[Two cases of advanced biliary tract cancer successfully treated with gemcitabine combination chemotherapy].

Case 1: A man in his sixties underwent extended right lobectomy of the liver for hepatic hilar cholangiocarcinoma (stage III, fCur B)in July2002. CT scans revealed cancerous pleuritis in March 2005, and he was treated with the chemotherapy of GEM alone as first-line, combined chemotherapy of S-1 and GEM as second-line, and CDDP and GEM as third-line treatment. These therapies have been effective for about 20 months. Case 2: A woman in her sixties was diagnosed with advanced gallbladder cancer(stage IVb)in September 2005. She was given combined chemotherapy of S-1+GEM as first-line, and CDDP+GEM as second-line treatment. The main tumor and metastatic lymph nodes were shrunk, allowing us to perform extended hepatectomy. Histopathologic examinations of the resected specimen of the liver involved by the tumor showed the increased infiltration of inflammatorycells and fibrosis. These patients have been managed on an outpatient basis with good QOL and cancer controlled. Although there has been no established standard regimen, the combined chemotherapy based on GEM will be a provisional standard regimen for patients with advanced biliarytract cancers.

[A long survival case of advanced colon cancer with lung metastasis and cancerous pleuritis responding to CPT-11 and S-1 combination therapy].

A 71-year-old man underwent right hemicolectomy for an ascending colon cancer (stage II, Cur A) in September 2001. Adjuvant chemotherapy with tegafur/uracil was performed, but CT scans and FDG-PET, conducted in May 2003, revealed cancerous pleuritis and lung metastasis. Although 2 courses of the chemotherapy with LV+5-FU (RPMI regimen) were completed, progressive disease was confirmed. Therefore, the chemotherapy with CPT-11 (100 mg/ day; day 1, 15)+S-1 (100 mg/day; day 1-21) was started in May 2004. After completion of 6 courses, CT scan showed a partial response. Only grade 2 vomiting was noted as an adverse reaction to the treatment, however, the patient has been managed on an outpatient basis for the last 3 years with good QOL and the cancer under control. This case suggests that this combination therapy can be expected to be highly effective as a safe approach for continuously maintaining the QOL of patients with advanced or recurrent colorectal cancer.

Successful resection of advanced pancreatic tail cancer after neoadjuvant gemcitabine chemotherapy: report of a case.

Pancreatic cancer with distant metastasis is not an indication for surgery, and the median survival of these patients is less than 3 months. We report the case of a patient who has survived for 21 months without any signs of recurrence after resection of advanced pancreatic cancer following a course of chemotherapy with gemcitabine (GEM). A 75-year-old man was hospitalized for anorexia and emaciation. Examinations showed pancreatic cancer with distant peritoneal metastasis. After the main tumor and metastasis had been shrunk by GEM chemotherapy, we performed distal pancreatectomy combined with splenectomy. Microscopically, the main tumor was confirmed as moderately differentiated tubular adenocarcinoma with interstitium and fibrosis. The radicality of the surgery was R0, according to the TNM classification of the UICC. The patient recovered well and has had no clinical symptoms for 40 months since the initial chemotherapy. This case suggests that multidisciplinary treatment with GEM may prolong the survival of some patients with unresectable pancreatic cancer.

[A case of advanced pancreatic cancer treated with gemcitabine hydrochloride].

We report the case of 75-year-old man with advanced pancreatic cancer who was successfully treated with gemcitabine. The patient was admitted to our hospital suffering from anorexia and body weight loss. CT and ERCP showed pancreatic tail cancer with Schnitzler metastasis. We judged that a curative operation was impossible. Gemcitabine was infused over 30 minutes on an outpatient basis (1,000 mg/m2/week x 3/4 weeks). After 4 courses, the tumor was reduced and the tumor markers decreased. Furthermore, the patient can take sufficient meals without any adverse effects. The patient continues to undergoing the therapy with gemcitabine, and his quality of life has been preserved.

Obstructive ileitis secondary to colon cancer: report of a case.

We report a case of obstructive ileitis (OI) secondary to colon cancer. A 62-year-old man was hospitalized for abdominal pain and a feeling of fullness. Examinations revealed a mechanical ileus caused by an obstructing carcinomatous lesion of the cecum. He underwent laparotomy on the tenth hospital day, and a right hemicolectomy was carried out with resection of the distended and edematous ileum. The histopathologic diagnosis was adenocarcinoma in the cecum involving the ileocecal valve and nonspecific inflammatory change of the ileum, with mucosal necrosis and neutrophilic infiltration involving the subserosal layer. His postoperative course was uneventful. OI does not always show similar histological features to obstructive colitis; however, they are both important types of obstructing lesions, and their possibility must be kept in mind during colorectal cancer surgery.

Different mechanisms for membrane and nuclear damages in apoptosis induced by an immunosuppressant, FTY720.

A novel immunosuppressant, FTY720, that was purified from cultures of Isaria sinclairii has been shown to cause apoptosis of lymphocytes, but its biochemical and molecular mechanisms are largely unknown. In this study, we investigated the signal transduction of FTY720-induced apoptosis in comparison with the Fas-induced apoptosis. Although FTY720 induced nuclear and membrane damages in a dose-dependent manner, nuclear damage, but not membrane damage, was suppressed by the caspase-3 inhibitor, DEVD-FMK. It blocked both the nuclear and membrane damages that were induced by the anti-Fas antibody. Experiments using enucleated cytoplasts also demonstrated that membrane damage was induced by FTY720. However, the ones that were induced by the anti-Fas antibody were not blocked by DEVD-FMK. Exogenously-added sphingolipids partially suppressed the FTY720-induced membrane damage. These results suggest that FTY720 induces membrane damage through the caspase-3-independent pathway that is modulated by sphingolipids.