Resection of Colorectal Cancer With Versus Without Preservation of Inferior Mesenteric Artery.

OBJECTIVE: To assess the clinical significance of preservation of the inferior mesenteric artery (IMA) in comparison with IMA ligation in surgery for sigmoid colon or rectal (colorectal) cancer. METHODS: Consecutive patients (n=862) with colorectal cancer who underwent intended surgical resection of the main tumor between 1986 and 2011 were retrospectively analyzed. The patients were divided into 2 groups: IMA preserved (n=745) and IMA ligated (n=117). RESULTS: No significant difference was observed in incidence of advanced stage III or IV disease between the 2 groups (P=0.56 and 0.51, respectively), whereas a longer operation time (287 [95 to 700] vs. 215 [60 to 900] min, respectively; P<0.001) and greater amount of intraoperative bleeding (595 [15 to 4530] vs. 235 [1 to 11565] mL, respectively; P<0.001) were observed in the IMA-ligated group. The overall incidence of surgery-related complications was higher in the IMA-ligated group than in the IMA-preserved group (53.0% vs. 38.5%, respectively; P=0.003). Urinary dysfunction and abdominal abscess were significantly more frequent in the IMA-ligated group (11.1% vs. 4.0%, P=0.001; and 6.8% vs. 2.6%, P=0.01, respectively), and postoperative hospitalization was longer (11 to 140, median 28 vs. 5 to 153, median 19 d, respectively; P<0.001). No significant difference was found in overall survival rate between the 2 groups. CONCLUSIONS: For colorectal cancer resection, IMA preservation may be no change to IMA ligation as to patient' survival, with small risk of operative morbidity.

Phase II Study of Neoadjuvant Chemotherapy With S-1 and CDDP in Patients With Lymph Node Metastatic Stage II or III Gastric Cancer.

OBJECTIVES: We conducted a phase II trial to investigate the efficacy and safety of neoadjuvant chemotherapy (NAC) comprising S-1 and cisplatin (CDDP) followed by extensive resection in the management of resectable locally advanced gastric cancer with lymph node (LN) metastases. METHODS: Patients with LN metastases from stage II or III gastric cancer received S-1 and CDDP, as NAC criteria for LN metastases were the involvement of ≥4 nodes <2 cm or ≥1 nodes ≥2 cm as confirmed by a total body computed tomography scan. All patients underwent extensive resection including D2 gastrectomy. The primary endpoint was complete resection rate and the secondary endpoints were 3-year relapse-free and overall survival. RESULTS: Fifty patients were assessable for the analysis. The complete resection rate was 87.8%. Three-year relapse-free survival was 44.9% and 3-year overall survival rate was 48.0%. CONCLUSIONS: NAC with S-1 and CDDP is safe and may improve the complete resection rate in patients with metastatic LN gastric cancer. This suggests that LN metastases would provide good target lesions in future clinical trials of NAC.

D2 gastrectomy with versus without bursectomy for gastric cancer.

OBJECTIVES: The purpose of this study was to determine the survival benefit of bursectomy by retrospectively comparing the prognosis in patients undergoing D2 lymphadenectomy and gastrectomy (D2 gastrectomy) with bursectomy for gastric cancer with that in patients undergoing D2 gastrectomy alone. METHODS: A total of 254 consecutive stage IA to IIIC gastric cancer patients undergoing curative intent surgery between 2004 and 2009 were enrolled. The patients were divided into 2 groups: a bursectomy group, which included patients undergoing curative D2 gastrectomy with bursectomy by one surgeon, and a nonbursectomy group, which included those undergoing curative D2 gastrectomy alone by other surgeons. RESULTS: No statistically significant difference was observed in the number of metastatic nodes or penetration of the serosa between the 2 groups. The overall incidence of surgery-related complications was 24.0% in the bursectomy group (29 of 121 patients) and 25.6% in the nonbursectomy group (34 of 133 patients). The 5-year overall survival rate was 85.8% in the bursectomy group and 80.8% in the nonbursectomy group (hazard ratio 0.82; 95% confidence interval, 0.37-1.74; P=0.60). CONCLUSIONS: The results of this retrospective study indicate no survival benefit for bursectomy plus D2 gastrectomy over D2 gastrectomy alone.

Complete response to uracil-tegafur alone in advanced rectal cancer.

We report a case of a complete response to treatment with uracil-tegafur (UFT) alone in advanced rectal cancer. The patient was an 84-year-old woman referred to our hospital complaining of anal bleeding. A colonoscopy revealed a Borrmann type II tumor in the rectum, which was diagnosed as an adenocarcinoma. Therefore, best supportive care was initiated in April 2011 with oral administration of UFT. The anal bleeding stopped 2 months later, and the patient's general condition remains good at one year. A further colonoscopy at one year after initiation of treatment in April 2012 resulted in reclassification of the tumor as an Isp lesion, and the biopsy was negative for cancer. The patient was still alive with no sign of recurrence at 21 months after commencing UFT alone with no surgical treatment. These results suggest that chemotherapy with UFT alone can yield complete remission from advanced rectal cancer.

Differing deregulation of HER2 in primary gastric cancer and synchronous related metastatic lymph nodes.

BACKGROUND: The aim of this study was to investigate how differences in expression of HER2 between primary gastric cancers (PGCs) and their corresponding metastatic lymph nodes (LMNs) might affect its potential as a prognostic indicator in treatments including anti-HER2 agents. METHODS: The analysis was conducted in 102 patients who underwent surgical resection for primary gastric cancers (PGCs; adenocarcinoma, intestinal type) with synchronous LNMs. HER2 gene status and protein expression were investigated by immunohistochemistry (IHC) in all patients; fluorescence in situ hybridization (FISH) was performed in 22 patients. The correlation between HER2 gene status in PGCs and their LNMs was evaluated. RESULTS: Positive HER2 expression as detected by IHC + FISH was observed in 27/102 PGC samples (26.5%) and 29/102 LNM samples (28.4%). HER2 amplification status in 102 paired PGC and LNM samples as evaluated by FISH + IHC was concordant in 92 patients (90.2%), 69 (67.6%) were unamplified and 23/102 (22.5%) were amplified at both sites, and discordant in 10 patients (9.8%), 4 (3.9%) were positive for PGC and negative for LNM, while 6 (5.9%) were positive for LNM and negative for PGC. The results of FISH + IHC showed very strong concordance in HER2 status between the PGC and LNM groups (k = 0.754). CONCLUSION: The high concordance between HER2 results for PGCs and their LNMs indicates that assessment of HER2 status in the primary cancer alone is a reliable basis for deciding treatment with anti-HER2 agents in patients with LNMs from gastric adenocarcinoma. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9365749431029643.

Pharmacokinetics of docetaxel in gastric cancer patients with malignant ascites.

PURPOSE: The purpose of this study was to investigate whether intravenous (i.v.) administration allowed docetaxel to penetrate ascites in gastric cancer patients with peritoneal dissemination. PATIENTS AND METHODS: Twelve patients with disseminated gastric carcinoma were enrolled in the study. All patients received docetaxel-containing drug regimens: i.v. administration of 40 mg/m(2) docetaxel in 6 patients, and 60 mg/m(2) in the remainder. Docetaxel concentrations in the plasma and ascites were measured. RESULTS: Docetaxel was detected in the ascites of 4 patients in the 40 mg/m(2) group and 5 patients in the 60 mg/m(2) group. The highest concentration of docetaxel in plasma was detected at immediately after administration (median: 1,660 ng/mL, 501-2,560 ng/mL), after which it gradually decreased. The highest concentration of docetaxel in ascites was observed at ~7 h after administration and varied among cases (median: 18 ng/mL, 11-52 ng/mL). CONCLUSION: Intravenous administration allows to penetrate ascites in gastric cancer patients with peritoneal dissemination.

A complete response to S-1 plus cis-diamminedichloroplatinum in advanced-stage esophageal and gastric adenocarcinoma: a case report.

BACKGROUND: Complete remission from advanced-stage synchronous double primary (SDP) esophageal and gastric adenocarcinoma by chemotherapy alone is rare. We report a case of advanced-stage SDP esophageal and gastric adenocarcinoma in which a complete response to treatment was obtained with S-1 and cis-diamminedichloroplatinum (CDDP). CASE PRESENTATION: The patient was a 74-year-old man referred to our hospital complaining of dysphagia. Gastrointestinal endoscopy was performed and advanced-stage SDP esophageal and gastric adenocarcinoma diagnosed. Computed tomography revealed multiple regional lymph node metastases in the mediastinum. Neoadjuvant chemotherapy with S-1 and CDDP for advanced esophageal and gastric cancer was planned. An endoscopy following two courses of chemotherapy revealed that the esophageal cancer had been replaced with a normal mucosal lesion and the gastric tumor with a scar lesion; the results of biopsies of both were negative for cancer. Computed tomography revealed that the multiple lymph node metastases had disappeared. We diagnosed a complete response to S-1 and CDDP in advanced-stage SDP esophageal and gastric cancer. The patient is still alive with no signs of recurrence 22 months after the disappearance of the original tumor and metastatic lesions without surgical treatment. CONCLUSION: These results suggest that complete remission from advanced-stage esophageal and gastric cancer can be obtained with chemotherapy with S-1 plus CDDP.

Complete response to chemoradiotherapy in a patient with synchronous double gastric and esophageal cancer.

UNLABELLED: A 77-year-old man with early synchronous double primary gastric and esophageal cancer showed complete response (CR) to chemoradiotherapy (CRT) with fluorouracil (5-FU) and cis-diamminedichloroplatinum (CDDP) and 60 Gy total dose of radiation. Gastrointestinal endoscopy had revealed type IIc squamous cell carcinoma in the lower oesophagus and type IIc adenocarcinoma in the mid-stomach region. Synchronous double primary early-stage esophageal and gastric cancer was diagnosed. The patient's age and chronic obstructive pulmonary disease (COPD) contraindicated radical esophageal surgery. Therefore, we decided to first administer CRT with 5-FU and CDDP for the esophageal cancer, and subsequently perform partial gastrectomy for the gastric cancer. After the CRT, neither of the tumors recurred. CR to CRT for the esophageal cancer and CR to chemotherapy for the gastric cancer were achieved. CONCLUSION: CRT with 5-FU and CDDP can produce CR in cases of early esophageal and gastric cancer.

A case of complete response to S-1 plus CDDP in early-stage mucosal esophageal cancer.

We report a case of early-stage mucosal esophageal cancer, showing a complete response to S-1 and cis-diamminedichloplatinum (CDDP). The patient was a 67-year-old man with synchronous double primary early-stage mucosal esophageal and advanced gastric cancer. We planned neoadjuvant chemotherapy with S-1 and CDDP for the advanced gastric cancer and endoscopic mucosal resection for the early-stage esophageal cancer. After the first course of chemotherapy, the endoscopy revealed that the esophageal cancer had become a normal mucosal lesion, and the biopsy was negative for cancer. We diagnosed a complete response to S-1 and CDDP in early-stage esophageal cancer. After two courses of chemotherapy, distal gastrectomy was performed. The patient is still alive with no sign of recurrence at 16 months after the disappearance of the original tumor. These results suggest that chemotherapy with S-1 plus CDDP may be effective in early-stage esophageal cancer.

[Successful treatment with S-1 + CPT-11 for hepatic metastasis from gastric cancer--a case report].

The patient was a 67-year-old male with Type 3 gastric cancer who underwent distal gastrectomy and D2 dissection in December 2004. It was diagnosed to be a cancer of se, n(1+), Stage IIIA. In October 2006, 22 months after the operations, abdominal CT showed multiple tumors with a maximum diameter of 35 mm in both hepatic lobes. The tumors were diagnosed as multiple hepatic metastases of the gastric cancer. After 5 courses of concomitant S-1+CPT-11 therapy, abdominal CT in February 2007 showed complete elimination of the multiple tumors in both hepatic lobes, and it was considered that a complete response (CR) had been obtained. After initiation of the treatment, 32 courses of S-1+CPT-11 therapy were performed, and at present, 24 months after the therapy, the patient has survived with no redevelopment of the cancer. All of the treatments were performed in an outpatient setting, and no side effects have been confirmed other than grade 1 gastric and skin symptoms. We experienced a case in which CR was achieved by S-1+CPT-11 therapy in a patient with hepatic metastasis of a gastric cancer.

Characteristics of ectopic pancreas in dynamic gadolinium-enhanced MRI.

The characteristics of jejunal ectopic pancreas in dynamic gadolinium-enhanced magnetic resonance imaging are described in a 40-year-old man with bowel obstruction. The pre-contrast signal intensity and post-contrast enhancement pattern of ectopic pancreas are the same as those of the pancreas.

[Complete remission with FLEP chemotherapy for multiple liver metastasis from alpha-fetoprotein-producing gastric cancer--report of a case].

The patient was a 51-year-old male diagnosed with gastric cancer in July 1999 by endoscopic examination, revealing multiple liver metastasis with abdominal computed tomography (CT). The serum levels of alpha-fetoprotein (AFP)were determined to be 91 ng/mL, and tumors were histopathologically identified as AFP-producing gastric cancer by immunohistological staining. We started combination chemotherapy with 5-fluorouracil (5-FU), Leucovorin (LV), etoposide (VP-16) and cis-diaminedichloroplatinum (CDDP) (designated as FLEP)in August 1999. The serum AFP value was normalized after two courses, and the liver metastases disappeared. The primary gastric tumor became a ulcer, and disappearance of the cancer was confirmed histologically. We continued adjuvant chemotherapy with S-1 as an outpatient. In April 2000, there was no sign of the liver metastases, but endoscopic examination showed IIc-like lesion in the stomach. We performed 2 courses of FLEP, but the tumor did not disappear. He underwent total gastrectomy with D2 dissection in June 2001. The pathological diagnosis was por 1, ss, ly2, v1, n(1+). He was still alive with no sign of recurrence 84 months after surgery. We experienced this AFP-producing gastric cancer in which CR was possible by FLEP. There was no recurrence after total gastrectomy for local recurrence.

Irinotecan plus S-1 for liver metastases of gastric cancer.

BACKGROUND/AIMS: This retrospective study evaluated the efficacy of and compliance with combined irinotecan hydrochloride (CPT-11) and S-1 chemotherapy in patients with liver metastases of gastric cancer. METHODOLOGY: A total of 28 gastric cancer patients with liver metastases received first-line chemotherapy. The response rate, overall survival, and toxicity were evaluated. Fourteen patients were treated with CPT-11+S-1 and they were compared with 14 patients who received cis-diamminedichloroplatinum (CDDP)+S-1. RESULTS: The CPT+S-1 group showed a higher response rate than the CDDP+S-1 group (57.1% [95% CI 31.2-83.1%] vs. 42.9% [95% CI 16.9-68.8%]; p < 0.44). The median survival time of the CPT-11+S-1 group was significantly longer than the CDDP+S-1 group (16.1 months [95% CI 10.5-21.2] vs. 7.3 months [95% CI 2.2-14.7]; hazard ratio for death, 0.35 [95% CI 0.14-0.83]; p < 0.02). By multivariate analysis for the treatment with CPT-11+S-1 was identified as an independent prognostic factor. The most common adverse effect of CPT-11+S-1 therapy was leukopenia (57.1%), which was Grade 3 in 3 patients (21.4%). However, all patients recovered rapidly and there were no significant differences of toxicity between the two regimens. CONCLUSIONS: CPT-11+S-1 therapy will achieve significantly longer survival than CDDP+S-1 without severe toxicity in gastric cancer patients with liver metastases.

[A patient with esophageal cancer recurrence responding to S-1 combined with cisplatin (CDDP)].

We administered a combination chemotherapy of S-1 plus cisplatin (CDDP) therapy to a patient with recurrenced cancer of esophagus in lymph node. S-1 (80 mg/m(2)/day), taken out of the capsule, was administered via the catheter for tube feeding on day 1 to day 21 and CDDP at 60 mg/m(2)/day by intravenous drip infusion on day 8 for 3 weeks followed by a drug-free 2 week period as the first course. After 2 courses, CT findings showed a complete regression of the lymph node for complete response (CR). He has been alive for 10 months without recurrence. Combined use of S-1 and CDDP is effective as chemotherapy for recurrenced esophageal cancer.

Effect of gastrectomy on the pharmacokinetics of S-1, an oral fluoropyrimidine, in resectable gastric cancer patients.

PURPOSE: The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated. PATIENTS AND METHODS: A dose of 40 mg/m(2) of S-1 was administered orally twice daily for 7 days (80 mg/m(2)/day) preoperatively in ten patients with resectable gastric cancer, and the same dose of S-1 was administered for 28 consecutive days after gastrectomy. Plasma concentrations of tegafur, gimeracil, and oteracil potassium, all the components of S-1, and 5-FU were measured on pre- and postoperative days. Concentrations of 5-FU in tumor and normal tissues were also determined. RESULTS: At day 4 from the initial preoperative administration of S-1, the AUC of 5-FU was 1,055 +/- 304 ng h/ml. At day 18, day 28, and day 42 after gastrectomy, it was 1,012 +/- 331, 1,070 +/- 403, and 946 +/- 226 ng h/ml, respectively. No significant differences for plasma 5-FU were observed between pre- and postoperative days. In the resected tumor tissues, concentrations of 5-FU were 242 +/- 83 ng/g around 4.5 h and 91.7 +/- 37.0 ng/g around 20 h after the final administration, respectively. CONCLUSION: Gastrectomy does not affect on pharmacokinetics of 5-FU derived from S-1 regardless of partial or total gastrectomy, indicating that S-1 can be a useful drug in postoperative adjuvant chemotherapy for gastric cancer.

Complete remission by chemotherapy in stage IE-IIE primary gastric lymphoma.

BACKGROUND/AIMS: There are many controversies regarding the treatment for primary gastric non-Hodgkin's lymphoma (PGL). We hypothesized that preoperative chemotherapy and extensive surgery would improve patient survival in the treatment of early stage patients with PGL. METHODOLOGY: Between 1997 and 2001, we prospectively evaluated 10 patients with stage IE and IIE PGL. The histological diagnoses were established by endoscopic biopsies in all cases. All patients received preoperative chemotherapy, i.e. CHOP or MACOP-B. Upon the completion of chemotherapy, the extensive surgery including total gastrectomy, splenectomy, cholecystectomy, and paraaortic lymphadenectomy were performed. The response rates of preoperative chemotherapy and overall survival were analyzed. RESULTS: All patients were still alive with no signs of recurrence with a median follow-up of 86 months (range, 40 to 102 months) after surgery. In all patients, microscopic examinations did not reveal residual lymphoma cells in the resected stomach or lymph nodes. Chemotherapy-related preoperative complications such as perforation or intestinal bleeding did not occur in any of the cases. Postoperative complications developed in 30% (3/10) of patients and consisted of 2 pancreatic fistulas, 3 intra-abdominal abscesses, and 1 anastomotic leak. CONCLUSIONS: Primary chemotherapy alone without surgery may produce complete remission in Stage IE-IIE PGL.

[Evaluation of combination chemotherapy with 5-FU, CDDP and CPT-11 for human gastric carcinoma transplanted into nude mice - comparative study of in vivo chemosensitivity test].

We performed in vivo chemosensitivity tests on human gastric carcinoma. To evaluate the efficacy of some combined chemotherapy for human gastric carcinoma maintained in the subcutaneous space in nude mice, we designed the following six experimental groups: 1) 5-FU group, 2) CDDP group, 3) CPT-11 group, 4) combined therapy group of 5-FU and CDDP, 5) combined therapy group of 5-FU and CPT-11, and 6) combined therapy group of CPT-11 and CDDP. An in vivo nude mice assay was performed. Histopathological changes of the tumors in nude mice, treated with anti-cancer agents,were also evaluated and compared to the results of the nude mice assay. Based on histopathological grading,the true positive rate of the nude mice assay was 0%, the true negative rate was 83.3%, and the accuracy rate was 83.3%. CPT-11 appeared to be highly efficacious when given in combination with CDDP in human gastric cancer cell lines. These results suggest that combination chemotherapy with CPT-11 and CDDP is clinically effective for gastric cancer patients.

Neoadjuvant chemotherapy with S-1 and CDDP in advanced gastric cancer.

PURPOSE: This retrospective study evaluated the effects of neoadjuvant chemotherapy in advanced gastric cancer. METHODS: Between 2002 and 2005, we treated 14 patients with advanced gastric cancer (involvement of more than five nodes or tumor invasion into pancreas) and 25 patients with Stage III gastric cancer. The group of 14 patients with advanced gastric cancer received combination chemotherapy with S-1 and cis-diamminedichloroplatinum (CDDP) as a neoadjuvant chemotherapy (NAC). This regimen was repeated every 5 weeks for a total of 2-5 cycles. The 25 patients with Stage III gastric cancer was carried surgery alone (SA). All patients underwent extensive surgery, including gastrectomy, and D2 lymphadenectomy. The rate of response and overall survival in the two groups were compared. RESULTS: All patients of NAC group completed the planned regimens of chemotherapy and surgery. Patients of the NAC group had a response rate of 78.6% (95% confidence interval 57.1-100.0%). The most common adverse effect was leukocytopenia (42.9%). However, only four patients (28.6%) had upper Grade 2 leukocytopenia, and all recovered promptly. Postoperative complications were not significant differentiated between NAC and SA group of patients (7.2 vs. 4.0%). Patients in the NAC group had a significantly better survival than those in the SA group (P = 0.03). The median survival has not been reached after 26.9 months of median follow-up for patients in the NAC group. 1-, 2-, and 3-year survival rates were 92.3, 92.3, and 61.5%, respectively. NAC was identified as an independent prognostic factor in all patients (P = 0.018). CONCLUSION: Neoadjuvant chemotherapy with TS-1 + CDDP improves the survival in patients with advanced gastric cancer.

Combination chemotherapy comprising 5-fluorouracil, leucovorin, etoposide, and cis-diamminedichloroplatinum for the treatment of advanced gastric cancer.

PURPOSE: The FLEP regimen (5-FU, LV, ETP, and CDDP) has been recommended as a combination chemotherapy to control advanced and recurrent gastric cancer. We performed a phase II study of this regimen in 49 patients with advanced gastric cancer. METHODS: The treatment regimen consisted of: 5-FU at 370 mg/m(2) (days 1-5, i.v. 24 h); LV at a dose of 30 mg (days 1-5, i.v. bolus); and ETP and CDDP each at 70 mg/m(2) (days 7 and 21, i.a. 2 h), which was repeated every five weeks. RESULTS: The overall response rate was 40.8% (20/49 patients) and the median survival time was 12.6 months (range 1.1-41.8). The adverse events were Grade 3/4 leukocytopenia (16.3%), Grade 3/4 thrombocytopenia (8.2%), Grade 3 nausea and/or vomiting (4.1%), and Grade 3 stomatitis (2.0%). CONCLUSIONS: Based on the encouraging response rate and prognosis, we recommend applying the FLEP regimen to patients with primary advanced gastric cancer.