Spontaneous reactivation of hepatitis B virus with multiple novel mutations in an elderly patient with resolved hepatitis B virus infection.

Spontaneous reactivation of the Hepatitis B virus (HBV) is rare in individuals with previously resolved infections. This report presents the case of a 71 year-old Japanese woman who experienced HBV reactivation without any prior immunosuppressive therapy or chemotherapy. Before the onset of liver injury, the patient was negative for hepatitis B surface antigen (HBsAg) but positive for hepatitis B surface antibody. She subsequently developed liver injury, with the reappearance of HBsAg and HBV DNA. The patient was successfully treated with tenofovir alafenamide, and prednisolone. Full-genome sequencing of HBV revealed subgenotype B1 without hepatitis B e-negative mutations in the precore and core promoter regions and 12 amino acid alterations in the pre-S1/S, P, and X genes. Notably, the S gene mutations D144A and K160N, which alter the antigenicity of HBsAg and potentially contribute to its reactivation, were identified. This case emphasizes the importance of vigilance for spontaneous reactivation of resolved HBV, highlighting the need for comprehensive genomic analysis to understand the associated virological intricacies.

Pancreatic Ductal Adenocarcinoma Encapsulated by a Tumor-Forming Type 1 Autoimmune Pancreatitis Located at the Pancreatic Tail: A Case Report.

Introduction: Autoimmune pancreatitis (AIP) is recognized as a disease with a good prognosis that responds well to steroids, but the complication of pancreatic ductal adenocarcinoma (PDAC) in AIP is a rare condition. We report a case of PDAC encapsulated by tumor-forming type 1 AIP. Case Presentation: The patient, a 65-year-old female, was found to have high CA19-9 levels and a pancreatic mass with a diameter of 30 mm on abdominal ultrasonography. Contrast-enhanced computed tomography revealed a 40-mm mass in the tail of the pancreas that had a 27-mm oligemic mass inside it. From these work-up examinations, this tumor was diagnosed as PDAC, with evidence of colonic invasion. As curative resection for PDAC, a distal pancreatectomy with splenectomy and combined colon resection were performed. Histopathological examination showed invasive PDAC surrounded by IgG4-positive plasma cell infiltration. Based on these findings, a diagnosis was made of PDAC located in the pancreatic tail capsulized by type 1 AIP. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. She underwent postoperative adjuvant chemotherapy with S-1 for 6 months, and no recurrence was noted for 2 years after operation. Conclusion: Currently, there are two hypothetical mechanisms of PDAC induction by AIP: (1) carcinogenic stimulation due to chronic inflammation and (2) paraneoplastic syndrome caused by AIP. Further study of the relationship between AIP and pancreatic cancer is needed, and follow-up should be conducted while keeping in mind the possibility of complications.

A Case of Autoimmune Hepatitis Complicated by Undiagnosed Factor VII Deficiency: A Pitfall of Coagulopathy.

Prothrombin time (PT) is a key parameter for assessing the severity of liver disease. We present the case of a 37-year-old woman with severe acute liver injury due to autoimmune hepatitis. Although prednisolone drastically improved her hepatocyte function, her PT did not recover to the reference range. A review of her medical records revealed that the patient had normal transaminase levels and prolonged PT 2 years previously. Further examinations of her coagulopathy revealed that she had low factor VII activity, suggesting a diagnosis of factor VII deficiency. Our experience suggests that altered coagulopathy should be considered in cases of liver injury with an extraordinary PT.

Extensively Invasive Gallbladder Cancer from Intracholecystic Papillary Neoplasm Treated with Pylorus-Preserving Pancreaticoduodenectomy and Extended Cholecystectomy: A Case Report and Literature Review.

Background: Intracholecystic papillary neoplasm (ICPN) is a rare tumor first classified by the World Health Organization in 2010. ICPN is a counterpart of the intraductal papillary mucinous neoplasm of the pancreas and intraductal papillary neoplasm of the bile duct. Previous reports on ICPN are limited; thus, the diagnosis, surgical intervention, and prognosis are controversial. Here, we report an extensively invasive gallbladder cancer arising in ICPN treated with pylorus-preserving pancreaticoduodenectomy (PPPD) and extended cholecystectomy. Case Presentation. A 75-year-old man presented to another hospital with jaundice for 1 month. Laboratory findings showed elevated total bilirubin, 10.6 mg/dL and carbohydrate antigen 19-9, 54.8 U/mL. Computed tomography showed a well-enhanced tumor located in the distal bile duct and dilated hepatic bile duct. The gallbladder wall was thickened and homogeneously enhanced. Endoscopic retrograde cholangiopancreatography revealed a filling defect in the distal common bile duct, and intraductal ultrasonography showed a papillary tumor in the common bile duct, indicating tumor invasion of the bile duct subserosa. Subsequent bile duct brush cytology revealed adenocarcinoma. The patient was referred to our hospital for surgical treatment and underwent an open PPPD. Intraoperative findings showed a thickened and indurated gallbladder wall, suggesting concurrent gallbladder cancer; thus, the patient subsequently underwent PPPD and extended cholecystectomy. Histopathological findings confirmed gallbladder carcinoma originating from ICPN, which extensively invaded the liver, common bile duct, and pancreas. The patient started adjuvant chemotherapy (tegafur/gimeracil/oteracil) 1 month after surgery and had no recurrence at follow-up after 1 year. Conclusions: Accurate preoperative diagnosis of ICPN, including the extent of tumor invasion is challenging. To ensure complete curability, the development of an optimal surgical strategy considering preoperative examinations and intraoperative findings is essential.

A case of pathological complete response with liposomal irinotecan + 5-FU/LV for unresectable locally advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer has one of the worst prognoses of any all cancers. 5-FU/leucovorin + irinotecan + oxaliplatin (FOLFIRINOX), gemcitabine (GEM) plus nab-paclitaxel regimens have been recognized as global-standard, first-line treatments for patients with advanced pancreatic cancer. The liposomal irinotecan (nal-IRI) + 5-FU/LV regimen is now included in treatment guidelines as a recommended and approved option for use in patients with metastatic pancreatic cancer that has progressed after GEM-based therapy and who have a suitable performance status and comorbidity profile. There is no report that nal-IRI + 5-FU/LV regimen was significantly effective, and we will report it because we experienced this time. CASE PRESENTATION: A 69-year-old man presented with epigastric pain, and a contrast computed tomography (CT) revealed an enhanced mass lesion measuring 33 × 27 mm on the pancreatic body with encasement of the common hepatic artery (CHA) and the splenic vein. An endoscopic ultrasound-guided fine needle aspiration was performed and demonstrated cytology consistent with adenocarcinoma. Therefore, we diagnosed the patient with unresectable locally advanced pancreatic cancer. The patient received the GEM and S-1 regimen; however, the adverse event was relatively severe. Then, 11 cycles of nal-IRI + 5-FU/LV regimen were administered. A CT scan revealed that the tumor had shrunk to 18 × 7 mm in diameter with encasement of the CHA. The encasement of the splenic vein had disappeared, without any distant metastases. From this post-chemotherapy evaluation and intraoperative frozen section of around the celiac artery, gastroduodenal artery and pancreas stump confirmed absence of tumor cells, we performed distal pancreatectomy with celiac axis resection. A histological examination of the surgical specimen revealed no evidence of residual adenocarcinoma, consistent with a pathological complete response to treatment. CONCLUSIONS: We present the first case of a pathological complete response with nal-IRI + 5-FU/LV for unresectable, locally advanced pancreatic cancer. In the future, nal-IRI may become a key drug for pancreatic cancer treatment.

Pure Laparoscopic Left Hepatectomy for Regrowth of Mucinous Cystic Neoplasm of the Liver after Laparoscopic Deroofing.

Background: Hepatic cystic lesions are common entities, most of which are simple hepatic cysts (SHCs). Mucinous cystic neoplasm of the liver (MCN-L) is a rare tumor characterized by ovarian-like stroma and accounts for <5% of all hepatic cysts. Distinguishing between SHCs and MCN-L is challenging because of the similarity in their imaging findings. Herein, we report a rare regrowth case of MCN-L after laparoscopic deroofing, treated with pure laparoscopic left hepatectomy. Case Presentation. A 63-year-old woman with a large hepatic cystic lesion and abdominal pain was referred to our hospital for surgical treatment. Computed tomography (CT) showed cystic lesions with septations arising from macrolobulations in the left medial segment. She underwent laparoscopic deroofing based on the diagnosis of SHCs; however, the final histopathological diagnosis was MCN-L. She chose observational follow-up, and MCN-L regrowth was detected on follow-up CT 6 months after the laparoscopic deroofing. We performed pure laparoscopic left hepatectomy for complete resection of the MCN-L. She had an uneventful postoperative course and no recurrence at the 5-year follow-up after the radical resection of the MCN-L. Conclusion: MCN-L is a rare entity, and accurate diagnosis with imaging modalities is greatly challenging. Laparoscopic hepatectomy for MCN-L should be considered as a strong alternative to secure safety and curability.

A novel second-stage surgical strategy for severely obese patient with pancreatic neuroendocrine tumor: a case report.

BACKGROUND: Severely obese patients can have other diseases requiring surgical treatment. In such patients, bariatric surgeries are considered a precursor to operations targeting the original disease for the purpose of reducing severe perioperative complications. Pancreatic ectopic fat deposition increases pancreas volume (PV) and thickness, which can worsen insulin resistance and islet ß cell function. To address this problem, we present a novel two-stage surgical strategy performed on a severely obese patient with pancreatic neuroendocrine tumor (PNET) consisting of laparoscopic sleeve gastrectomy (LSG) as a metabolic surgery followed by laparoscopic spleen-preserving distal pancreatectomy (LSPDP). CASE PRESENTATION: A 56-year-old man was referred to our hospital for further investigation of a pancreatic tumor. His initial body weight and body mass index (BMI) were 94.0 kg and 37.2 kg/m2, respectively. Contrast computed tomography revealed an enhanced tumor measuring 15 mm on the pancreatic body. The pancreas thickness and PV were 32 mm and 148 mL, respectively. An endoscopic ultrasonographic fine needle aspiration identified the tumor as PNET-G1. We first performed LSG, the patient's body weight and BMI had decreased dramatically to 64.0 kg and 25.3 kg/m2 at 6 months after LSG. The pancreas thickness and PV had also decreased to 17 mm and 99 mL, respectively, with no tumor growth. Since LSG has been shown to reduce the perioperative risk factors of LSPDP, and to improve insulin resistance and recovery of islet ß cell function, we performed LSPDP for PNET-G1 as a second-stage surgery. The postoperative course was unremarkable, and the patient was discharged on postoperative day 14 without symptomatic postoperative pancreatic fistula (POPF). He was followed without recurrence or type 2 diabetes (T2D) onset for 6 months after LSPDP. CONCLUSIONS: We present a novel two-stage surgical strategy for a severely obese patient with PNET, consisting of LSG as a metabolic surgery for severe obesity, followed by LSPDP after confirmation of good weight loss and metabolic effects. LSG before pancreatectomy may have a potential to reduce pancreas thickness and recovery of islet ß cell function in severely obese patients, thereby reducing the risk of clinically relevant POPF and post-pancreatectomy T2D onset.

Morphological and Molecular Characteristics in Low Grade Fetal Adenocarcinoma of the Lung: Two Case Reports and Literature Review.

Background: Low-grade fetal adenocarcinoma of the lung is a rare pulmonary tumor resembling fetal lung histologically. Due to its rarity, there is limited information regarding the pathogenesis and biological characteristics of low-grade fetal adenocarcinoma of the lung. Here, we describe two cases of low-grade fetal adenocarcinoma of the lung treated at our hospital and summarize cases of low-grade fetal adenocarcinoma of the lung reported in the literature. Case presentation: We examined two cases (one woman and one man; 30 and 67 years old, respectively). Histologically, tumor tissues from both cases had a complex glandular component with clear cuboidal and columnar cells that resembled the histological features of fetal lung. In some areas, squamous morules were prominent. Immunohistochemically, nuclear/cytoplasmic expression of ß-catenin was detected in both cases. Mutation analysis revealed a CTNNB1 mutation in both cases and a DICER1 mutation in 1 case. No mutations in EGFR, BRAF, KRAS, or PIK3CA were found. Conclusions: Low-grade fetal adenocarcinoma of the lung showed a high frequency of CTNNB1 mutations and low frequencies of EGFR, KRAS, BRAF, and PIK3CA mutations in our examined cases and in previous studies. This rare tumor has unique clinicopathological characteristics with specific genetic aberrations involving the Wnt pathway. These results provide a molecular basis for development of new therapies to treat these tumors.

A case of hepatic intraductal papillary neoplasm of the bile duct.

In this report, we present a 57-year-old female with a history of mild alcoholic liver disease during a medical check-up. Abdominal computed tomography and magnetic resonance imaging showed a multicystic mass with a solid enhancing mural nodule in the right lobe of the liver. Subsequently, laparoscopic right liver lobectomy was performed and pathological findings revealed intraductal papillary neoplasm of the bile duct (IPNB) with an associated invasive carcinoma. IPNB is a relatively rare disease that should be considered in the differential diagnosis of hepatic cystic tumours. Our case report highlights the importance of capturing image findings of the IPNB as this disease has a high potential for malignancy.

The Concept of Indeterminable NASH Inducted by Preoperative Diet and Metabolic Surgery: Analyses of Histopathological and Clinical Features.

Practitioners routinely perform intraoperative liver biopsies during laparoscopic sleeve gastrectomy (LSG) to evaluate nonalcoholic fatty liver disease (NAFLD). In some patients, hepatocyte ballooning, inflammation, and fibrosis without steatosis are observed, even in the absence of other etiologies. We call this finding indeterminable nonalcoholic steatohepatitis (Ind-NASH). In this study, we clarified the prevalence, as well as histopathological and clinical features, of Ind-NASH through intraoperative liver biopsy in Japanese patients presenting with severe obesity. We enrolled 63 patients who had undergone LSG and intraoperative liver biopsy. In patients diagnosed with histopathological NASH, we performed protocol liver biopsies at 6 and 12 months after LSG. We statistically analyzed these histopathological findings and clinical parameters and found the prevalence rate of Ind-NASH discovered through intraoperative biopsy to be 15.9%. Protocol liver biopsy also revealed that Ind-NASH was an intermediate condition between NASH and normal liver. The clinical features of patients with Ind-NASH are a higher body weight compared to NASH (134.9 kg vs. 114.7 kg; p = 0.0245), stronger insulin resistance compared to nonalcoholic fatty liver (homeostasis model assessment-insulin resistance: 7.1 vs. 4.9; p = 0.0188), and mild liver dysfunction compared to NASH. Patients with Ind-NASH observed positive weight-loss effects from a preoperative diet compared to the postoperative course (percentage total weight loss: 32.0% vs. 26.7%; p < 0.0001). Patients with Ind-NASH may also be good candidates for metabolic surgery owing to their good treatment response; therefore, efforts should be made by specialists in the near future to deeply discuss and define Ind-NASH.

[Treatment of secondary engraftment failure with granulocyte colony-stimulating factor and eltrombopag after allogeneic peripheral blood stem cell transplantation in adult T-cell leukemia/lymphoma].

A 67-year-old woman diagnosed with adult T-cell leukemia/lymphoma received an induction chemotherapy and showed a partial response. She then underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical sibling donor. Although cyclosporine (CS) was stopped at 120 days after transplantation, chronic graft-versus-host disease (cGVHD) of the skin developed. She was treated with a topical steroid, without exacerbation of the GVHD. She was admitted to our hospital due to the sudden development of pancytopenia at 212 days after the transplantation. She had an EB virus-associated post-transplant lymphoproliferative disorder (PTLD) in the hilum of the lung. The cGVHD of the skin resolved after the administration of prednisolone and CS. However, pancytopenia and PTLD persisted. Treatment with four cycles of rituximab (4×375 mg/m2/week) led to the complete resolution of PTLD, but transfusion-dependent cytopenia did not improve. Secondary engraftment failure was diagnosed, and granulocyte colony-stimulating factor (G-CSF) and eltrombopag (100 mg/day) were administered, leading to gradual improvement of pancytopenia. It was observed that persistent pancytopenia was caused by secondary engraftment failure due to cGVHD in this case. This case suggested that the treatment with G-CSF and eltrombopag is effective for cGVHD-associated secondary engraftment failure.

Low-grade fibromyxoid sarcoma arising from the lung: A case report.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare sarcoma subtype that most commonly arises in young adults. This tumor typically presents in the deep soft tissues of the proximal extremities or trunk as a painless mass. Although the most common site of LGFMS metastasis is the lung, it is rarely the primary site. Here, we report a case of primary pulmonary LGFMS. A 22-year-old asymptomatic man was referred to our hospital for investigation of a lung mass that had been discovered incidentally. Computed tomography (CT) showed a well-defined mass 4.0 cm in diameter in the upper lobe of the right lung. Malignancy was suggested by focal uptake of 18F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET). Following surgery, postoperative histological analysis of the resected specimen demonstrated LGFMS based on histological and immunohistological findings. In particular, mucin 4 showed diffuse positivity in the spindle-shaped tumor cells. In conclusion, LGFMS can arise in the lungs, and physicians should consider this entity as a differential diagnosis for solitary lung mass in young adults.

Pancreatic ductal adenocarcinoma in a patient with pancreas divisum and gastrointestinal duplication cyst: a case report.

BACKGROUND: The complication of duplication of alimentary tracts and pancreas divisum (PD) is a rare malformation and the development of pancreatic ductal adenocarcinoma (PDAC) in this malformation is also extremely rare. There have been some reports of complication of malignancy in a gastric duplication cyst (GDC) and PD. However, there have been no reports of complication of PDAC in cases with GDC and PD. CASE PRESENTATION: A 54-year-old woman was followed up at the previous hospital due to a history of ovarian endometrial adenocarcinoma. She also had a surgical history of partial excision for a GDC and pancreatic tail of PD in her childhood. A gynecological follow-up computed tomography (CT) examination revealed the pancreatic body tumor and the bifurcated main pancreatic duct dilatation. Furthermore, magnetic resonance cholangiopancreatography also revealed that the ventral main pancreatic duct communicated with the GDC. The initial levels of tumor markers were high, but we could not achieve preoperative histopathological diagnosis. The preoperative diagnosis was PDAC occurring in a case with PD and GDC. She received two courses of neoadjuvant chemotherapy with gemcitabine and nab-paclitaxel. A CT examination after neoadjuvant chemotherapy revealed the shrinkage of the tumor, and then we performed distal pancreatectomy with splenectomy and GDC resection. A histopathological examination revealed invasive PDAC and lymph node metastases; pathological staging was T1N1M0, stage III. Furthermore, PD and GDC were also histopathologically detected. The postoperative course was uneventful, and she was discharged on the postoperative day 25. She received S-1 monotherapy for 6 months, and no recurrence has been detected at 1 year after radical resection. CONCLUSIONS: We herein presented an extremely rare combined case of PD, GDC and PDAC. We successfully treated it by neoadjuvant chemotherapy and distal pancreatectomy with GDC resection, and postoperative chemotherapy.

High frequency and long persistency of ballooning hepatocyte were associated with glucose intolerance in patients with severe obesity.

Nonalcoholic steatohepatitis (NASH) and glucose intolerance are associated with an increased risk of mortality in patients with severe obesity; however, whether histological findings of the liver are related to glucose intolerance in these patients remain unknown. Sixty-nine consecutive patients who underwent metabolic surgery between June 2008 and February 2020 were included; histological findings of the liver and laboratory data were analyzed. Twenty patients with biopsy-proven NASH were chronologically evaluated using sequential biopsies; data before metabolic surgery was considered as the baseline. Glucose intolerance-demonstrated by an increased area under the curve (AUC) for blood sugar (BS) during the 75-g oral glucose tolerance test-and increased homeostatic model assessment for insulin resistance (HOMA-IR) correlated with the grade of hepatocyte ballooning in patients. Patients with persistent ballooning at the follow-up biopsy had a higher HOMA-IR, high AUC for BS, and lower adiponectin level than those in patients in whom ballooning was eliminated, while there was no significant difference in body weight. We concluded that glucose intolerance was associated with the grade of hepatocyte ballooning; additionally, persistent hepatocyte ballooning sustained glucose intolerance, while elimination of hepatocyte ballooning improved the condition. Glucose intolerance may, thus, mediate balloon formation of the hepatocyte.

Two hepatectomy cases for initially unresectable hepatocellular carcinoma after achieving a radiological complete response to sequential therapy with lenvatinib and transcatheter arterial chemoembolization.

We herein report two cases of locally advanced unresectable hepatocellular carcinoma (u-HCC) that were resected after achieving a radiological complete response to initially administered lenvatinib followed by transcatheter arterial chemoembolization (LEN-TACE sequential therapy). A 78-year-old woman and an 80-year-old man with HCC of Barcelona Clinic Liver Cancer classification stage C were treated for 15 and 14 months with lenvatinib, respectively. Both patients were subsequently treated with TACE, resulting in complete remission on imaging. The α-fetoprotein level in the woman and man decreased markedly from 9370 ng/ml to 46 ng/ml and from 6380 ng/ml to 3 ng/ml, respectively, leading to hepatectomy. A histopathological examination showed coagulative necrosis of the entire HCC in one case, while the other showed a small population of viable HCC cells. The results showed that LEN-TACE sequential therapy has a synergic effect and could be a promising option for locally advanced u-HCC.

Pulmonary epithelial-myoepithelial carcinoma without AKT1, HRAS or PIK3CA mutations: a case report.

BACKGROUND: Pulmonary epithelial-myoepithelial carcinoma is a rare subtype of lung cancer. Because of its rarity, the molecular information on this carcinoma is insufficient. CASE PRESENTATION: We report a case of pulmonary epithelial-myoepithelial carcinoma without AKT1, HRAS or PIK3CA mutations in a 76-year-old woman. Computed tomography revealed a tumor located in the left lower lung. Thoracoscopic left lower lobectomy was performed. Histopathologically, the tumor consisted of duct-like structures and polygonal and spindle cell features. The duct-like structures were composed of two distinct cell layers. The inner layer consisted of cuboidal cells that were positive for pan-cytokeratin and negative for p63, whereas the outer layer consisted of polygonal and spindle cells that were positive for p63 and weakly positive for pan-cytokeratin. We evaluated mutations in AKT1, BRAF, CTNNB1, HRAS, KRAS and PIK3CA but did not detect any mutations. CONCLUSION: Pulmonary epithelial-myoepithelial carcinoma is a rare subtype of lung cancer, with only 56 previous cases reported in the English literature. The genetic alterations in pulmonary epithelial-myoepithelial carcinoma are still unknown. We examined the 6 genes mutation analysis, however no mutation was detected.

Expression of mucosal addressin cell adhesion molecule-1 on the reticular framework between white pulp and the marginal zone in the human spleen.

The antigenic heterogeneity of the reticular framework of the white pulp and marginal zone is well documented in the human adult spleen. Immunostaining of α-smooth muscle actin characterizes the heterogeneity of the reticular framework of the white pulp and marginal zone. In the human spleen, the blood cells flow in an open circulation. T and B lymphocytes flow out from the arterial terminal, and migrate in the reticular framework. Homing of lymphocytes to lymphoid tissues is regulated by selective interactions between cell surface homing receptors and tissue vascular addressins at sites of lymphocyte recruitment from the blood. In the present study, mucosal addressin cell adhesion molecule-1 was selectively expressed on α-smooth muscle actin-positive reticular framework. The reticular framework may function in lymphocyte homing and segregation into the periarteriolar lymphoid sheath, lymph follicle and marginal zone.