patients should they face such a rare anatomy.

Portal-endocrine and gastric-exocrine drainage technique of pancreas transplantation provides an easy access for evaluation of pancreatic allograft dysfunction: six-year experience at a single center.

BACKGROUND: The aim of this study is to report our six-year experience with portal-endocrine and gastric-exocrine drainage technique of pancreatic transplantation, which was first developed and implemented at our center in 2007. METHODS: In this study, the outcomes of all patients at our center who had pancreas transplantation with portal-endocrine and gastric-exocrine drainage technique were evaluated. RESULTS: From October 2007 to November 2013, 38 patients had pancreas transplantation with this technique - 31 simultaneous kidney pancreas and seven pancreas alone. Median duration of follow-up was 3.8 years. One-, three-, and five-year patient and graft survival rates were 94%, 87%, 70% and 83%, 65%, 49%, respectively. For pancreas allograft dysfunction evaluation, 51 upper endoscopies were performed in 14 patients; donor duodenal biopsies were successfully obtained in 45 (88%). We detected nine episodes of acute rejection (eight patients) and seven episodes of cytomegalovirus (CMV) duodenitis (six patients). No patient developed any complication due to upper endoscopy. CONCLUSIONS: Portal-endocrine and gastric-exocrine drainage technique of pancreas transplantation provides lifelong easy access to the transplanted duodenum for evaluation of pancreatic allograft dysfunction.

Curative resection of pancreatic adenocarcinoma with major venous resection/repair is safe procedure but will not improve survival.

OBJECTIVE: To evaluate the safety and survival benefit of combined curative resection (CR) of the pancreas and major venous resection in the management of borderline resectable pancreatic adenocarcinoma. METHODS: In this IRB approved retrospective cohort study, patients who had pancreatic surgery (n=274) between 1998-2012 were reviewed. One hundred and seventy-five patients had malignant causes, of which 119 underwent CR. One hundred and two patients who did not require venous resection/repair (Group-I) were compared with 17 patients who had major vascular involvement (portal-vein/superior-mesenteric-vein) and underwent a vascular resection/repair (Group-II) during the CR. Demographics, operative and follow-up data were reviewed. RESULT: Type of the operations were: standard Whipple (n=53), pylorus-sparing-Whipple (n=41), total pancreatectomy (n=11), and distal pancreatectomy (n=13). In Group-II, venous involvement was excised and primarily repaired (n=12), or repaired using other veins (n=4) or a synthetic patch (n=1). Group-II had a significantly larger tumor size and more perineural invasion and peripancreatic soft tissue involvement (P<0.05). While complication rate, margin status, and duration of stay were not different between the groups, the median-overall-survival was higher for Group-I (15.34 months) than Group-II patients (7.18 months) (P=0.003). CONCLUSION: Pancreatic CR requiring intra-operative venous resection/repair is feasible and safe, but the survival of the patients who have pancreatic adenocarcinoma with venous involvement is poor irrespective of a successful venous resection.

Mucinous cystic neoplasm of pancreas in a male patient: a case report and review of the literature.

Mucinous cystic neoplasms (MCNs) are among the most common primary cystic neoplasms of pancreas. These lesions usually occur in body and tail of the pancreas and are characterized by the presence of ovarian type stroma in the pathological evaluation. Mucinous cystic neoplasms have significant malignant potential; therefore, their diagnosis and resection is of utmost importance. Mucinous cystic neoplasms typically occur in women. Only a few cases have been previously reported in male patients. In this case report, we present a 48-year-old man who was referred to our center due to an incidentally found cystic lesion in the tail of the pancreas that was increasing in size in serial evaluation. The patient underwent open distal pancreatectomy. The pathology showed mucinous cystic neoplasm with characteristic ovarian type stroma and positive staining for estrogen and progesterone receptors. This case report shows that mucinous cystic neoplasms can occur in men and should be considered in differential diagnosis of cystic pancreatic lesions in this population.

Peripancreatic soft tissue involvement: independent outcome predictor in patients with resected pancreatic adenocarcinoma.

The impact of cancer involving the peripancreatic soft tissue (PST), irrespective of margin status, following a resection of pancreatic adenocarcinoma is not known. The purpose of this study is to determine such an impact on a cohort of patients. Data from 274 patients who underwent pancreatic surgery by our team between 1998 and 2012 was reviewed. Of those 119 patients who had pancreatic resection for adenocarcinoma were retrospectively analyzed. Patients were categorized into 3 groups: Group 1 = R1 resection (N = 39), Group 2 = R0 with involved PST (N = 54), and Group 3 = R0 with uninvolved PST (N = 26). Demographics, operative data, tumor characteristics and overall survival (OS) were evaluated. Operations performed were: Whipple (N = 53), pylorus sparing Whipple (N = 41), total pancreatectomy (N = 11), and other (N = 14). Median OS for Groups 1, 2, and 3 were 8.5 months, 12 months, and 69.6 months respectively (P < 0.001). Tumor size (P = 0.016), margin status (P = 0.006), grade (P = 0.001), stage (P = 0.037), PST status (P < 0.001), complications (P = 0.046), transfusion history (P = 0.003) were all predictors of survival. Cox regression analysis demonstrated that grade (HR = 3.1), PST involvement (HR = 2.7), transfusion requirement (HR = 2.6) and margin status (HR = 2.0) were the only independent predictors of mortality. PST is a novel predictor of poor outcome for patients with resected pancreatic cancer.

Impact of Plasma Glucose Level at the Time of Fluorodeoxyglucose Administration on the Accuracy of FDG-PET/CT in the Diagnosis of Pancreatic Lesions.

BACKGROUND: High fasting plasma glucose (FPG) levels before fluorodeoxyglucose (FDG) administration for positron emission tomography/computed tomography (PET/CT) might affect the accuracy of 18-fluoro-deoxy-glucose-positron emission tomography-computed tomography (FDG-PET/CT) in diagnosis of pancreatic lesions. Current guidelines require FPG levels of < 200 mg/dL before FDG administration; however, the literature on the effect of FPG levels of < 200 mg/dL on the accuracy of FDG-PET/CT is scarce. OBJECTIVES: The aim of this study was to evaluate the effect of FPG levels of < 200 mg/dL on the accuracy of FDG-PET/CT in diagnosis of pancreatic lesions. PATIENTS AND METHODS: In this retrospective study, 161 patients who had FDG-PET/CT for initial diagnosis of pancreatic lesions were included. Fasting plasma glucose levels before FDG administration were recorded. Accuracy of FDG-PET/CT in diagnosis of pancreatic lesions was compared between patients who were non diabetic (FPG < 126 mg/dL) and hyperglycemic (126 ≤ FPG < 200 mg/dL). RESULTS: Thirty-four patients were hyperglycemic and 127 non diabetic. Sensitivity, specificity, positive predictive value and negative predictive value of FDG-PET/CT were 90%, 88%, 87% and 91% in non diabetic and 82%, 92%, 95% and 73% in hyperglycemic patients, respectively. Overall, the accuracy was higher in non diabetic than hyperglycemic patients (89% vs. 85%). CONCLUSIONS: Accuracy of FDG-PET/CT for primary diagnosis of pancreatic lesions is higher in patients with FPG levels < 126 mg/dL than in patients with FPG levels between 126 and 200 mg/dL.

Laparoscopic versus open liver resection for benign and malignant solid liver tumors: a case-matched study.

BACKGROUND: Laparoscopic liver resection (LLR) is proposed as an alternative to open liver resection (OLR) for treatment of liver tumors. The aim of this study was to compare the surgical and oncological outcomes of LLR versus OLR in benign and malignant solid liver tumors. STUDY DESIGN: In this case-matched study, charts of 497 patients with liver lesions who had LLR or OLR in our center were retrospectively reviewed. Among them, 54 consecutive patients with benign or malignant solid liver tumors who had LLR were matched with a similar number of patients with OLR based on the pathology and extent of liver resection. Additionally, the surgical and oncological outcomes such as operating room time, amount of blood transfusion requirement, free resection margin rate, length of hospital stay, complication rate, perioperative mortality, and survival were compared between the two groups. RESULTS: Demographics, pathological characteristics of the tumor, and extent of liver resection were similar between the two groups. Twenty-nine (54%) patients in each group had malignant lesions. There were no statistically significant differences between the two groups in terms of operating room time, amount of blood transfusion requirement, free resection margin, or postoperative complication rate or survival. However, hospital stay was significantly shorter in the laparoscopic group (5.9 versus 9 days, P=.006). Although no perioperative mortality was observed in patients with benign tumors, among the patients with malignant tumors, 2 died perioperatively in each group. CONCLUSIONS: Our results in accordance with previous studies demonstrated that although the oncological outcomes of LLR and OLR were comparable, LLR patients had a shorter hospital stay.

Accuracy of multi-detector computed tomography, fluorodeoxyglucose positron emission tomography-CT, and CA 19-9 levels in detecting recurrent pancreatic adenocarcinoma.

CONTEXT: We compared the accuracy of fluorodeoxyglucose positron emission tomography-CT (FDG-PET-CT), multi-detector computed tomography (MDCT) and CA 19-9 levels in detecting pancreatic cancer recurrence in patients with resected CA 19-9 positive pancreatic adenocarcinomas. METHODS: We retrospectively evaluated 122 patients with pancreatic adenocarcinomas who underwent surgical resection of the tumor between January 2002 and December 2011. Twenty-five patients had MDCT, FDG-PET-CT and CA 19-9 levels performed no less than six weeks post-operation and within 8 weeks of each other for detection of tumor recurrence. Of these, 20 patients had high pre-operative CA 19-9 levels that dropped to a normal level postoperatively which will be the focus of this study. The sensitivity, specificity, positive and negative predictive value (PPV, NPV), and accuracy of MDCT, FDG-PET-CT, and CA 19-9 in detecting recurrence were compared. RESULTS: Operations performed included pyloric sparing pancreaticoduodenectomy (n=9), pancreaticoduodenectomy (n=7), distal pancreatectomy (n=3) and total pancreatectomy (n=1). Three patients had no recurrence, but local recurrence and distant metastasis were seen in 8 (40%) and 12 (60%) patients, respectively. In our study, sensitivity, specificity, PPV, NPV and diagnostic effectiveness (accuracy) were: 82%, 100%, 100%, 50%, 85% for MDCT; 82%, 100%, 100%, 50%, 85% for FDG-PET-CT and 94%, 100%, 100%, 75%, 95% for CA 19-9. The difference in recurrence detection accuracy of the tests was not statistically significant. A combination of CA 19-9 with MDCT or FDG-PET-CT was 100% accurate in detecting cancer recurrence in our patients. CONCLUSION: Our data suggests that CA 19-9 levels can be used reliably to detect recurrent pancreatic adenocarcinomas in patients with CA 19-9-positive primary tumors. Combination of CA 19-9 with MDCT or FDG-PET-CT is potentially the most accurate approach in detecting pancreatic cancer recurrence.

Strategy for effective percutaneous drainage of pancreatic collections: results on 121 patients.

UNLABELLED: There is a lack of technical guidelines for image-guided percutaneous drainage (IGPD) of pancreatic fluid collections (PFCs). To fill that void, we present a strategy and guidelines for systematic IGPD for effective PFCs evacuation. METHODS: Institutional Review Board (IRB)-approved study of 121 pancreatitis patients with symptomatic PFCs that underwent IGPD. IGPD strategy aimed at evacuation of the PFCs compartments using vigorous catheter drainage and manipulations. PFCs resolution and patients' outcome were measured. RESULTS: Pancreatitis pathogenesis and etiology included: necrotizing, 79 patients (alcoholic, 40; biliary, 20; hyperlipidemia, 8; other, 11); traumatic, 32 patients; and chronic ductal, 10 patients (pseudocysts). An ipsilateral retroperitoneal access was used for pararenal spaces PFCs (61, 50% patients), a transabdominal IGPD approach for anterior PFCs (49 patients, 41%), an intercostal/subcostal access for left subphrenic PFCs (22 patients, 18%), and a transgastric drainage route for retrogastric PFCs (9 patients, 7%). Table 1 lists the site of the pancreatic fluid collections and number and size of the catheter(s) used for IGPD of the PFCs in the 121 patients. Fifty-seven (47%) patients had positive cultures PFCs. Of these, 24 (20%) had polymicrobial infections, and 18 (15%) had fungal infections. There were 20 (11%) patients with multi-compartment drainage. PFCs resolution occurred in 102 (84%) patients. PFCs recurrence was treated by surgery (four patients) or IGPD (one patient). Pancreatic fistulas closed, except in one patient. Nine patients (7%) experienced multiorgan failure/death; 5 (4%) were lost to follow-up.