[A Case of Gallbladder Cancer with Long Survival Treated with Resection after Downstaging with GC Therapy].

A 68-year-old woman with a chief complaint of obstructive jaundice was referred to our hospital. She was diagnosed with gallbladder cancer with invasion to the liver, extrahepatic bile duct, right hepatic artery and portal vein. After endoscopic retrograde biliary drainage, she received chemotherapy with gemcitabine and cisplatin. After 9 courses, the size of the tumor and the lymph nodes decreased, and we planned surgery. There were no unresectable factors, and the right hepatic artery and portal vein were detached from the tumor. We performed a subtotal stomach-preserving pancreaticoduodenectomy and gallbladder bed resection. We then performed adjuvant chemotherapy with S-1 for 1 year. The patient remains alive without recurrence, 5 years after the surgery. We report the case of advanced gallbladder cancer with downstaging after GC therapy.

[Malignant gastrointestinal lymphoma with cicatricial stenosis after complete response to chemotherapy].

A 75-year-old woman presented complaining of anorexia. A malignant gastrointestinal lymphoma was diagnosed, and chemotherapy was initiated. After 2 months, she developed vomiting. Computed tomography (CT) revealed thickening of the jejunal wall and dilatation of the intestine proximal to that area. Positron emission tomography-CT showed no uptake. Small bowel stenosis due to cicatricial stenosis after chemotherapy was suspected. Laparoscopic partial resection of the stenotic small bowel segment was performed. Histopathologically, only granulation tissue was seen with no evidence of tumor. Occasionally, cicatricial stenosis can develop after chemotherapy for malignant gastrointestinal lymphoma. Therefore, this condition must be considered an important complication of treatment for this disease.

A case of IgG4-related lymphadenopathy, pericarditis, coronary artery periarteritis and luminal stenosis.

Immunoglobulin G4 (IgG4)-related disease is an emerging new clinicopathological disorder that is characterized by elevation of serum IgG4 levels and histological findings of IgG4-positive plasmacytic infiltration. IgG4-related disease may appear synchronously or metachronously in a wide variety of organs. The current patient was found to have pericardial effusion and retroperitoneal fibrosis. He was subsequently diagnosed with coronary artery stenosis. (18)F-FDG positron emission tomography showed enhanced FDG uptake in lymph nodes as well as pericardial and peri-aortic tissue. Histopathology of the mediastinal lymph node showed the infiltration of numerous IgG4-positive cells, leading to the diagnosis of IgG4-related lymphadenopathy with pericardial and periarterial involvement.

Lipopolysaccharides accelerate hepatic steatosis in the development of nonalcoholic fatty liver disease in Zucker rats.

Nonalcoholic fatty liver disease (NAFLD) can develop into end-stage disease that includes cryptogenic cirrhosis and hepatocellular carcinoma. Bacterial endotoxin, for example lipopolysaccharide (LPS), plays an important role in the pathogenesis of NAFLD. The aim of this study was to assess the role of LPS in the development of NAFLD. Twenty-one male Zucker (fa/fa) rats were divided into three groups: rats fed for twelve weeks on a diet rich in disaccharide (D12 group), rats similarly managed but treated with LPS (LPS group), and those on the same diet for 24 weeks (D24 group). Histological examination demonstrated that this protocol induced hepatic steatosis in the LPS and D24 groups. Significant, marked accumulation of lipid droplets was observed in the LPS group, compared with the D24 group. Rats from the LPS group showed a decrease in plasma adiponectin levels, an increase in plasma leptin levels, and greater expression of FAS and SREBP-1c mRNA in the liver, compared with rats from the D24 group. These finding coincided with histological findings. We therefore suggest that LPS may accelerate the progression of hepatic steatosis.

A case of eosinophilic cholecystitis: Radiologic-pathologic correlation.

Eosinophilic cholecystitis (EC) is a rare condition that is characterized by eosinophilic infiltration in the gallbladder wall. We report the case of a 35-year-old woman who presented with unremitting right upper quadrant pain for 1 month. Computed tomography showed a strongly enhanced inner layer of the gallbladder wall. Magnetic resonance imaging of the same area showed low signal intensity on T2-weighted imaging. Cholecystectomy was performed, and histological examination of the surgical specimen revealed >100 eosinophils per high-power field in the inner subserosal layer. The area of these histological findings corresponded to the strongly enhanced inner layer of the gallbladder wall identified on computed tomography.

Multiple calcifying fibrous tumors from gastric and retroperitoneal tissue: A case report.

INTRODUCTION AND IMPORTANCE: Calcifying fibrous tumor (CFT) is a rare benign mesenchymal lesion that has been occurred in the gastrointestinal tract, especially occurs most commonly in the stomach and the small and large intestines. CASE PRESENTATION: 74-year-old woman was admitted to our hospital with complaints of epigastric discomfort. Whole-body computed tomography (CT) revealed a 2.2-cm mass with a 1.2-cm low-density area at the anterior wall in the gastric cardia and lesser omentum; however, no abnormal uptake at the same site was noted on positron emission tomography (PET). We performed laparoscopic tumor resection of the two sites. The postoperative course was good without complications. Histopathological findings revealed collagen fibrous granulation connective tissue and psammomatous calcification. Subsequently, the patient has been relapse-free for 6 months. CLINICAL DISCUSSION: CFT is a rare benign tumor that commonly occurs in soft tissues, such as the subcutaneous extremities and neck. In particular, development from the stomach and lesser omentum has never been reported. Our case was incidentally found on a general examination. In our case, CT showed a low-density area, MRI showed a low-intensity area, and PET examination showed no uptake; it was difficult to establish a preoperative diagnosis. Therefore, in our case, laparoscopic tumor resection was performed, with GIST as the differential diagnosis. CONCLUSIONS: We herein reported a rare gastric and lesser omentum CFT that was successfully treated by laparoscopic surgery. For curative treatment of CFT, complete surgical resection is necessary.

Laparoscopic splenectomy for sclerosing angiomatoid nodular transformation of the spleen: Report a case.

INTRODUCTION AND IMPORTANCE: Sclerosing angiomatoid nodular transformation (SANT) of the spleen is an extremely rare benign lesion. CASE PRESENTATION: Here, we describe the case of a 52-year-woman who was diagnosed with sclerosing angiomatoid nodular transformation of the spleen. Abdominal contrast-enhanced CT revealed a solid lesion in the splenic hilum that was slowly enhanced between the portal venous and equilibrium phases incidentally. Fluorodeoxyglucose positron emission tomography (FDG-PET) revealed FDG accumulation within the mass, with a maximum standardized uptake value (SUVmax) of 2.57. Based on these findings, the patient was scheduled for laparoscopic splenectomy. The total operating time was 193 min, and the intraoperative blood loss was 20 ml. The resected specimen was 9.0 × 8.4 × 5.6 cm and dark brown in colour with a large central stellate fibrotic scar. CLINICAL DISCUSSION: Pathological examination revealed nodular angioma lesions and the proliferation of fibrotic interstices and inflammatory cells. We could diagnose the SANT by the only HE staining without Immunohistochemical staining. CONCLUSION: Although SANT is a rare benign lesion, which is difficult to definitively diagnose based on preoperative imaging findings alone, it should be considered in cases of solitary splenic lesions, and we recommend performing LS and subsequent histological examination for the diagnosis of this disease.

Case report of a Japanese patient with chronic renal failure who developed SARS-CoV-2 in a hospital cluster during treatment for acute respiratory failure: An autopsy report.

This article reports a clinical and histopathological perspective which noted not only COVID-19 pneumonia but also exacerbation of chronic renal failure potentially caused by thrombus in the kidney, possibly COVID-19-related lesions. The accumulation of autopsy cases will elucidate the pathogenesis of COVID-19 and aid in the development of effective therapeutics.

An operative case of hepatic pseudolymphoma difficult to differentiate from primary hepatic marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

Hepatic pseudolymphoma (HPL) and primary hepatic marginal zone B cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are rare diseases and the differential diagnosis between these two entities is sometimes difficult. We herein report a 56-year-old Japanese woman who was pointed out to have a space occupying lesion in the left lateral segment of the liver. Hepatitis viral-associated antigen/antibody was negative and liver function tests including lactic dehydrogenase, peripheral blood count, tumor markers and soluble interleukin-2 receptor were all within normal limit. Imaging study using computed tomography and magnetic resonance imaging were not typical for hepatocellular carcinoma, cholangiocarcinoma, or other metastatic cancer. Fluorodeoxyglucose-positron emission tomography examination integrated with computed tomography scanning showed high standardized uptake value in the solitary lesion in the liver. Under a diagnosis of primary liver neoplasm, laparoscopic-assisted lateral segmentectomy was performed. Liver tumor of maximal 1.0 cm in diameter was consisted of aggregation of lymphocytes of predominantly B-cell, containing multiple lymphocyte follicles positive for CD10 and bcl-2, consistent with a diagnosis of HPL rather than MALT lymphoma, although a definitive differentiation was pending. The background liver showed non-alcoholic fatty liver disease/early non-alcoholic steatohepatitis. The patient is currently doing well with no sign of relapse 13 months after the surgery. Since the accurate diagnosis is difficult, laparoscopic approach would provide a reasonable procedure of diagnostic and therapeutic advantage with minimal invasiveness for patients. Considering that the real nature of this entity remains unclear, vigilant follow-up of patient is essential.

Total pancreatectomy for pancreatic remnant carcinoma five years after pancreaticoduodenectomy: Report a case.

INTRODUCTION AND IMPORTANCE: The prognosis of non-invasive intraductal papillary mucinous neoplasma (IPMN) is better than that of pancreatic cancer. However, if the first surgical finding revealed an invasive IPMC, the risk of recurrence was found to be 7-21%. CASE PRESENTATION: A 76-year-old Japanese man had undergone subtotal stomach-preserving pancreaticoduodenectomy for intraductal papillary mucinous carcinoma non-invasive type at our hospital. No signs of adenocarcinoma at the resection margin were found by pathological examination of frozen sections. Five years later, a blood analysis showed increased serum CA19-9 level. A contrast-enhanced computed tomography scan of the abdomen revealed a mass adjacent to the pancreaticogastrostomy anastomosis. The patient underwent a total pancreatectomy. The tumor was identified as a recurrent IPMC with subserosal invasion, but without nodal involvement. The resection margins were negative. The patient's postoperative course was uneventful, and he was discharged after 12 days. He is being followed up without adjuvant chemotherapy. DISCUSSION: The prognosis of IPMN is better than that of pancreatic cancer. However the risk of recurrence in invasive IPMC was found to be 7-21%. Therefore, IPMC must be surveilled every three months using tumor markers and imaging. Local recurrence in remnant pancreas is usually treated with systemic therapy. The median long-term survival after total pancreatectomy (range 7-24 months) was shown to be better than when chemotherapy alone was used (range 10-13 months). CONCLUSION: We chose secondary surgery in term of survival time although there are quality of life drawbacks that currently make total pancreatectomy more inappropriate in patients than chemotherapy.

Granular cell tumor coexisting with adenocarcinoma in the stomach: Report of a rare case.

INTRODUCTION: and importance: Granular cell tumor (GCT) is a benign, mesenchymal tumor that originates from Schwann cells. CASE PRESENTATION: A 75-year-old Japanese woman was referred to our hospital due to epigastric discomfort. Upper gastrointestinal endoscopy revealed an ulcerated cancer lesion, approximately 1.2 cm in diameter, at the angle of the stomach in the posterior gastric wall and a yellowish submucosal tumor, 5 mm in diameter, near an anal ulcerated lesion. Based on these findings, the patient was scheduled for laparoscopic distal gastrectomy and lymph node dissection. The pathological diagnosis was a moderately differentiated tubular adenocarcinoma invading mucosal stroma without lymph node metastasis and GCT in the stomach. Tumor cells were positive for S-100 and were consistent with the characteristics of GCT. CLINICAL DISCUSSION: To the best of our knowledge, this is an extremely rare case with reports of only 6 cases of such a combination, including our case. CONCLUSIONS: We believe that the coexistence of a GCT and gastric cancer in our patient was accidental and that there was no relation between them.

Collision Tumor Comprising Primary Malignant Lymphoma and Adenocarcinoma in the Ascending Colon.

We describe the case of a 78-year-old man with collision tumor from the primary malignant lymphoma and adenocarcinoma in the ascending colon. He suffered anemia from sigmoid colon cancer, and colonoscopy revealed early-stage colorectal cancer with a diameter of 20 mm in the cecum, the biopsy specimen showed moderately differentiated adenocarcinoma. Contrast-enhanced computed tomography (CT) revealed bowel wall thickening with contrast enhancement at the cecum; however, no lymph node and organ metastases were found. As above, we performed laparoscopic ileocecal resection with D3 lymph node dissection. The postoperative course was uneventful, and he was discharged from the hospital on postoperative day 11. Histopathological findings were moderately differentiated adenocarcinoma which invaded the muscularis propria and serosa from the submucosa, while the adjacent serosa showed a highly diffuse proliferation of atypical cells with an irregular nuclear-to-cytoplasmic ratio. Besides, immunohistochemical staining findings were diffuse large B-cell lymphoma, and diffuse large B-cell lymphoma was coexistent with moderately differentiated adenocarcinoma. We treated the patient with cyclophosphamide, doxorubicin, vincristine, and prednisolone in combination with rituximab (R-CHOP therapy) during 3 months postoperatively. When the 8 courses had been completed, postoperative positron emission tomography-CT (PET-CT) confirmed complete response, and the disease control has been doing well. Malignant lymphoma of the colorectal region is relative rare, and the occurrence of synchronous lymphoma and adenocarcinoma of the colon is also rare. Furthermore, collision tumor by these different entities is very unusual. We presented here such a case. The accurate clinical determination of the dominant tumor and a close follow-up is required for proper treatment in these cases.

Cytologic findings of metastatic hepatocellular carcinoma of the nasal cavity: a report of 2 cases.

BACKGROUND: Hepatocellular carcinoma metastasizing to the nasal cavity is rare, but nasal bleeding caused by it is difficult to treat. The reason is that a large majority of patients have a bleeding tendency due to liver cirrhosis. Accordingly, early and correct diagnosis is essential. CASES: Case 1, a Japanese man in therapy for C type liver cirrhosis and hepatocellular carcinoma, was diagnosed as metastasis to the bones, and then he was admitted. After hospitalization, he complained of nasal obstruction. Fine needle aspiration biopsy from a tumor occupying nasal and maxillary cavities showed overlapped cells and scattered cells having a round to oval nucleus containing one or a few large nucleoli. The characteristics of cells indicated metastasis of hepatocellular carcinoma. In case 2, a Japanese man under treatment for liver cancer visited our hospital with a complaint of nasal obstruction. In fine needle aspiration biopsy from a mass in the right nasal cavity, cohesive clusters and sparse neoplastic cells similar to those observed in the first case were found. CONCLUSION: Aspiration cytology is useful in the diagnosis and treatment of hepatocellular carcinoma metastatic to the nasal cavity. Finding characteristic cells is important in the diagnosis. Clinical information is sure to be a convincing clue.

Clinicopathological analysis of recurrence patterns and prognostic factors for survival after hepatectomy for colorectal liver metastasis.

BACKGROUND: Hepatectomy is recommended as the most effective therapy for liver metastasis from colorectal cancer (CRCLM). It is crucial to elucidate the prognostic clinicopathological factors. METHODS: Eighty-three patients undergoing initial hepatectomy for CRCLM were retrospectively analyzed with respect to characteristics of primary colorectal and metastatic hepatic tumors, operation details and prognosis. RESULTS: The overall 5-year survival rate after initial hepatectomy for CRCLM was 57.5%, and the median survival time was 25 months. Univariate analysis clarified that the significant prognostic factors for poor survival were depth of primary colorectal cancer (≥ serosal invasion), hepatic resection margin (< 5 mm), presence of portal vein invasion of CRCLM, and the presence of intra- and extrahepatic recurrence. Multivariate analysis indicated the presence of intra- and extrahepatic recurrence as independent predictive factors for poor prognosis. Risk factors for intrahepatic recurrence were resection margin (< 5 mm) of CRCLM, while no risk factors for extrahepatic recurrence were noted. In the subgroup with synchronous CRCLM, the combination of surgery and adjuvant chemotherapy controlled intrahepatic recurrence and improved the prognosis significantly. CONCLUSIONS: Optimal surgical strategies in conjunction with effective chemotherapeutic regimens need to be established in patients with risk factors for recurrence and poor outcomes as listed above.

Significance of chymase-dependent angiotensin II formation in the progression of human liver fibrosis.

AIM: Angiotensin II may contribute to liver fibrogenesis. In addition to angiotensin-converting enzyme (ACE), chymase, which is expressed by mast cells, is also known to be an angiotensin II-forming enzyme. However, it is unclear which of these two angiotensin II-forming enzymes plays a more important role in liver cirrhosis progression. In the present study, the role of angiotensin II-forming enzymes in the progression of liver cirrhosis was clarified. METHODS: A total of 77 patients (16 in F0 stage, 10 in F1 stage, 22 in F2 stage, 12 in F3 stage, and 17 in F4 stage) were classified according to the new Inuyama classification into a non-cirrhosis (F0) group, an early cirrhosis (F1 + F2) group, and a chronic cirrhosis (F3 + F4) group. RESULTS: Both chymase and total angiotensin II-forming activities were significantly higher in chronic cirrhosis patients than in the other two groups. However, there was nodifference among the three groups in ACE activity. On immunohistology, the number of chymase- and angiotensin II-positive cells was significantly higher in the chronic cirrhosis group than in the non-cirrhosis and early cirrhosis groups. There were significant correlations between the number of chymase-positive cells and the number of angiotensin II-positive cells, between the number of chymase-positive cells and the degree of fibrosis, and between the number of angiotensin II-positive cells and the degree of fibrosis. CONCLUSION: These results suggest that chymase-dependent angiotensin II formation may play an important role in hepatic fibrosis of patients with cirrhosis.

Laparoscopic Excisional Cholecystectomy with Full-Thickness Frozen Biopsy in Suspected Gallbladder Carcinoma.

Owing to the advantages of a laparoscopic approach, laparoscopic cholecystectomy (LC) is thought to be the treatment of choice in gallbladder disease, even in cases of suspected malignancy. However, it is difficult to differentiate between cholecystitis and gallbladder carcinoma (GBC). We performed radical hepatectomy in patients with pT2 GBC diagnosed by full-thickness frozen biopsy. A 75-year-old Japanese man presented to our hospital with discomfort in the right upper quadrant of the abdomen. This patient was diagnosed with suspected GBC and was scheduled to undergo LC and intraoperative histological examination. Following the procedure, we made a diagnosis of GBC with negative invasion of the cystic duct stump. We converted the laparoscopic procedure to an open surgery involving wedge liver resection with lymphadenectomy. The patient was discharged from our hospital in remission 14 days following the radical hepatectomy. Histological examination showed that the GBC had invaded the liver (T3a), but there was no lymph node metastasis (N0): stage IIIA. Between April 2009 and September 2018, 580 patients underwent cholecystectomy for gallbladder disease at our hospital. Among these, 8 (1.4%) were suspected to have GBC preoperatively and underwent laparoscopic excisional cholecystectomy. We performed elective surgery in the early stage in two patients and second-look surgery in two patients recently. We were able to perform what we termed a laparoscopic excisional cholecystectomy, involving LC with a full-thickness frozen biopsy, even in situations where intraoperative histological examination was not available. Altogether, laparoscopic excisional cholecystectomy is an effective surgical treatment for suspected early GBC.

Delta-like 3 is silenced by HBx via histone acetylation in HBV-associated HCCs.

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. We previously showed that expression of Delta-like 3 (DLL3), a member of the family of Delta/Serrate/Lag2 ligands for the Notch receptor, is silenced by aberrant DNA methylation and that overexpression of DLL3 in an HCC cell line induces cellular apoptosis. However, how DLL3 expression is regulated during hepatocarcinogenesis is still unclear. Here, we show that silencing of DLL3 during hepatocarcinogenesis is closely related to viral infection, especially hepatitis B virus (HBV) infection (p = 0.005). HepG2.2.15 cells, which are stably transformed with the HBV genome, showed lower DLL3 expression than the parent cell line, HepG2 cells. Treatment with Hepatitis B virus X protein (HBx) small interfering RNA upregulated DLL3 expression in HepG2.2.15 cells, and overexpression of HBx in HepG2 cells downregulated DLL3 expression. Treatment of cells with a histone deacetylase inhibitor induced DLL3 expression in HepG2.2.15 cells. These data suggest that DLL3 expression is silenced during hepatocarcinogenesis in association with HBV infection via an epigenetic mechanism.

A case of multiple inflammatory hepatic pseudotumor protruding from the liver surface after colonic cancer.

INTRODUCTION: Inflammatory hepatic pseudotumor (IHPT) is an important benign liver disease because it is difficult to clinically and radiologically distinguish from malignant tumors. PRESENTATION OF CASE: Here, we describe a case of a 67-year-old male patient diagnosed with multiple inflammatory hepatic pseudotumors. The patient had undergone left hemicolectomy for descending colonic cancer (T3 N0 M0 stage IIA) 2 years prior. He underwent segment 6 and segment 7 partial hepatectomy because of suspected liver metastasis. The patient had an unremarkable postoperative course and was discharged 7days after surgery. Marked infiltration of inflammatory cells was observed on histological examination. The patient was finally diagnosed with IHPT of the fibrohistiocytic type. DISCUSSION: Repeated imaging studies over 1 month showed the spontaneous regression of the hepatic tumors. Therefore, knowledge regarding this condition is necessary to allow for treatment, even in the absence of experience. During examination, it may be important to ascertain lesion size. Moreover, percutaneous needle biopsy and follow-up examinations are necessary for cases of suspected IHPT. CONCLUSION: Hepatectomy should be considered if the lesion is suspected to be an IHPT.