Haga N

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.

Usefulness of indocyanine green angiography for evaluation of blood supply in a reconstructed gastric tube during esophagectomy.

We report a case of necrosis of a reconstructed gastric tube in a 77-year-old male patient who had undergone esophagectomy. At the time of admission, the patient had active gastric ulcers, but these were resolved by treatment with a proton pump inhibitor. Subtotal esophagectomy with gastric tube reconstruction was performed. Visually, the reconstructed gastric tube appeared to be well perfused with blood. Using indocyanine green (ICG) fluorescence imaging the gastroepiploic vessels were well enhanced and no enhancement was visable 3 to 4 cm from the tip of the gastric tube. Four days after esophagectomy, gastric tube necrosis was confirmed, necessitating a second operation. The necrosis of the gastric tube matched the area that had been shown to lack blood perfusion by ICG angiography imaging. It seems that ICG angiography is useful for the evaluation of perfusion in a reconstructed gastric tube.

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.

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.

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.

Heterotopic Mesenteric Ossification After a Ruptured Abdominal Aortic Aneurism: Case Report With a Review of Literatures

Heterotopic mesenteric ossification (HMO) is a rare disease that results in intra-abdominal ossification of unknown origin. An 88-year-old man developed an intestinal obstruction 2 weeks after undergoing an operation for a ruptured abdominal aortic aneurysm, resulting in intestinal obstructions those did not improved concervatively. During relaparotomy performed 30 days after the first operation, hard adhesions of the small intestine and mesentery were found; these adhesions were difficult to separate without damaging the serosa of the small intestine. We removed 240 cm of the small intestine and performed a jejuno-ileo anastomosis. Microscopically, trabecular bone tissue had increased irregularly in the fat tissue of the nodules with fibrosis, which were partially lined with osteoblasts. Accordingly, we histopathologically diagnosed the patient as having HMO. The patient was treated with NSAIDs and cimetidine to prevent the recurrence of HMO. No signs of recurrence have occurred as of one year after the second operation.

Clinicopathologic Characteristics and Clinical Outcomes of Esophageal Basaloid Squamous Carcinoma: Experience at a Single Institution

This retrospective study investigated the clinicopathologic characteristics and clinical outcomes of esophageal basaloid squamous carcinoma (BSC). Among 190 patients with esophageal carcinoma treated surgically between 1998 and 2011, we identified 9 (4.7%) with BSC. All of the patients were male, with a median age of 65 years. The frequencies of venous invasion, lymphatic invasion, and lymph node metastasis were 56%, 89%, and 67%, respectively. A total of 2 patients were pathologic stage 1, 5 were stage 2, and 2 were stage 3. Tumor recurrence was observed in 56% of the patients. The 5-year survival rate for patients with esophageal BSC was 40%, which was compatible with the figure of 53.8% for control patients (n = 18) with typical squamous cell carcinoma matched for sex, age, tumor location, and pathologic stage (P = 0.45). Although esophageal BSC shows aggressive lymph-vascular invasion and has a high likelihood of recurrence, its prognosis seems identical to that of typical squamous cell carcinoma.

Distal gastrectomy via minilaparotomy for non-overweight patients with T1N0-1 gastric cancer: initial experience of 30 cases.

Minilaparotomy is considered to be a useful treatment alternative to laparoscopic-assisted surgery from the viewpoint of minimal invasiveness, although it has several limitations for the resection of malignant tumors. We evaluated the usefulness of distal gastrectomy via minilaparotomy for non-overweight patients with clinically diagnosed T1N0-1 gastric cancer. Clinicopathological and surgical data on 30 patients attempted to undergo distal gastrectomy via minilaparotomy (skin incision, ≤7cm) without laparoscopic assistance were analyzed. Inclusion criteria were clinically (preoperatively) diagnosed T1N0-1 gastric cancer that was not suitable for endoscopic mucosal resection located in the middle- or lower-third of the stomach and the patient body mass index ≤ 25.0 kg/m(2). The minilaparotomy approach was successful in 27 patients (90%), while laparoscopic assistance was required to accomplish the procedures in three patients (10%). The type of lymph node dissection was D1 + α in 23 patients and D1 + β in 7 patients. The duration of surgery was 105-170 min (median, 143.5 min) and blood loss was 25-520 mL (median, 152.5 mL). Pathological stage was stage IA in 26 patients, IB in two patients, and stage II in two patients. Postoperative complications were wound infection in one patient, bleeding in one patient, and anastomotic ulcer in one patient. The length of postoperative stay was 7-41 (median, 11) days. With a median follow-up of 31 months, there was no recurrence. Distal gastrectomy via minilaparotomy seems feasible and safe in the majority of non-overweight patients with clinically diagnosed T1N0 gastric cancer.