Impact of nutritional status in the era of FOLFOX/FIRI-based chemotherapy.

BACKGROUND: The nutritional status plays a pivotal role during anticancer therapy. This study analyzed whether nutritional status influences the outcomes in the era of FOLFOX/FIRI therapy. METHODS: The patients were divided into two groups according to whether the nutritional status was well (serum albumin level ≥ 3.8 g/dL or a ≥ 1.0 g/dL increase as compared with the value before chemotherapy) or not before and 2 and 6 months after the start of chemotherapy. Chemotherapy-related adverse events (AE), treatment effect, and compliance were evaluated according to the nutritional status. The progression-free survival (PFS) and overall survival (OS) were assessed based on the nutritional status at 6 months. RESULTS: Between 2010 and 2013, data on 108 consecutive patients were analyzed. At 2 months after chemotherapy, the hematotoxicic AE and the value of tumor markers did not differ significantly. The non-hematotoxic AE were less frequent in patients in the well-nourished group (grade 2, 15.9 vs. 38.5%, p < 0.01). Based on the nutritional status at 6 months after chemotherapy, the hematotoxicic AE (grade 3, 9 vs. 19.5%, p = 0.03) and non-hematotoxic AE (grade 2, 31.3 vs. 51.2%, p = 0.04; grade 3, 6.0 vs. 24.4%, p < 0.01) were less frequent, and the median CEA value (5.3 vs. 27.75 mg/L, p < 0.01) was significantly lower in the well-nourished group. The median PFS (364 vs. 233 days, p < 0.01) and 5-year OS (26.5 vs. 11.1%, p = 0.01) are significantly better in the well-nourished group. CONCLUSIONS: The well-nourished at initial 6 months may predict a better treatment response and fewer adverse events in FOLFOX/FIRI chemotherapy.

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.

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.

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.

Complete remission by transarterial infusion with cisplatin for recurrent bile duct tumor thrombus of hepatocellular carcinoma: report of a case.

Bile duct tumor thrombus (BDTT) of a hepatocellular carcinoma (HCC) is a rare entity which was found microscopically in 1 to 9.2% of the resected specimen.A 54-year-old male was found to have a 65-mm hepatocellular carcinoma in segment VI of the liver with a huge intrahepatic bile duct tumor thrombus. As the main trunk of the posterior segment branched from the left bile duct, the BDTT of the posterior branch extended to the common bile duct via the left bile duct. When the posterior segment was resected along with the left lobe, the estimated remnant liver volume was less than 30%. Therefore, the patient underwent extended posterior segmentectomy with choledochotomy and all of the BDTT was removed via the common bile duct.Three months later, his serum bilirubin (6.63 mg/dL) and des-gamma-carboxy prothrombin (410 ng/mL) were re-elevated due to recurrent BDTT. A well-enhanced BDTT was observed by computed tomography (CT) at the left bile duct. Transarterial chemotherapy with cisplatin was scheduled, followed by endoscopic retrograde bile duct drainage. After four sessions of this chemotherapy, the BDTT had vanished and the tumor marker was decreased to within the normal range. The patient was stably treated with this regimen and has remained recurrence-free for five years.

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.

Dual primary gastric and colorectal cancer: is the prognosis better for synchronous or metachronous?

OBJECTIVES: The purpose of this study was to investigate the prognosis and clinicopathologic features of synchronous and metachronous dual primary gastric and colorectal cancer (DPGCC). METHODS: We reviewed clinical data of 96 patients with DPGCC, comprising 63 men and 33 women, from among 4523 patients with gastric or colorectal cancer who underwent surgical treatment or chemotherapy, but no endoscopic resection, for colorectal cancer between 1990 and 2009. The selected patients were classified into 2 groups according to the time of gastric or colorectal cancer detection as follows: synchronous group (n= 42) and metachronous group (n = 54). RESULTS: Among 4523 patients treated for gastric and colorectal cancer, DPGCC was diagnosed in 96 (2.1%). In terms of clinicopathologic features, the proportion of early-stage gastric and colorectal cancer was higher in the metachronous DPGCC group, with P values of 0.02 and 0.01, respectively. Overall survival in the metachronous DPGCC group was significantly longer than in the synchronous DPGCC group (P = 0.02). Metachronous DPGCC was identified as an independent predictor of survival by both univariate and multivariate analyses, with a P value of 0.02 and 0.006, respectively. CONCLUSION: Metachronous DPGCC had a better prognosis than synchronous DPGCC due to the tendency for metachronous DPGCC to occur in patients with early-stage cancer.

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.

Prognostic significance of a new system for categorization of the number of lymph node metastases in gastric cancer.

BACKGROUND/AIMS: We examined whether a new system for categorization of the number or level of lymph node metastases would improve survival prediction in patients with gastric cancer. METHODOLOGY: Node-positive gastric cancer patients (361) were retrospectively studied. Cox proportional-hazards model analysis of the numbers of metastatic lymph nodes (numbers 1 to 11) showed the first peak of the hazard ratio for death at a threshold value of 4 lymph node metastases. We calculated cumulative 5-year survival rates and examined prognostic factors by multivariate analysis according to the numbers and levels of lymph node metastases. The effects of other prognostic factors were also examined. RESULTS: We divided the number of lymph node metastases into two groups (1-3 vs. > or =4), and classified the level of lymph node metastasis as level I or level II as defined by the Japanese Classification of Gastric Carcinoma. The 5-year survival rate differed significantly according to the number of lymph node metastases (1-3 vs. > or = 4) (p<0.0001). On multivariate regression analysis, the level of lymph node metastasis (level I or level II) and the number of lymph node metastases (1-3 or > or = 4) were independent predictors of survival. CONCLUSIONS: Categorization of the number of metastatic lymph nodes (1-3 or > or = 4) was easy and provided an accurate predictor of survival in patients with gastric cancer.

Malignant Peritoneal Mesothelioma Mimicking Ischemic Colitis.

The prognosis of malignant peritoneal mesothelioma is extremely poor with a mean survival time of 12 months. The initial symptoms are poor and atypical. Because of its rare entity and little knowledge of its treatments, there are few reports of long-term survival. We encountered a very unique case with strong impression on radiological findings of malignant peritoneal methothelioma. We had misdiagnosed it because of the findings and because the time course was similar to that of ischemic colitis. The radiological findings on CT and enema disappeared within one week after antibiotic therapy.

[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.

[Elderly patient with metastatic gallbladder cancer treated by cisplatin, epirubicin and continuous infusion 5-fluorouracil].

An 80-year-old woman, who was followed as an A-bomb victim, was diagnosed to have advanced gallbladder cancer with liver metastasis on December, 2005. Due to her advanced age, her previous doctor recommended the best supportive care. Therefore, her general condition was good, so we decided to treat her with cisplatin, epirubicin and continuous infusion of 5-fluorouracil(CEF therapy). She was given 5-fluorouracil 500 mg/body per day via continuous infusion on days 1 to 5, cisplatin 50mg body and epirubicin 20mg body on day 1 every 28 days, and these dosages have been reduced. CEF therapy was started from February, 2007. Primary lesion and liver metastasis decreased remarkably after completion of 2 cycles, and we judged it as a complete response. After 10 cycles, lung metastasis was found by CT scan in August, 2007. We tried chemotherapy with gemcitabine as a second-line treatment. The result of gemcitabine was again a progressive disease, so we switched her regimen to S-1 as a third-line treatment on January, 2008. Chemotherapy is continued by the outpatient care now, 25 months after the medical treatment started. The present result suggests that CEF therapy may be useful for metastatic gallbladder cancer.