Clostridioides difficile-related toxic megacolon after Cryptococcus neoformans cellulitis: A complex of two rare infections in an immunocompromised host.

A 76-year-old Japanese woman was admitted due to uncontrolled cellulitis of the right lower leg. She had deep vein thrombosis on the right limb. Moreover, she had a long history of rheumatoid arthritis treated with corticosteroids. Skin biopsy and lumbar puncture were performed to diagnose disseminated cryptococcosis. She was administered antifungal agents (liposomal amphotericin B and 5-fluorocytosine). On treatment day 14, debridement was performed, and cryptococcosis was controlled. However, she developed toxic megacolon due to Clostridioides difficile infection (CDI). On day 32, she was transferred to the intensive care unit due to severe acidosis and acute kidney injury secondary to CDI-related toxic megacolon. Vancomycin, metronidazole, and tigecycline were administered for treatment of CDI. After several weeks of intensive care, toxic megacolon was improved, but renal replacement therapy was discontinued according to the patient's will. On day 73, she died of renal failure. We experienced a complex of rare diseases, Cryptococcus neoformans cellulitis and Clostridioides difficile-related toxic megacolon. Both diseases were presumed to be the result of corticosteroid and methotrexate use. Hence, careful monitoring is required when treating immunocompromised hosts to reduce the risk of developing complications.

[A Case of Portal Vein Thrombosis Occurring during CapeOX and Bevacizumab Combination Therapy for Liver Metastasis].

A73 -year-old man underwent a sigmoidectomy for sigmoid colon cancer with liver metastasis. After the operation, he received CapeOX combined with bevacizumab therapy. After 6 courses, the liver metastasis was undetectable on computed tomography scans. After 15 courses, computed tomography revealed ascites, and chemotherapy was discontinued. Two months later, computed tomography revealed portal vein thrombosis. Owing to the chronic nature of the thrombosis, thrombolytic therapy was not initiated. However, preservation therapy using antiplatelet drugs for 1 month resolved the ascites and the thrombosis. The risk of serious thrombosis must be considered when using bevacizumab.

A randomized phase III trial exploring the prognostic value of extensive intraoperative peritoneal lavage in addition to standard treatment for resectable advanced gastric cancer: CCOG 1102 study.

A randomized controlled trial has started in Japan to evaluate the efficacy of extensive intraoperative peritoneal lavage in the treatment of resectable advanced gastric cancer. Patients with T3 or deeper carcinoma of the stomach are intraoperatively randomized to either extensive intraoperative peritoneal lavage + arm or extensive intraoperative peritoneal lavage- arm. A total of 300 patients will be accrued from 20 institutions. The primary endpoint is disease-free survival, and secondary end-points are overall survival, peritoneal recurrence-free survival and incidence of adverse events.

Multicenter phase II study of modified FOLFOX6 as neoadjuvant chemotherapy for patients with unresectable liver-only metastases from colorectal cancer in Japan: ROOF study.

BACKGROUND: Neoadjuvant chemotherapy for unresectable colorectal liver metastases can reduce tumor size, which sometimes leads to curative resection. The aim of the present study was to identify and describe patients with initially unresectable liver-only metastases from colorectal cancer who obtained sufficient chemotherapeutic benefit that eventually lead to the removal of the metastatic diseases in the liver. METHODS: A phase II multicenter cooperative study was conducted in 38 medical institutions using modified FOLFOX6 (mFOLFOX6) as neoadjuvant chemotherapy from January 2008 to June 2009. Patients with liver-only metastases from colorectal cancer that was deemed not optimally resectable by liver surgeons received mFOLFOX6 as preoperative neoadjuvant chemotherapy for 6-8 cycles. Patients were reassessed for resectability after 6 cycles of mFOLFOX6. Surgery was carried out 3-6 weeks after chemotherapy. The primary endpoint was the rate of macroscopic curative surgery including liver resection. RESULTS: 36 patients (23 male/13 female, ECOG performance status 0-1) were enrolled. The median age of the patients was 62.5 years; 78% (28 patients) had 5 or more metastatic tumors, and 50% (18 patients) had metastatic tumors over 5 cm diameter. The mFOLFOX6 regimen was safety administered resulting in 18 partial responses (50%), 12 stable disease, and 4 progressive disease. There was no grade 3/4 neurotoxicity. Fourteen patients (38.9%) underwent surgery (R0: 13; R1: 1). Of these, thirteen patients (36.1%) underwent R0 surgery. CONCLUSIONS: Our data suggest that mFOLFOX6 has a high response rate in patients with liver-only metastases from colorectal cancer, allowing for R0 resection of liver metastases in a proportion of patients initially not judged to be optimally resectable.

The efficacy and safety of bevacizumab beyond first progression in patients treated with first-line mFOLFOX6 followed by second-line FOLFIRI in advanced colorectal cancer: a multicenter, single-arm, phase II trial (CCOG-0801).

PURPOSE: The aim of this study was to evaluate the efficacy and safety of the planned continuation of bevacizumab beyond first progression (BBP) in Japanese patients with metastatic colorectal cancer (mCRC). METHODS: Previously untreated patients with assessable disease were treated with mFOLFOX6 plus bevacizumab until tumor progression, followed by FOLFIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. Secondary endpoints of the study were overall survival (OS), survival beyond first progression (SBP), progression-free survival (PFS), response rate (RR), disease control rate (DCR), and safety. RESULTS: In the first-line setting, 47 patients treated with mFOLFOX6 plus bevacizumab achieved RR of 61.7 %, DCR of 89.4 %, and median PFS of 13.1 months (95 % CI, 8.7-17.5 months). Thirty-one patients went on to receive a second-line therapy with FOLFIRI plus bevacizumab and achieved RR of 27.6 %, DCR of 62.1 %, and median PFS of 7.3 months (95 % CI, 5.0-9.6 months). Median 2nd PFS was 18.0 months (95 % CI, 13.7-22.3 months). The median OS and SBP were 30.8 months (95 % CI, 27.6-34.0 months) and 19.6 months (95 % CI, 13.5-25.7 months), respectively. No critical events associated with bevacizumab were observed during the second-line therapy. CONCLUSION: The planned continuation of bevacizumab during a second-line treatment, BBP strategy, is feasible for the Japanese mCRC patients.

[Cetuximab-associated skin ulceration in patient with metastatic colorectal cancer: a case report].

An 82-year-old female was diagnosed with rectal cancer. Hartmann's procedure was performed and a curative resection was successfully achieved. Postoperative staging according to the classification of the Japanese Society for Cancer of the Colon and Rectum(The 7th Edition)was stage III. She received adjuvant chemotherapy after surgery with tegafur(UFT 300 mg/body/day)orally for 6 months. One year after the surgery, paraaortic lymph node metastasis and a local recurrence were diagnosed. She was treated with modified FOLFOX6 chemotherapy combined with bevacizumab. After 13 courses of treatment with FOLFOX6 and bevacizumab, multiple lung metastases were found. Therefore, we changed the chemotherapy regimens to FOLFIRI plus cetuximab. After 18 weeks of this new treatment she had two skin ulcerations around her stoma, a known side effect associated with cetuximab. We stopped cetuximab and continued chemotherapy with FOLFIRI alone. Seven weeks after cetuximab withdrawal, her skin ulcer healed with the support of a dermatologist and a wound ostomy continence nurse. We reintroduced cetuximab in a chemotherapy regimen with a reduced dose. After two infusions of cetuximab, skin ulceration recurred. We stopped cetuximab again and continued chemotherapy with FOLFIRI. Nine weeks later we resumed cetuximab, but this time the skin ulcer did not occur, and we were able to continue the chemotherapy regimen with FOLFIRI and cetuximab.

[Elderly patient with recurrent rectal cancer successfully responded to modified FOLFOX6 chemotherapy with bevacizumab--a case report].

An 80-year-old female visited our hospital with the chief complaint of lower abdominal pain and diarrhea. She was diagnosed to have rectal cancer. Hartmann operation was performed and curative resection was successfully achieved. Postoperative stage was III according to the classification of the Japanese Society for Cancer of the Colon and Rectum(The 7th Edition). She was treated with oral tegafur(UFT 300mg/body/day)as adjuvant chemotherapy for 6 months. Paraaortic lymph node metastasis and local recurrence were diagnosed by abdominal CT 1 year after the surgery. Her performance status score was 0. She was treated with modified FOLFOX6 chemotherapy combined with bevacizumab. Abdominal CT revealed a partial response after 5 courses. She experienced grade 2 leukocyopenia, grade 3 neutropenia, grade 2 proteinuria and grade 2 hypertension.

The efficacy and toxicity of FOLFOX regimen (a combination of leucovorin and fluorouracil with oxaliplatin) as first-line treatment of metastatic colorectal cancer.

BACKGROUND: Oxaliplatin is the third-generation platinum complex to be active in advanced colorectal cancer. In Japan, it was approved in April 2005. FOLFOX regimen(a combination of leucovorin and fluorouracil with oxaliplatin) has been one of the standard chemotherapy regimens for metastatic colorectal cancer. METHODS: To evaluate the efficacy and feasibility of FOLFOX4 and mFOLFOX6 regimens as first-line chemotherapy in Japanese patients with metastatic colorectal cancer, 23 consecutive patients with histologically confirmed colorectal cancer who were treated between June 2005 and August 2007 were investigated in this retrospective study. FOLFOX4 was used for treatment in 13 patients(57%), and mFOLFOX6 was in 10 patients(43%). RESULTS: The objective response rate was 50.0%. The median survival time was 17.4 months. The median number of cycles was 8.0, with a median relative dose intensity of 74.5% for oxaliplatin. Grade 3 or 4 hematological toxicities were leukocytopenia in four patients, and neutropenia in 12 patients, while non-hematological toxicities such as nausea, anorexia and sensory neuropathy occurred in only one patient each adverse event. No treatment-related deaths occurred. CONCLUSION: FOLFOX regimen has good efficacy in Japanese patients with metastatic colorectal cancer as first-line chemotherapy, with an acceptable overall toxicity profile.

[A case of advanced gastric cancer effectively treated with paclitaxel/S-1 as neoadjuvant chemotherapy].

We report a patient with advanced gastric cancer responding remarkably to neoadjuvant combination chemotherapy consisting of paclitaxel and S-1. The patient was a 65-year-old female who had large type 2 advanced gastric cancer with severe lymph node metastasis(cT3, cN3, cH0, cP0, cM0, cStage IV), treated with paclitaxel/S-1 as neoadjuvant chemotherapy. After the second course, according to UGI, gastroscope and CT findings, a significant tumor reduction was obtained. Distal gastrectomy with D2 nodal dissection were performed. The histological diagnosis was pT1, pN1, pStage IB. The histological effect of main tumor was judged to be Grade 2. The patient has now been in good health without a recurrence for 10 months after surgery. This case suggests that neoadjuvant chemotherapy with paclitaxel/ S-1 is a potential regimen for advanced gastric cancer.

Expression of CXCL12 and CXCR4 in pT3-stage gastric cancer does not correlate with peritoneal metastasis.

CXCR4, a chemokine receptor, is considered to be involved in the metastastic formation of various types of cancer and could influence survival. More recently, CXCR4 was reported to be associated with peritoneal metastasis in gastric cancer, and CXCL12, its ligand, as a prognostic determinant among gastric cancer of various stages. In order to more specifically delineate the relevance of CXCR4 in peritoneal metastasis, 98 patients with pT3-stage gastric cancer who underwent gastrectomy and detection of intra-abdominal free cancer cells in the peritoneal washing samples were evaluated. Immunostaining with anti-CXCL12 and anti-CXCR4 antibodies were performed for the primary tumor specimens, and correlation of the immunoreactivities with various clinicopathologic factors was evaluated. CXCR4 was detected in 61 specimens and CXCL12 in 76 specimens. No significant correlation was observed between presence of free cancer cells in the peritoneal cavity or development of clinical peritoneal carcinomatosis and expression of either the chemokine or the receptor. On the other hand, there was a trend towards correlation of expression of these molecules with recurrences to the distant lymph nodes or to the liver, although the number of events in these categories were insufficient to reach a statistical significance. In gastric cancer, CXCL12/ CXCR4 axis seems to be more strongly associated with lymphatic or hematogenous metastasis than the establishment of peritoneal deposits.