Synchronous Jejunal Sarcomatoid Carcinoma and Incidentally Associated Localized Peritoneal Malignant Mesothelioma.

Sarcomatoid carcinoma (SCA) of the small bowel is a rare aggressive variant of small intestinal cancer accompanying a poor prognosis. The tumor primarily affects middle-aged and elderly patients. We report herein a 67-year-old Japanese male who manifested anemia. He had a history of asbestos exposure 30 years earlier. An abdominal computed tomography (CT) scan showed a 6.5-cm aneurysmal, dilated mass of the small intestine. Capsule endoscopy revealed a large circumferential hemorrhagic ulcerative lesion in the jejunum. Biopsy indicated sarcomatoid carcinoma, and partial resection of the small bowel and adjacent transverse colon and omentum was performed. In addition to the T3N0M0 jejunal giant sarcomatoid carcinoma (SCA), a 3-mm small localized peritoneal (omental) malignant mesothelioma (LMM) was also incidentally included. Synchronous presentation of small intestinal and mesothelial malignancies is extremely rare, and the avoidance of incorrect clinical staging is critically important. Surgical resection is still considered the best first-line therapy, because of a poor response to chemotherapy and radiotherapy. Dual-color fluorescent in situ hybridization (FISH) for p16/CDKN2A and chromosome 9 indicated homologous deletion of p16/CDKN2A in SCA and a normal pattern in LMM. Methylthioadenosine phosphorylase (MTAP) was negative in SCA but positive in LMM. Both tumors consistently expressed BRCA1-associated protein 1 (BAP1). Tumor necrosis factor receptor-associated factor 7 (TRAF7) was suppressed, and neural cell adhesion molecule L1 precursor (NCAML1/L1CAM) was agitated in both tumors. Diffuse and strong expression of programmed death-ligand 1 (PD-L1) and the association of tumor-infiltrating lymphocytes in SCA may indicate a potential for PD-L1-targeted immunotherapy for treating this type of aggressive cancer. PD-L1 was focally expressed in LMM. The postoperative course was uneventful for two years.

Acalculous Ischemic Cholecystitis Caused by Spontaneous Celiac Artery Dissection.

We herein report a case of spontaneous isolated dissection of the celiac artery. A Japanese man in his 50s visited an emergency unit, complaining of sudden epigastralgia. Contrast-enhanced computed tomography indicated dissection of the celiac artery with patent false and true lumina, extending to the splenic and common hepatic arteries. On day 3 of hospitalization, the dissection progressed to the proper and right hepatic arteries. Progression of the dissection to the right hepatic artery provoked acalculous ischemic cholecystitis, and cholecystectomy followed. The resected gallbladder revealed extensive aseptic necrosis with little inflammatory reaction, and the gallbladder neck was spared from ischemia.

A Rare Collision Tumor: Adenocarcinoma in the Ampulla of Vater and Neuroendocrine Tumor in the Lower Part of the Common Bile Duct.

In the biliary tree, only three cases of neuroendocrine tumor (NET) synchronous with adenocarcinoma have been reported so far. We experienced a case of NET, grade 2 (G2), of the common bile duct associated with adenocarcinoma of the ampulla of Vater (AoV). A Japanese man at his 60's visited a local doctor, and obstructive jaundice was pointed out. Under the clinical diagnosis of carcinoma of the AoV, 20 x 20 mm, T3aN0M0 stage IIB, pylorus-preserving pancreaticoduodenectomy was performed. Dynamic computed tomography in an artery-dominant phase and microscopic examination revealed that the mass consisted of two different components; hypovascular, 2.5 cm-sized, exophytic adenocarcinoma in the AoV and hypervascular, 1.5 cm-sized, polypoid NET (G2) in the lower part of the common bile duct. The NET diffusely expressed neuroendocrine markers, including somatostatin receptor-2 (SSTR2), and adenocarcinoma cells arising from tubular adenoma focally expressed the neuroendocrine markers. Both malignancies were positive for caudal-type homeobox-2 (CDX2). It is presumed that NET occurred from intestinal-type adenoma/adenocarcinoma.

Pancreatic Intraductal Papillary Mucinous Neoplasm with Hyaline Globules (Thanatosomes): Report of Two Cases.

Hyaline globules (HGs; thanatosomes) represent a morphologic entity representing a metabolic imbalance common to all cell types. HGs, intracytoplasmic eosinophilic globular accumulations of proteinaceous material of varying sizes, have been observed in varied tumors and benign tissues. Different explanations have been proposed for their formation, according to the tumor type and anatomic location. An earlier study suggested that HGs were closely related to apoptosis. There are some reports describing HGs in pancreatic neoplasms, such as intraductal oncocytic papillary neoplasm, solid-pseudopapillary neoplasm, oncocytic endocrine neoplasm, and invasive ductal adenocarcinoma; however, this is the first report describing HGs in pancreatic intraductal papillary mucinous neoplasm (IPMN). An ultrastructural study was performed to visualize HGs in two pancreatic IPMNs of gastric type (one non-invasive malignancy and another adenoma). Light microscopically, intracytoplasmic HGs were clustered multifocally. HGs were periodic acid-Schiff-positive and diastase-resistant, and fuchsinophilic with Masson's trichrome stain. The diameter ranged from 4.7 to 20.6 µm (mean: 13.3, median: 14.1). They were mainly seen at the supranuclear position and occasionally with subnuclear location. Ultrastructurally, HGs were round in shape and homogenously electron-dense without mitochondria or chromatin-like condensation. The nuclei of HGs-containing mucous columnar cells appeared intact without evidence of apoptosis. It is worth emphasizing that HGs in the pancreatic IPMN of gastric type belong not to apoptotic bodies but to proteinaceous secretory materials.

CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer.

It has been reported that an increased population of regulatory T cells (Tregs) is one of the reasons for impaired anti-tumor immunity. Recently, Foxp3 has been reported as a reliable marker of Tregs. The authors investigated the frequency of Foxp3(+) Tregs within CD4(+) cells in TILs, regional lymph nodes and PBLs of gastric cancer patients (n = 45). Furthermore, to elucidate the mechanisms behind Treg accumulation within tumors, they evaluated the relationship between CCL17 or CCL22 expression and the frequency of Foxp3(+) Tregs in gastric cancer. CD4(+)CD25(+)Foxp3(+) Tregs as a percentage of CD4(+) cells were counted by flow cytometry and evaluated by immunohistochemistry. Moreover, an in vitro migration assay using Tregs derived from gastric cancers was performed in the presence of CCL17 or CCL22. As a result, the frequency of Foxp3(+) Tregs in TILs was significantly higher than that in normal gastric mucosa (12.4% +/- 7.5% vs. 4.1% +/- 5.3%, p < 0.01). Importantly, the increase in Tregs in TILs occurred to the same extent in early and advanced disease. Furthermore, the frequency of CCL17(+) or CCL22(+) cells among CD14(+) cells within tumors was significantly higher than that of normal gastric mucosa, and there was a significant correlation between the frequency of CCL17(+) or CCL22(+) cells and Foxp3(+) Tregs in TILs. In addition, the in vitro migration assay indicated that Tregs were significantly induced to migrate by CCL17 or CCL22. In conclusion, CCL17 and CCL22 within the tumor are related to the increased population of Foxp3(+) Tregs, with such an observation occurring in early gastric cancer.

[Experience of weekly paclitaxel combined with orally administered doxifluridine therapy for advanced and recurrent gastric cancer-preliminary study].

We designed a new regimen to evaluate the efficacy and feasibility of weekly paclitaxel combined with orally administered 5'-DFUR therapy against advanced and recurrent gastric cancer. Nine patients were enrolled. Weekly paclitaxel administration (PTX 60 mg/m2, 2 consecutive weeks, 1-week break) and oral administration of 5'-DFUR (460 mg/m2, 14 consecutive days) were performed on an ambulatory basis. This was repeated every 3 weeks until disease progression and/or severe toxic events occurred. The overall response rate was 44.4% with 22.2% complete response and 22.2% partial response in addition to 44.4% no changes beyond 3 months. In NC criteria, 3 patients showed clinical improvements, such as decreasing tumor markers, releasing from the ileus, and improvement of liver dysfunction. These results suggested that clinical benefits in 89% of patients. On the other hand, toxic events were restricted to grade 3 with 11.1% general fatigue and 11.1% appetite loss. Therefore, the weekly administration of PTX in conjunction with daily oral administration of 5'-DFUR therapy seems to be extremely useful, with excellent anti-tumor effect and tolerable adverse reactions for the treatment of recurrent gastric cancer on an ambulatory basis.

[Weekly paclitaxel administration and intraabdominal CBDCA injection possibly beneficial treatment for recurrent breast cancer associated with metastatic ovarian cancer and peritoneal dissemination after operation--a case report].

A 46-year-old woman who had received mastectomy for breast cancer 6 years earlier complained of abdominal distension. Computed tomography and ultrasonography revealed massive ascites and ovarian swelling of both sides. She was diagnosed as having primary ovarian cancer and peritoneal dissemination, and underwent a total hysterectomy as well as ovarectomy on both sides. After surgery, she received a sequential chemotherapy, ie, intraabdominal injection of carboplatin (CBDCA 300 mg/m2) and div administration of paclitaxel (PTX 180 mg/m2) as a standard regimen for advanced ovarian cancer. However, detailed histological examinations showed that the ovarian cancer had metastasized from her breast cancer. It is well-known that breast cancer easily metastasizes to the bone, liver, pleura and lymph node, but rarely to the ovarium or peritoneum when chemotherapy is conducted. Therefore, no standard therapy has been established for breast cancer metastasizing to the ovarium. Our patient received 4 cycles of weekly administration of PTX (PTX 80 mg/m2, 3 consecutive weeks, 1-week break), followed by oral administration of doxifluridine+anastrozole on an outpatient basis. No evidence of recurrence of breast cancer has been noted 1 year after surgery. This result suggests that weekly administration of PTX and intraabdominal injection of CBDCA might be beneficial in the treatment of recurrent breast cancer associated with metastatic ovarian cancer and peritoneal dissemination after operation.

[Weekly administration of paclitaxel might be beneficial against TS-1-resistant recurrent gastric cancer--a case report].

At one year after postoperative adjuvant therapy consisting of TS-1, UFT, and PSK, lymph-node metastasis and recurrent suprarenal metastasis were confirmed in a patient with Stage IV gastric cancer. Despite TS-1 therapy (120 mg/body, 4 consecutive weeks, 2-week break), the therapeutic effect remained PR, and the severity of adverse reactions, such as skin symptoms, leukopenia, and diarrhea, ranged from grade 1 to 3. Although this therapy was continued intermittently, the therapeutic effect worsened to PD and, as a result, the therapy was discontinued. Next, in accordance with the treatment of recurrent and advanced breast cancer, weekly paclitaxel (PTX 80 mg/m2, 3 consecutive weeks, 1-week break) administration was performed on an outpatient basis. CR was achieved after 4 cycles. In addition, no adverse reactions were seen. Therefore, the weekly administration of PTX for the treatment of recurrent gastric cancer resistant to 5-FU anticancer agents is extremely useful, as the antitumor effect of this therapy was great, no adverse reactions were seen, and it can be performed on an outpatient basis.