Purse-string approximation vs. primary closure with a drain for stoma reversal surgery: results of a randomized clinical trial.

PURPOSE: Stoma reversal carries a risk of surgical site infection (SSI). Purse-string approximation (PSA) has been reported as an attractive alternative to conventional primary wound closure for stoma reversal, but its efficacy is still under debate. METHODS: Patients undergoing elective stoma reversal were randomized to undergo PSA or primary closure with a drain (PCD). All patients received preoperative bowel cleansing and antimicrobial prophylaxis. The primary endpoint was the incidence of wound healing at the stoma site 30 days after surgery. The secondary endpoint was the 30-day SSI rate after surgery. RESULTS: A total of 159 patients (PCD group, n = 79; PSA group, n = 80) were eligible for this study. The incidence of wound healing at the stoma site was 92.4% in the PCD group and 62.5% in the PSA group [difference (95% confidence interval - 29.9% (- 42.9 to - 16.9%)]. The 30-day SSI rate at the stoma site, as the secondary endpoint, was 8.9% in the PCD group and 5.0% in the PSA group (P = 0.35). CONCLUSIONS: These results suggest that PCD may remain the standard procedure for stoma reversal surgery.

Correction to: Purse-string approximation vs. primary closure with a drain for stoma reversal surgery: results of a randomized clinical trial.

In the original publication, surname of first author is misspelt as "Amamo". It should be "Amano" as given in this Correction.

Short-term intravenous antimicrobial prophylaxis for elective rectal cancer surgery: results of a prospective randomized non-inferiority trial.

PURPOSE: To investigate the non-inferiority of postoperative single-dose intravenous antimicrobial prophylaxis to multiple-dose intravenous antimicrobial prophylaxis in terms of the incidence of surgical site infections (SSIs) in patients undergoing elective rectal cancer surgery by a prospective randomized study. METHODS: Patients undergoing elective surgery for rectal cancer were randomized to receive a single intravenous injection of flomoxef (group 1) or five additional doses (group 2) of flomoxef after the surgery. All the patients had received preoperative oral antibiotic prophylaxis (kanamycin and erythromycin) after mechanical cleansing within 24 h prior to surgery, and had received intravenous flomoxef during surgery. RESULTS: A total of 279 patients (including 139 patients in group 1 and 140 in group 2) were enrolled in the study. The incidence of SSIs was 13.7% in group 1 and 13.6% in group 2 (difference [95% confidence interval]: -0.2% [-0.9 to 0.7%]). CONCLUSION: The incidence of SSIs was not significantly different in patients undergoing elective rectal surgery who were treated using a single dose of postoperative antibiotics compared to those treated using multiple-dose antibiotics when preoperative mechanical and chemical bowel preparations were employed.

Current Developments in the Prevention and Improvement of Intestinal Disorders: A Mini-Review.

BACKGROUND: Recently, the number of patients who manifest intestinal disorders has increased. Particularly, Irritable Bowel Syndrome (IBS) patients and Inflammatory Bowel Disease (IBD) patients, which include Ulcerative Colitis (UC) and Crohn's Disease (CD), are on the rise, especially in the young generation. Behcet's disease (an autoimmune disease) and bowel obstruction are also common intestinal disorders. Furthermore, colorectal cancer, including colon and rectum cancer and small intestinal cancer, are the typical disorders in the intestine. Other disorders in the digestive tract are infectious diseases like Helicobacter pylori infection. Even though symptomatic treatments have been increasing for the treatment of intestinal disorders, the ways of improving and preventing these diseases are still controversial. OBJECTIVE: The progress of medicine and treatment is rapid. However, recent approaches to the prevention and improvement of these intestinal disorders are suppressing dysbiosis and preventing chronic inflammation. This mini-review discusses the hypothesis of whether the improvement of the diet is a preferable choice for the prevention of these intestinal disorders. Dietary interventions are beneficial for the prevention and improvement of intestinal disorders since the first approach to intestinal disorders is dietary intervention. The Mediterranean diet, the diet from the 5-a-day campaign, and the Japanese diet are well-known healthy dietary strategies. A healthy diet regimen is not only beneficial for the prevention of intestinal disorders but also a useful strategy to reduce stress and ameliorate mental illness. In addition, the intake of phytochemicals is good for keeping healthy gut microbiota and preventing intestinal disorders. Furthermore, vitamin D3 intake with these phytochemicals works as an adjuvant to improve gut microbiota and upregulate immune responses. As a result, the decreasing production of TNF-α ameliorates chronic inflammation and intestinal disorders at an early stage. CONCLUSION: In recent years, prevention of the non-disease condition "ME-BYO" has been a popular approach for healthy and long living in Japan. This idea prevents the manifestation of diseases before the onset and is also applicable to intestinal disorders. This mini-review discusses ways of preventing and ameliorating intestinal disorders.

[Clinical significance of serum anti-p53 antibody measurement for colorectal cancer].

We investigated the usefulness of serum anti-p53 antibody (anti-p53) measurement for the diagnosis of colon cancer. carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and anti-p53 were measured by enzyme-linked immunosorbent assay in 375 colorectal cancer patients and 115 healthy volunteers(control group). When the cut-off level of the serum anti-p53 antibody was set to 1.3 U/mL, 114 (30.4%) of the colorectal cancer patients tested positive. Twelve positive cases(10.4%) were recognized in the control group. The median levels of anti-p53 were 0.69 U/mL(0.69- 10,610) and 0.69 U/mL (0.69-19.5) in the colorectal cancer patients and control group, respectively. The positive rates of CEA level (cut-off value 6.7 ng/mL) and CA19-9 level (cut-off value 37 U/mL) were 40.0% and 18.9%, respectively. Of these tumor markers, positive cases with only anti-p53 were observed in 60 patients (16%). The positive rate of all markers examined was 61.6%. No significant correlation was observed between the level of anti-p53 and other markers. The positive rates of anti-p53 in each stage of the colon cancer patients were as follows: stage 0 and I, 19.4%; stage II, 27.0%; stage III,36.1%; and stage IV,61.0%. The positive rate of anti-p53 was higher than that of CEA and CA19-9 in the early stages of colorectal cancer. Furthermore, a combination of these markers improved the diagnosis of colorectal cancer by approximately 60%. These results suggest that the measurement of anti-p53 is useful for diagnosis of colorectal cancer in clinical practice.

[A long-term survivor of colorectal cancer associated with multiple liver metastases and peritoneal carcinomatosis treated through a multidisciplinary approach].

Even in the era of new anticancer drugs, an optimal treatment strategy for colorectal cancer associated with liver metastasis and peritoneal carcinomatosis has yet to be established. Here we report the case of a long-term survivor with very advanced colon cancer who underwent repeated resective surgery and chemotherapy. This 69-year-old man underwent a Hartmann's procedure and the resection of peritoneal metastases of cancer of the rectosigmoid, which had infiltrated the retroperitoneum giving rise to multiple liver metastases and peritoneal carcinomatosis. The resection margin was positive for cancer. After 14 courses of a modified FOLFOX6 (mFOLFOX6) regimen, a partial response with no development of new lesions was obtained. Multiple partial hepatectomies were subsequently performed. After the completion of an additional 6 courses of mFOLFOX6, a positron-emission tomography (PET)/computed tomography (CT) examination demonstrated a hot spot in segment 4. This hot deposit disappeared after a further 8 courses of mFOLFOX6. The patient then underwent a left lateral segmentectomy for a newly developed lesion in segment 3, which was detected 2 years and 7 months after the first operation. The patient has remained free from recurrence for 2 years since his last operation.

[Clinical outcome of Stage IV colorectal cancer on the basis of the seventh edition of the TNM classification].

Recent advances in chemotherapy for stage IV colorectal cancer have improved clinical outcome. According to the seventh edition of the TNM classification of colorectal cancer, stage IV is classified into stage IVA and stage IVB. In this study, we assessed the clinical validity of this classification as a prognostic factor. The subjects were 170 patients with stage IV colorectal cancer(stage IVA, n=78; stage IVB, n=92)treated between January 2006 and December 2011 at our institute. Of 92 patients with stage IVB, peritoneal carcinomatosis alone was recognized in 21 patients. The median survival periods for patients with stage IVA and IVB were 29.2 and 16.1 months, respectively( p=0.13). The median survival period for patients with peritoneal carcinomatosis alone was 37.6 months, and there was no difference between survival in patients with stage IVA and those with peritoneal carcinomatosis alone. Our present results suggest that it may be reasonable and useful to classify peritoneal carcinomatosis alone into stage IVA instead of stage IVB in clinical practice.

[The clinical significance of serum anti-p53 antibody as a monitoring marker in colorectal cancer].

We examined alterations in the level of serum anti-p53 antibody(S-p53 Ab) in colorectal cancer patients who underwent curative resection and analyzed the usefulness of S-p53 Ab as a monitoring marker for postoperative observation. The measurement of S-p53 Ab was performed preoperatively and postoperatively in 16 stage II/III colorectal cancer patients with a high level of S-p53 Ab. A time course analysis of both S-p53 Ab and CEA levels was performed in 6 of these patients who were carcinoembryonic antigen (CEA) positive. The median S-p53 Ab level was 29.9 U/mL and the half-life of the S-p53 Ab level was 40.3 days. In 4(25%) cases, the level of S-p53 Ab recovered to within normal limits by 79-142 days. When the half-lives of S-p53 Ab and CEA were analyzed in 6 patients who were both S-p53 Ab and CEA positive, the half-lives of S-p53 Ab and CEA were 32.3 and 13.2 days, respectively. In the case of recurrence with liver metastasis after resection of ascending colon cancer, the S-p53 Ab level did not respond quickly while the CEA level increased. Therefore, it is difficult to use the level of S-p53 Ab as a marker for monitoring treatment, and priority should be given to the examination of CEA and imaging modality.

[Predictive value of Köhne's index on the efficacy of FOLFIRI regimen in the treatment of unresectable liver metastatsis of colorectal cancer].

The aim of this retrospective study was to analyze the predictive value of Köhne's index on the efficacy of FOLFIRI regimen in the treatment of unresectable liver metastasis of colorectal cancer. The subjects were 44 patients with unresectable liver metastasis from colorectal cancer treated with FOLFIRI regimen as second-line, for all of whom oxaliplatin-based regimen had previously failed. Bevacizumab was concomitantly used in 23 patients. Classification of the Köhne's index revealed high risk in 22 patients, intermediate risk in 7 patients, and low risk in 15 patients. The response rate was 13.6% in the patients with high risk(H group) and 27.3% in the patients with intermediate or low risk(non-H group)(p=0.45). The disease control rate was 50% in the H group and 68.2% in the non-H group (p=0.36). In the H group, the median progression -free survival time was 4.1 months and in the non-H group it was 7.1 months (p=0.33). Compared with the H group, the non-H group showed significantly better overall survival (10.8 months vs 23.9 months, p=0.03). None of the patients has received hepatectomy (conversion therapy). These results suggest that the predictive value of Köhne's index is limited in terms of the effect of shrinkage of liver metastases, including conversion therapy.

[Clinical outcomes in refractory colorectal cancer patients with wild-type K-ras treated with bevacizumab and oxaliplatin-based chemotherapy as a first-line treatment].

The clinical outcomes, including adverse events, in 34 unresectable advanced colorectal cancer patients with wild-type K-ras, who were treated with bevacizumab and oxaliplatin-based chemotherapy as a first-line treatment, were analyzed for confirmation of the effectiveness and safety of this treatment. The response rate of the patients was 44% (complete remission, 2 patients; and partial remission, 13 patients). The median progression-free survival and overall survival in these patients was 11.1 and 25.1 months, respectively. Adverse events of greater than grade 3 were observed in 18 patients. Of these patients, 10 exhibited grade 3/4 neutropenia, and 6 had peripheral neuropathy. Our results were similar to those of randomized phase III trials from abroad, including those using anti-epidermal growth factor receptor antibody, with respect to effectiveness and safety. Furthermore, patients with liver metastasis had poor prognosis compared to those with metastasis to organs other than the liver. Further analysis will be required to better understand these results.

[Adjuvant chemotherapy comprising modified FOLFOX6 after curative resection of synchronous or metachronous metastasis from colorectal cancer].

PURPOSE: This retrospective study evaluated the outcome of adjuvant chemotherapy comprising modified FOLFOX6 (mFOLFOX6) after potentially curative metastasectomy from colorectal cancer. PATIENTS AND METHODS: The subjects were 40 patients with colorectal cancer who underwent potentially curative metastatectomy without any prior chemotherapy between December 2003 and November 2011. Patient background, type of adjuvant chemotherapy, and prognosis were examined. RESULTS: Adjuvant chemotherapy was given in 30 patients (mFOLFOX6, n=26; oral fluoropyrimidines, n=4). The median relapse-free survival tended to be longer in patients treated with mFOLFOX6 compared to those treated with fluoropyrimidines (28.5 months vs 14.8 months; p=0.11). The median overall survival did not differ significantly between the 2 groups (37.9 months vs 31.3 months, p=0.56). When the analysis was restricted to patients treated with mFOLFOX6, no significant differences were found in relapse-free survival (p=0.46), overall survival (p=0.29), and frequency of adverse events during chemotherapy(Grade 3, p=0.32) between patients with synchronous metastasis(n=11) and those with metachronous metastasis (n=15). CONCLUSION: These results suggest that mFOLFOX6 might contribute to prolonging the time to relapse and that the timing of developing metastasis(synchronously or metachronously) may not have any effect on the outcome of adjuvant mFOLFOX6.

[Prediction of the efficacy of first-line oxaliplatin-based chemotherapy for unresectable liver metastases of colorectal cancer by Köhne's index].

PURPOSE: This retrospective study was undertaken to examine the usefulness of Köhne's index(KI) for predicting the efficacy of first-line oxaliplatin-based chemotherapy for unresectable liver metastases of colorectal cancer. PATIENTS AND METHODS: The subjects were 84 patients with unresectable liver metastases of colorectal cancer in whom first-line oxaliplatin- based chemotherapy was administered. The outcome of treatment was analyzed in relation to the KI. RESULTS: The patients were classified into 3 groups: high risk group (n=12), intermediate risk group (n=20), and low risk group (n=52). There were no significant differences between the groups with regard to response rate, disease control rate, disease-free survival, overall survival, and the rate of conversion to hepatic metastatectomy. CONCLUSION: Our results suggest that KI might not be useful for predicting the efficacy of first-line oxaliplatin-based chemotherapy for unresectable liver metastases of colorectal cancer.

[Clinical differences between palliative gastrectomy and reduction surgery for gastrectomy in curatively unresectable gastric cancer].

Surgical treatments for curatively unresectable gastric cancer include reduction surgery and palliative surgery(palliative gastrectomy and bypass operation). Both palliative gastrectomy and reduction surgery reduce the tumor volume. In this study, the clinical significance of these treatment methods was investigated. The subjects were 58 patients with unresectable gastric cancer for which surgery was performed as the primary treatment. Of these patients, 38 patients underwent reduction surgery and 20 patients underwent palliative surgery. On univariate analysis, age and gender were not significant. Pre-operative performance status(PS) in patients treated with reduction surgery was favorable compared to that in patients receiving palliative surgery(PS 0: 65.8 vs 40.0%, p=0.06). The administration rate of post-operative chemotherapy in patients treated with reduction surgery was higher than that in patients with palliative surgery (92.1 vs 65.0%, p<0.01). The median survival time in patients treated with reduction surgery was 18.2 months, while that in patients with palliative surgery was 11.0 months (p<0.01). These results indicated that reduction surgery was clinically different compared to palliative surgery in terms of the administration rate of post-operative chemotherapy and prognosis.

Impact of prior abdominal surgery on curative resection of colon cancer via minilaparotomy.

PURPOSE: To evaluate the impact of prior abdominal surgery on curative resection of colon cancer via a minilaparotomy approach. METHODS: Feasibility, safety, and oncological outcomes were evaluated retrospectively in 263 patients scheduled to undergo curative resection of colon cancer via a minilaparotomy approach, defined as a skin incision of ≤ 7 cm, between September 2000 and March 2009. RESULTS: Abdominal adhesions were found in 59 (77.6%) of 76 patients who had undergone prior abdominal surgery (PAS group) and in 4 (2.1%) of 187 patients who had not (control group). The success rate of the minilaparotomy approach was 92.1% in the PAS group and 97.3% in the control group (P = 0.08). The incidence of extending the minilaparotomy wound for adhesiolysis was significantly higher in the PAS group than in the control group (6.6% vs 0.5%; P < 0.01). The two groups did not differ significantly in terms of the types of surgery, pathological stage, body mass index, operative time, blood loss, incidence of postoperative complications, length of postoperative hospital stay, and disease-free survival. CONCLUSIONS: These results suggest that prior abdominal surgery might require an extension of the minilaparotomy incision but that it does not seem to contraindicate a minilaparotomy approach for curative colectomy.

Curative resection of transverse colon cancer via minilaparotomy.

Minilaparotomy has been reported to be a minimally invasive alternative to laparoscopically assisted surgery. We retrospectively evaluated the usefulness of minilaparotomy for the resection of transverse colon cancer, which has generally been considered difficult to resect laparoscopically. Patients for whom curative resection was attempted for transverse colon cancer (n = 21) or sigmoid colon cancer (n = 81) via minilaparotomy (skin incision, < or = 7cm) were analyzed. The 2 groups did not significantly differ in terms of success rate of minilaparotomy (90.5% versus 97.5%), age, sex, pathologic stage, body mass index, operative time (mean, 133.5 minutes versus 122.5 minutes), blood loss (119.7 mL versus 92.4 mL), number of lymph nodes harvested, incidence of postoperative complications (9.5% versus 12.3%), postoperative length of stay, and 5-year disease-free survival rate (86.6% versus 79.6%). Minilaparotomy is feasible, safe, and favorable in terms of early oncologic outcome in patients with transverse colon cancer as well as those with sigmoid colon cancer.

Minilaparotomy for perforated duodenal ulcer.

The usefulness of the minilaparotomy approach for perforated duodenal ulcer repair was retrospectively evaluated in 37 patients (26 men; mean age, 56.5 years). Simple closure with an omental patch by minilaparotomy (skin incision, < or = 7 cm) was successful in 86.5% of the cases, with an operative mortality of 2.7%. Compared with the results in historic control patients who underwent conventional open surgery (n = 27), a shorter operative time (P < 0.01), lower frequency of analgesic use (P = 0.03), earlier passage of flatus (P < 0.01), and shorter hospital stay (P = 0.04) were obtained in the patients undergoing minilapartomoy. The postoperative morbidity was identical between the two groups (16.2% versus 33.3%, P = 0.40). On multivariate analysis, a large amount of intraabdominal fluid was the only significant risk factor for extension of the minilaparotomy wound (P = 0.012). The minilaparotomy approach appears to be a feasible, safe, and less invasive approach compared with the conventional open approach and could be a useful alternative to the laparoscopic approach in selected patients with perforated duodenal ulcer.

Three-dimensional vascular anatomy relevant to oncologic resection of right colon cancer.

We analyzed data on the three-dimensional vascular anatomy of the right colon from the operative documents of 215 patients undergoing oncologic resection for right colon cancer. The right colic artery (RCA) was absent in 146 patients (67.9%), with the ileocolic artery (ICA) crossing the superior mesenteric vein (SMV) ventrally in 78 patients (36.3%). When the RCA was present, both the ICA and the RCA crossed the SMV ventrally in 44 patients (20.5%), dorsally in 10 patients (4.7%), the RCA crossed the SMV ventrally and the ICA dorsally in 10 patients (4.7%), and the RCA crossed the SMV dorsally and the ICA ventrally in 5 patients (2.2%). The arterial branches toward the hepatic flexure crossed the SMV ventrally in 151 eligible cases: the branch originated from the common trunk of the middle colic artery in 97 patients (64.2%) and 1 and 2 arteries directly originated from the SMA in 49 patients (32.5%) and in 5 patients (3.3%), respectively. These data would be useful to safely perform lymph node dissection around the SMV.

Significance of hepatic lymph node metastasis in patients with unresectable synchronous liver metastasis of colorectal cancer.

The frequency and significance of hepatic lymph node (HLN) metastasis were retrospectively evaluated in 43 patients with unresectable synchronous liver metastasis of colorectal cancer who underwent resection of the primary tumor and histopathologic evaluation of HLNs between March 1997 and August 2007. HLN metastasis was detected in 12 patients (27.9%). No significant correlations were observed between the presence of HLN metastasis and any of the 12 clinicopathologic factors examined. On multivariate analysis using the Cox proportional hazards model, the presence of HLN metastasis (P = 0.002), along with a large number (> or = 4) of regional lymph node metastases (P = 0.003), and nonuse of oxaliplatin-based chemotherapy (P = 0.005) were identified as independent risk factors for shorter survival. To establish a new therapeutic strategy for initially unresectable liver metastasis of colorectal cancer, HLNs should be examined histologically in patients undergoing resection of hepatic lesions when they are rendered resectable by effective chemotherapy.

Oncologic outcome of stages II/III colon cancer treated via minilaparotomy.

We analyzed clinicopathologic, surgical, and survival data on consecutive series of patients with stages II/III colon cancer for whom curative resection via minilaparotomy (skin incision, < or = 7 cm) was attempted between September 2002 and March 2009 to clarify the oncologic safety of this type of surgery. There were 64 men and 55 women; the median age was 70 years (range, 25-91 years). The median body mass index was 21.7 kg/ m2 (range, 15.1-28.9 kg/m2). The minilaparotomy approach was successful in 115 cases (96.6%). The cumulative 5-year disease-free and overall survival rates were 89.7% and 82.4%, respectively, in patients with stage II disease (n = 62) and were 68.4% and 82.4%, respectively, in patients with stage III disease (n = 57), all of which were compatible with those of the historical control patients who underwent conventional open surgery. Minilaparotomy approach for stages II/III colon cancer seems to be oncologically equivalent to conventional open surgery.

[The Relationship between the efficacy of mFOLFOX6 treatment and the expression of TS, DPD, TP, and ERCC-1 in unresectable colorectal cancer].

It has been reported that thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and excision repair cross-complementing-1 (ERCC-1) were useful markers to predict the efficacy of anti cancer agents including 5-fluorouracil (5-FU) and oxaliplatin for unresectable advanced colorectal cancer. In this study, we analyzed the relationship between the expression of these enzymes and the clinical significance in 49 Stage IV colorectal cancer patients who received mFOLFOX6 as a first-line treatment and evaluated the usefulness of these enzymes for predicting the efficacy of mFOLFOX6. There was no relationship between the expression of each enzyme and response rate. The progression-free survival of the patients with low TP expression was significantly longer than that of the patients with high TP expression( p<0.01). In the analysis of overall survival, the patients with low TP or low DPD expression were better than that with high TP expression or high DPD expression (p=0. 04, p=0. 04, respectively). Our results indicated that TP and DPD expression would be a useful marker to predict the efficacy of mFOLFOX6 in the patients with unresectable colorectal cancer.