[A case of unresectable intrahepatic cholangiocarcinoma receiving sustainable pembrolizumab therapy].

A 65-year-old man had unresectable intrahepatic cholangiocarcinoma with a malignant biliary stricture. We used an endoscopic plastic stent to drain the bile. Despite receiving standard chemotherapy, the tumor eventually progressed and cancerous peritonitis developed. We had to exchange plastic stents frequently because of stent occlusion. We had a re-biopsy with EUS-FNA and tested for microsatellite instability, which came back as MSI-high. We administered pembrolizumab, which resulted in a significant reduction of tumor size. We were able to administer long-term chemotherapy without serious side effects by repeatedly exchanging plastic stents for stent occlusion. He has maintained partial response for more than 20 months after receiving pembrolizumab.

[A case of SIADH due to pancreatic cancer was improved by tolvaptan].

We report the case of a 68-year-old man, who presented in emergency care with inarticulate speech. The patient was diagnosed with syndrome of inappropriate antidiuretic hormone (SIADH) associated with pancreatic cancer. All diagnostic criteria for SIADH were met, and cancer of the pancreatic tail was identified by computed tomography. Standard treatment for SIADH includes water restriction, oral NaCl, continuous intravenous infusion of 3% NaCl, and intravenous infusion of furosemide. However, these treatments have varying effectiveness and are difficult for both patients and medical staff. Furthermore, unless treatment of the underlying disease is successful, continued hospitalization is needed and the patient's quality of life is significantly impaired. In this case, hyponatremia improved with this standard treatment, but ascites and edema developed. We treated the patient with tolvaptan due to decreased cardiac function, and symptoms improved rapidly. Although surgery and chemotherapy could not be performed for pancreatic cancer, the SIADH was treated for 7 months without relapse. In summary, a case of SIADH complicated by pancreatic cancer was difficult to control with standard treatment, but responded rapidly to tolvaptan, and outpatient treatment could be continued for a long period. Tolvaptan is useful for the treatment of SIADH associated with cancer.

[A case of thrombotic microangiopathy during chemotherapy with gemcitabine in a patient with pancreatic cancer].

A 57-year-old male patient with unresectable pancreatic head cancer was treated with chemotherapy, 5 courses of gemcitabine plus nab paclitaxel therapy, and 9 courses of gemcitabine monotherapy. After 12 months of treatment, he was admitted to our hospital with headache and dyspnea. He was diagnosed with gemcitabine-induced thrombotic microangiopathy (TMA) due to acute kidney dysfunction, hemolytic anemia, and thrombocytopenia. Gemcitabine was discontinued, and symptoms were improved without using hemodialysis and plasma exchange. After his renal function recovered, we started S-1 chemotherapy. Eighteen months later, the patient was alive. Looking back, we realized that fragment red blood cells appeared in complete blood count and serum LDH elevated at 5 months prior to admission, serum creatinine level increased slowly at 4 months prior to admission, and blood pressure elevated significantly at 2 months prior to admission. Therefore, physicians must be aware of TMA as a possible adverse event to gemcitabine. As in this case, hemolytic findings and hypertension in patients treated with gemcitabine may help early detection of TMA.

Gaussian Curvature Entropy for Curved Surface Shape Generation.

The overall shape features that emerge from combinations of shape elements, such as "complexity" and "order", are important in designing shapes of industrial products. However, controlling the features of shapes is difficult and depends on the experience and intuition of designers. Among these features, "complexity" is said to have an influence on the "beauty" and "preference" of shapes. This research proposed a Gaussian curvature entropy as a "complexity" index of a curved surface shape. The proposed index is calculated based on Gaussian curvature, which is obtained by the sampling and quantization of a curved surface shape and validated by the sensory evaluation experiment while using two types of sample shapes. The result indicates the correspondence of the index to perceived "complexity" (the determination coefficient is greater than 0.8). Additionally, this research constructed a shape generation method that was based on the index as a car design supporting apparatus, in which the designers can refer many shapes generated by controlling "complexity". The applicability of the proposed method was confirmed by the experiment while using the generated shapes.

[A case report of suspected Stauffer syndrome presenting with fever, extensive inflammation, and abnormal liver function tests].

A man was referred to our hospital because of malaise and abnormal liver function tests. He had had a kidney removed for early renal cell carcinoma. We performed ultrasonography, CT scan, and liver biopsy, all of which were normal. However, FDG-PET revealed abnormal, diffuse uptake in the bone. A bone biopsy showed abnormal clear cells resembling renal cell carcinoma. Because there was no other primary origin, this histopathological finding led to the diagnosis of bone metastasis of renal cell carcinoma, and the abnormal liver function test was thus inferred to be due to Stauffer syndrome.

A case of hepatic reactive lymphoid hyperplasia: the review of 23 cases from the literatures.

A 70-year-old woman was referred to our hospital because of slight elevation of soluble interleukin-2 receptor (sIL-2R) and accumulation of 18F-fluorodeoxyglucose (FDG) in S8 of the liver on positron emission tomography. The mass was strongly suspected to be malignant because of contrast enhancement and enlargement in size of the mass, and suspicion of portal vein invasion. Hepatic S8 subsegmentectomy was performed for diagnostic and therapeutic purposes. Hematoxylin and eosin staining of the resected specimen showed small lymphocytes with no atypia and no formation of lymphoid follicles. Immunostaining showed CD3-positive cells in the interfollicular region and CD20-positive cells in the lymphoid follicles. Both CD10 and BCL-2 were negative in the follicular germinal center. CD138-positive plasma cells were observed and there was no light chain restriction. Based on polyclonal growth pattern of lymphocytes in the lymphoid follicles and interfollicular region, she was diagnosed with hepatic reactive lymphoid hyperplasia (RLH).Review of the English literature of hepatic RLH which referred to imaging findings yielded 23 cases, including this case. As a result, we suggest that liver biopsy should be performed for definitive diagnosis, when hepatic RLH is suspected by imaging findings and backgrounds.

[CT enterography with polyethylene glycol electrolyte solution for diagnosis of Crohn's disease].

This study aimed to assess the diagnostic usefulness of CT enterography (CTE) in Crohn's disease in Japanese patients. A total of 32 cases with bowel symptoms underwent CT enterography with polyethylene glycol electrolyte solution as oral contrast medium, among which 18 were clinically diagnosed as Crohn's disease and 14 were not: ulcerative colitis 1, Beçhet disease 1, simple ulcer 1, inflammatory bowel disease without definite diagnosis 5 and bowel symptoms of unknown origin 6. The incidence of bowel wall thickening, mural hyperenhancement, "the comb sign", mesenteric lymph nodes swelling, and stenosis were significantly higher in Crohn's disease than in other disease. Moreover, uneven bowel wall thickening and unilateral mural hyperenhancement on CTE were characteristic features of Crohn's disease, which our original quantitative evaluation with imaging analysis could support. Consequently, CTE is useful in Japanese patients with Crohn's disease.

Efficacy and Safety of Lenvatinib for Patients With Advanced Hepatocellular Carcinoma: A Retrospective, Real-world Study Conducted in Japan.

AIM: We evaluated real-world efficacy and toxicity of lenvatinib in 142 patients with advanced hepatocellular carcinoma (HCC) at six tertiary referral centres. PATIENTS AND METHODS: The patients with advanced HCC treated with lenvatinib were grouped into two categories based on REFLECT criteria for analysis of efficacy and safety. The primary endpoint was progression-free survival (PFS). RESULTS: The objective response rate (ORR) at week 12 of therapy was 41.5%, with a median PFS of 176 days. Child-Pugh score of 5 points, the presence of extrahepatic metastasis and adverse effects grade 2 or higher were considered independent factors associated with both better PFS and ORR. The ORR for patients who fulfilled the REFLECT inclusion criteria was significantly higher than that for those who did not. However, no significant differences in PFS were observed between the two groups. The incidence rate of adverse effects grade 3 or higher was 40.1%, which was similar for the two groups. CONCLUSION: Lenvatinib is safe and effective for patients, whether or not they satisfy REFLECT criteria. The result warrants replication in a larger study.

[A case of jejunal adenocarcinoma with serum DUPAN-2 elevation].

A 50-year-old woman was admitted to our hospital because of abdominal pain and vomiting. Ileus with ulcerated jejunal tumor was diagnosed and biopsy revealed adenocarcinoma. Because her serum level of DUPAN-2 was high, she was examined by PET scan, which revealed that she had a left ovarian mass in addition to the jejunal tumor. Surgical resection was performed: both tumors were adenocarcinoma, but the ovarian tumor was considered to be metastatic clinically and histologically. Immunostaining for DUPAN-2 was positive in the both tumors. The serum level of DUPAN-2 returned to normal after the surgery, and has been within normal limits for about 3 years without any additional therapy. This case shows a possible relation between small bowel adenocarcinoma and DUPAN-2.

Chronic Gastritis Due to Helicobacter Pylori Associated with Increased Serum Levels of CA54/61: A Report of Three Cases.

BACKGROUND The bacterial pathogen Helicobacter pylori (H. pylori) can cause chronic gastritis. CA54/61 is a serum tumor marker that has been shown to be positive in the several types of human malignancy. However, the association of between chronic gastritis due to H. pylori and elevated serum levels of CA54/61 has not been previously reported. This report is of three cases of increased serum levels of CA54/61 associated with H. pylori chronic gastritis. CASE REPORT Case 1 was a 44-year-old Japanese woman with a serum CA54/61 level of 138 U/ml (normal level: 12 U/ml). Following treatment and eradication of H. pylori the serum CA54/61 level decreased to 14 U/ml. Case 2 was a 73-year-old Japanese man with a serum level of less than 2 U/ml before completion of successful eradication therapy of H. pylori with a small peak of 30 U/ml after therapy. Case 3 was a 54-year-old Japanese man who maintained a serum CA54/61 level of approximately 20 U/ml before and until 603 days after eradication therapy. None of the three patients had malignancy, which is usually suggested by this serum marker. CONCLUSIONS These three case reports suggest the possibility of an association between chronic gastritis involving H. pylori infection and an elevated serum level of CA54/61. It is possible that the inflammatory gastric mucosal cells supply CA54/61 to the bloodstream. However, further studies are required to confirm the association between serum levels of CA54/61 and H. pylori chronic gastritis and the underlying mechanisms of this association.

Immunoglobulin G4-related hepatic inflammatory pseudotumor invading the abdominal wall.

A 50-year-old woman presented with epigastralgia. Computed tomography (CT) of the abdomen revealed a 6-cm well-enhanced mass extending from the left lobe of the liver to the abdominal wall, suggestive of cholangiocarcinoma. Liver and skin mass biopsies did not provide evidence of hepatic malignancy but were rich in plasma cells and sclerotic lesions. Subsequent detection of elevated serum immunoglobulin G4 (IgG4) led to a diagnosis IgG4-related inflammatory pseudotumor (IPT) of the liver. Treatment with systemic corticosteroids resulted in rapid clinical improvement. This case is the first report of an IgG4-related hepatic IPT invading the abdominal wall.

Helicobacter pylori-negative gastric cancer: advanced-stage undifferentiated adenocarcinoma located in the pyloric gland area.

The incidence of Helicobacter pylori-negative gastric cancer (HpNGC) is extremely low. A 78-year old female without H. pylori infection was diagnosed with type 4 advanced-stage gastric prepylorus cancer. Distal gastrectomy was performed as for HpNGC (cT3N0M0). Histological findings of the resected specimen showed poorly differentiated adenocarcinoma and signet ring cell carcinoma, which were located in the pyloric gland area, diffusely invaded beyond the serosa without lymph node metastasis (pT4aN0M0). Most cases of undifferentiated-type HpNGC are diagnosed in the early stage and are located in the fundic gland area. We report the first case of advanced-stage undifferentiated HpNGC located in the pyloric gland area.

Early diagnosis of pancreatic necrosis based on perfusion CT to predict the severity of acute pancreatitis.

BACKGROUND: Perfusion CT can diagnose pancreatic necrosis in early stage of severe acute pancreatitis, accurately. However, no study to date has examined whether early diagnosis of pancreatic necrosis is useful in predicting persistent organ failure (POF). METHODS: We performed a multi-center prospective observational cohort study to investigate whether perfusion CT can predict the development of POF in the early stage of AP, based on early diagnosis of the development of pancreatic necrosis (PN). From 2009 to 2012, we examined patients showing potential early signs of severe AP (n = 78) on admission. Diagnoses for the development of PN were made prospectively by on-site physicians on the admission based on perfusion CT (diagnosis 1). Blinded retrospective reviews were performed by radiologists A and B, having 8 and 13 years of experience as radiologists (diagnosis 2 and 3), respectively. Positive diagnosis for the development of PN were assumed equivalent to positive predictions for the development of POF. We then calculated the area under the curve (AUC) of the receiver operating characteristic for POF predictions. RESULTS: Fourteen (17.9%) and 23 patients (29.5%) developed PN and POF, respectively. For diagnoses 1, 2, and 3, AUCs for POF predictions were 74, 68, and 73, respectively. CONCLUSIONS: Perfusion CT diagnoses pancreatic necrosis and on that basis predicts the development of POF; http://www.umin.ac.jp/ctr/index-j.htm,UMIN000001926 .

Spontaneous regression of hepatocellular carcinoma: its imaging course leading to complete disappearance.

Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. We followed a detailed clinical course of a spontaneous and complete disappearance of HCC during a short interval. A 73-year-old man with hepatitis B virus infection presented with a 15-mm mass in the right anterior superior segment of the liver. The mass was diagnosed as HCC by imaging findings. We found an elevated serum α-fetoprotein (AFP) level of 748 ng/ml. The tumor regressed to 6 mm on imaging examination, and the AFP serum level decreased to 87.8 ng/ml 1 month after the diagnostic hepatic angiography. Therefore, the patient was followed up without any treatment for HCC. The tumor disappeared 5 months later when the AFP serum level was 5.0 ng/ml. The diagnostic hepatic angiography might have had some effect on the spontaneous regression of HCC in the present case.

Risk of HCV transmission after needlestick injury, and the efficacy of short-duration interferon administration to prevent HCV transmission to medical personnel.

BACKGROUND: We carried out this study to assess the risk of hepatitis C virus (HCV) transmission after needlestick injuries in medical personnel, and to evaluate the efficacy of short-duration interferon administration to prevent HCV transmission. METHODS: A total of 684 personnel who had been occupationally exposed to an anti-HCV-positive source and followed for more than 3 months were retrospectively examined. RESULTS: Of the 684 subjects, 279 (41%) were treated with 1 to 3 days of interferon either just after or 1 to 12 days after the injury. One case of HCV infection was found in each of the treated (1/279; 0.4%) and nontreated (1/405; 0.2%) groups. There was no significant difference in the transmission of HCV between the two groups. Both infected patients were treated with interferon after developing acute hepatitis, and HCV was subsequently cleared. CONCLUSIONS: There is a lower risk of HCV transmission after needlestick accident than previously reported, and short-duration interferon administration at an early stage after the needlestick injury, to prevent HCV transmission, is unnecessary.