Efficacy and safety of irinotecan plus S-1 (IRIS) therapy to treat advanced/recurrent colorectal cancer.

BACKGROUND: 5-Fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX) therapy and 5-FU, leucovorin, and irinotecan (FOLFIRI) therapy are standard chemotherapies to treat advanced/recurrent colorectal cancer. However, these chemotherapies require continuous infusion of 5-FU for a prolonged time of 40 h or more, every two weeks. Accordingly, these chemotherapies require hospitalization and placement of a central venous catheter. Because of frequent catheterization, long-term use of these therapies potentially risks complications such as infection and thrombosis. In contrast, S-1 (tegaful, gimeracil, oteracil) combined with irinotecan (IRIS) therapy involves giving one drug orally and infusing the other for about two hours every two weeks, so placement of a central venous catheter is not necessary. The current study examined the efficacy and safety of IRIS therapy in 90 patients at this Hospital who underwent such therapy to treat advanced/recurrent colorectal cancer. PATIENTS AND METHODS: The study comprised 90 patients who underwent IRIS therapy to treat advanced/recurrent colorectal cancer from December 2004 to December 2011. RESULTS: The ratio of male-to-female patients was 64:26. The mean age at the start of IRIS therapy was 64.5 years, and patients underwent an average of 11 courses of therapy. The response rate to IRIS therapy was 14.8%, the disease control rate was 60.5%, and the overall survival time was 26.7 months. The incidence of adverse events was 70.0%, and the incidence of grade 3 or more severe adverse reactions was 17.8%. CONCLUSION: In comparison to the standard therapies of FOLFOX and FOLFIRI, IRIS therapy had a lower response rate but led to an equivalent overall survival time. IRIS therapy had a low incidence of serious adverse events and allowed patients to continue therapy on an out-patient basis. These findings indicate that IRIS therapy may be a useful form of chemotherapy to treat advanced/recurrent colorectal cancer.

The effect of lentinan combination therapy for unresectable advanced gastric cancer.

BACKGROUND: Developed as a biological response modifier (BRM), lentinan mitigates patients' symptoms by boosting the immune system. In combination with S-1 (tegafur, gimeracil, oteracil), lentinan is reported to mitigate adverse reactions to therapy for unresectable recurrent gastric cancer and prolong survival. However, there are few reports from actual clinical practice, and precise methods of using lentinan have not yet been established. This study retrospectively examined the usefulness of lentinan in patients. PATIENTS AND METHODS: The subjects of this study were 39 patients who were diagnosed with unresectable gastric cancer, based on preoperative examinations or findings at laparotomy in our Department. These patients underwent S-1/paclitaxel therapy. Nineteen of the patients received lentinan while 20 did not, and these two groups of patients were compared. RESULTS: There were no significant differences in patients' characteristics such as the male:female ratio, age at the start of chemotherapy, and staging classification of the 19 patients receiving lentinan and the 20 patients not receiving lentinan. Comparison of the two groups revealed no significant differences in overall survival time, but comparison of the duration of therapy revealed that therapy tended to be longer for the group taking lentinan than the group not taking lentinan. Adverse events were noted in 61.5% (24 patients) of the total patients group; such events tended to occur less frequently in the group receiving lentinan. CONCLUSION: Lentinan inclusion in therapy did not seem to prolong survival. Nevertheless, the duration of therapy tended to be longer for patients taking lentinan. This may be due to the fact that adverse events tended to occur less frequently in these patients during therapy. A decline in the incidence of adverse events increases the duration of therapy and improves the patients' quality of life (QOL); it may also prolong survival. Optimal methods of using lentinan need to be established.

Clinical course of colorectal cancer in patients with ulcerative colitis.

BACKGROUND: Colorectal cancer that develops as a complication of ulcerative colitis (UC) is a serious problem that affects the patient's prognosis. Such cancer is characterized by development at an early age, a high incidence of multiple tumors, poorly differentiated carcinoma and mucinous carcinoma. Special attention should therefore be paid to the diagnosis and treatment of such cancer. PATIENTS AND METHODS: One hundred and seventy-four patients with UC underwent surgery in our Department between July of 1985 and December of 2009. Of these, 22 had concomitant colorectal cancer. We performed a retrospective study to investigate these patients. RESULT: The incidence of colorectal cancer as a complication of UC was 12.6%. The male:female ratio was 14:8, and the average age at surgery was 54.6 (32-79) years. In addition, when examining the lesion type of UC, it was revealed that the total colitis type accounted for 77.3% of colorectal cancer cases in UC patients. Regarding the site of development of colorectal cancer, 14 out of the 22 patients had cancer in the distal end. The average period from the development of UC to the diagnosis of colorectal cancer was 14.7 (0.6-40.5) years. The cumulative incidence rates over 10 and 20 years were 5.1% and 17.5%, respectively. Histologically, poorly differentiated adenocarcinoma and mucinous carcinoma were confirmed in 38.1% of the patients, and dysplasia was also confirmed in 53.8%. In addition, multiple tumors were confirmed at a rate as high as 27.3%. Cancer detection through surveillance has increased, and colorectal cancer was detected in 13 out of the 22 patients by routine surveillance. In cases where cancer was detected by surveillance colonoscopy, 46.2% of lesions were early cancer. We therefore consider that surveillance is useful. However, we experienced a case that could not be diagnosed by endoscopy that was successfully diagnosed by fluoroscopy. The case was noted to have stricture. CONCLUSION: The cumulative incidence rates over 10 and 20 years were 5.1% and 17.5%, respectively. Since the average period from the onset of UC to the diagnosis of colorectal cancer was 14.7 years, routine surveillance examinations are necessary for patients with a history of UC of at least 10 years. In addition, patients with strictures must be examined using both colonoscopy and fluoroscopy because diagnosis with colonoscopy alone may be inadequate.

Clinical features of and chemotherapy for cancer of the small intestine.

BACKGROUND: Cancer of the small intestine is a rare disease, and its clinical features have not been clearly elucidated. Techniques such as double balloon endoscopy and capsule endoscopy allow the preoperative diagnosis of cancer of the small intestine, but this cancer is often detected at an advanced state and in many cases postoperative chemotherapy is required. This study evaluated the pre- and postoperative clinical course of cancer of the small intestine and the effectiveness of chemotherapy. PATIENTS AND METHODS: Patients who underwent surgery for cancer of the small intestine in this Department from July 1985 to December 2008 were included in this study. Duodenal cancer has vastly different origins, methods of diagnosis, and surgical procedures, so this form of cancer was excluded. There were 8 cases of jejunal or ileal cancer treated during the study period. The pre- and postoperative course of these cases was reviewed, as well as the effectiveness of chemotherapy in cases of recurrence. RESULTS: The male:female ratio of the 8 patients was 6:2, the mean age at surgery was 59.7±15.9 (35-76) years, and the mean postoperative follow-up was 41.1±48.0 (7-152) months. Six patients underwent a partial resection of the small intestine, and a right hemicolectomy, and a bypass were performed in one case each. The tumor type according to Borrmann's classification indicated that 5 tumors were type 2, 2 were type 3, and 1 was type 5; the mean tumor size was 6.3±5.3 (2.5-18.0) cm. TNM staging indicated that 3 tumors were stage II, 1 was stage III, and 4 were stage IV. Six patients underwent postoperative chemotherapy. One patient underwent adjuvant chemotherapy of, and 5 patients with recurring or advanced cancer underwent therapeutic chemotherapy of. The course of chemotherapy for the 5 patients with recurrent or advanced cancer resulted in 4 patients with progressive disease (PD) and 1 with stable disease (SD). Three out of the four patients with PD died. CONCLUSION: The basic treatment for cancer of the small intestine is surgical resection. Palliative surgery and chemotherapy are considered in cases where resection is not possible or the cancer recurs. Nevertheless, there is no established regimen for such chemotherapy. Cancer of the small intestine is currently being treated with chemotherapy based on the treatment strategies for colon cancer, but there are few reports of its success. Chemotherapy was unsuccessful in treating any of the patients with recurring or advanced cancer reviewed in this report. The diagnosis must therefore be improved and postoperative chemotherapy will be needed to treat cancer of the small intestine given its increasing incidence, and therefore physicians are working as quickly as possible to establish an optimal treatment regimen. Compiling and studying such cases are crucial to accomplishing that goal.

A study of the postoperative course in cases of GIST of the stomach. The efficacy of imatinib in cases of recurrence.

BACKGROUND: The postoperative course of cases of gastrointestinal stromal tumor (GIST) of the stomach was studied in patients who underwent surgery in this Department. In addition, treatment with the molecular-targeted drug imatinib was studied in cases of recurrence. PATIENTS AND METHODS: We studied 40 cases with a diagnosis of GIST of the stomach where the patient subsequently underwent surgery in this Department between July 1985 (when this facility opened) and December 2007. Six of these cases involved patients with carcinoma or carcinoid tumors, which could have affected the procedure and prognosis, and 2 cases involved patients who developed cancer during the postoperative course of the GIST. Therefore these 8 patients were excluded, thus resulting in the study of a total of 32 patients. RESULTS: The male:female ratio for the 32 patients was 17:15, the average tumor size was 4.7+/-3.4 cm (with a range of 1.3-16.0 cm), and the median follow-up was 92.2+/-73.7 months (with a range of 2-238 months). Recurrence occurred in 6 out of the 32 patients (18.8%) and was observed in the liver of 5 patients, in the lungs of 2 patients, in the peritoneum of 2 patients, locally in 1 patient, and in the bone of 1 patient (including patients with multiple sites). With respect to the tumor size, the incidence of recurrence of tumors smaller than 2 cm was 0%, 16.7% for patients with tumors 2 to 5 cm in size, and 27.3% for these with tumors larger than 5 cm. The incidence of recurrence was particularly marked in patients with tumors larger than 10 cm (66.7%). The treatment for recurrence was transcatheter arterial embolization for 1 patient and imatinib for 5 patients. In cases where imatinib was administered, 1 patient exhibited partial response, 1 patient exhibited stable disease, and 3 patients exhibited progressive disease, indicating a response rate of 20%. Postoperative recurrence of GIST of the stomach in this study occurred in 6 of 32 patients (18.8%). The incidence of recurrence of tumors larger than 10 cm was 2 out of 3 patients. CONCLUSION: In cases of recurrence, the response rate to imatinib was 20%. Imatinib was effective against GIST that were positive for KIT protein, but future study is needed to clarify the risk factors for recurrence and indications for adjuvant therapy in cases of GIST.

Infliximab treatment for anal fistula in patients with Crohn's disease.

BACKGROUND: Infliximab has played a central role in the treatment of luminal Crohn's disease (CD) due to its great usefulness. Although the seton placement has been widely used for the treatment of anal fistula in patients with CD, we have used infliximab for severe cases in which improvement was not achievable by the seton placement, or for patients in whom improvement of quality of life (QOL) could be expected. PATIENTS AND METHODS: The anal region of 383 patients with CD was examined during the period from July 1985 to December 2005 and the presence of a lesion in the anal region was confirmed in 326 patients. Among them, the number of cases with fistula was highest (245), followed by those with skin tags (115), those with fissures (106), those with anal tumefaction and enlarged papillae (61), and those with anal stenosis (56). The seton placement was used for 93 patients with anal fistula; of these, 86 patients received the treatment for one year or more. During the treatment, infliximab was used for 19 patients and their pathology and progress were evaluated. RESULTS: Infliximab was used for 11 severe cases in which improvement had not been achieved using the seton placement, and for 8 patients for improvement of their QOL. For evaluation, the patients who did not undergo additional treatment after infliximab administration were assigned to the good response group, those who underwent additional treatment other than surgical treatment to the intermediate response group and those who required surgical treatment to the poor response group. The good, intermediate and poor response groups included 8 (42.1%), 5 (26.3%) and 6 (31.6%) patients, respectively. A study of the relationship between the diagnostic indications of magnetic resonance imaging (MRI) and the course of disease showed that most of the patients with a localized inflammation of the anal fistula had better courses and most of the patients with diffuse inflammation had poor courses. CONCLUSION: Approximately 70% of the patients required no surgical treatment. In addition, it was considered important to appropriately select patients for infliximab treatment. MRI was useful as a examination to be performed before infliximab administration because it enabled close examination of the localization of anal fistula and the range of inflammation.

Study of colorectal cancer with Crohn's disease.

BACKGROUND: Crohn's disease (CD) cases have been increasing and prolonged cases are now frequent. In addition, in Japan, more cases with concomitant malignant disease have also recently been reported. There is a particularly high risk of cancer occurring simultaneously in the lower rectum and the anal area. PATIENTS AND METHODS: Two-hundred and eighty-six patients with CD had undergone surgery at this department, up to December, 2005. We studied malignant diseases concomitant with CD, based on empirical examples. RESULTS: Thirteen (4.5%) were cases concomitant with malignant disease: six patients had colorectal cancer, 1 had rectal carcinoid, 1 had stomach cancer, 1 had uterine cancer, 1 had thyroid cancer, 1 had skin cancer and 2 had acute leukemia. Regarding the seven cases other than colorectal cancer, they were all juvenile patients under the age of 50, except for the stomach cancer case (69 years of age). Among the 6 cases of colorectal cancer, 5 cases were anorectal cancer and 1 was lower rectal cancer. The average age was 42.8 years (30-54 years) and the average term from CD occurrence to cancer diagnosis was 208 months (69-387 months). The one case with lower rectal cancer was intramucosal cancer which did not recur after surgery. The five cases of anorectal cancer were advanced, with invasion of the adjacent organs and 2 of them were unresectable. Four cases were of the infiltrative type, and regarding the histological findings, 4 cases were cancer with mucous production and 1 case was a poorly-differentiated endocrine tumor. Four cases had a history of anal fistula, but there was no clear causal relationship. CONCLUSION: In Japan, prolonged CD cases have been increasing and more and more cases of malignant disease with concomitant CD have been reported. There is a particularly high risk of cancer occurring simultaneously in the lower rectum and the anal area. Therefore, careful observation, taking all appropriate diagnostic surveillance modalities into consideration, is thus believed to be important in order to achieve an early detection of such cancer.