Impact of Induction Chemotherapy and Preoperative Chemoradiotherapy on Operative Morbidity and Mortality in Patients with Locoregional Adenocarcinoma of the Stomach or Gastroesophageal Junction

Background Significant tumor downstaging has been achieved in patients with localized gastric or gastroesophageal adenocarcinoma by induction chemotherapy and preoperative chemoradiotherapy (CTX–CTXRT). However, the influence of CTX–CTXRT on operative morbidity and mortality has not yet been clarified. The aim of the present study was to document the frequency and nature of morbidity and mortality after surgery combined with CTX–CTXRT, and identify factors predictive of postoperative complications in patients with localized gastric or gastroesophageal adenocarcinoma. Methods A prospectively collected database on 71 consecutive patients who underwent CTX–CTXRT at M.D. Anderson Cancer Center between January 1997 and August 2004 was reviewed. Postoperative morbidity and mortality were investigated, and risk factors for overall complications were identified by multivariate logistic regression analysis. Results Overall morbidity and mortality rates were 38.0% (27 patients) and 2.8% (2 patients), respectively. Age greater than 60 years [relative risk 11.3 (95% confidence interval 2.50–50.6)] and body mass index (BMI) of 26 kg/m² or above [relative risk 4.08 (95% confidence interval 1.08–15.4)] were significant risk factors for overall complications. Conclusions CTX–CTXRT can be performed safely with an acceptable operative morbidity and a low operative mortality rate in patients with gastric or gastroesophageal cancer, with careful consideration of added risk associated with age and obesity.     

Sluggish glucose tolerance in tuberculosis patients.

OBJECTIVE: To examine glucose tolerance in sputum-positive non-treated pulmonary tuberculosis (TB) patients as part of a general metabolic profile. Subjects. Sixty-three sputum-positive non-treated patients (male and female) attending the pulmonary clinic at Mthatha General Hospital in the Eastern Cape and 89 apparently healthy sex and age-matched volunteers. METHODS: Sixty-three untreated TB patients who came to the Mthatha General Hospital's pulmonary clinic with classic symptoms of TB, confirmed by sputum analysis, were recruited for the study. Eighty-nine apparently healthy sex and age-matched volunteers served as the control group. Anthropometric measurements were taken using an electronic scale. Standard oral glucose tolerance tests (OGTTs) were performed in both groups in the morning after an overnight fast. Anticoagulant-treated blood was analysed for glucose and insulin using Peridochrome Glucose (Boehringer Mannheim, Mannheim, Germany) and radioimmunoassay (RIA) (Diagnostic Products Corporation, Los Angeles, USA) respectively. RESULTS: There was sluggish response to glucose and insulin in the TB patient group compared with the control group. Glucose and insulin levels were significantly higher in patients at 0, 30, 60, 120, and 180 minutes. Analysis of variance gave the following p-values, viz. p = 0.0000, 0.0004, 0.0000, 0.0000 and 0.0000 for glucose, and p = 0.0317, 0.0071, 0.0000, 0.0005 and 0.0000 for insulin respectively. CONCLUSIONS: The results of this study suggest an altered glucose/insulin metabolism in TB patients. This might play an important role in the clinical course of the disease.     

Effect of intravenous alpha-difluoromethylornithine on the polyamine levels of normal tissue and a transplantable fibrosarcoma

The effect of a continuous i.v. infusion of alpha-difluoromethylornithine (DFMO) on the polyamine metabolism of tumor and normal host tissue was determined. Non-tumor-bearing Fischer 344 rats or rats bearing a transplantable fibrosarcoma received continuous infusions of DFMO through a central venous catheter at three dose levels. Treatment with DFMO resulted in a time- and dose-dependent, cytostatic effect on the growth of the tumor. In fibrosarcoma-bearing rats the tumor putrescine levels were reduced after 6 and 12 days of DFMO treatment. Tumor spermidine levels were consistently reduced after 6 and 12 days of treatment with the reduction being dose dependent. The decrease in tumor ornithine decarboxylase activity was dose dependent. Erythrocyte putrescine levels were decreased in tumor- and non-tumor-bearing rats, suggesting that DFMO reduces the tumor contribution to the erythrocyte pool. Erythrocyte spermidine levels of fibrosarcoma- and non-tumor-bearing rats were elevated at the lower DFMO doses administered for 12 days but returned to normal as the dose was increased. Erythrocyte spermine levels were elevated in both groups of rats at all DFMO doses. Although normal host tissue weights were not affected by treatment with DFMO, the putrescine and spermidine levels of liver, spleen, and kidney and ornithine decarboxylase activity of the liver and kidney were decreased. These data demonstrate that i.v. DFMO has a cytostatic effect toward a rapidly growing fibrosarcoma associated with the depletion of both tumor putrescine and spermidine levels.     

Prospective cohort study of antioxidant vitamin supplement use and the risk of age-related maculopathy

In a prospective cohort study, the authors examined whether self-selection for antioxidant vitamin supplement use affects the incidence of age-related maculopathy. The study population consisted of 21,120 US male physician participants in the Physicians' Health Study I who did not have a diagnosis of age-related maculopathy at baseline (1982). During an average of 12.5 person-years of follow-up, a total of 279 incident cases of age-related maculopathy with vision loss to 20/30 or worse were confirmed by medical record review. In multivariate analysis, as compared with nonusers of supplements, persons who used vitamin E supplements had a possible but nonsignificant 13% reduced risk of age-related maculopathy (relative risk = 0.87, 95 percent confidence interval (CI) 0.53-1.43), while users of multivitamins had a possible but nonsignificant 10% reduced risk (relative risk = 0.90, 95% CI 0.68-1.19). Users of vitamin C supplements had a relative risk of 1.03 (95% CI 0.71-1.50). These observational data suggest that among persons who self-select for supplemental use of antioxidant vitamin C or E or multivitamins, large reductions in the risk of age-related maculopathy are unlikely. Randomized trial data are accumulating to enable reliable detection of the existence of more plausible small-to-moderate benefits of these agents alone and in combination on age-related maculopathy.     

Recent developments in oral chemotherapy options for gastric carcinoma

The incidence of carcinoma of the stomach is low in the United States, Canada, and Australia but is a significant health problem in Asia, South America, Eastern Europe, and countries of the previous Soviet Union. For patients with advanced disease, chemotherapy remains palliative. With the increasing emphasis on patients' quality of life, convenience, and cost containment, oral chemotherapy has come into increasing focus. We review oral chemotherapy agents for use in patients with advanced gastric carcinoma. Etoposide, given intravenously, has modest activity in gastric carcinoma. We studied oral etoposide, which was administered to 28 patients at the starting dose of 50 mg/m2/day for 21 days followed by a 7-day rest period. Five patients achieved a partial response and 4 patients achieved a minor response. The drug was well tolerated. Common toxicities included myelosuppression, alopecia, and nausea. Oral etoposide thus shows evidence of modest activity against gastric carcinoma. In Japan, considerable advances have been made in the oral chemotherapy of gastric carcinoma. The second generation fluorouracil prodrug tegafur/uracil (UFT) has been extensively evaluated in Japan, Korea, and Spain. Data predominantly from Japan indicate that tegafur/uracil has a response rate of approximately 20% in treatment naive patients with advanced gastric carcinoma. When combined with other active agents, tegafur/uracil has a response rate of more than 30% in these patients. The available data also suggest that tegafur/uracil is well tolerated and that patient acceptance is high. In conclusion, future clinical research is likely to focus on the development of convenient outpatient regimens with efficacy equal to that of intravenous regimens.     

Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome.

PURPOSE: Preoperative chemoradiotherapy may increase the R0 (curative) resection rate, overall survival (OS) duration, and disease-free survival (DFS) duration. We evaluated paclitaxel-based induction chemotherapy and chemoradiotherapy in patients with localized gastric or gastroesophageal adenocarcinoma to determine its feasibility, impact on the R0 resection rate, type of pathologic response, OS, and DFS. PATIENTS AND METHODS: Patients with operable, localized gastric, or gastroesophageal adenocarcinoma were eligible. Staging included endoscopic ultrasonography (EUS) and laparoscopy. Patients received two 28-day cycles of induction chemotherapy of fluorouracil, paclitaxel, and cisplatin followed by 45 Gy of radiation and concurrent fluorouracil plus paclitaxel. The cancer was restaged and surgery was attempted. Postsurgery pathologic findings and R0 resection were correlated with OS and DFS. RESULTS: Forty-one patients were enrolled. Most carcinomas were proximal (83%) and pretreatment stage EUST3 (85%). Forty patients (98%) underwent surgery, and 78% had an R0 resection. We observed a pathologic complete response (pathCR) rate of 20% and a pathologic partial response (pathPR) rate of 15% (< 10% residual cancer cells in the resected specimen). No pretreatment parameter (sex, cancer location, baseline T stage, or baseline N stage) predicted the type of postsurgery pathologic response, OS, or DFS. However, pathCR (P = .02), pathCR + pathPR (P = .006), R0 resection (P < .001), and postsurgery T and N stages (P = .01 and P < .001, respectively) were associated with OS. Same parameters were significantly correlated with DFS. Toxicity was manageable. CONCLUSION: The type of pathologic response but not pretreatment parameters was associated with OS and DFS. Efforts to increase the rate of pathologic response and better systemic cancer control are warranted.     

Impact of radiation dose on late clinical outcome after intracoronary radiation therapy: three-year follow-up of Long WRIST.

To determine the safety and efficacy, including the impact, on the late recurrence rate of an incremental gamma-radiation dose from 15 to 18 Gy, we report the 3-year clinical outcome of Washington Radiation for In-Stent Restenosis Trial for Long Lesions (Long WRIST). One hundred eighty patients with recurrent in-stent restenosis (ISR) were enrolled in the Long WRIST series and treated with (192)Ir with 1 month of antiplatelet therapy. Between 6 months and 3 years, the need for repeat revascularization was low and similar among the three groups. At 3 years, target lesion revascularization (TLR) and major adverse cardiac events (MACE) were less frequent in the 18 Gy group than in the 15 Gy group (P = 0.12 for TLR, P < 0.05 for MACE) and less frequent in the 15 Gy group as compared to the placebo group (P < 0.05 for TLR and MACE). At 3 years, a higher dose of 18 Gy with (192)Ir continues to improve the outcome of patients treated for ISR when compared to patients treated with 15 Gy or placebo.