Kimihiko Funahashi

Development and validation of a modified fecal incontinence quality of life scale for Japanese patients after intersphincteric resection for very low rectal cancer

PurposeFecal incontinence is a frequently observed symptom after lower rectal surgery with sphincter manipulation. The aim of this study was to evaluate a proposed modification to the fecal incontinence quality of life (FIQL) scale for the assessment of the quality of life among patients with very low rectal cancer who have undergone intersphincteric resection.MethodsA single 14-item composite scale was prepared that was derived from items in the “Lifestyle” and “Coping” subscales of the original FIQL. The scale was tested with a convenience sample of 152 postoperative patients. In addition to classic psychometric evaluation, newer statistical techniques, such as a multiple correspondence analysis and partial credit model, were performed to evaluate the item response patterns.ResultsThe proposed scale exhibited an item-rest correlation of 0.66–0.84 and a Cronbach’s alpha of 0.96, and was correlated with concurrently measured Social Functioning subscale of the Medical Outcomes Study Short Form 36 (−0.70), physical role limitation (−0.61), and Wexner continence grading scale (−0.61). Multiple correspondence analysis supported a uni-dimensional construct, and the partial credit model showed a varying yet overlapping range of item response thresholds across items. Several items, such as “Locating bathroom whenever going out”, reflected more a serious condition than items such as “Avoiding eating-out.” Weighted item scores based on estimated thresholds provided results comparable with those based on non-weighted scores.ConclusionsThe proposed modification to the FIQL scale exhibited high internal consistency and satisfactory concurrent and convergence validity. The modified scale is practical to administer and is sensitive to a range of functional problems associated with fecal incontinence among patients who have undergone intersphincteric resection.

Transanal rectal dissection: A procedure to assist achievement of laparoscopic total mesorectal excision for bulky tumor in the narrow pelvis

BACKGROUND Laparoscopic approaches for colorectal surgery have been improved recently; however, it is often difficult to achieve total mesorectal excision (TME) for lower rectal cancer laparoscopically because of a narrow pelvis and a thickened mesentery. METHODS TME was successfully performed in 6 patients (4 men, 2 women) with dissection of the rectum transanally from the anal side of the tumor. The preoperative stage was T3N1M0 in 1 patient and T3N0M0 in 5 patients. The mean body mass index was 29.8 kg/m(2) (range, 28.7-31.2 kg/m(2)), and the mean tumor size was 46.5 mm (range, 30-60 mm). RESULTS The mean duration of the anal portion of the operation was 64 minutes (56 minutes in women, 79 minutes in men). No complications occurred during surgery or postoperatively. CONCLUSION This technique is a simple and effective procedure for successfully performing laparoscopic TME of lower rectal cancer in patients with bulky tumors, narrow pelvises, and thickened mesenteries.

Clinical efficacy of Daikenchuto for gastrointestinal dysfunction following colon surgery: a randomized, double-blind, multicenter, placebo-controlled study (JFMC39-0902)

Objective This exploratory trial was performed to determine whether Daikenchuto accelerates recovery of gastrointestinal function in patients undergoing open colectomy for colon cancer. Methods A total of 386 patients undergoing colectomy at 1 of the 51 clinical trial sites in Japan from January 2009 to June 2011 were registered for the study (JFMC39-0902). Patients received either placebo or Daikenchuto (15.0 g/day, t.i.d) between post-operative day 2 and post-operative day 8. Primary end-points included time to first bowel movement, frequency of bowel movement and stool form. The incidence of intestinal obstruction was evaluated post-operatively. The safety profile of Daikenchuto until post-operative day 8 was also evaluated. Results The results for 336 patients (Daikenchuto, n = 174; placebo, n = 162) were available for statistical analysis. The time to first bowel movement did not differ significantly between the two groups. All patients reported having diarrhea or soft stools immediately after surgery, and the time until stool normalization (50th percentile) in the Daikenchuto and placebo groups was 6 days and 7 days, respectively. The placebo group had a significantly greater number of hard stools at post-operative day 8 (P = 0.016), and bowel movement frequency continued to increase until post-operative day 8 as well. In contrast, bowel movement frequency in the Daikenchuto group increased until post-operative day 6, however decreased from post-operative day 7 and was significantly lower at post-operative day 8 compared with the placebo group (P = 0.024). Conclusion The moderate effects of Daikenchuto were observed ∼1 week after the operation. Although Daikenchuto had an effect on gastrointestinal function after open surgery in patients with colon cancer, this study did not show its clinical benefits adequately.

Chemoradiation therapy with S-1 for primary squamous cell carcinoma of the rectum: report of three cases

PurposeAlthough successful treatment of squamous cell carcinoma (SCC) of the rectum using chemoradiation therapy (CRT) has been reported, a standard protocol has yet to be established. The aim is to ascertain the effectiveness of CRT with S-1 for three patients with SCC of the rectum.Case presentationWe treated three female patients complaining of rectal bleeding. The patients were diagnosed as having primary SCC of the rectum by means of routine examinations; one of them was a very rare case because of the presence of two lesions in the lower rectum. We treated the patients using CRT with S1 at a radiation dose of 1.8 Gy/fraction given five times weekly (Monday to Friday) to a median dose of 59.4 (45 to 59.4) Gy; S-1 (80 mg/m2/day) was administered orally during radiation therapy. One of three patients had an adverse event involving massive hemorrhage from the tumor. All patients exhibited an excellent response to CRT with S-1; two patients had a complete response, and one patient had a partial response and underwent a posterior pelvic exenteration with advancement flap reconstruction as a salvage treatment. Pathological examination of the resected specimen and lymph nodes revealed no tumor cells indicating a pathological complete response. In this series, the response rate was 100%.ConclusionsWe suggest that CRT with S-1 be chosen as the first-line therapy for SCC of the rectum. However, a large study will be required to establish a safe and effective regimen.

Down-regulation of MutS homolog 3 by hypoxia in human colorectal cancer.

Down-regulation of hMSH3 is associated with elevated microsatellite alterations at selected tetranucleotide repeats and low levels of microsatellite instability in colorectal cancer (CRC). However, the mechanism that down-regulates hMSH3 in CRC is not known. In this study, a significant association between over-expression of glucose transporter 1, a marker for hypoxia, and down-regulation of hMSH3 in CRC tissues was observed. Therefore, we examined the effect of hypoxia on the expression of hMSH3 in human cell lines. When cells with wild type p53 (wt-p53) were exposed to hypoxia, rapid down-regulation of both hMSH2 and hMSH3 occurred. In contrast, when null or mutated p53 (null/mut-p53) cells were exposed to hypoxia, only hMSH3 was down-regulated, and at slower rate than wt-p53 cells. Using a reporter assay, we found that disruption of the two putative hypoxia response elements (HREs) located within the promoter region of the hMSH3 abrogated the suppressive effect of hypoxia on reporter activity regardless of p53 status. In an EMSA, two different forms of HIF-1α complexes that specifically bind to these HREs were detected. A larger complex containing HIF-1α predominantly bound to the HREs in hypoxic null/mut-p53 cells whereas a smaller complex predominated in wt-p53 cells. Finally, HIF-1α knockdown by siRNA significantly inhibited down-regulation of hMSH3 by hypoxia in both wt-p53 and mut-p53 cells. Taken together, our results suggest that the binding of HIF-1α complexes to HRE sites is necessary for down-regulation of hMSH3 in both wt-p53 and mut-p53 cells.

Clinical Outcome of Laparoscopic Intersphincteric Resection Combined with Transanal Rectal Dissection for T3 Low Rectal Cancer in Patients with a Narrow Pelvis

Purpose. The purpose of this study was to analyze the safety and feasibility of laparoscopic intersphincteric resection (ISR) combined with transanal rectal dissection (TARD) for T3 low rectal cancer in a narrow pelvis. Methods. We studied 20 patients with a narrow pelvis of median body mass index 25.3 (16.9–31.2). Median observation period was 23.6 months (range 12.2–56.7). Results. Partial, subtotal, and total ISR was performed in 15, 1, and 4 patients, respectively. Median duration of TARD was 83 min (range 43–135). There were no major complications perioperatively or postoperatively. Surgical margins were histologically free of tumor cells in all patients, and there was no local recurrence. Excluding urgency, frequency of bowel movements, and incontinence status improved gradually after stoma closure. Conclusion. Laparoscopic ISR combined with TARD is technically feasible for selective T3 low rectal cancer in patients with a narrow pelvis.

Enhancing the Objectivity of the Japanese Classification of Peritoneal Metastases from Colorectal Cancer

OBJECTIVE The Japanese classification of peritoneal metastases from colorectal cancer is easy to use for general surgeons in routine clinical practice. However, the objectivity of this classification has not been determined. This study aimed to clarify the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer. METHODS The data of patients with Stage IV colorectal cancer between 1991 and 2007 in 16 hospitals, who were members of the Japanese Society for Cancer of the Colon and Rectum, were investigated. The size, number and extent (nine areas) of peritoneal metastases according to the Japanese classification (P1, P2 and P3) were investigated using Akaikes information criterion. RESULTS Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 had hematogenous metastases. The minimum Akaikes information criterion was obtained with the cutoff value of one area for P1 metastasis and two or more areas for P2 metastasis (P < 0.0001). When P2 metastasis was compared with P3 metastasis, the cutoff value of the number of peritoneal metastases was 10. CONCLUSIONS The present study proposes a revision that would give objectivity to the present Japanese classification as follows: P1 is defined as peritoneal metastases 20 mm or smaller confined to one area; P2 is defined as 10 or fewer peritoneal metastases disseminated in two or more areas, or peritoneal metastases confined to one area but the size is >20 mm and P3 is defined as >10 peritoneal metastases disseminated in two or more areas.

A rare case of repeated anastomotic recurrence due to tumor implantation after curative surgery for sigmoid colon cancer

BackgroundAnastomotic recurrence is often experienced at colocolic or colorectal anastomoses. Tumor cell implantation has been reported as the mechanism of anastomotic recurrence. However, anastomotic recurrence occurring repeatedly after curative surgery is rare. We herein report a rare case of repeated anastomotic recurrence after curative surgery for sigmoid colon cancer.Case presentationA 51-year-old man underwent radical surgery for sigmoid colon cancer. However, anastomotic recurrence developed three times during three years and six months after the initial operation in spite of irrigation with 5% povidone-iodine before anastomosis. The serum carcinoembryonic antigen (CEA) level had been within normal limits after sigmoidectomy. Finally, the patient underwent abdominoperineal resection. The clinico-pathological findings revealed that possible tumor cell implantation caused these anastomotic recurrences. The patients survived without recurrence during the follow-up period of seven years and nine months.ConclusionWe experienced a rare case of repeated anastomotic recurrence due to possible tumor implantation after curative surgery for sigmoid colon cancer; however the prognosis was ultimately very good. CEA monitoring was insensitive for detection of anastomotic recurrence in this case.

A role of 18F-fluorodeoxyglucose positron emission/computed tomography in a strategy for abdominal wall metastasis of colorectal mucinous adenocarcinoma developed after laparoscopic surgery

Metastasis to the abdominal wall including port sites after laparoscopic surgery for colorectal cancer is rare. Resection of metastatic lesions may lead to greater survival benefit if the abdominal wall metastasis is the only manifestation of recurrent disease. A 57-year-old man, who underwent laparoscopic surgery for advanced mucinous adenocarcinoma of the cecum 6 years prior, developed a nodule in the surgical wound at the lower right abdomen. Although tumor markers were within normal limits, the metastasis to the abdominal wall and abdominal cavity from the previous cecal cancer was suspected. An abdominal computed tomography scan did not provide detective evidence of metastasis. 18F-fluorodeoxyglucose positron emission/computed tomography (18F-FDG PET/CT) was therefore performed, which demonstrated increased 18F-fluorodeoxyglucose uptake (maximum standardized uptake value: 3.1) in the small abdominal wall nodule alone. Histopathological examination of the resected nodule confirmed the diagnosis of metastatic mucinous adenocarcinoma. Prognosis of intestinal mucinous adenocarcinoma is reported to be poorer than that of non-mucinous adenocarcinoma. In conclusion, this case suggests an important role of 18F-FDG PET/CT in early diagnosis and decision-making regarding therapy for recurrent disease in cases where a firm diagnosis of recurrent colorectal cancer is difficult to make.

Is high serum programmed death ligand 1 level a risk factor for poor survival in patients with gastric cancer

Although the clinicopathological significance of the expression of programmed death ligand 1(PD‐L1) in various cancer tissues has been reported, serum PD‐L1 level has not been evaluated in patients with surgically treated gastric cancer. Therefore, we evaluated the clinicopathological characteristics and prognostic significance of preoperative serum PD‐L1 levels in patients with gastric cancer.