[A case of eosinophilic gastroenteritis caused after the use of Seprafilm®].

Eosinophilic gastroenteritis is a fairly uncommon condition. It has been suggested that allergic reactions may have played a role in the development of this illness. The case of a 66-year-old woman who had a total hysterectomy due to a right ovarian tumor is described here. At this operation, a sodium hyaluronate carboxymethylcellulose bioresorbable membrane (Seprafilm®) was used. She was admitted to our hospital 47 days after the operation with abdominal pain. Laboratory data indicated elevated WBC (29450/µl) and eosinophilia (69.2%), and CT scan showed thickening of intestinal wall and ascites around there. Ascites cytology showed a significant increase of eosinophils (94.0%). She began taking oral steroids after being diagnosed with eosinophilic gastroenteritis, and her symptoms improved quickly. Despite the fact that Seprafilm® was thought to be a reliable and safe tool, it was suggested that a foreign body reaction to Seprafilm® could lead to eosinophilic gastroenteritis.

Significance of in vitro photodynamic cytodiagnosis with 5-aminolevulinic acid in biliary brush cytology for malignant biliary stricture.

BACKGROUND: For the early diagnosis of malignant biliary stricture due to biliary-pancreatic carcinoma, conventional biliary brush cytology with endoscopic retrograde cholangiopancreatography (ERCP; the conventional method) is not sensitive enough. METHODS: Two hundred nine patients with biliary stricture who were admitted between September 2015 and June 2020 were enrolled in this study. Biliary brush cytology was performed on all patients. Samples were diagnosed independently by an expert pathologist and medical doctor with conventional cytology and photodynamic diagnosis (PDD) with 5-aminolevulinic acid. RESULTS: The definitive diagnoses were 49 benign and 160 malignant diseases. The conventional method had a sensitivity of 77.5% (124/160) and specificity of 100% (49/49). The PDD method had a sensitivity of 77.5% (124/160) and specificity of 67.3% (33/49). The conventional method identified 36 malignant diseases as false negatives, while the PDD method enabled successful diagnoses of malignant diseases in 19 of these 36 patients. When PDD was combined with the conventional method, the sensitivity significantly increased to 89.4% (143/160, P = 0.006), and for biliary tract diseases only, the sensitivity increased to 95.6% (88/92, P = 0.001). CONCLUSIONS: Malignant biliary stricture can be diagnosed effectively and safely with the in vitro PDD method. The sensitivity could be further increased by combining PDD with the conventional method.

Oral Zinc Supplementation Decreases the Risk of HCC Development in Patients With HCV Eradicated by DAA.

We have reported that the plasma zinc concentration gradually decreases with the progression of fibrosis and is related to hepatocellular carcinoma (HCC) development. The aim of this study was to examine the impact of the zinc concentration on HCC development (study 1) and the relationship between zinc intake and HCC development (study 2) in patients with hepatitis C virus (HCV) eradicated by direct-acting antivirals (DAAs). A total of 599 sustained virological response (SVR) patients treated with DAAs without a history of HCC were retrospectively analyzed in this study. Eighty patients received supplemental zinc (Zn treatment group), and 519 patients did not receive zinc (no Zn treatment group). In study 1, the cumulative incidence rate of HCC was compared between the Zn treatment group and the no Zn treatment group. In study 2, the risk factors for HCC development were examined in the no Zn treatment group. In study 1, in the Zn treatment group, HCC did not develop during follow-up, and the cumulative risk of HCC was significantly lower in the Zn treatment group than in the no Zn treatment group (P = 0.048). In study 2, the 1-year and 3-year cumulative incidence rates of HCC were 1.8% and 5.6%, respectively. The risk factors for HCC identified by multivariate analysis were male sex, cirrhosis, low platelet count before treatment, and low serum zinc concentration 12 weeks after the end of DAA therapy. Conclusion: The Zn concentration is related to HCC development in patients with HCV eradicated by DAA therapy. Oral zinc supplementation is recommended as a means of suppressing HCC development in patients who have achieved SVR.

Early Administration of Tolvaptan Can Improve Survival in Patients with Cirrhotic Ascites.

(1) Backgrounds and aim: Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved for ascites, and its short-term efficacy and safety have been confirmed. However, it is still unclear whether this novel drug may improve long-term survival rates in cirrhotic patients with ascites. (2) Patients and methods: A total of 206 patients who responded insufficiently to conventional diuretics and were hospitalized for refractory ascites for the first time were retrospectively enrolled in this study. Among them, the first 57 consecutive patients were treated with conventional diuretics (the conventional therapy group); the latter 149 consecutive patients were treated with tolvaptan in addition to the conventional therapy (the tolvaptan group). (3) Results: The exacerbation of renal function was significantly milder in the tolvaptan group than in the conventional therapy group. The prognostic factors for survival in the tolvaptan group were being male, having hyperbilirubinemia, having a high blood urea nitrogen (BUN), and receiving high-dose furosemide at the start of tolvaptan treatment. The one-year and three-year cumulative survival rates were 67.8 and 45.3%, respectively, in patients with low-dose furosemide (<40 mg/day) at the start of tolvaptan treatment. The prognosis was significantly better in the tolvaptan group with low-dose furosemide than in the conventional therapy group (p < 0.001). (4) Conclusion: Tolvaptan can improve survival in patients with cirrhotic ascites, especially when tolvaptan is started before high-dose furosemide administration.

Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma.

Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients), were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were observed to be lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p < 0.001). According to serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dL (p < 0.001). Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dL.

A case of spontaneous splenic rupture during chemotherapy for B-cell chronic lymphoid leukemia.

Spontaneous splenic rupture is a life-threatening disease and an important differential diagnosis of acute abdomen. Early clinical diagnosis and rapid intervention is required to ensure patient survival. Spontaneous splenic rupture may be induced by hematological, inflammatory or infiltrative diseases affecting the spleen. Splenomegaly may also significantly increase the risk of rupture. Other contributory factors include male, adulthood, rapid growth of the spleen and splenic abscess. Here, we present the case of a 69-year-old man who was undergoing chemotherapy for B-cell chronic lymphoid leukemia. He was admitted to our hospital after he suddenly developed persistent upper abdominal pain. Computed tomography and ultrasonography revealed accumulation of free fluid in and around the spleen. He was diagnosed as having spontaneous splenic rupture and an emergency operation was performed. During the operation, we found a massively enlarged spleen with several capsular tears, and performed a splenectomy. The patient made a good recovery. Pathological examination revealed that the spleen was infiltrated by CD20-, CD5- and CD23-positive lymphoid blasts. We encountered a case of spontaneous splenic rupture in a patient receiving chemotherapy for exacerbating B-cell chronic lymphoid leukemia. In a case of abdominal pain of acute onset in patients with hematological disease, spontaneous splenic rupture should be suspected.

[Synchronous double cancer of the gallbladder and rectum successfully treated with S-1 as second-line chemotherapy- a case report].

A 66-year-old man was referred to our hospital with obstructive jaundice. Computed tomography(CT)scan showed thickening of the gallbladder wall, invasion into the liver bed, and thickening of the rectal wall. Colonoscopy revealed a type 2 rectal cancer, in which adenocarcinoma was identified by endoscopic biopsy. He was diagnosed with double-cancer of the gallbladder and rectum. Because his gallbladder cancer was more life threatening than his rectal cancer, gemcitabine was administered at 1, 000 mg/m2 on days 1, 8, and 15 of a 28-day course. After 3 courses of gemcitabine, the CT scan showed that the lymph nodes in the hepatoduodenal ligament had been enlarged, and duodenal stenosis had occurred as a result of gallbladder cancer invasion. S-1 was administered orally at doses of 120 mg/day twice daily on days 1-28 of a 42-day course. Partial response was confirmed by CT scan. After 8 courses of S-1, the gallbladder cancer had progressed and liver metastases had appeared. He subsequently died of disease progression. He survived for 17 months after the first course of chemotherapy, and the progression-free survival with S-1 was 10 months. Therefore, S-1 could be an effective agent for synchronous double cancer of the gallbladder and rectum.

Poorly differentiated endocrine carcinoma of the pancreas responded to gemcitabine: Case report.

Poorly differentiated endocrine carcinoma (PDEC) of the pancreas is a rare and aggressive tumor. First-line treatment is commonly a combination of etoposide and cisplatin, but there is no consensus regarding further treatment recommendations. In this report, we describe a case of pancreatic PDEC treated with gemcitabine as third-line chemotherapy. A 62-year-old man with pancreatic PDEC was administered etoposide plus cisplatin as first-line treatment; he then received irinotecan for tumor relapse. However, because irinotecan induced ileus in this patient, we chose gemcitabine as third-line chemotherapy. After two cycles of gemcitabine (1000 mg/m(2) on days 1, 8 and 15 every 4 wk), a partial tumor response was noted by computed tomography (approximately 68% reduction in tumor size). Our patient survived for 15 mo after diagnosis. This is a rare case of unresectable pancreatic PDEC, which showed a partial response to gemcitabine after the failure of two other regimens. Gemcitabine could be an effective treatment option for pancreatic PDEC that is resistant to other treatments.

Phosphorylation of Numb regulates its interaction with the clathrin-associated adaptor AP-2.

Numb is thought to participate in clathrin-dependent endocytosis by directly interacting with the clathrin-associated adaptor complex AP-2, although the underlying mechanisms are unknown. Numb is also known to be phosphorylated at Ser(264)in vitro and in vivo. Here, we found that Numb is phosphorylated in vitro by Ca(2+)/calmodulin-dependent protein kinase I on Ser(283). This phosphorylation was also observed in transfected COS-7 cells, indicating its physiological relevance. Pull-down experiments showed that the phosphorylation of Numb impaired its binding to the AP-2 complex and simultaneously recruited 14-3-3 proteins in vitro. Based on experiments using Numb mutants, both the initial phosphorylation of Ser(264) and the subsequent phosphorylation of Ser(283) are sufficient to abolish the binding of Numb to AP-2 and to promote the interaction with 14-3-3 protein. These findings suggest a novel mechanism for the regulation of Numb-mediated endocytosis, namely through direct phosphorylation.

Phosphorylation of Numb family proteins. Possible involvement of Ca2+/calmodulin-dependent protein kinases.

To search for the substrates of Ca2+/calmodulin-dependent protein kinase I (CaM-KI), we performed affinity chromatography purification using either the unphosphorylated or phosphorylated (at Thr177) GST-fused CaM-KI catalytic domain (residues 1-293, K49E) as the affinity ligand. Proteomic analysis was then carried out to identify the interacting proteins. In addition to the detection of two known CaM-KI substrates (CREB and synapsin I), we identified two Numb family proteins (Numb and Numbl) from rat tissues. These proteins were unphosphorylated and were bound only to the Thr177-phosphorylated CaM-KI catalytic domain. This finding is consistent with the results demonstrating that Numb and Numbl were efficiently and stoichiometrically phosphorylated in vitro at equivalent Ser residues (Ser264 in Numb and Ser304 in Numbl) by activated CaM-KI and also by two other CaM-Ks (CaM-KII and CaM-KIV). Using anti-phospho-Numb/Numbl antibody, we observed the phosphorylation of Numb family proteins in various rat tissue extracts, and we also detected the ionomycin-induced phosphorylation of endogenous Numb at Ser264 in COS-7 cells. The present results revealed that the Numb family proteins are phosphorylated in vivo as well as in vitro. Furthermore, we found that the recruitment of 14-3-3 proteins was the functional consequence of the phosphorylation of the Numb family proteins. Interaction of 14-3-3 protein with phosphorylated Numbl-blocked dephosphorylation of Ser304. Taken together, these results indicate that the Numb family proteins may be intracellular targets for CaM-Ks, and they may also be regulated by phosphorylation-dependent interaction with 14-3-3 protein.