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.

Clinical significance of serum anti-p53 antibody expression following curative surgery for colorectal cancer.

The aim of the present study was to investigate the usefulness of serum anti-p53 antibody (Ap53Ab) measurement for the diagnosis of colorectal cancer (CRC), and the clinical significance of the association between Ap53Ab expression and survival rate. Ap53Ab, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 were measured by ELISA in 674 CRC patients and 115 healthy volunteers (control group). The half-life time of Ap53Ab and CEA was calculated. The association between positive Ap53Ab expression and clinicopathological characteristics, including survival rate, was analyzed. Of the 674 CRC patients, 195 (28.9%) were positive for Ap53Ab expression, while the positive rates of CEA and CA19-9 level were 39.9 and 16.9%, respectively. Positivity for Ap53Ab alone was observed in 94 patients (13.9%), whereas the positivity rate of any markers examined was 58.7%. The mean half-life of Ap53Ab and CEA was 30.7 and 11.3 days, respectively. Positive expression of Ap53Ab was significantly associated with the depth of tumor invasion (P<0.001), lymph node metastasis (P=0.024), stage (P<0.001) and CEA level (P=0.005). No significant correlation between Ap53Ab expression and poor survival rate was observed. The positive rate of Ap53Ab was higher compared with that of CEA and CA19-9 in early-stage CRC. The combination of these markers improved the diagnostic yield of CRC up to ~60%. Furthermore, Ap53Ab expression was associated with lymph node metastasis, but not with shorter survival. These results indicated that the measurement of Ap53Ab may contribute to increased rate of detection of CRC, particularly in patients with early-stage disease, in clinical practice.

Metastatic Tumor of the Spermatic Cord in Adults: A Case Report and Review.

Metastatic spermatic cord (SC) tumor is extremely rare. Recently, we experienced a case of late-onset metastatic SC tumor from cecal cancer. This case is a 68-year-old man presenting with a painless right SC mass. He had undergone a right hemicolectomy for cecal cancer 6 years ago. Radical orchiectomy and adjuvant chemotherapy with S-1 were performed. No recurrence was found after one year of follow-up. We identified a total of 25 cases, including our case, on a literature search via PubMed from January 2000 to April 2015. The most frequent primary sites of the tumors metastasizing to the SC were the stomach (8 cases, 32%) and the colon (8 cases, 32%), next the liver (2 cases, 8%), and kidney (2 cases, 8%). The majority of the cases underwent radical orchiectomy for the metastatic tumors of the SC. Over half of the cases received adjuvant interventions based on the regimens for the primary tumors. Prognosis in the patients with metastatic tumor of the SC was unfavorable except for late-onset metastasis. In patients with a mass in the SC and a history of neoplasm, especially in gastrointestinal tract, the possibility of metastasis from the primary cancer should be considered.

[The efficacy and safety of FOLFIRI or combined FOLFIRI and bevacizumab treatment as second-line chemotherapy for metastatic colorectal cancer patients aged 75 years and older].

The safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic colorectal cancer patients ≥ 75 years was retrospectively evaluated. We analyzed 106 patients, who received FOLFIRI or a combination of FOLFIRI and bevacizumab following oxaliplatin-based first-line chemotherapy. The clinical characteristics and outcome in elderly patients ≥75 years(elderly[EP]group; n=18)were compared with those in patients aged<75 years(control group; n=88). The number of patients treated by a combination of FOLFIRI and bevacizumab in the EP group was lower than that in the control group (27.8% vs 55.7%; p=0.03). The comparison revealed no significant differences in response rate, progression-free survival, overall survival, and the frequency of overall adverse events after the start of second-line chemotherapy, although the frequency of anemia(Bgrade 3, p=0.07)and alopecia(grade 1/2, p=0.054)tended to be higher in the EP group than in the control group. Although this study retrospectively analyzed a limited number of patients, our results indicate that the safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic colorectal cancer are almost equal in patients ≥ 75 years and those aged<75 years.

Comparison between transverse mini-incision and longitudinal mini-incision for the resection of locally advanced colonic cancer.

We performed a retrospective review of non-overweight (body mass index ≤ 25 kg/m(2)) patients scheduled to undergo a curative resection of locally advanced colon cancer via a transverse mini-incision (n = 62) or a longitudinal mini-incision (skin incision ≤7 cm, n = 62), with the latter group of patients randomly selected as historical controls matched with the former group according to tumor location. Extension of the transverse mini-incision wound was necessary in 3 patients (5%). Both groups were largely equivalent in terms of demographic, clinicopathological, and surgical factors and frequency of postoperative complications. Postoperative analgesic was significantly less (P = 0.04) and postoperative length of the hospital stay was significantly shorter (P < 0.01) in the transverse mini-incision group. Concerning a mini-incision approach for locally advanced colonic cancer, a transverse incision seems to be advantageous with regard to minimal invasiveness and early recovery compared with a longitudinal incision.

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.

Oxaliplatin-based chemotherapy in patients aged 75 years or older with metastatic colorectal cancer.

AIM: To evaluate the tolerability and efficacy of oxaliplatin-based chemotherapy (OBC) in patients ≥ 75 years old with metastatic colorectal cancer (CRC). PATIENTS AND METHODS: We reviewed the medical records of 126 patients with unresectable stage IV CRC in terms of OBC administered as first-line chemotherapy whenever feasible. RESULTS: Use of first-line OBC was significantly less frequent in patients ≥ 75 years old (n=18) than in patients <75 years old (n=108) (46% vs. 81% p<0.01). When analysis was restricted to patients receiving OBC, the two age groups did not differ significantly in terms of response rate (44% vs. 36%, p=0.54), progression-free survival (18.7 months vs. 13.0 months, p=0.44), overall survival (25.4 months vs. 17.5 months, p=0.53), and frequency of grade 3-4 toxicity (72% vs. 58%, p=0.26). CONCLUSION: In selected patients aged 75 years or greater, the clinical outcomes of OBC seem equivalent to those of younger patients.

Polymorphisms of GSTP1, ERCC2 and TS-3'UTR are associated with the clinical outcome of mFOLFOX6 in colorectal cancer patients.

The aim of the current study was to examine whether polymorphisms in drug metabolism genes have any clinical impact on patients treated with 5-fluorouracil (FU)/oxaliplatin for metastatic colorectal cancer (MCRC). In total, 63 patients with MCRC were recruited and treated with a modified FOLFOX6 (mFOLFOX6) treatment as a first-line chemotherapy. Polymorphisms in five drug metabolism genes and two DNA-repair genes were assessed in these patients using polymerase chain reaction (PCR), a PCR restriction fragment length polymorphism (PCR-RFLP) technique or invader techniques. These included a 28-bp tandem repeat in the 5'-untranslated region (UTR) and 6-bp deletions in the 3'-UTR of thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR; Ala677Val), glutathione S-transferase π (GSTP1; IIe105Val), GST θ1 (GSTT1; deletion) and GST µ1 (GSTM1; deletion) and the two DNA-repair genes, excision repair cross-complementing-1 (ERCC1; Asp118Asn) and ERCC2 (Lys751Gln). The correlation between these polymorphisms and the clinical outcome, including drug response, progression-free survival (PFS), overall survival (OS) and the incidence of peripheral neuropathy, were evaluated. Patients with the GSTP1-105 A/A genotype had poor responses to mFOLFOX6 treatment compared with those with the GSTP1-105 A/G and G/G genotypes (P=0.01). The median PFS of patients with the ERCC2-751 A/A genotype tended to be longer than that of patients with the ERCC2-751 A/C genotype (P=0.05). Patients with the TS-3'-UTR -6/-6 genotype had a significantly longer OS compared with patients with other genotypes (P=0.003). A statistically significant association between the incidence of peripheral neuropathy higher than grade 2 and the GSTP1-105 (P=0.03) and GSTM1 genotypes (P=0.02) was identified by multivariate logistic regression analyses. Results demonstrated that polymorphisms in GSTP1-105, ERCC2-751 and the 3'-UTR of TS may be a statistically significant predictors of clinical outcome. GSTP1-105 and GSTM1 genotypes may be useful markers of severe peripheral neuropathy in MCRC patients treated with 5-FU/oxaliplatin as first-line chemotherapy.

[Theoretical background of our original single-incision laparoscopic-assisted surgery technique for colon cancer via a periumbilical approach].

We assessed the theoretical background of our original single-incision laparoscopic-assisted surgery( SILS) technique involving a periumbilical approach. The subjects included 10 cases who underwent periumbilical SILS colectomy and had their surgical wounds photographed before and after skin incision between September 2009 and October 2010. Using an image analyzer, we estimated the theoretical oval area after a 3/4-circumferential periumbilical skin incision, the actual oval area after placement of the wound retractor, and the length of the skin incision. The mean oval area after the placement of the wound retractor was 2.9 times (range: 1.6-5.0 times) larger than that of the theoretical area. The square of the length of the skin incision positively correlated with the actual oval area created by placing the wound retractor( p=0.04, r=0.67). There were 5 patients, whose actual oval area was ≤700 mm2, and thus required additional radial skin incision( s)( 1 in 3 cases, 2 in 1 case and 3 in 1 case). When performing our original SILS via the periumbilical approach, the area of the actual surgical window can be predicted by measuring the distance from the center of the umbilicus to its edge.

[Effect of chemotherapy in primary tumor of MSI-H colon cancer aged 50 years or younger].

Microsatellite instability( MSI) in colorectal carcinoma is reportedly associated with resistance to 5-fluorouracil-based chemotherapy. Moreover, colorectal cancer patients aged ≤ 50 years could potentially have Lynch syndrome. In the present study, we examined 11 colorectal cancer patients with unresectable Stage IV disease who underwent resection of the primary tumor between January 2006 and December 2012. The relationship between the MSI status and the efficacy of first- line oxaliplatin-based chemotherapy was retrospectively examined. The MSI status included MSI-H in 1 patient, MSS-L in 2 patients, and MSS in 8 patients. The MSI-H in 1 patient was associated with familial adenomatous polyposis. Following chemotherapy, among 8 MSS patients, 3 showed stable disease (SD) and 1 showed partial response (PR). Moreover 2 MSH-L patients and 1 MSI-H patient showed progressive disease (PD) after chemotherapy. However, additional data collection is required to determine the effect of oxaliplatin-based chemotherapy for MSS-H or MSS-L colorectal patients aged ≤ 59 years.

[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.

[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 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.

Outcome in disappearing colorectal cancer liver metastases during oxaliplatin-based chemotherapy.

Some colorectal cancer liver metastases (CLMs) disappear on serial imaging during chemotherapy and the optimal treatment strategy for such lesions remains undetermined. The purpose of this study was to investigate the outcome in disappearing CLMs, as few studies have focused on this topic, with conflicting results. Among 125 patients with CLMs treated with modified FOLFOX6 with or without bevacizumab, those in whom all CLMs disappeared on computed tomography were identified. Recurrence of such disappearing lesions in situ was examined on a tumor-by-tumor basis. Five (4%) patients with a total of 44 CLMs met the evaluation criteria. The median number of CLMs prior to chemotherapy was 8 (range, 2-16). The median maximal diameter of the CLMs was 1.8 cm (range, 1.0-2.4). The median time-to-disappearance of all eligible lesions was 6.5 months (range, 4.5-7.5). Histological examination of scar lesions on the liver surface revealed no viable cancer cells. Two lesions were surgically resected. During clinical follow-up of the remaining 42 lesions, in situ recurrence was observed in 8. The cumulative 1-, 2- and 3-year rates of relapse in situ were 9.1, 9.1 and 31.1%, respectively. Given the low risk of recurrence in situ, the results suggest that the sites of disappearing CLMs may be left unresected but should be carefully monitored during follow-up, with resection an option if the lesion should recur. However, to validate such a treatment strategy, further investigation with a larger series of patients is warranted.