Sporadic gastric juvenile polyposis with a novel SMAD4 nonsense mutation in a mosaic pattern.

A 50-year-old female was diagnosed with gastric hyperplastic polyps 7 years before and was followed up at another hospital. She was referred to our hospital because of the growth of gastric polyps and progression of anemia. She had no family history of polyposis. The polyps were observed only in the stomach, increased in size and number, and the erythematous edema got worse. Endoscopic mucosal resection (EMR) of the gastric polyp was performed. Pathologically, the gastric polyp was hamartomatous polyp, and the intervening mucosa between polyps showed no atypical structure without inflammation. Given that gastric juvenile polyposis (GJP) was clinically suspected, a genetic test using peripheral blood was performed. Target resequencing and Sanger sequencing analysis revealed a nonsense mutation in the SMAD4 gene at codon 169. The mutation was detected at a low frequency of 11%, and considered a mosaic mutation. Therefore, she was diagnosed with a sporadic GJP, and total gastrectomy was performed. Immunostaining of SMAD4 for the resected specimen showed a mixture of stained and unstained area in the epithelium of the polyp, indicating partial loss of SMAD4 expression. To our knowledge, this is the first reported case of GJP with a nonsense SMAD4 mutation at codon 169 in a mosaic pattern.

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.

[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 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.

[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.

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 rare case of Epstein-Barr virus-positive early gastric carcinoma with lymphoid stroma successfully treated by endoscopic submucosal dissection alone.

Gastric carcinoma with lymphoid stroma (GCLS), a rare subset of gastric cancer, has a low frequency of lymphovascular invasion and a relatively better prognosis compared with conventional gastric cancer. We herein report a rare case of early GCLS successfully treated by endoscopic submucosal dissection alone. The lesion was located in the upper gastric body and approximately 9 mm in size. We assessed that the lesion was within an absolute indication for endoscopic resection. We performed endoscopic submucosal dissection and succeeded in en bloc resection. A histopathological assessment disclosed that the carcinoma was poorly differentiated with massive infiltration of lymphocyte and invaded the submucosal layer massively at 1000 µm in depth. There were no visible lymphovascular invasions in the specimen. Since the Epstein-Barr virus (EBV)-encoded small RNA in situ hybridization revealed that cancer cells were positive for EBV, the patient was finally diagnosed with EBV-positive GCLS. We persuaded the patient to receive an additional surgery; however, the patient refused to undergo it. The patient has been followed for more than 5 years without recurrence.

A rare cause of multiple liver masses.

Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease. However, if atypical hepatic masses are observed, hepatic MALT lymphoma should be considered in the differential.

Endoscopic placement of covered versus uncovered self-expandable metal stents for palliation of malignant gastric outlet obstruction.

OBJECTIVE: Stenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results. DESIGN: In a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours. RESULTS: Overall survival was poor with no difference between groups (probability at 3 months 49.7% for covered vs 48.4% for uncovered stents; log-rank for overall survival p=0.26). Within that setting of short survival, the proportion of stent dysfunction was significantly higher for uncovered stents (35.2% vs 23.4%, p=0.01) with significantly shorter time to stent dysfunction. This was mainly relevant for patients with extrinsic tumours (stent dysfunction rates for uncovered stents 35.6% vs 17.5%, p<0.01). Subgrouping was also relevant with respect to tumour ingrowth (lower with covered stents for intrinsic tumours; 1.6% vs 27.7%, p<0.01) and stent migration (higher with covered stents for extrinsic tumours: 15.3% vs 2.5%, p<0.01). CONCLUSIONS: Due to poor patient survival, minor differences between covered and uncovered stents may be less relevant even if statistically significant; however, subgroup analysis would suggest to use covered stents for intrinsic and uncovered stents for extrinsic malignancies.

A Rare Case of Lymph Node Metastasis from Early Gastric Cancer.

Gastric cancers that fulfill the Japanese criteria for curative endoscopic resection show a low risk of lymph node (LN) metastasis. Here, we report a case of LN metastasis from early gastric cancer that fulfilled the curative criteria. A 74-year-old Japanese woman was referred to our hospital for treatment of early gastric cancer identified at the site of a hyperplastic polyp that had been diagnosed 10 years prior to presentation. Contrast-enhanced computed tomography did not show any lymphadenopathy and laparoscopy-assisted distal gastrectomy was performed. Histopathological examination revealed a predominantly moderately differentiated adenocarcinoma that measured 15 mm in size and was confined to the mucosa. However, a single metastatic regional LN was observed. A few cancer cells showed positive staining for alpha-fetoprotein. It should be noted that early gastric cancer can be accompanied by LN metastasis even if it fulfills the criteria for curative endoscopic resection.

Edwardsiella tarda-associated cholangitis associated with Lemmel syndrome.

Edwardsiella tarda is an unusual human pathogen. Gastroenteritis is the most frequently reported manifestation of E.tarda infection and extraintestinal infection including cholangitis has rarely been reported. The overall mortality rate for E.tarda bacteremia is, however, reported to be up to 50% (Janda and Abbott, 1993). We describe a 80-year-old diabetic woman with cholangitis and E.tarda bacteremia with a biliary obstruction associated with a large juxtapapillary duodenal diverticulum (Lemmel syndrome) in the setting of past partial hepatectomy and cholecystectomy. She was successfully treated with endoscopic biliary drainage and antibacterials.

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.