Keiichiro Ishibashi

Short-term intravenous antimicrobial prophylaxis in combination with preoperative oral antibiotics on surgical site infection and methicillin-resistant Staphylococcus aureus infection in elective colon cancer surgery: Results of a prospective randomized trial

PurposeWe performed a prospective randomized study to assess the effectiveness of short-term intravenous antimicrobial prophylaxis in combination with preoperative oral antibiotics on a surgical site and methicillin-resistant Staphylococcus aureus (MRSA) infection in elective colon cancer surgery.MethodsThe patients were administered preoperative oral antibiotics, kanamycin and erythromycin, after mechanical cleansing, which began within 24 h of elective surgery for colon cancer. The patients were randomly assigned to receive the intravenous administration of cefmetazol or cefotiam on the day of surgery (group 1) or for 3 days (group 2). A total of 275 patients (136 for group 1 and 139 for group 2) were eligible for the study.ResultsThe incidence of a surgical site infection was 5.1% in group 1 and 6.5% in group 2 (P = 0.80). The incidence of MRSA infection was 2.2% in group 1 and 2.9% in group 2 (P > 0.99). A multivariate logistic regression analysis showed that the American Society of Anesthesiologists physical status score and the duration of surgery were independent significant factors affecting the surgical site infection and MRSA infection.ConclusionThese findings suggest that short-term intravenous antimicrobial prophylaxis in combination with preoperative oral antibiotics may be successfully applied to colon cancer surgery that is generally performed in Japan.

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.

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.

Angiogenesis in Superficial Esophageal Squamous Cell Carcinoma: Assessment of Microvessel Density Based on Immunostaining for CD34 and CD105

OBJECTIVE The esophagus is the only organ where changes in the superficial microvasculature from normal squamous epithelium to invasive cancer are evident by magnifying endoscopy. We investigated in detail the features of angiogenesis in early-stage esophageal cancer using CD34 and CD105 immunostaining, and also the correlation between angiogenesis and mononuclear cell infiltration. MATERIALS AND METHODS Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia, and 45 samples of superficial esophageal cancer, we determined the microvessel density at hot spots showing positive staining for CD34 and CD105. We observed the histological features of CD34- and CD105-positive microvessels that corresponded to observations made by magnifying endoscopy. We then investigated the correlation between microvessel density and each histological situation or the grade of mononuclear cell infiltration. RESULTS The histological features of CD34- and CD105-positive microvessels were able to explain the morphological changes in the microvasculature during cancer progression observed by magnifying endoscopy. The microvessel density for CD34 or CD105 was significantly correlated with each of the histological types (P < 0.001, rS = 0.51 and 0.76, respectively). Mononuclear cell infiltration at CD105 hot spots was most frequent in M1 and M2 cancer (94.7%). The correlation between the degree of mononuclear cell infiltration and microvessel density for CD105 staining was also significant (P < 0.001, rS = 0.49). CONCLUSIONS The microvessel density based on CD34 and CD105 immunostaining can be used to corroborate observations of superficial esophageal squamous cell carcinoma made by magnifying endoscopy. Mononuclear cell infiltration may play an important role in angiogenesis at the early stage of cancer progression.

Prediction of metastasis to mesorectal, internal iliac and obturator lymph nodes according to size criteria in patients with locally advanced lower rectal cancer

OBJECTIVE This study was performed to clarify whether size criteria could be applied to the prediction of metastasis to the mesorectal, internal iliac and obturator lymph nodes in patients with lower rectal cancer. METHODS A total of 915 lymph nodes (416 mesorectal, 199 internal iliac and 300 obturator) from 53 patients with lower rectal cancer who underwent a curative resection were examined; 83 lymph nodes were positive. The sizes of the lymph nodes immediately after removal and those of paraffin-embedded sections were compared for 175 lymph nodes. Then, size criteria for discriminating the status of metastasis were evaluated in 915 paraffin-embedded lymph nodes. RESULTS Regardless of the metastatic status and the site of the lymph nodes, a positive relationship was observed between the sizes of the lymph nodes immediately after removal and those of paraffin-embedded sections (P < 0.01). The area under the curve generated by a receiver-operating characteristics curve showed no significant differences between the short-axis diameter and the long-axis diameter, regardless of the lymph node location. Specifically, the optimal cutoff value of the short-axis diameter for discriminating the status of metastasis in mesorectal, internal iliac and obturator lymph nodes extrapolated to the living body was set at 6.2, 5.0 and 4.8 mm, with accuracies of 72.4, 63.8 and 59.3% and with positive predictive values of 29.9, 16.3 and 7.1%, respectively. CONCLUSIONS Size criteria were applicable for discriminating the metastatic status of lymph nodes from three different locations, although the positive predictive values of the size criteria for the internal iliac and obturator lymph nodes were lower than that for the mesorectal lymph nodes.

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

PurposeTo evaluate the impact of prior abdominal surgery on curative resection of colon cancer via a minilaparotomy approach.MethodsFeasibility, 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.ResultsAbdominal 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 diseasefree survival.ConclusionsThese 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.

Identification of Risk Factors for Recurrence in High-Risk Stage II Colon Cancer

To identify risk factors for recurrence in patients with stage II colon cancer, Cox proportional hazards regression analysis was performed in 194 patients with stage II colon cancer who underwent curative surgery between April 1997 and December 2008. Thirteen clinical and pathologic factors, including use of fluoropyrimidine-based adjuvant chemotherapy in 113 of the patients (58.2%), were assessed. By multivariate analysis, only obstruction, perforation, and T4-level invasion were identified as independent risk factors affecting disease-free survival (DFS) (P < 0.01). The 5-year DFS rate was 70.6% in patients with one or more risk factors (n = 68) and 96.0% in patients with no risk factors (n = 126) (P < 0.01). These results suggest that obstruction, perforation, and T4-level invasion are suitable candidates for prediction of tumor recurrence in patients with stage II colon cancer. The oxaliplatin-based adjuvant chemotherapy, which has been reported to be effective in stage III colon cancer patients, may improve the prognosis in high-risk stage II colon cancer patients.

Phase II Trial of Chemotherapy plus Bevacizumab as Second-Line Therapy for Patients with Metastatic Colorectal Cancer That Progressed on Bevacizumab with Chemotherapy: The Gunma Clinical Oncology Group (GCOG) trial 001 SILK Study

Objectives: BRiTE and ARIES (observational cohort studies) provided valuable information on continued use of bevacizumab (BV) beyond progression (BBP). This trial evaluates the efficacy and safety of BBP for patients with metastatic colorectal cancer that progressed on first-line chemotherapy. Methods: A total of 39 patients received FOLFIRI + BV (after FOLFOX + BV) or FOLFOX + BV (after FOLFIRI + BV) as protocol treatment. The primary endpoint was the response rate. Secondary endpoints were overall survival (OS), total survival from initiation of first-line treatment (TS), progression-free survival (PFS), and safety. Results: All 39 treated patients were evaluated for toxic effects. Two patients did not meet all of the eligibility criteria and were excluded from efficacy analyses. The response rate was 16.2%. The disease control rate was 76%. The median PFS was 150 days (range 117–224). The median OS was 417 days (range 233–813). The median TS was 988 days (range 600–1,268). Grade 3/4 adverse events (% of patients) related to treatment were neutropenia (33%), fatigue (23%), and hypertension (18%). Conclusions: This is the first report to show the effect of BBP in patients who had progressive disease on first-line treatment including BV confirmed by RECIST criteria. This analysis suggests the possibility of prolonged survival with continued use of BV.

Prediction of Lateral Lymph Node Metastasis in Lower Rectal Cancer: Analysis of Paraffin-embedded Sections

OBJECTIVE In the surgical treatment for lower rectal cancer, preoperative selection of patients at high risk for lateral lymph node metastasis is important, since lateral lymph node dissection might impair genitourinary functions. We examined whether the status of lateral lymph node metastasis can be predicted from the lymph node size. METHODS The subjects were 533 (35 positive and 498 negative) lateral lymph nodes from 47 patients with lower rectal cancer who underwent curative resection with lateral lymph node dissection. The sizes of the lateral lymph nodes immediately after removal and those in paraffin-embedded sections were compared for 108 lateral lymph nodes from 13 patients. In addition, receiver-operating characteristic curves were generated for the 533 paraffin-embedded lateral lymph nodes from the 47 patients to determine the optimal cut-off size for discriminating between positive and negative lateral lymph nodes. RESULTS Irrespective of the presence/absence of metastasis and the long-/short-axis diameter, a positive relationship was noted between the sizes of the lateral lymph nodes measured immediately after removal and those measured on paraffin-embedded sections (P< 0.01). The area under the curve for the short-axis diameter differed little from that for the long-axis diameter (0.77 vs. 0.76, P =0.80). The optimal cut-off values of the short- and long-axis diameter extrapolated to the living body were 5.4 and 8.4 mm, respectively, with an accuracy of 72.8% for the short-axis diameter and 71.9% for the long-axis diameter. CONCLUSIONS Prediction of the status of lateral lymph node metastasis from the lymph node size (long-/short-axis diameter) may be a simple and reliable method. The optimal cut-off diameter should be validated in prospective imaging studies.

A Prospective Randomized Study to Assess the Optimal Duration of Intravenous Antimicrobial Prophylaxis in Elective Gastric Cancer Surgery

The duration of antimicrobial prophylaxis in gastric cancer surgery is not yet established. This prospective randomized study was performed to confirm the noninferiority of single-dose versus multiple-dose antimicrobial prophylaxis in terms of the incidence of surgical-site infection in gastric cancer surgery. Three hundred twenty-five patients undergoing elective resection for gastric cancer were randomized to receive only single-dose cefazolin (1 g) during surgery (single-dose group) or an additional 5 doses every 12 hours postoperatively (multiple-dose group). The overall incidence of surgical-site infections was 9.1% in the single-dose group and 6.2% in the multiple-dose group [difference (95% confidence interval): -2.9% (-5.9%-0.0%)]. Multivariate logistic regression analysis identified blood loss, being overweight, and advanced age as significant independent risk factors for surgical-site infection. Single-dose antimicrobial prophylaxis seemed to be acceptable, and choosing multiple-dose prophylaxis may have little impact on the prevention of surgical-site infections in elective gastric cancer surgery.