Glecaprevir/Pibrentasvir and Renal Dysfunction in Deceased Donor Renal Transplantation: A Case Report.

BACKGROUND: Glecaprevir/pibrentasvir is a novel anti-hepatitis C virus (HCV) drug, and it is currently the only drug available for patients with severe renal impairment. Here we report a case with renal dysfunction after an administration of glecaprevir/pibrentasvir. CASE REPORT: The case was 66-year-old Japanese man who turned out to be HCV-positive 14 years ago at the time of his second deceased renal transplantation. He had no prior history of HCV treatment. HCV genotype was serogroup 1, and baseline HCV-RNA was 5.3 LOG IU/mL. Since glecaprevir/pibrentasvir became available, he started to take it for treatment of HCV. His immunosuppressants were tacrolimus (trough levels 4.3∼6.5 ng/mL) and 5 mg of prednisolone. His baseline renal function was serum creatinine (Cr) 2.1 mg/dL and urine protein (-). Shortly after starting glecaprevir/pibrentasvir, the serum Cr started to increase. Serum Cr reached up to 2.92 mg/dL and urine protein was (+) at day 36. Right pleural effusion was observed while cardiac function was normal. His liver function had been consistently normal. We concluded glecaprevir/pibrentasvir was the cause of renal dysfunction as no other drugs were added. Immediately after discontinuation of glecaprevir/pibrentasvir at day 36, serum Cr decreased to 1.9 mg/dL and urine protein turned negative at day 64. Although the patient completed a half course of glecaprevir/pibrentasvir, HCV-RNA turned to be negative at day 36. CONCLUSIONS: We experienced a case with renal dysfunction after the initiation of glecaprevir/pibrentasvir in deceased donor renal transplant recipient. Renal dysfunction caused by glecaprevir/pibrentasvir has not been reported so far.

A case of poorly differentiated mucinous carcinoma of the gallbladder that exhibited a peculiar morphology.

A 65-year-old female presented with an elevated lesion that was identified in the gallbladder fundus via abdominal ultrasound during a medical checkup. The tumor was a pedunculated lesion, measuring 30mm in diameter, that exhibited a blood flow pattern with gradual dense staining throughout the equilibrium phase on the abdominal contrast computed tomography and a high signal intensity on T2-weighted magnetic resonance imaging. Histopathological findings revealed the proliferation of poorly differentiated adenocarcinoma, including signet ring cells, throughout the tumor along with the formation of a mucous lake. The patient was consequently diagnosed with poorly differentiated mucinous carcinoma of the gallbladder.

[A case of pancreatic neuroendocrine tumor presenting with main pancreatic duct invasion].

A 52-year-old male visited a local clinic with a subjective complaint of pain in the left side of his abdomen. Abdominal CT revealed the presence of a pancreatic body tumor. On EUS, the tumor presented hypoechoic signals with an obscure boundary, which continued from the pancreatic parenchyma to the inside of the main pancreatic duct. Abdominal contrast CT revealed a hypervascular tumor with densely stained pancreatic parenchyma. ERP findings revealed that main pancreatic duct invasion was suspected based on partial radiolucency in the duct. Distal pancreatectomy was performed, and a definitive diagnosis of pancreatic neuroendocrine tumor (WHO class G1) was made histopathologically.

Localized type 1 autoimmune pancreatitis superimposed upon preexisting intraductal papillary mucinous neoplasms.

A 70-year-old woman was found to have 2 cystic lesions in the head of the pancreas on abdominal ultrasonography during a routine medical examination. Endoscopic ultrasonography (EUS) and magnetic resonance cholangiopancreatography showed multilocular cysts in the head of the pancreas without dilation of the main pancreatic duct. The patient was followed-up semiannually with imaging studies for suspected branch duct-type intraductal papillary mucinous neoplasm (IPMN). At 3 years after initial presentation, hypoechoic lesions were observed around each pancreatic cyst by EUS. Diffusion-weighted imaging showed high-intensity regions corresponding to these lesions. Therefore, a diagnosis of invasive carcinoma derived from IPMN could not be excluded, and subtotal stomach-preserving pancreaticoduodenectomy was performed. The macroscopic examination of the surgical specimen showed whitish solid masses in the head of the pancreas, with multilocular cysts within each mass. Microscopically, each solid mass consisted of inflammatory cells such as lymphocytes and plasma cells. Furthermore, immunochemical staining revealed immunoglobulin G4-positive cells, and many obliterating phlebitides were observed. The cysts consisted of mucus-producing epithelial cells and showed a papillary growth pattern. Based on these findings, we diagnosed multiple localized type 1 autoimmune pancreatitis occurring only in the vicinity of the branch duct-type IPMN.

[A case of dermoid cyst of the pancreas].

A 58-year-old man visited a local clinic after experiencing epigastric and dorsal pain. A computed tomography scan revealed a hypovascular mass in the pancreatic tail. T1-weighted magnetic resonance imaging (MRI) of the tumor showed a heterogeneous isointense signal and T2-weighted MRI showed a hyperintense signal. Contrast studies revealed contrast enhancement, showing a cystic wall and parts of a septal structure and lumen. Endoscopic ultrasonography revealed a multilocular hypoechoic tumor containing large quantity of debris. We experienced difficulty arriving at a diagnosis and are reporting this case of a pancreatic dermoid cyst, which was diagnosed based on pathological findings.

Acute pancreatitis caused by an ectopic mediastinal parathyroid adenoma.

A 22-year-old man was admitted to our hospital because of epigastric pain. Blood tests showed leukocytosis (8940 cells/mm(3)) and increased serum amylase levels (787 IU/L); an abdominal computed tomography (CT) scan revealed an enlarged pancreas and peripancreatic fluid collection. On the basis of these findings, he was diagnosed with acute pancreatitis. Hypercalcemia (13.5 mg/dL) and increased levels of parathormone (>3200 pg/dL) were also detected using a high-sensitivity assay; we therefore considered hypercalcemia and primary hyperparathyroidism to be the possible causes of the acute pancreatitis. A (99m)Tc-sestamibi scan showed accumulation of parathyroid tissue in the left mediastinum, and a tumor was noted on the left side of the aortic arch on a thoracic CT scan. Our final diagnosis was acute pancreatitis due to hypercalcemia induced by an ectopic mediastinal parathyroid adenoma. Ectopic parathyroid tumors can thus cause acute pancreatitis, and (99m)Tc-sestamibi and CT scans are useful for their diagnosis and localization.

Intraductal tubulopapillary neoplasm of the pancreas with somatic BRAF mutation.

Intraductal tubulopapillary neoplasm (ITPN) is a rare pancreatic tumor belonging to a newly recognized entity that is coined in the 2010 WHO classification. We present a case of ITPN-associated microinvasive adenocarcinoma that developed in an asymptomatic 78-year-old patient. The tumor demonstrated all the clinical, radiological, and pathological characteristics of ITPN, but it differs from other reported cases of ITPN in molecular analysis, which revealed a somatic mutation in BRAF (c.1799T>A; p.V600E) but no mutation in PIK3CA. Post-operative recurrence was discovered 34 months after tumor resection with negative margins and a 6-month course of adjuvant chemotherapy. To the best of our knowledge, this is the first case of ITPN with BRAF mutation. This case suggests that an activation of RAS-mitogen-activated protein kinase signaling pathway may play a role in development of some of ITPNs. A possible mechanism of tumor recurrence in ITPN is also discussed. Further case series with molecular study are awaited to delineate the clinicopathological and molecular characteristics of ITPN.

Total pancreatectomy for metastatic renal cell carcinoma with marked extension into the main pancreatic duct.

A 59-year-old man who had undergone left nephrectomy for renal cell carcinoma (RCC) 14 years previously was admitted for the treatment of obstructive jaundice. Imaging studies showed head-to-tail dilation of the main pancreatic duct (MPD) and a few ring-shaped enhanced nodules. Main duct-type intraductal papillary mucinous neoplasm was suspected and total pancreatectomy was performed. Pathologically, the entire length of MPD was filled with tumor. It consisted mainly of necrotic material, but included some clear cell carcinoma; the final diagnosis was metastatic RCC of the pancreas. This is an extremely rare case of pancreatic metastasis from RCC, with marked extension into MPD.

[One case of pancreatic mucinous carcinoma discovered due to acute pancreatitis].

The patient was a woman, aged 69, diagnosed with acute pancreatitis by a local physician; simultaneously, with US, a low-echo tumor was indicated in the pancreas' uncinate process. Diagnosis was made of acute pancreatitis resulting from a pancreatic IPMN, and the patient was referred. Ultrasound showed hypoechoic tumor images accompanied by posterior echo enhancement. With radiography-CT, from the pancreas parenchymal phase, the peripheral portion was densely stained, while internally, images showed densely stained dendriforms towards the equilibrium phase. With MRI T1-weighted images, there was appearance at low intensity, and with T2-weighted images, there was appearance at high intensity; with MRCP, there was depiction at relatively high intensity. In the final pathological diagnosis, there was prominent formation of mucinous nodules, and mucinous carcinoma including large quantity of mucous.