[A case of aortic thrombus during chemotherapy for esophageal cancer].

A 59-year-old man presented to our hospital with a chief complaint of epigastric pain. Pertinent history included a distal gastrectomy for gastric cancer and alcohol dependence. He underwent contrast-enhanced computed tomography (CT) and esophagogastroduodenoscopy, which led to a diagnosis of esophageal cancer (cT2N2M1, stage IVb). Subsequently, he underwent chemotherapy using 5-fluorouracil and cis-diamminedichloroplatinum and radiotherapy. A total of 44 days after treatment initiation, the patient experienced nausea and hepatobiliary enzyme elevation. CT and abdominal ultrasonography were performed, and he was diagnosed with an abdominal aortic thrombus. Intravenous heparin was administered as an anticoagulant therapy. Twenty-two days after treatment initiation, the thrombus was no longer visible on abdominal ultrasonography. The patient was then treated with warfarin. It cannot be ruled out that the patient's hepatobiliary enzyme elevation was induced by the anticancer drugs. However, enzyme elevation improved with the disappearance of the abdominal aortic thrombus, suggesting that the aortic thrombus may have contributed to the hepatobiliary enzyme elevation. No thrombus recurrence was observed until the patient's death after an initial treatment with antithrombotic agents. This case indicates that malignant tumors and chemotherapy can cause aortic thrombi, and thus, care should be exercised in monitoring this potential complication.

Efficacy of Endoscopic Resection for Rectal Neuroendocrine Tumors Smaller than 15 mm.

BACKGROUND: Local resection, including endoscopic resection, is recommended for rectal neuroendocrine tumors (NETs) < 15 mm in patients without risk factors for metastasis, though the short- and long-term outcomes are unclear. AIMS: This study investigates the efficacy of endoscopic resection for rectal NETs < 15 mm. METHODS: The short- and long-term outcomes of patients with rectal NETs < 15 mm who underwent endoscopic resection and the outcomes of each endoscopic technique were analyzed. The tumors were stratified as < 10 mm (small-size group, SSG) and 10-14 mm (intermediate-size group, IMG). RESULTS: Overall, 139 lesions (SSG, n = 118; IMG, n = 21) were analyzed. All tumors were classified as G1 (n = 135) or G2 (n = 4) according to the 2019 World Health Organization grading criteria. The complete resection rate was not different between the groups (P = 0.151). Endoscopic submucosal dissection (ESD) and endoscopic submucosal resection with a ligation device (ESMR-L) achieved complete resection rates > 90% in the SSG. The ESMR-L procedure time (P < 0.001) and hospitalized period (P < 0.001) were significantly shorter than those of ESD. ESD achieved a complete resection rate of 80.0% in the IMG. The tumor size did not affect the overall survival or rate of lymph node/distant metastases. CONCLUSIONS: Endoscopic resection is a feasible and effective treatment for patients with rectal NETs < 15 mm without the risk factors of metastasis. ESMR-L and ESD are optimal techniques for resecting tumors smaller than 10 mm and 10-14 mm, respectively.

Adult hypertrophic pyloric stenosis that improved by spontaneous double channel pylorus formation.

Adult hypertrophic pyloric stenosis (AHPS) is a rare disease and presents as pyloric obstruction. Double pylorus is also a rare condition due to a gastroduodenal fistula connecting from the gastric antrum to the duodenum. A 42-year-old woman without a history of vomiting in infancy presented with postprandial abdominal distension and repeated vomiting. Abdominal computed tomography showed gastric dilatation and wall thickening of the distal stomach. Endoscopy and contrast gastrography revealed gastric outlet obstruction due to stenosis and an ulcer in the antral and pyloric region. Endoscopic ultrasonography revealed circumferential thickening of the muscularis propria layer of the pylorus. Her symptoms improved with treatment consisting of drainage, fasting, and a proton pump inhibitor. Two weeks after onset, follow-up endoscopy revealed a healing ulcer and double channel pylorus. Based on her clinical course and findings of clinical images, she was diagnosed with gastric outlet obstruction due to AHPS that was improved by double channel pylorus formation. In conclusion, AHPS that was improved by double channel pylorus formation is an extremely rare condition, and we should be aware of this disease entity.

Long-term Outcomes of Therapeutic Endoscopic Retrograde Cholangiopancreatography for Choledocholithiasis in Patients ≥90 Years Old: A Multicenter Retrospective Study.

Objective The safety and prognosis of complete stone removal for the treatment of choledocholithiasis in older patients are unknown. This multicenter retrospective study assessed the outcomes of complete stone removal in elderly patients (≥90 years) with respect to the prognosis. Methods We divided patients who underwent endoscopic cholangiopancreatography for choledocholithiasis into two groups: complete stone removal or incomplete stone removal with plastic stent insertion. The patient characteristics, adverse events, number of endoscopic cholangiopancreatographies, overall survival rates, and disease-specific cumulative death were compared between the groups. Patients Two hundred and twenty-three participants ≥90 years old were included in the study, including 48 (22%) men and 175 (78%) women. The median age was 92 (range, 90-104) years old. There were 160 (72%) and 63 (28%) patients in the complete and incomplete groups, respectively. Results The age, performance status, comorbidities, severe complication rates, and stone diameter were comparable between the groups. The proportion of patients with at least 5 stones was significantly higher in the incomplete group than in the complete group [complete group: 8.1% (13/160) and incomplete group: 21% (13/63), p<0.01]. The overall survival rate was significantly higher in the complete group (p<0.01), while the disease-specific cumulative death rate was higher in the incomplete group (p<0.01). Conclusion Complete stone removal for choledocholithiasis may contribute to a better prognosis in elderly patients ≥90 years old.

Acute liver injury secondary to hemophagocytic lymphohistiocytosis triggered by Epstein-Barr virus infection.

We present a 23-year-old man with hemophagocytic lymphohistiocytosis (HLH) triggered by Epstein-Bar virus (EBV) infection. This patient presented with persistent fever and acute liver injury 6 weeks after having an infectious mononucleosis associated with EBV infection. He had hypofibrinogenemia, hyperferritinemia, increased soluble interleukin-2 receptor, elevated prothrombin time, and pancytopenia. Bone marrow examination for evaluation of pancytopenia revealed that macrophages had phagocytosed mature erythrocytes. Based on these findings, we suspected an HLH triggered by EBV infection (EBV-HLH). To distinguish from HLH triggered by malignant lymphomas accompanying EBV infection, we performed a percutaneous liver biopsy, which revealed that atypical T-lymphocytes had infiltrated the liver tissues. The T-lymphocytes were positive for EBV-encoded RNA in situ hybridization, and no distinct monoclonal T-cell receptor chain gene rearrangement was detected. These findings indicated EBV hepatitis and, accordingly, malignant lymphoma was ruled out. We finally made a diagnosis of EBV-HLH. The patient was treated with corticosteroid and etoposide, according to HLH-2004 guideline recommendations, and the patient's symptoms and laboratory values improved. After that, he experienced no recurrence. Prompt recognition and initiation of treatment remains the key to the survival of patients with EBV-HLH, and the liver biopsy was helpful in making the diagnosis.

Hereditary Hemorrhagic Telangiectasia Induced Portosystemic Encephalopathy: A Case Report and Literature Review.

Hereditary hemorrhagic telangiectasia (HHT) is a rare disorder characterized by telangiectasias and arteriovenous malformations (AVMs), which can involve multiple organ systems. Although hepatic involvement is common, the development of portosystemic encephalopathy is extremely rare. We herein report a 72-year-old woman with HHT-induced portosystemic encephalopathy secondary to hepatic arteriovenous malformations. She presented with disturbance of consciousness, and her serum ammonia level was elevated at 270 mg/dL. Color Doppler ultrasonography and contrast-enhanced computed tomography showed hepatic AVMs and shunts, which were useful for making the definite diagnosis. Portosystemic encephalopathy should be considered as a differential diagnosis in HHT patients presenting with disturbance of consciousness.

A case report of adenosquamous cell carcinoma of the duodenal papilla.

Adenosquamous carcinoma of the duodenal papilla is rare. A 73-year-old man was referred to the Saiseikai-Matsusaka General Hospital with upper abdominal pain and liver dysfunction. Computed tomography (CT) revealed dilatation of the common bile duct (CBD) and intrahepatic bile duct along with a tumor in the distal CBD. The tumor showed enhancement in the arterial phase on contrast-enhanced CT. We performed endoscopic retrograde cholangiopancreatography and noted a red, erosive, bleeding mass in the duodenal papilla with obstruction of the distal CBD, and dilatation of the CBD. Histopathological inspection of a biopsy of the duodenal papilla showed a mixture of adenocarcinoma and squamous cell carcinoma, suggesting the presence of adenosquamous cell carcinoma in the duodenal papilla. Abdominal examinations including positron emission tomography/CT showed no metastasis or lymph node swelling. The clinical stage was determined to be cT2N0M0 Stage IB. We performed subtotal stomach-preserving pancreaticoduodenectomy. Histopathological inspection of the specimen showed a mixture of adenocarcinoma and squamous cell carcinoma, and squamous cell carcinoma accounted for 40% of the tumor. The tumor was defined as pathological Stage IIA, AcbBd, mixed type, med, pT3b, sci, INFb, ly2, v1, ne2, pN1, HM0, PM0, EM0, PV0, A0, R0, pT3N0M0. We suggested adjuvant chemotherapy, but the patient declined adjuvant chemotherapy and wished to be discharged. Abdominal ultrasonography revealed multiple liver metastases 3 months postoperatively. The patient opted for best supportive care and died 9 months postoperatively. Examination of 23 reports of adenosquamous cell carcinoma of the duodenal papilla in Japan suggested that adenosquamous cell carcinoma of the duodenal papilla has a poorer prognosis compared with adenocarcinoma of the duodenal papilla. Some reports have stated that the growth rate is faster for squamous cell carcinoma than for adenocarcinoma. In our case, the tumor was enhanced in the arterial phase and this represents a feature of adenosquamous cell carcinoma of the duodenal papilla. Chemotherapy has not been established for adenosquamous cell carcinoma of the duodenal papilla. We are confident that we can establish effective chemotherapies in the future.

Differential requirements of cellular and humoral immune responses for Fv2-associated resistance to erythroleukemia and for regulation of retrovirus-induced myeloid leukemia development.

To assess the possible contribution of host immune responses to the exertion of Fv2-associated resistance to Friend virus (FV)-induced disease development, we inoculated C57BL/6 (B6) mice that lacked various subsets of lymphocytes with FV containing no lactate dehydrogenase-elevating virus. Fv2(r) B6 mice lacking CD4(+) T cells developed early polycythemia and fatal erythroleukemia, while B6 mice lacking CD8(+) T cells remained resistant. Erythroid progenitor cells infected with spleen focus-forming virus (SFFV) were eliminated, and no polycythemia was observed in B cell-deficient B6 mice, but they later developed myeloid leukemia associated with oligoclonal integration of ecotropic Friend murine leukemia virus. Additional depletion of natural killer and/or CD8(+) T cells from B cell-deficient B6 mice resulted in the expansion of SFFV proviruses and the development of polycythemia, indicating that SFFV-infected erythroid cells are not only restricted in their growth but are actively eliminated in Fv2(r) mice through cellular immune responses.

Bone metastasis from early gastric cancer following non-curative endoscopic submucosal dissection.

A 67-year-old male underwent endoscopic submucosal dissection (ESD) to treat early gastric cancer (EGC) in 2001. The lesion (50 mm × 25 mm diameter) was histologically diagnosed as poorly differentiated adenocarcinoma, with an ulcer finding. Although the tumor was confined to the mucosa with no evidence of lymphovascular involvement, the ESD was regarded as a non-curative resection due to the histological type, tumor size, and existence of an ulcer finding (as indicated by the 2010 Japanese gastric cancer treatment guidelines, ver. 3). Despite strong recommendation for subsequent gastrectomy, the patient refused surgery. An alternative follow-up routine was designed, which included five years of biannual clinical examinations to detect and measure serum tumor markers and perform visual assessment of recurrence by endoscopy and computed tomography scan after which the examinations were performed annually. The patient's condition remained stable for eight years, until a complaint of back pain in 2010 prompted further clinical investigation. Bone scintigraphy indicated increased uptake. Histological examination of biopsy specimens taken from the lumbar spine revealed adenocarcinoma resembling the carcinoma cells from the EGC that had been treated previously by ESD, and which was consistent with immunohistochemical findings of gastrointestinal tract cancer. Thus, the diagnosis of bone metastasis from EGC was made. The reported rates of EGC recurrence in surgically resected cases range 1.4%-3.4%, but among these bone metastasis is very rare. To our knowledge, this is the first reported case of bone metastasis from EGC following a non-curative ESD and occurring after an eight-year disease-free interval.

Increased liver temperature efficiently augments human cellular immune response: T-cell activation and possible monocyte translocation.

Hyperthermia (HT), in combination with other conventional therapeutic modalities, has become a promising approach in cancer therapy. In addition to heat-induced apoptosis, an augmented immunological effect is considered to be a benefit of hyperthermic treatment over chemo- or radiotherapy. Here, we investigated the effect of regional HT targeting the liver on immune cells, especially T cells and antigen-presenting cells, which are important in recognizing and eliminating tumor cells and pathogens such as viruses. In healthy volunteers exposed to such regional HT, both CD4(+) and CD8(+) T cells that express an activation marker CD69 increased transiently at 1 h post-treatment, with a subsequent decrease to base levels at 6 h after the treatment. At 24 h post-treatment, the percentage of CD69-positive cells significantly increased again but only among CD8(+) T cells. IFN-gamma production from PHA-stimulated peripheral blood mononuclear cells was gradually and significantly increased in the 2 days following the heating procedure, peaking at 36 h post-treatment. Furthermore, we found marked increases in plasma levels of IL-1beta and IL-6 starting at 24 h post-treatment. With regard to the number of each leukocyte subpopulation, a transient and dramatic decrease in the number of a subset of monocytes, CD14(+) CD16(-) cells, was observed at 1 h after the hyperthermic treatment, suggesting that the regional HT aimed at the liver may have influenced the extravasation of blood monocytes. No significant changes in T-cell activities or monocyte counts were observed in the volunteers exposed to heating of the lungs or the legs. These results suggest that heating of the liver may efficiently induce cellular immune responses to liver cancers.

Peptide-induced immune protection of CD8+ T cell-deficient mice against Friend retrovirus-induced disease.

CD8+ CTLs and virus-neutralizing antibodies have been associated with spontaneous and vaccine-induced immune control of retroviral infections. We previously showed that a single immunization with an env gene-encoded CD4+ T cell epitope protected mice against fatal Friend retrovirus infection. Here, we analyzed immune cell components required for the peptide-induced anti-retroviral protection. Mice lacking CD8+ T cells were nevertheless protected against Friend virus infection, while mice lacking B cells were not. Virus-producing cells both in the spleen and bone marrow decreased rapidly in their number and became undetectable by 4 weeks after infection in the majority of the peptide-immunized animals even in the absence of CD8+ T cells. In the vaccinated animals the production and class switching of virus-neutralizing and anti-leukemia cell antibodies were facilitated; however, virus-induced erythroid cell expansion was suppressed before neutralizing antibodies became detectable in the serum. Further, the numbers of virus-producing cells in the spleen and bone marrow in the early stage of the infection were smaller in the peptide-immunized than in unimmunized control mice in the absence of B cells. Thus, peptide immunization facilitates both early cellular and late humoral immune responses that lead to the effective control of the retrovirus-induced disease, but CD8+ T cells are not crucial for the elimination of virus-infected cells in the peptide-primed animals.

Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected status in Italians.

OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals possess no detectable HIV genome and show T-cell memory responses to the viral antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals suggests their possible immune resistance against HIV. We tested if the above HIV-1-exposed but uninfected status was associated with genetic markers other than a homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome 15 of a gene controlling the production of neutralizing antibodies in a mouse retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at polymorphic loci in the syntenic segment of human chromosome 22, and compared them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a closed testing procedure. RESULTS: A significant association was found between chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1 immune responses in the exposed but uninfected individuals. Distributions of linkage disequilibrium across chromosome 22 also differed between the exposed but uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the presence of a new genetic factor associated with the HIV-1-exposed but uninfected status.