[Peritoneal Mesothelioma Diagnosed with a Sister Mary Joseph's Nodule].

In August 2022, a 59-year-old female noted a mass in her umbilicus and sought evaluation at Toyokawa City Hospital. Abdominal computed tomography(CT)scan revealed a 1.6 cm mass in the umbilical region, ascites in the pelvis, and increased absorption in the omentum. Peritoneal dissemination of the carcinoma and Sister Mary Joseph's nodule due to an unknown primary tumor were suspected because no abnormalities were detected during upper and lower gastrointestinal endoscopy. She underwent an umbilical lumpectomy and diagnostic laparoscopy to establish a definitive diagnosis. The surgical findings included numerous white nodules throughout the abdominal cavity. The umbilical mass and omental white nodules were resected. A final diagnosis of epithelial peritoneal mesothelioma was made based on the histopathologic examination. In general, peritoneal mesothelioma has a poor prognosis, and early treatment is essential; however, making a timely definitive diagnosis is difficult. Peritoneal mesothelioma should be included in the differential diagnosis for a patient with unexplained ascites and abdominal pain. Diagnostic laparoscopy and biopsy will facilitate the establishment of a definitive diagnosis.

[A Case of Rectal Cancer with Lymph Node Metastasis Diagnosed as Intramucosal Cancer].

The patient was a 62-year-old man in whom 0-Ⅱa plus Ⅱc lesions in Rs were identified during follow-up observation of multiple colorectal polyps that were found during colonoscopy performed for the examination of fecal occult blood. CT showed no lymphadenopathy or distant metastasis to other organs. Laparoscopic-assisted high anterior resection of the rectum was performed with a diagnosis of clinical stage Ⅰ. Pathologically, there was a well-to-moderately differentiated tubular adenocarcinoma that remained in the lamina propria; however, 1 metastasis was found in the lymph node adjacent to the rectum(#251). Therefore, adjuvant chemotherapy was performed for 6 months after the operation, and 5 years have passed with no recurrence. Here, we report a case with no apparent submucosal invasion but with lymph node metastasis. We confirm recurrence-free survival for 5 years after surgery.

[A Case of Colostomy-Free and Long-Term Survival with 5-FU/CDDP for Local Recurrence of Anal Cancer after Chemoradiation Therapy].

We report a case of colostomy-free, long-term survival following 5-FU/CDDP for the local recurrence of anal cancer after chemoradiation therapy(CRT). The patient was a 48-year-old woman who was diagnosed with cStage ⅢA anal cancer. She was treated with CRT(5-FU/MMC plus 59 Gy)and achieved a complete response upon treatment completion. A local recurrence was detected on the left-side wall of her rectum after 6 months. We recommended abdominoperineal resection but the patient refused operation. The patient was treated with chemotherapy consisting of 5-FU(1,000mg/m / 2/day)on days 1-5 and CDDP(100mg/m / 2/day)on day 2. Grade 3 peripheral neuropathy appeared following the completion of 5 courses. Therefore, the dose was reduced to 60%. Twenty-five courses of this treatment were continued and chemotherapy was completed. The patient has been alive with no sign of recurrence for 6 years and 8 months from the initial treatment. CRT for anal cancer is becoming a standard therapy but local recurrence is possible. In these cases, abdominoperineal resection is required. Chemotherapy with 5-FU/CDDP in cases of recurrence can be a colostomy-free option.

[A Case of Resected Pancreatic Metastasis of Rectal Cancer after Multiple Resections of Metastatic Lesions].

A 71-year-old man underwent low anterior resection for rectal cancer 10 years prior. He underwent resection of liver metastasis once and that of lung metastases multiple times after the primary surgery. Computed tomography revealed a mass measuring 22mm in size in the pancreatic body 10 years after the rectal resection. We inspected it before surgery by performing EUS-FNA. On suspicion of metastasis of rectal cancer or primary pancreatic cancer, we performed distal pancreatectomy. The pancreatic tumor was diagnosed as metastasis of the rectal cancer. There were multiple metastases in the resected specimen that we were unable to indicate at the preoperative inspection. Resectable pancreatic metastasis from colorectal cancer is rare, but some patients with long-term survival have been reported. If a patient is tolerant to pancreatectomy and has no metastasis in other organs, the patient should be considered as a good candidate for pancreatectomy.

Phosphoinositide 3-kinase inhibitor (wortmannin) inhibits pancreatic cancer cell motility and migration induced by hyaluronan in vitro and peritoneal metastasis in vivo.

In order to block peritoneal metastasis of pancreatic cancer cells, we have attempted to block the signal transduction pathway involving hyaluronan (HA), Src, phosphoinositide 3-kinase (PI3K) and Akt. We examined the effects of Src, PI3K and Akt inhibitors on pancreatic cancer cell motility, invasion and metastasis. The pancreatic cancer cell line SW1990, known to cause peritoneal metastasis efficiently in nude mice, was used in this study. SW1990 cells were stimulated by HA to induce Akt phosphorylation. Then, the inhibitory effects of PI3K and Src kinase inhibitors were examined. Cell motility and cell migration assays were adopted to assess the cancer cell motility and its migration capability. We also examined the therapeutic efficacies of PI3K inhibitor wortmannin on peritoneal metastasis of SW1990 cells in the nude mouse model. Stimulation of SW1990 cells by HA markedly induced the Src-PI3K-Akt signaling, thus enhancing cancer cell motility and its migration. Significantly, we found that wortmannin could exert marked inhibition of the peritoneal metastasis of SW1990 in nude mice in vivo. These findings indicate that the PI3K-Akt signaling pathway plays an essential role in peritoneal metastasis and PI3K inhibitors such as wortmannin can be novel modalities to prevent peritoneal metastasis of invasive cancers such as pancreatic cancer.

[Efficacy of intraperitoneal chemotherapy for advanced Borrmann type IV gastric carcinoma].

We report four patients with advanced Borrmann type IV gastric carcinoma, in whom intraperitoneal chemotherapy with low-dose CDDP and 5-FU plus MMC via a peritoneal port was effective against peritoneal metastasis. However, none of the four patients survived for a long period. During treatment, they were followed on an outpatient basis and received intraperitoneal chemotherapy biweekly with good control of peritoneal metastasis. The ratio of the outpatient follow-up period was more than 50% in all these patients. Intraperitoneal chemotherapy may be effective for controlling peritoneal metastasis of advanced Borrmann type IV gastric carcinoma, and contribute to maintaining the patient's quality of life.

FOLFIRI plus bevacizumab as a first-line treatment for Japanese patients with metastatic colorectal cancer: a JACCRO CC-03 multicenter phase II study.

PURPOSE: The purpose of this multicenter phase II study was to evaluate the efficacy and safety of a combination of irinotecan, 5-fluorouracil (5-FU), and leucovorin (FOLFIRI) plus bevacizumab as first-line chemotherapy in Japanese patients with metastatic colorectal cancer. METHODS: Patients with metastatic colorectal cancer were eligible for enrollment. On day 1 of a 14-day cycle, patients received bevacizumab 5 mg/kg, irinotecan 150 mg/m², and L-leucovorin 200 mg/m² as an intravenous infusion, followed by 5-FU 400 mg/m² as an intravenous bolus and then 5-FU 2,400 mg/m² as an 46-h intravenous infusion. This treatment cycle was repeated. The primary endpoint was progression-free survival (PFS). RESULTS: We enrolled 40 patients, but one withdrew consent before starting treatment. The remaining 39 patients received a total of 509 cycles of FOLFIRI plus bevacizumab (median 11 per patient; range 1-30). The median PFS was 11.5 months, the median overall survival (OS) was 22.0 months, and the 1-year OS rate was 81.8 %. All 39 patients had adverse events. Grade 3 or 4 neutropenia and stomatitis occurred in 21 (53.9 %) and 4 (10.3 %) patients, respectively. CONCLUSION: Our results suggest that FOLFIRI plus bevacizumab is a clinically effective regimen with a manageable toxicity profile as first-line chemotherapy in patients with metastatic colorectal cancer.

Solitary intraperitoneal recurrence of alpha-fetoprotein-producing gastric carcinoma: report of a case.

A solitary recurrence of gastric carcinoma in the peritoneal cavity is extremely rare. We herein present a case of solitary intraperitoneal recurrence in a patient with alpha-fetoprotein (AFP)-producing gastric carcinoma. As far as we can determine, this is the first report of such a form of recurrence in a patient with gastric carcinoma who underwent a successful resection. A review of our eight patients who had AFP-producing gastric carcinoma showed a frequent association with hepatic metastasis and a poor prognosis as has been reported previously. Our patient received intra-arterial chemotherapy with low-dose cisplatin and 5-fluorouracil to prevent hepatic recurrence, but eventually developed multiple hepatic metastases after ceasing this therapy. Therefore, adjuvant intra-arterial chemotherapy may have altered the site of first recurrence in this patient.

Calpain is involved in the HIV replication from the latently infected OM10.1 cells.

Treatment of OM10.1 cells latently infected with human immunodeficiency virus type 1 (HIV-1) with phorbol ester and calcium ionophore (A23187) induced virus replication which was blocked by N-Ac-Leu-Leu-norleucinal (ALLnL), a calpain inhibitor I, and not by lactacystin, a specific proteasome inhibitor. When the purified NF-kappa B/I kappa B complex was treated with mu-calpain, the specific DNA-binding activity was demonstrated by using electrophoretic mobility shift assay in vitro. This effect of mu-calpain was inhibited by ALLnL and calpastatin and not by lactacystin. In fact, we found that mu-calpain efficiently degraded I kappa B alpha. Furthermore, our Western blotting analysis has revealed that mu-calpain cleaves I kappa B alpha at its N-terminal and C-terminal regions that were previously reported to be involved in the interaction with NF-kappa B p65. These observations indicate that in monocyte/macrophage cells calcium signaling is involved in NF-kappa B activation through activation of calpain and thus calpain inhibitors may be effective in inhibiting the activation of latently infected HIV.