aMAP score prediction of hepatocellular carcinoma occurrence and incidence-free rate after a sustained virologic response in chronic hepatitis C.

AIMS: Hepatocellular carcinoma (HCC) can still occur in hepatitis C virus (HCV) patients who have achieved a sustained virologic response (SVR), which remains an important clinical issue in the direct-acting antivirals era. The current study investigated the clinical utility of the aMAP score (consisting of age, male, albumin-bilirubin, and platelets) for predicting HCC occurrence in HCV patients achieving an SVR by direct-acting antivirals. METHODS: A total of 1113 HCV patients without HCC history, all of whom achieved an SVR, were enrolled for clinical comparisons. RESULTS: Hepatocellular carcinoma was recorded in 50 patients during a median follow-up period of 3.7 years. The aMAP score was significantly higher in the HCC occurrence group than in the HCC-free group (53 vs. 47, p < 0.001). According to risk stratification based on aMAP score, the cumulative incidence of HCC occurrence for the low-, medium-, and high-risk groups was 0.14%, 4.49%, and 9.89%, respectively, at 1 year and 1.56%, 6.87%, and 16.17%, respectively, at 3 years (low vs. medium, low vs. high, and medium vs. high: all p < 0.01). Cox proportional hazard analysis confirmed aMAP ≥ 50 (hazard ratio [HR]: 2.78, p = 0.014), age≥ 70 years (HR: 2.41, p = 0.028), ALT ≥ 17 U/L (HR: 2.14, p < 0.001), and AFP ≥ 10 ng/mL (HR: 2.89, p = 0.005) as independent risk factors of HCC occurrence. Interestingly, all but one patient (99.5%) with aMAP less than 40 was HCC-free following an SVR. CONCLUSION: The aMAP score could have clinical utility for predicting HCC occurrence in HCV patients achieving an SVR.

[Two cases of chronic upside down stomach with "reverse incarceration" in the abdominal cavity].

Upside down stomach (UDS) is a rare type of hiatal hernia. It is categorized by herniation of either the entire stomach or most of the gastric portion of the stomach into the posterior mediastinum. Acute UDS usually presents with abdominal and thoracic symptoms immediately after the stomach rotates, while chronic UDS often has either mild or no symptoms with the entire stomach rotated in the mediastinum. The first case was a 70-year-old female who was admitted with complaints of sudden vomiting and epigastric pain after eating. Computed tomography (CT) revealed UDS. Almost the entire stomach was twisted in the mediastinum, but the fornix was located in the abdominal cavity. After endoscopic reduction, the entire stomach was located in the mediastinum. Her symptoms disappeared and she was able to eat. The second case was another 70-year-old female with multiple hospitalizations due to frequent vomiting after eating. A review of previous CT scans showed a typical chronic UDS with the entire stomach located in the mediastinum. During her most current hospitalization, she was admitted with complaints of frequent vomiting and chest pain after overeating, and a CT showed UDS with only the fornix located in the abdominal cavity. Following hospitalization, the persistent vomiting disappeared and a CT scan at that point revealed that the fornix had returned to the mediastinum and she now had a normal UDS. These results indicate that chronic UDS caused acute symptoms due to "reverse incarceration" in the abdominal cavity through the diaphragmatic hiatus following eating. Chronic UDS is often either asymptomatic or only mildly symptomatic. However, these cases suggest that there is a mechanism whereby chronic UDS may cause acute UDS-like symptoms when the fornix becomes "reversely incarcerated" in the abdominal cavity following eating.

[A case of early syphilitic hepatitis with jaundice cured by high-dose amoxicillin and probenecid].

A 44-year-old man was admitted because of general malaise, jaundice, and epigastric pain. The patient had no significant medical history. However, the patient visited a brothel 3 months ago and noticed initial induration on his penis 2 months ago. Physical examination revealed swelling surface lymph nodes in the inguinals. Laboratory examination showed moderate hepatic disorder and jaundice. Hepatitis virus markers and various types of autoantibodies were negative, but serological test for syphilis was positive. The symptoms and abnormal data improved immediately after the patient was treated with amoxicillin (3000mg/day) and probenecid (750mg/day). Thus, a diagnosis of early syphilitic hepatitis was established. In addition, syphilis is not just a genital disease. This disease should be thought of in a patient with liver dysfunction, especially among people of high sexual activity.

Effectiveness of Glecaprevir/Pibrentasvir for Hepatitis C: Real-World Experience and Clinical Features of Retreatment Cases.

Glecaprevir/pibrentasvir (G/P) are direct-acting antivirals (DAAs) that achieve a high sustained virological response (SVR) rate for hepatitis C virus (HCV) infection. We investigated G/P effectiveness for HCV patients based on real-world experience and the clinical features of retreatment cases. HCV patients (n = 182) were compared for clinical features and outcomes between first treatment (n = 159) and retreatment (n = 23) G/P groups. Overall, 77 patients (42.3%) were male, the median age was 68 years, and 86/66/1/4 cases had genotype 1/2/1+2/3, respectively. An SVR was achieved in 97.8% (178/182) of cases by intention-to-treat analysis and 99.4% (178/179) of cases by per-protocol analysis. There were no remarkable differences between the first treatment and retreatment groups for male (42.8% vs. 39.1%, p = 0.70), median age (68 vs. 68 years, p = 0.36), prior hepatocellular carcinoma (5.8% vs. 8.7%, p = 0.59), or the fibrosis markers AST-to-platelet ratio index (APRI) (0.5 vs. 0.5, p = 0.80) and fibrosis-4 (FIB-4) index (2.2 vs. 2.6, p = 0.59). The retreatment group had a significantly more frequent history of interferon treatment (12.3% vs. 52.2%, p < 0.01) and the Y93H mutation (25.0% vs. 64.7%, p = 0.02). The number of retreatment patients who had experienced 3, 2, and 1 DAA treatment failures was 1, 3, and 19, respectively, all of whom ultimately achieved an SVR by G/P treatment. In conclusion, G/P was effective and safe for both HCV first treatment and retreatment cases despite the retreatment group having specific resistance mutations for other prior DAAs. As G/P treatment failure has been reported for P32 deletions, clinicians should consider resistance mutations during DAA selection.

[Responsiveness of well-differentiated PanNET G3 to platinum-based chemotherapy: a case report].

According to the 2017 WHO classification (4th version), PanNEC G3 was subdivided into two groups:well-differentiated PanNET G3 and poorly differentiated PanNEC. Considering the insufficient number of case reports, appropriate chemotherapy for the new category PanNET G3 remains unknown. Here, we report a case of PanNET G3 that responded to platinum-based chemotherapy.

[Gastric myxoid epithelioid gastrointestinal stromal tumor harboring PDGFRA gene mutation:a case report].

A 67-year-old man visited our hospital with an enlarging abdominal mass several months after he had first noticed his symptoms. An elastic firm tumor was palpated on the left side of the abdomen upon physical examination. The blood test results were normal. Contrast-enhanced computed tomography of the abdomen revealed a 10-cm-diameter homogeneous low-density cystic tumor located at the dorsal portion of the gastric corpus. Enhancement of a few net-like structures was noted, but most of the lesion was not enhanced. Gastroendoscopy revealed the lesion to be a submucosal tumor with a smooth mucosal surface and no ulceration. Endoscopic ultrasonography showed the tumor arising from the fourth layer of the gastric wall. The tumor was completely resected by laparotomy and partial gastrectomy. It was capsulated and contained serous fluid with little solid tissue. Histologically, there were sparse tumor cells within the myxoid interstitium. Immunostaining results were weakly positive for KIT and CD34-positive accompanied by mast cell infiltration. A platelet-derived growth factor receptor alpha (PDGFRA) exon 18 (D842V) mutation was identified, and the lesion was ultimately diagnosed as myxoid epithelioid gastrointestinal stromal tumor (GIST) of intermediate- and low-risk according to Fletcher's classification and Miettinen's classifications, respectively. GISTs with PDGFRA D842V mutations are reportedly resistant to imatinib, and GISTs originating from the stomach are reportedly less malignant than others. The patient was observed without adjuvant therapy after surgery because of the relatively low risk of metastasis or recurrence and the potential risk of imatinib resistance. No recurrence was observed for ≥5 years after the surgery. We herein report this rare case and describe its clinical characteristics.

Past history of hepatocellular carcinoma is an independent risk factor of treatment failure in patients with chronic hepatitis C virus infection receiving direct-acting antivirals.

Direct-acting antiviral (DAA) treatment can achieve a high sustained virological response (SVR) rate in patients with hepatitis C virus (HCV) infection regardless of a history of hepatocellular carcinoma (HCC [+]). We examined 838 patients (370 men, median age: 69 years) who were treated with DAAs for comparisons of clinical findings between 79 HCC (+) (9.4%) and 759 HCC (-) (90.6%) patients and associations with treatment outcome. Male frequency was significantly higher in the HCC (+) group (60.8% vs 42.4%, P = 0.006). There were significant differences between the HCC (+) and HCC (-) groups for platelet count (115 vs 152 ×109 /L, P < 0.001), baseline alpha fetoprotein (AFP) (9.9 vs 4.5 ng/mL, P < 0.001) and the established fibrosis markers of FIB-4 index (4.7 vs 3.0, P < 0.001), AST-to-platelet ratio index (APRI) (1.1 vs 0.7, P = 0.009), M2BPGi (3.80 vs 1.78 COI, P < 0.001) and autotaxin (1.91 vs 1.50 mg/L, P < 0.001). The overall SVR rate was 94.7% and significantly lower in the HCC (+) group (87.3 vs 95.5%, P = 0.001). Multivariate analysis revealed that a history of HCC was independently associated with DAA treatment failure (odds ratio: 3.56, 95% confidence interval: 1.32-9.57, P = 0.01). In conclusion, patients with chronic HCV infection and prior HCC tended to exhibit more advanced disease progression at DAA commencement. HCC (+) status at the initiation of DAAs was significantly associated with adverse therapeutic outcomes. DAA treatment for HCV should therefore be started as early as possible, especially before complicating HCC.

[A case of non-alcoholic fatty liver disease (NAFLD) aggravated after treatment with raloxifene].

A 70-year-old woman presented with abnormal liver function test 3 months after the introduction of daily intake of raloxifene, a selective estrogen receptor modulator, for osteoporosis. She had a history of NAFLD, diabetes mellitus and depression. The ratio of the computed-tomographic value of the liver against that of the spleen decreased remarkably. Pathological examination of the liver biopsy revealed severe steatosis. We thought her NAFLD was aggravated by raloxifene and discontinued the drug. The liver function test results improved and the computed tomographic liver-spleen ratio rose. This is the second case report of NAFLD becoming aggravated after treatment with raloxifene. It still remains unclear how raloxifene affects liver. Monitoring liver function is recommended when treating with raloxifene.

[A case of gastrointestinal AL amyloisosis requiring emergency surgery].

A 69-year-old man tarry stools received emergency endoscopy. Which revealed a solitary submucosal tumor about 15mm in diameter with a central ulcer, exhibiting woozing bleeding in the duodenal second portion. Endoscopic hemostasis was unsuccessful so emergency surgery was performed. Histological examination revealed amyloid with A-lambda immunoreactivity. Usually, this type of amyloidosis appears multiple submucosal masses. However this case presented as a single nodule at initial examination. We should keep in mind the potential of encountering this atypical form of amyloidosis.

Expression of p21Cip1/Waf1 and p27Kip1 in small cell neuroendocrine carcinoma of the uterine cervix.

Small-cell neuroendocrine carcinoma of the uterine cervix (SCCC), a rare but malignant cervical neoplasm, has a highly aggressive phenotype that requires more intensive treatment than other cervical tumors. Immunohistochemical methods were used to compare the expression of p21Cip1/Waf1 and p27Kip1 in SCCC and squamous cell carcinoma, the most common type of cervical cancer. In SCCC, p21 expression was significantly reduced compared with squamous cell carcinoma, whereas expression of p27 was similar in both carcinomas. Reduced expression of p21 could be a helpful diagnostic marker and may contribute to the invasive phenotype of SCCC.

Nuclear expression of STAT5 in intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) are noninvasive lesions of the pancreas and classified as intraductal papillary mucinous adenomas (IPMAs), borderline IPMNs, and intraductal papillary mucinous carcinomas (IPMCs). Expression patterns of the specific genes alter during IPMN progression. Based on the evidence that signal transducers and activators of transcription (STAT) 5 play important roles in tumor development, we tested STAT5 expression in IPMAs, borderline IPMNs, and IPMCs by immunohistochemical method. STAT5 frequently expressed in the nuclei of tumor cells of borderline IPMNs or IPMCs but was not observed in those of IPMAs. Nuclear expression of STAT5 protein correlated to the Ki-67 labeling index of the examined IPMNs. STAT5 protein could contribute to the progression and proliferation of IPMNs.

[A case of apocrine adenocarcinoma suspected as an axillary lymph node metastasis from cecal cancer].

The patient was a 69-year-old male. He had a 2-year history of subcutaneous tumor in the left axilla. Biopsy of the tumor showed the features of metastatic adenocarcinoma. FDG PET to check the primary lesion revealed the collection of an ileocecal junction and left axilla. After CT scan and colonoscopy, we diagnosed cecal cancer and metastasis of the axillary lymph nodes from it. He underwent ileocecal resection and a wide local resection of the axillary tumor. Histopathological examination showed the axillary tumor was different from the cecal cancer. Axillary tumor was diagnosed not as metastasis of axillary lymph nodes from cecal cancer but apocrine adenocarcinoma.