Immunoglobulin G4-related autoimmune hepatitis simultaneously concomitant with autoimmune pancreatitis: a case report.

Thus far, there have been limited case reports on immunoglobulin G4-related autoimmune hepatitis (IgG4-AIH), and its clinical features have not been elucidated. We herein report a rare case of IgG4-AIH simultaneously concomitant with autoimmune pancreatitis (AIP). A 73-year-old female was admitted to our hospital for further investigation of elevated levels of liver transaminase and pancreatic enzymes. Her serological tests showed a high antinuclear antibody titer, and elevated IgG and IgG4 levels. Liver biopsy revealed interface hepatitis and bridging necrosis with IgG4-positive lymphoplasmacytic infiltration in the portal area. Moreover, contrast-enhanced computed tomography (CECT) showed pancreatic tail enlargement, and magnetic resonance cholangiopancreatography showed skipped narrowing of the main pancreatic duct in the pancreatic tail. Endoscopic ultrasonography-fine needle aspiration specimens showed no malignant cells. Based on these results, we diagnosed her with IgG4-AIH simultaneously concomitant with probable type 1 AIP. She was started on prednisolone (PSL) at 35 mg/d, and her symptoms and liver transaminase levels improved. One month after starting treatment, CECT showed improvement of pancreatic tail enlargement. She is maintained on 5 mg PSL/d and has been in remission for two years.

A Rupture of a Lung Metastatic Lesion of Colon Cancer, Leading to Pneumothorax Caused by Bevacizumab.

The patient was a 57-year-old man who was diagnosed with multiple lung metastases of sigmoid colon cancer. The patient developed progressive disease after 8 courses of bevacizumab + capecitabine and oxaliplatin therapy, therefore, bevacizumab + irinotecan, leucovorin, and 5-fluorouracil therapy was started. During the fifth course, he experienced pain on the left side of his chest. On computed tomography, bleeding from the pulmonary metastatic lesions was suspected. Two days later, a pneumothorax was detected. Although several cases of pneumothorax induced by bevacizumab have been reported, this case is the first documentation that bevacizumab caused a rupture of the lung metastatic lesion, leading to a pneumothorax.

Rare type of pancreatitis as the first presentation of anti-neutrophil cytoplasmic antibody-related vasculitis.

A pancreatic tumor was suspected on the abdominal ultrasound of a 72-year-old man. Abdominal computed tomography showed pancreatic enlargement as well as a diffuse, poorly enhanced area in the pancreas; endoscopic ultrasound-guided fine needle aspiration biopsy and endoscopic retrograde cholangiopancreatography failed to provide a definitive diagnosis. Based on the trend of improvement of the pancreatic enlargement, the treatment plan involved follow-up examinations. Later, he was hospitalized with an alveolar hemorrhage and rapidly progressive glomerulonephritis; he tested positive for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA) and was diagnosed with ANCA-related vasculitis, specifically microscopic polyangiitis. It appears that factors such as thrombus formation caused by the vasculitis in the early stages of ANCA-related vasculitis cause abnormal distribution of the pancreatic blood flow, resulting in non-uniform pancreatitis. Pancreatic lesions in ANCA-related vasculitis are very rare. Only a few cases have been reported previously. Therefore, we report our case and a review of the literature.

Loss of HER2 Positivity after Trastuzumab in HER2-Positive Gastric Cancer: Is Change in HER2 Status Significantly Frequent?

Trastuzumab has recently been introduced as a treatment for HER2-positive metastatic and/or unresectable gastric cancer (MUGC); however, compared with breast cancer, some issues concerning HER2 and trastuzumab therapy for gastric cancer remain unclear. A 74-year-old woman received trastuzumab-containing chemotherapy for HER2-positive MUGC. She had a marked response to 8 months of chemotherapy, and gastrectomy and hepatic metastasectomy with curative intent were performed. The resected specimen showed complete loss of HER2 positivity in the residual tumor. For MUGC, a change in HER2 status during the course of the disease with or without chemotherapy has rarely been reported. However, in breast cancer, a significant frequency of change in HER2 status during the course of disease has been reported, and reevaluation of HER2 positivity in metastatic/recurrent sites is recommended. The choice of trastuzumab for MUGC is currently based on the HER2 status of the primary tumor at the time of initial diagnosis, without reassessment of HER2 status during the course of disease and/or in metastatic/recurrent sites, on the assumption that HER2 status is stable. However, our case casts doubt on the stability of HER2 in gastric cancer.

[Perioperative primary thrombosis prophylaxis for colorectal cancer in an asymptomatic antiphospholipid antibody carrier -a case report and literature review-].

An 82-year-old woman presented with hematochezia and was diagnosed with resectable colon cancer. Laboratory analysis revealed prolonged activated partial thromboplastin time and false-positive reactions in serological tests for syphilis; results that were subsequently found to be caused by the presence of antiphospholipid antibody. Because she had no history of thrombotic events or pregnancy morbidity, she was considered to be an asymptomatic antiphospholipid antibody carrier (aaPL carrier). Throughout the perioperative period, anticoagulation was performed without complications, including thrombosis. aaPL carriers are not uncommon in clinical practice, and the attending gastroenterologist should assess the risk of future thrombotic events and the most effective means of preventing thrombosis. However, there are few evidence-based recommendations for primary thrombosis prevention in aaPL carriers over the long-term and in high-risk periods, such as the perioperative period. Here, we discuss aaPL carrier management with a focus on the perioperative period together with a review of the literature.

[Colorectal carcinoma with hemiparesis due to isolated brain metastases as an initial symptom - a case report].

We present a rare case of colorectal carcinoma in which hemiparesis was the initial symptom. A 75-year-old woman presented with incomplete left-sided hemiparesis. Brain magnetic resonance imaging(MRI)revealed a 13-mm mass in the right frontal lobe; the mass was resected via craniotomy. Pathological findings, which included the results of immunohistochemical analysis, indicated brain metastasis from colorectal cancer. Colonoscopy revealed advanced colon cancer in the ascending colon, and computed tomography(CT)did not reveal any extracranial metastases. Left-sided hemicolectomy was performed. Whole-brain radiotherapy was scheduled, but before initiation of the therapy, metastases were detected in the neck lymph node and right arm skin, and the brain metastases relapsed. The relapsed brain metastatic lesions were resected, and radiotherapy was administered to the whole brain and the severely painful site of skin metastasis. However, the patient died 201 days after presentation. Historically, systemic chemotherapy was considered ineffective for metastatic brain tumor, and the standard treatments for brain metastasis were surgery and radiotherapy. Although recent advances in systemic chemotherapy for colorectal cancer have resulted in improved patient survival, patients with brain metastases from colorectal cancer still have a poor prognosis. Modern chemotherapeutic agents, including molecularly targeted agents such as bevacizumab, should be validated for the management of brain metastases.

[Gallbladder cancer with elevated serum α-fetoprotein, α-fetoprotein-L3, and human chorionic gonadotropin levels].

A 61-year-old woman presented with fever and was diagnosed with choledocholithiasis, which was removed endoscopically. Incidentally, a markedly elevated serum α-fetoprotein(AFP)level was detected(1,951 ng/mL), but computed tomography( CT)showed only diffuse gallbladder wall thickening. Subsequently, markedly elevated serum AFP-L3 and human chorionic gonadotropin(HCG)levels were detected(99.6%and 2,867mIU/mL, respectively). Fluorodeoxyglucose(FDG)- positron emission tomography/CT demonstrated high FDG uptake only in the gallbladder. Gallbladder cancer was suspected and the patient was scheduled for a cholecystectomy. However, CT just prior to surgery revealed multiple liver metastases. Percutaneous gallbladder biopsy revealed a moderately differentiated adenocarcinoma positive for AFP but not HCG. The patient underwent chemotherapy consisting of gemcitabine and cisplatin. A CT scan obtained 12 weeks later showed disease progression and AFP and HCG levels were found to have increased to 4,021 ng/mL and 66,000mIU/mL, respectively. Although immunohistochemistry of biopsy specimen did not demonstrate HCG production, increased serum HCG level on disease progression definitely suggested HCG production of gallbladder cancer. We believe the biopsy specimen was very small and therefore did not prove HCG production. Gallbladder cancer with simultaneous production of AFP and HCG is rare, and we therefore report this case together with a review of the literature.

[A case of recurrent gastric cancer showing partial response to capecitabine/CDDP after treatment with S-1/CDDP].

S-1 and capecitabine are orally administered fluoropyridines reported to be effective in the treatment of advanced gastric cancer(AGC). In fact, both S-1/CDDP and capecitabine/CDDP are considered to be the standard first-line treatments for AGC.However, no information concerning on the activity of capecitabine in S-1-pretreated patients with AGC has been reported. Here, we present a case of recurrent gastric cancer that showed a partial response resulting in 6 months of progres-sion-free survival, thanks to capecitabine/CDDP after the failure of multiple anticancer drugs such as S-1/CDDP. S -1 and capecitabine may exhibit cross-resistance because they both have the same final active metabolite: 5-fluorouracil(5-FU). Dihydropyrimidine dehydrogenase(DPD)is the rate-limiting enzyme in the degradation of 5-FU, and S-1 contains the inhibitor of DPD. Thus, S-1, but not capecitabine, is active against tumors with high DPD expression. On the other hand, capecitabine is activated to 5-FU by thymidine phosphorylase(TP)within the tumor tissue and is more effective against tumors with high TP expression. The present case suggests that S-1 and capecitabine do not always exhibit cross-resistance, and that capecitabine may be effective in S-1-pretreated patients with AGC.

Myogenic lineage differentiated mesenchymal stem cells enhance recovery from dextran sulfate sodium-induced colitis in the rat.

BACKGROUND: Although mounting evidence implicates mesenchymal stem cells (MSCs) in intestinal tissue repair, uncertainty remains concerning the distribution, function, and fate of repopulating MSCs in recipient colonic tissues. Therefore, we investigated the role of transplanted MSCs in the repair phase of DSS colitis. METHODS: LacZ-labeled rat MSCs were transplanted into rats with colitis induced by 4% DSS on day 2. Regular water replaced the DSS solution on day 6. Therapeutic effect was evaluated on day 9 by clinicopathologic and growth factor/cytokine expression profiles. We analyzed the Notch signaling pathway by Western blotting and characterized immunofluorescence of lacZ-labeled MSCs with confocal laser microscopy. In vivo differentiation of MSC was confirmed by transmission electron microscopy (TEM). RESULTS: Recovery of colitis was modestly but significantly promoted by MSC transplantation due to proceeding cell cycle and inhibiting apoptosis in the epithelia. Tgfa mRNA expression increased significantly, while Notch signaling was inhibited in the colonic tissues with MSC transplantation. ß-Galactosidase-positive cells, which expressed α-SMA, desmin, and vimentin, were infrequently detected in the lamina propria stroma. DSS exposure in vitro proved to be the most potent inducer for α-SMA in MSCs where TEM demonstrated myogenic lineage differentiation. CONCLUSIONS: We found that MSCs transplantation modestly promoted the repair of DSS colitis. The donor-derived MSCs were likely reprogrammed to differentiate to myogenic lineage cells by cues from the micro milieu. Further characterization of these cells is warranted as a basis for applying cell-based therapy for inflammatory bowel disease.

Enhancing epithelial engraftment of rat mesenchymal stem cells restores epithelial barrier integrity.

The cellular origin, in vivo function and fate of donor bone marrow-derived cells residing in the recipient intestinal epithelial cells, pericryptal myofibroblasts or endothelial cells remain obscure. Although 'immunoprivileged' mesenchymal stem cells (MSCs) are prime candidates for cell- and gene-based therapy, their precise role in colitis remains largely undetermined. Using a dextran sulphate sodium (DSS) colitis with busulphan (BU)-induced hypoplastic marrow model, we examined the therapeutic effects of MSC transplantation, focusing on the role of MSCs as both cell providers and immunomodulators. Donor-derived MSCs were detected by eGFP immunofluorescence and fluorescence in situ hybridization for Y-chromosome (Y-FISH) analysis. Western blot analysis of apical-most tight junction proteins was performed with antibodies against claudin-2, -7, -8, -12, -13, -15 and ZO-1. Cytokine and cell cycle profiles were analysed by semi-quantitative RT-PCR and flow cytometry. Susceptibility to DSS colitis was significantly increased by co-existing BU-induced bone marrow hypoplasia and this increase was significantly reduced by enhancing epithelial engraftment of MSCs, an effect depending on restoring epithelial barrier integrity rather than inhibiting host immune responses. We provide evidence that implicates MSCs in maintaining epithelial barrier function by reassembling apical-most tight junction proteins, claudins. The therapeutic efficacy of extrinsic MSCs depends on enhancing epithelial engraftment in damaged crypts by busulphan conditioning. Such a role for the MSC-derived intestinal cells in colitis therapy merits further examination and may offer a promising new treatment for inflammatory bowel disease (IBD).

[Superficial esophageal carcinoma successfully treated with combined chemotherapy and radiotherapy].

A 47-year-old man was admitted to our hospital with the chief complaint of epigastralgia. Endoscopic examination revealed a 0-IIa + IIc lesion in the middle thoracic esophagus, and a biopsy specimen was diagnosed as squamous cell carcinoma. The depth of the cancerous invasion was judged to be sm by endoscopic ultrasonography, and no metastasis to other organs or lymph nodes was detected. Although we believed curative resection was possible, we performed combined chemotherapy and radiotherapy because the patient refused surgery. After 2 courses of chemoradiotherapy, the cancer had disappeared clinically. We have found no evidence of recurrence for 1 year and 8 months. For the patient with superficial esophageal carcinoma who has a high risk or refuses surgery, chemoradiotherapy may be a reasonable alternative.