Mixed germ cell tumor with embryonal carcinoma, choriocarcinoma, and epithelioid trophoblastic tumor in the ovary of a cynomolgus monkey

A seven-year-old female cynomolgus monkey had a mass in the left ovary with metastasis to the lung and the right ovary. The mass of these organs showed three different characteristics, and its immunohistochemical profiles were consistent with embryonal carcinoma (EC), choriocarcinoma (CC), and epithelioid trophoblastic tumor (ETT). The EC was characterized with sheets and glandlike structures with large pleomorphic, single-nucleated epithelial cells that were immunohistochemically positive for α-fetoprotein, octamer-4, and CD30, and with multinucleated giant cells resembling syncytiotrophoblasts. The CC also represented biphasic proliferation of the cytotrophoblast positive for cytokeratin 7 (CK7), which showed negative immunoreactivity for all three of the above antibodies, and it was syncytiotrophoblast positive for human chorionic gonadotropin. The ETT showed numerous floating cells in an abundant eosinophilic extracellular matrix with vacuolated or eosinophilic cytoplasm and was immunohistochemically positive for CK7, p63, and α-inhibin, which features nodule or cordlike structures. Collectively, this neoplasm was identified as a mixed germ cell tumor with EC, CC, and ETT. To our knowledge, this is the first report of EC in nonhuman primates as a component of mixed germ cell tumor.     

Informed consent for surgical treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) differs from other gastrointestinal cancers due to the following characteristics: 1) a high rate of recurrence, including multicentric recurrence; 2) the treatment modality or surgical method is often selected based on liver function: and 3) the indications for medical treatment versus surgery are not clearly defined and ther is no consensus on standard indications between surgeons and hepatologists. Therefore special informed consent must be obtained from HCC patients for surgery in addition to the standard written informed consent form. Moreover, because liver surgery carries the risk of massive intraoperative hemorrhage or postoperative liver failure, sufficient time must be spent explaining the associated risks to patients before obtaining informed consent.     

Liver perfusion chemotherapy for selected patients at a high-risk of liver metastasis after resection of duodenal and ampullary cancers

OBJECTIVE: To evaluate the prognostic benefit of postoperative liver perfusion chemotherapy (LPC) in patients who undergo curative resection of duodenal and ampullary cancers. SUMMARY BACKGROUND DATA: Both nodal involvement and pancreatic invasion are poor prognostic indicators after curative resection of ampullary or duodenal cancers due to high incidences of liver metastasis. Therefore, we have performed postoperative LPC on a number of such "high-risk" patients. METHODS: During the period of 1990 to 2005, 72 consecutive patients successfully underwent curative (R0) resection of duodenal or ampullary carcinomas at our institution, The Osaka Medical Center for Cancer and Cardiovascular Diseases. Of these 72 patients, 38 were found to have positive nodal involvement and/or pancreatic invasion based on an intraoperative inspection, and of these, 28 were deemed to be suitable candidates for intraoperative catheterization: 1 catheter was placed into the gastroduodenal artery; another into the portal vein (group A). Postoperatively, they received an infusion of 5-fluorouracil (5-FU: 125 mg/d) via each of the 2 catheters for a period of 28 continuous days. The remaining 44 patients (group B) did not receive any other adjuvant therapy. The survival rates and patterns of disease failure were compared between these 2 groups and their subgroups. RESULTS: All 72 patients survived the operation, and all 28 patients in group A completed their courses of LPC without showing any significant adverse signs. Postoperative histopathology was later performed to get a more accurate picture regarding the degree of nodal involvement and/or pancreatic invasion: In group A, 21 patients (group A1) proved positive for nodal and/or pancreatic invasion whereas 7 patients (group A2) proved negative; and in group B, 16 patients proved positive (group B1) whereas 28 proved negative (group B2). Although group A displayed higher incidences of nodal involvement and pancreatic invasion, the 5-year survival rates for the 2 groups varied only slightly. The 5-year survival rate was 70% in group A1, 85% in group A2, 35% in group B1, and 92% in group B2, respectively. The difference between B1 and B2 and the difference between A1 and B1 were statistically significant, and these differences were conclusively found to be attributable to the different incidences of liver metastasis. CONCLUSION: Through this research, both nodal involvement and pancreatic invasion were confirmed to be reliable predictors of liver metastasis after curative resection of ampullary and duodenal cancers. Since LPC was proven to be effective in preventing the postoperative development of liver metastasis, it should be more actively performed for patients with a high-risk of liver metastasis.     

Skin hemodynamics during change from supine to lateral position.

The purpose of this study was to identify the skin hemodynamics during the position change from supine to lateral in patients with neurodegenerative diseases. The participants were 19 patients with neurodegenerative diseases and 12 healthy volunteers. The alteration in the total concentration of oxyhemoglobin and deoxyhemoglobin, indicative of change in blood volume, was measured in the skin of the left flank by using a portable noninvasive tissue oxygen monitor by near-infrared spectroscopy. The positions were changed from the left and right lateral with a return to the supine between each procedure. In healthy volunteers, total hemoglobin concentration (skin blood volume) increased when the position changed from supine to left lateral and decreased when changed from supine to right lateral. The decreased skin blood volume gradually recovered after a change from the supine to the right lateral position in healthy volunteers. However, it did not recover in three sporadic olivopontocerebellar atrophy (OPCA) patients with marked autonomic dysfunction and one Parkinsonian patient with severe orthostatic hypotension. Our study identified that the intracutaneous blood was changing dynamically during the position change from supine to lateral and was regulated by autonomic nerve function.     

BRCA1 haploinsufficiency impairs iron metabolism to promote chrysotile-induced mesothelioma via ferroptosis resistance

Malignant mesothelioma (MM) is still a social burden associated with asbestos exposure. Local iron accumulation thereby represents the major pathogenesis, followed by oxidative DNA strand breaks and genomic alterations in the mesothelium. BRCA1 is a critical component of homologous recombination repair directed to DNA double-stranded breaks, whereas BRCA1 germline mutation is an established risk for breast/ovarian cancer, its role in MM development remains to be elucidated. Murine Brca1 mutant models so far have not reproduced human phenotypes. However, a rat Brca1 mutant model (Mut; L63X/+ ) recently reproduced them at least partially. Here we describe the differential induction of MM in Brca1 mutant rats by intraperitoneal injection of chrysotile or crocidolite. Only Mut males injected with chrysotile revealed a promotional effect on mesothelial carcinogenesis in comparison with wild-type and/or females, with all the MMs Brca1 haploinsufficient. Array-based comparative genomic hybridization of MMs disclosed a greater extent of chromosomal deletions in Brca1 mutants, including Cdkn2a/2b accompanied by Tfr2 amplification, in comparison with wild-type tumors. Mutant MMs indicated iron metabolism dysregulation, such as an increase in catalytic Fe(II) and Ki67-index as well as a decrease in Fe(III) and ferritin expression. Simultaneously, mutant MMs revealed ferroptosis resistance by upregulation of Slc7A11 and Gpx4. At an early carcinogenic stage of 4 weeks, induced Brca1 expression in mesothelial cells was significantly suppressed in chrysotile/Mut in comparison with crocidolite/Mut, whereas significant preference to iron with a decrease in Fe(III) has been already established. In conclusion, chrysotile exposure can be a higher risk for MM in BRCA1 mutant males, considering the rat results.