[Endoscopic Submucosal Dissection(ESD)as a "Loco-Regional Cancer Therapy" for Colorectal Tumors].

INTRODUCTION: Endoscopic submucosal dissection(ESD)for colorectal tumors has been covered by the national health insurance system in Japan since April 2012, and is widely used. We analyzed colorectal ESD cases we performed. PATIENTS AND METHODS: We investigated 515 patients with colorectal lesions(580 lesions)for whom ESD was performed between November 2005 and April 2017. Clinicopathological data, technical methods, complications, and outcomes were analyzed. RESULTS: Most tumors were found in the transverse colon(134 lesions). The average diameter was about 26 mm. The largest lesion was 120 mm. The en bloc resection rate was high(96.2%). The average operative time was 51 minutes. Among complications, the number of delayed major bleeding cases was 7(1.2%). Minor perforations occurred in 3 cases(0.5%). The perforation could be closed with endoscopic clips. About 70% of the cases were adenomas, and the remainder were carcinomas. One patient with carcinoma in situ showed a mucosal recurrence 4 months later and received repeat endoscopic treatment. The cure rate was 99.8%. Among 29 deep submucosal invasion cases, additional colectomy was performed in 21; 3 patients had persistent carcinoma in the colonic wall and another patient had lymph node metastasis. CONCLUSIONS: Colorectal ESD can be performed for all sites in the large intestine, and en bloc resection was possible for a large lesion. A good outcome was observed for "Loco-Regional Cancer Therapy" in early colorectal carcinoma.

[A case of successful treatment with OK-432 administration into lymphatic cyst formed after resection of rectal cancer].

We herein report a case of successful treatment with OK-432 administration into lymphatic cyst formed after resection of rectal cancer. A 61-year-old male patient underwent a very low anterior resection with D3 lymphadenectomy for locally advanced rectal cancer. Four months after the surgery, he arrived at our department with lower abdominal fullness. He was diagnosed as having bilateral intra-pelvic abscess by CT scan, and underwent a tube-drainage. After drainage, abscess lesions were shrunk, but a serous discharge remained. Because we diagnosed lymphatic cysts caused by the delayed lymphatic discharge after lymphadenectomy, an administration of OK-432 into cysts was performed. After administration, the discharge was decreased, and then fistula was closed.

[A prediction of prognosis by A-L score in patients with stage IV colorectal cancer].

We analyzed the relationship between A-L score classified by serum albumin level and lymphocytes/white blood cells ratio and clinicopathological features in patients with Stage IV colorectal cancer. Seventy-nine patients were classified by the A-L score. In lower-scored cases, the populations of elderly patients, patients with emergency operation and patients with poorer PS were increased. Additionally, the 2-year survival rate was decreased as low as A-L score. In the multivariate analysis, the A-L score was independent prognostic factor in Stage IV colorectal cancer.

[A clinical experience in treatment with bevacizumab for unresectable colorectal cancer].

Bevacizumab, a humanized monoclonal antibody to VEGF for advanced recurrent colorectal cancer, has been known for complications of gastrointestinal perforation, hemorrhage, thromboembolism and proteinuria, as adverse effects. These findings must be taken care as well as adverse drug reactions (ADR) caused by combination chemotherapy. We here in present a clinical experience in treatment with bevacizumab for unresectable colorectal cancer. Six patients treated with bevacizumab for over two courses until April 2008 were analyzed for this study. PR was obtained in one case with mFOLFOX6. Even though, grade 3 neutropenia was observed in only one case with FOLFIRI, the other cases had grade 2 or less in ADR. In addition, there were no any specific ADRs related with bevacizumab, so we concluded that combination chemotherapy for advanced recurrent colorectal cancer with bevacizumab was well-tolerated.

Overexpression of human X-box binding protein 1 (XBP-1) in colorectal adenomas and adenocarcinomas.

BACKGROUND: Human X-box binding protein 1 (XBP-1) is a transcription factor essential for hepatocyte growth, as well as for plasma cell differentiation. Recently, overexpression of XBP-1 has been reported in breast cancer including non-invasive carcinomas, and was suggested to play an important role in breast carcinogenesis. To investigate the involvement of XBP-1 in colorectal tumorigenecity, the expression of XBP-1 was examined in four colon cancer cell lines, six colorectal polyps and five colorectal carcinomas. MATERIALS AND METHODS: The study population consisted of eleven patients who had undergone resection for colorectal cancer or adenoma from 2000 to 2002. Four colon cancer cell lines, DLD1, SW480, HCT15 and WiDr, were also analyzed for expression of XBP-1. Reverse transcription-polymerase chain reaction was performed using eleven primary colon tumors. XBP-1 expression was then investigated using an immunohistochemical method for archived paraffin-embedded sections. RESULTS: The XBP-1 gene was overexpressed in four cases out of five primary colorectal carcinomas and in four cases out of six colorectal adenomas. Also all four cancer cell lines expressed XBP-1 mRNA. Immunohistochemical staining demonstrated that XBP-1 protein was strongly stained in the cytoplasms of cancer cells, whereas it was unreactive in the normal colon epithelial cells and stromal cells. CONCLUSION: These data indicate that increased expression of XBP-1 gene may play some role in human colon carcinogenesis through impairment of cell differentiation regulation.

Triangulating anastomosis using a linear cutter in a colectomy.

BACKGROUND/AIMS: We have performed end-to-end anastomosis by the triangulating method using a linear cutter for the reconstruction in colectomy. In this report, we present our technique of triangle anastomosis and its convenience and merits. METHODOLOGY: Patients who underwent end-to-end anastomosis with the triangulating method, or the Gambee procedure, for reconstruction after colon cancer surgery from 1998 to 2003 in our department, were analyzed retrospectively. The anastomosis time and complications were compared in these two groups. RESULTS: The mean anastomosis time was 14.7+/-3.5 minutes, which is 17+/-0.7 shorter than the 31.7+/-4.2 minutes it took for the Gambee anastomosis performed during the same period. There were no significant differences in the incidences and variety of complications. CONCLUSIONS: Triangulating anastomosis using a linear cutter is a safe and easy technique that can be performed in a short amount of time. It is, therefore, considered a useful method for reconstructive surgery for colon cancer.

[Extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion--a case report].

A 72-year-old woman, who had the carcinoma of cecum with unresectable multiple liver metastases, underwent ileocecal resection and insertion of hepatic arterial infusion catheter. Hepatic arterial infusion (HAI) chemotherapy using Leucovorin. 5-FU caused to decrease liver metastases after an initiation of HAI. However, the metastatic nodule at the right lobe of lung was found. Then systemic chemotherapy with CPT-11 CDDP was performed alternately with HAI chemotherapy. After the initiation of revised regimen, all metastatic lesions were shrunk. We here in present the case of extra- and intra-hepatic metastasis successfully treated with alternative chemotherapy with hepatic arterial infusion and systemic intravenous infusion after responding to hepatic metastasis from colon cancer by hepatic arterial infusion.

Indication and efficacy of adjuvant chemotherapy with oral fluoropyrimidines for dukes' B colorectal cancer.

BACKGROUND: Identifing patients prone to colorectal cancer recurrence is of importance in providing appropriate adjuvant chemotherapy. In this retrospective study on Dukes' B colorectal cancer, patients at high risk of recurrence were identified by clinicopathological factors, and the efficacy of adjuvant chemotherapy with oral fluoropyrimidines was evaluated. PATIENTS AND METHODS: The subjects were 229 patients with Dukes' B colorectal cancer who had undergone curative surgical resection. The relationship between each factor and cancer-related survival was examined. RESULTS: In all the patients, the 5-year cumulative survival rate was 83.5% and the recurrence rate was 20.1%. The multivariate analyses indicated that the depth of invasion was the most significant prognostic factor. The cases with tumor exposed at the serosa or which invaded other organs were considered as a high-risk group. The 5-year survival rate in high-risk patients with adjuvant chemotherapy was significantly better than those without chemotherapy (75.8% and 44.0%, respectively, p=0.0008). The patients who received chemotherapy tended to show a decrease in the recurrence rate, especially in the liver and lung (p=0.0346). CONCLUSION: In Dukes' B colorectal cancer, the cases with invasion depth se or si were considered to be at high risk of recurrence or death. Adjuvant chemotherapy was effective for such high-risk patients, especially decreasing recurrence in the liver and lung.

[Can the survival of patients with recurrent disease after curative resection of colorectal cancer be prolonged by the administration of cimetidine?].

Administration of cimetidine after curative surgery can improve prognosis of patients with colorectal cancer. In this study, we analyzed whether cimetidine can influence the survival of patients with a recurrent disease after colorectal surgery. The subjects were 29 patients with recurrent disease: 14 patients were administered with cimetidine and 15 patients were not. In the cimetidine administered group, seven cases were recurrent in the liver, 5 cases in a local site and 1 case in the lymph node, whereas 7 cases were recurrent in the liver, 4 cases in a local site and 3 cases in the lung for the non-cimetidine administered group. There were no significant differences for both groups in terms of patient's survival after recurrence. Although it was not significant, the patient's survival after curative resection of recurrent disease for the cimetidine administered group was better than the non cimetidine administered group. Although the results did not show cimetidine could influence the overall survival of the patients after recurrence, it might be possible to improve the survival of the patients after resection of the recurrent disease.

[Hepatic arterial infusion of low-dose leucovorin/5-FU chemotherapy for unresectable hepatic metastases from colorectal cancer].

Hepatic arterial infusion (HAI) chemotherapy for unresectable liver metastases from colorectal cancer (CRC) is generally indicated to patients without extrahepatic lesions. This study was performed to examine whether or not it was possible to obtain a comparable survival time, response rate (RR) and modest toxicity combining low-dose LV and 5-FU (LV/5-FU) with HAI for the patients with unresectable liver metastases from CRC. Twenty two patients with unresectable multiple liver metastases were enrolled in the study. These were patients who had been admitted from 1994 to 2003 in our hospital. Patients were given LV at 25 mg/body immediately followed by 5-FU at 500 mg/body as a 2-hour HAI daily for 5 consecutive days every 5 weeks. The median survival time (MST) of HAI patients was 24.5 months. According to the treatment in the HAI patients, one patient was CR, 6 were PR, 9 were NC, 6 were PD, and the response rate (RR) was 31.8% (7 of 22 patients). The toxicities to this regimen on HAI were observed in 12 patients, and grades 3 or 4 were in 3 patients only. These results suggested that HAI with LV/5-FU can be useful for unresectable liver metastases from CRC.

A new staging system for colorectal carcinoma with liver metastasis.

PURPOSE: The prognosis of colorectal carcinoma (CRC) with liver metastasis varies from case to case. A standardized classification system for evaluation of the prognosis and the treatment is needed. Therefore, we developed a new staging system for CRC with liver metastasis (HM-stage) based on the survival data. PATIENTS AND METHODS: We evaluated 148 CRC patients with liver metastasis treated between 1985 and 1999. Prognostic factors were identified based on a multivariate analysis. According to the final prognostic factors and hazard ratios, we defined the HM- stage. RESULTS: Three factors, including extent of liver metastasis, depth of tumor invasion and peritoneal metastasis, were identified to be the final prognostic factors. These factors were then assigned points. The patients were classified as being HM-stage I to IV by the sum total. The median survival time for each HM-stage were 37 months for HM-stage I, 23 months for II, 10 months for III and 7 months for IV respectively. A significant difference among each stage was recognized (p<0.0001). CONCLUSION: This new staging system for CRC with liver metastasis is simple and should be clinically useful for both estimation of the prognosis and evaluation of the therapy in patients.

Low-dose leucovorin and 5-Fluorouracil for unresectable multiple liver metastasis from colorectal cancer.

UNLABELLED: In the present study, a retrospective investigation was conducted to determine whether or not it was possible to obtain a comparable survival time, response rate (RR) and modest toxicity combining low-dose leucovorin (LV) and 5-Fluorouracil (5-FU) (LV/5-FU) with hepatic arterial infusion (HAI) or systemic intravenous infusion (SI) for patients with unresectable liver metastasis from colorectal cancer (CRC). PATIENTS AND METHODS: Patients were given LV at 20 mg/m2 immediately followed by 5-FU at 370 mg/m2 with a 2-hour SI or HAI daily for 5 consecutive days with courses repeated every 5 weeks. Twenty patients received HAI and 16 patients received SI. Survival, response and toxicity were assessed. RESULTS: The median survival time (MST) of all patients was 20.0 months. The MST of the HAI and SI patients was 24.5 and 18.9 months, respectively. Two patients had complete remission (CR), 8 partial response (PR) and 14 no change (NC), which resulted in an RR of 28%. The MST according to the responses of CR/PR, NC and progressive disease (PD) patients was 45.5, 20.2 and 11.2 months, respectively. Severe toxicity (grades 3 or 4) to this regimen occured only in 0-10% of the cases, and there were no treatment-related deaths. CONCLUSION: There was no difference in response and survival between HAI and SI, which could be interpreted as a favorable result. Regardless of the route of administration, low-dose LV/5-FU treatment should be considered for patients with liver metastasis from CRC.

How many lymph nodes should be examined in Dukes' B colorectal cancer? Determination on the basis of cumulative survival rate.

BACKGROUND/AIMS: We analyzed how many lymph nodes should be examined to establish the presence or absence of lymph node metastasis, a staging factor, based on cumulative survival rate in colorectal cancer. METHODOLOGY: Among those who had undergone curative resection of colorectal cancer and lymphadenectomy exceeding D2, 94 patients with Dukes' B colorectal cancer (group B) and 108 patients with Dukes' C colorectal cancer (group C) were investigated, excluding obvious deaths from other diseases. Group B was divided into two groups by the number of lymph nodes examined, and the minimum number of retrieved lymph nodes yielding significant difference in survival rate was determined. RESULTS: Dividing group B into two groups by the number of lymph nodes examined, survival rate was studied. The minimum number of retrieved lymph nodes yielding significant difference in survival rate between the two groups was observed when group B was divided into one group with 9 or more lymph nodes (72 patients) and the other with less than 9 (22 patients), with cumulative five-year survival rate of 86.7% and 66.7%, respectively. More favorable prognoses were observed in the 9 or more group compared with the less than 9 group or Dukes' C group (p=0.0284, p=0.0032, respectively). On the other hand, survival rate of the less than 9 group was similar to that of the Dukes' C group (p=0.8167). CONCLUSIONS: Based on survival rate, 9 or more lymph nodes should be examined in order to correctly ascertain nodal negativity in lymphadenectomy exceeding D2 for Dukes' B colorectal cancer.

[Hepatic arterial infusion (HAI) chemotherapy achieved a complete response (CR) for multiple liver metastases of colorectal cancer--two case reports].

We encountered two cases of concurrent multiple liver metastases of colorectal cancer in two patients who achieved a complete response (CR) to hepatic arterial infusion (HAI) chemotherapy. The first case is a 64-year old man who was found to have anemia, and a diagnosis of ascending colon cancer was made. There were 6 metastatic lesions in both lobes of the liver. A right hemicolectomy was performed. Postoperative chemotherapy consisted of 2 g of oral UFT-E as well as 3 mg of CDDP and 500 mg of 5-FU administered by HAI. The metastatic lesions disappeared after 9 courses of chemotherapy were carried out. A partial hepatectomy was performed in the scarred area. Histopathological examination revealed no cancer cells. No recurrence has been observed for 4 years and 10 months since achieving CR. The second case is a 69-year-old man who had thin stool and bloody stool. Rectal cancer was diagnosed. Five metastatic lesions were noted in both lobes of the liver. A low anterior resection was performed. l-LV 25 mg and 5-FU 500 mg were given postoperatively by HAI. After three courses of chemotherapy postoperatively, metastatic lesions disappeared. No recurrence has been noted for 2 years and 1 month since achieving CR. HAI chemotherapy is considered one of the useful treatment options for patients with multiple liver metastases of colorectal cancer.

Prophylactic efficacy of allopurinol ice ball for leucovorin/5-fluorouracil therapy-induced stomatitis.

BACKGROUND: Stomatitis in cancer chemotherapy manifests with pronounced subjective symptoms, lowers the patient's quality of life (QOL) and may necessitate the discontinuation of chemotherapy. There have been few effective therapies established to date for chemotherapy-induced stomatitis. PATIENTS AND METHODS: We used frozen allopurinol solution (allopurinol ice balls) in the prevention of stomatitis associated with leucovorin (LV)/5-fluorouracil (5-FU) therapy for colon cancer. RESULTS: Among 32 patients undergoing LV/5-FU therapy, without the use of the allopurinol ice balls, 15 patients developed stomatitis. On the other hand, only 3 patients developed stomatitis among 20 patients receiving the chemotherapy in conjunction with allopurinol ice balls (p=0.0187). Seven patients who developed stomatitis during a course of chemotherapy without allopurinol ice balls were administered the ice balls in the subsequent course; 6 of these patients responded with lessened severity of stomatitis. In 2 of these responders, stomatitis of comparable severity recurred on discontinuation of the medication. CONCLUSION: Concomitant use of allopurinol ice balls is effective in preventing stomatitis in patients undergoing LV/5-FU therapy.

[Host immunity in colorectal cancer patients treated with low-dose Leucovorin plus 5-fluorouracil].

In colorectal cancer, low-dose Leucovorin plus 5-FU therapy does not induce any severe adverse effects, and patients could receive this therapy for many cycles. The aim of this study was to investigate the relationship between host immunity and this regimen. Seven patients were enrolled in this study. Host immunity was investigated before and after chemotherapy. The ratio of Th1/Th2, PHA response, serum IAP level and the productions of IL-6, IL-10 and soluble IL-2 receptor did not change significantly before and after chemotherapy. Since low-dose Leucovorin plus 5-FU therapy might not influence host immunity, patients could receive the therapy for a long duration without toxicity.