[A case of colorectal neuroendocrine carcinoma effectively treated with bevacizumab+levofolinate+5-FU chemotherapy].

A 76-year-old woman was admitted to our hospital with diarrhea and weight loss in February 2007. A CT scan revealed a tumor in the abdominal cavity, and although a thorough investigation was conducted, no diagnosis was made. Therefore, she underwent diagnostic surgery in April 2007. Intraoperatively, the tumor was determined to have originated in the transverse colon, with invasion to other organs. The patient underwent a transverse colectomy, partial ileal resection, and partial resection of the bladder and peritoneum were performed. The pathological diagnosis was colorectal neuroendocrine carcinoma. FOLFOX4 chemotherapy was initiated in May 2007. However, a CT scan in June 2007 revealed a recurrent tumor in the right pelvis. Although right hemicolectomy and right oophorectomy were performed in August, a CT scan in September 2007 revealed a recurrent tumor in the right pelvis. Following treatment with bevacizumab+levofolinate+5-FU, the tumor disappeared. The patient continued to receive this chemotherapy regimen until August 2010, and CT scans showed a complete response. Even though colorectal neuroendocrine carcinoma is known to have a poor prognosis, the present case was effectively treated with bevacizumab+levofolinate+5-FU chemotherapy. Herein we provide discussion and suggestions about treatment for colorectal neuroendocrine carcinoma.

[Adverse events in patients treated with capecitabine as adjuvant chemotherapy after surgery for colorectal cancer--countermeasures against hand-foot syndrome].

Although the 2009 edition of the Guidelines for Colorectal Cancer Therapy recommend capecitabine as a standard postoperative adjuvant chemotherapy for colorectal cancer therapy, a characteristic adverse event, hand-foot syndrome, develops at a high incidence, and appropriate management is necessary to continue therapy. We investigated countermeasures against adverse events, particularly hand-foot syndrome, in patients treated with capecitabine. The subjects were 47 patients aged 64 years (27-84 years) who underwent surgery for colorectal cancer. They received 8 (2-16) courses of drug administration. No grade 3 blood or non-blood toxicity was noted, and the therapy was relatively safe excluding an enhanced anticoagulant effect. Grade-3 hand-foot syndrome developed in 3 patients, but there were only 10 grade-2/3 cases (21.7%) because humectants and oral vitamin B6 preparation (supportive therapy) were administered from therapy initiation. The incidence increased to 32.6% (15 patients) after June. Symptoms aggravated due to mechanical stimulation of the hands and legs in 5 patients because they were farmers growing cherries, suggesting that investigation of patient living background is also important. The incidence of grade-2/3 hand-foot syndrome was 21.1 and 75% in 39 and 8 patients, respectively, who were treated with supportive therapy from the initiation of drug administration and after several courses of drug administration or development of symptoms. This suggested the usefulness of early supportive therapy. The importance of preventive measures against hand-foot syndrome will increase as capecitabine is increasingly administered. Information exchange between medical staffs and providing patients with appropriate information may lead to management of adverse events and subsequently to continuation and obtaining effects of therapy.

[Combination of hepatic arterial infusion therapy and FOLFOX for colorectal cancer with multiple unresectable liver metastases causing severe liver dysfunction].

PURPOSE: The purpose of this study was to evaluate the efficacy of the combination of hepatic arterial infusion therapy and FOLFOX for colorectal cancer with multiple unresectable liver metastases causing severe liver dysfunction. SUBJECTS AND METHODS: The subjects were 13 colorectal cancer patients who had undergone resection of the primary tumor, and showed multiple, unresectable liver metastases and severe liver dysfunction. They consisted of 8 men and 5 women, with a median age of 63(29-77)years. Of these patients, 7 and 6 had colon and rectum cancers, respectively. They had an average of 8(3-22)liver metastases of 4.6(1.5-14.5)cm in diameter. During surgery, extrahepatic lesions were found in 3 patients(P in 2, and CY in 1). The preoperative serum LDH and ALP levels were high, at 1,099 (322-1,418)and 1,011(644-2,384), respectively. The follow-up period was approximately 500(248-928)days. Only 5-FU in FOLFOX4 or 6 m therapy was infused into the hepatic artery, and LV and L-OHP were injected into the central venous port about every two weeks. Response rates and adverse events were evaluated according to the RECIST criteria and CTCAE ver 3.0, respectively. RESULTS: The therapy was performed 14(6-22)times, with a response rate of 84.6% for liver metastases, facilitating hepatectomy in 1 patient. The overall response rate was 61.5%, with 1 patient dying of the primary cancer on the 265th day. Grade 3 adverse events were neutropenia and anorexia in only 1 patient each, and no adverse events were specific to hepatic arterial infusion. CONCLUSION: Since the follow-up period after this therapy was still short, only 13 patients have received the therapy. However, it appears that it can be performed relatively safely, and is effective for the control of extrahepatic lesions as well. Therefore, this therapy provides good control, and can be a treatment option.

Randomized, multicenter trial of antibiotic prophylaxis in elective colorectal surgery: single dose vs 3 doses of a second-generation cephalosporin without metronidazole and oral antibiotics.

HYPOTHESIS: Use of prophylactic antibiotics in elective colorectal surgery is essential. Although single-dose prophylactic antibiotics are recommended, the efficacy of single-dose cephalosporin without metronidazole and oral antibiotics is not fully proven. We conducted a multicenter, randomized trial of a single dose vs 3 doses of the second-generation cephalosporin cefmetazole. DESIGN: A prospective, randomized, multicenter trial in patients undergoing elective colorectal surgery. SETTING: Seven major hospitals in Japan that offer cancer treatment. PATIENTS: Patients with colorectal cancer treated from May 6, 2004, to April 25, 2005. INTERVENTIONS: Patients were randomized to 1 of 2 groups: a single-dose group given a single dose of cefmetazole just before skin incision and a 3-dose group given 2 additional doses of cefmetazole every 8 hours after the first dose just before skin incision. MAIN OUTCOME MEASURES: Incidences of incisional surgical site infection (SSI), organ or space SSI, and all other infectious complications within 30 days after surgery. RESULTS: A total of 384 patients were enrolled. Seven patients were excluded because of additional surgery or the inability to tolerate mechanical preparation. The incidence of incisional SSI was higher in the single-dose group (27/190 or 14.2%) than in the 3-dose group (8/187 or 4.3%) (P = .009). Incidences of organ or space SSI and other postoperative infectious diseases did not differ significantly between the 2 groups. In multivariate analysis, antibiotic dose was the only significant factor related to the incidence of incisional SSI. CONCLUSION: Three-dose cefmetazole administration is significantly more effective for prevention of incisional SSI than single-dose antibiotic administration. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00292708.

Chromosomal aberrations detected by comparative genomic hybridization predict outcome in patients with colorectal carcinoma.

To obtain comprehensive information regarding the correlation between genomic changes and clinicopathological parameters such as disease stage, metastases, and survival, we investigated genomic changes by comparative genomic hybridization (CGH) in 73 patients with colorectal cancer (CRC), and assessed the associations of such charges with clinicopathological parameters. Gains of 8q21-22, 13q21-31 and 20q12-qter and loss of 17p12-pter were detected in >50% of stage I tumors. Gain of 8q23-qter and losses of 8p12-pter and 18q12-qter were observed more frequently in stage III/IV tumors than in stage I tumors (all P<0.05). Loss of 8p12-pter and gain of 8q23-qter were linked to nodal metastasis (all P<0.05). Loss of 18q12-qter and gain of 8q23-qter were associated with distant organ metastasis at diagnosis and/or recurrence after surgery (all P<0.05). Moreover, losses of 8p12-pter and 18q12-qter and gains of 8q23 and 8q24-qter were associated significantly with unfavorable prognosis (all P<0.05). Furthermore, combined examination of the above four changes can provide a more accurate assessment for patient's prognosis. Specifically, 11 of 19 patients with these four changes died, but only 1 of 21 cases without these four changes died during the follow-up period (P<0.0001). Multivariate analysis revealed that loss of 18q12-qter is an independent prognostic marker (P=0.031). Our findings indicate that genetic aberrations detected by CGH may predict outcome in patients with CRC.

[A case of recurrent GIST of the esophagus which completely responded to imatinib mesilate].

Middle and lower esophagectomy was performed in a 68-year-old man in 1997 for the local recurrence of esophageal submucosal tumor after enucleation of the tumor. We subsequently performed partial hepatectomy for multiple liver metastases in 2001. The tumor was first diagnosed as GIST in the histological examinations of the liver metastases. However, 12 months after the hepatectomy, further recurrent lesions were found in multiple lymph nodes, in the remnant liver, and in the pancreas, as well as in the subcutaneous tissue. The lesions were initially considered unresectable, and we thus started an internal use of Glivec (400 mg/day) since July 2004. Within 2 months,all detected recurrent lesions changed into liquid forms,and the size of the subcutaneous tumor was also remarkably reduced. Accumulation of FDG was not seen on FDG-PET examination, suggesting the complete response of the tumor to Glivec. We still continue internal use of Glivec, and new recurrent lesions have not been detected up to now. Furthermore, the sizes of the liquid-regenerated lesions are gradually reducing.

Two subtypes of mucinous colorectal carcinoma characterized by laser scanning cytometry and comparative genomic hybridization.

To data, there have been no comprehensive cytogenetic studies of mucinous colorectal carcinomas (MUCs). We used comparative genomic hybridization (CGH) and laser scanning cytometry (LSC), to analyze cytogenetic changes in 21 MUCs and to compare the results with those of our previous study of 60 non-MUCs. Six of 21 MUCs were aneuploid and 15 were diploid. Gains of 13q, 8q, 2q, 12p and 18p were more frequent aberrations. Recurrent decreases in DNA copy number were found frequently at 17p, 22q, 1p, 16p and 8p. Amplifications of 8q, 5p, 12, 18p, 13q and 20p were observed in aneuploid tumors. The average number of DNA sequence copy number aberrations (DSCNAs) was significantly higher in aneuploid MUCs than in diploid ones. Aneuploid MUCs were clinicopathologically more aggressive, with greater lymph node involvement, distant organ metastasis, recurrence after surgery, higher stage and poorer prognoses. Gain or amplification of 18p was detected in 5 of 6 aneuploid MUCs but not in diploid MUCs or non-MUCs. When the average number of DSCNAs was compared among MUCs and well, moderately, and poorly differentiated adenocarcinomas, the average number of DSCNAs was significantly lower in diploid MUCs; however, with aneuploid tumors, the average number of DSCNAs in MUCs was similar to that in poorly differentiated adenocarcinomas but higher than that in well and moderately differentiated cancers. Moreover, tumor cells were well differentiated in diploid MUCs but poorly differentiated in aneuploid MUCs. These data suggest that MUCs have two types with different genetic pathways, histologic characteristics, and behavior.

Characteristics of a hepatozoonosis in lungs of Japanese black bears (Ursus thibetanus japonicus).

In a survey of pathologic agents in the wild animals of central Japan, we found a Hepatozoon sp. in the lungs of Japanese black bears in Fukui, Shiga, and Gifu Prefectures, Japan. Histopathologic examination of organs and tissues from the 18 bears inspected showed hepatozoonosis in all. Immature and mature meronts were found in all lobules and between alveoli, with a few found between pleura and in connective tissue. In the lungs, inflammatory cells were not found around meronts, merozoites, or tubercles made of macro-phages including zoites, but inflammatory cells were found around degenerating cells, zoites, and tubercles. A Hepatozoon sp. has not been reported as being detected in bears of any species before.