Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer

BACKGROUND: We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. METHODS: Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. RESULTS: Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites. CONCLUSIONS: Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.     

Care of esophageal cancer patients with diabetes mellitus--preoperative management and treatment

The care of esophageal cancer patients with diabetes mellitus is described. The main points are as follows. 1. Prevention and control of infection. 2. Sufficient nutritional support (2000 Kcal/day) and hydration. 3. Control of plasma glucose level (150 mg/dl-250 mg/dl) by means of insulin. 4. An absence of ketone bodies and minimum glucose level (< 10 g/day) in the urine. 5. Prevention and control of hypoglycemia. Good control of diabetes mellitus in esophageal cancer patients may contribute to reduced surgical rislcs.     

The management of cervical esophageal cancer by head and neck surgeons

Aspergillosis became an important opportunistic mycosis during the last years, with a great variety of clinical manifestations. To contribute to the replenishing of this mycosis serodiagnosis, biologic reactives (antigens and antisera) were prepared from strains of the species Aspergillus niger, Aspergillus flavus and Aspergillus terreus for their use in immunoprecipitation assays. The reactives were assessed by double immunospreading versus a reference commercial system; satisfactory results were obtained, and this guarantees the widening of the aspergillosis serodiagnosis in the Mycology Laboratory of the "Pedro Kourí" the Tropical Medicine Institute (IPK) with important imports savings.     

Chemotherapy as a part of each treatment fraction in a twice-a-day hyperfractionated schedule: a new chemoradiotherapy approach for advanced head and neck cancer

In allergic asthma, there is convincing evidence that changes in eosinophil and lymphocyte state of activation in blood may reflect disease activity. We evaluated whether simple blood eosinophil or lymphocyte counts in atopic children with asthma could reflect the degree of allergic sensitization. Seventy-six asthmatic children, sensitized to house dust mites (HDM), in stable conditions at the time of the study, and 53 sex- and age-matched controls (CTR) were studied. As compared to CTR, allergic patients showed higher eosinophil numbers and percentages (p < 0.001) but similar lymphocyte numbers and proportions (p > 0.1). Both in CTR and in allergic patients, eosinophil counts did not correlate with lymphocyte counts (p > 0.05; each comparison) but positive correlations were observed between eosinophil numbers and percentages and paper radio immunosorbent test (PRIST) levels or radio-allergo sorbent test (RAST) classes (p < 0.001; each comparison). When allergic asthmatic individuals were subdivided according to their age into two subgroups (Gr), no differences were found in eosinophil and lymphocyte counts and in PRIST levels and RAST values between Gr1 (< or =5 years old [preschool children]) and Gr2 (>5 years old [school children]) (p > 0.05; each comparison). Interestingly, although positive correlations between eosinophil counts and PRIST levels were found in both subgroups (p < 0.05; each comparison), only in Gr2 did eosinophil counts correlate positively with RAST classes (p < 0.001). No correlations between lymphocyte counts and PRIST levels or RAST classes were demonstrated (p > 0.05; each comparison). These data suggest that although blood eosinophilia was similar in preschool and in allergic asthmatic school children sensitized to HDM, only in the oldest children did blood eosinophil counts appear to be related to the degree of HDM-specific sensitization.     

The roles of multimodality treatment and lymphadenectomy in the management of esophageal cancer

PURPOSE: To review the current status of multimodality treatment and lymphadenectomy in the management of esophageal cancer. DATA SOURCES: Literature review. STUDY SELECTION: Multimodality treatment and lymphadenectomy in esophageal cancer. DATA EXTRACTION: Results in research papers published selected by literature search. RESULTS: Numerous studies have been carried out attempting to define the roles of various neoadjuvant or adjuvant regimens in the treatment of esophageal cancer. These included the use of radiotherapy or chemotherapy alone or in different combinations, with or without surgical resection. Randomized trials have failed to show significant improvement compared with surgical resection alone, although downstaging of disease and benefits on subgroups of patients could be demonstrated. Whether the extent of resection can influence outcome was tested by varying the surgical approach, and by increasing the extent of lymphadenectomy. Although indirect evidence exists suggesting more extensive resection may improve long term prognosis, definitive proof is lacking. CONCLUSIONS: More well organized randomized controlled trials are needed to further elucidate the roles of these approaches in the treatment of esophageal cancer.     

Chemotherapy of gastric cancer

At present curative resection is the only radical treatment for gastric cancer, although recently developed combination chemotherapy shows increased activity in treating locally advanced and metastatic disease. Among several combination regimens, those based on biochemical modulation, such as sequential methotrexate/5-fluorouracil or low-dose CDDP/5-fluorouracil, are thought to provide increased efficacy with decreasing adverse reactions in unresectable gastric cancer. Therefore, a prospective randomized clinical trial comparing the prognosis of patients receiving adjuvant multi-agent chemotherapy with those treated only surgically should be pursued for estimation of the clinical benefit of these agents.     

Induction therapy for esophageal cancer with paclitaxel and hyperfractionated radiotherapy: a phase I and II study

OBJECTIVE: Induction chemoradiotherapy followed by surgery may improve survival rates among patients with esophageal carcinoma. We designed a novel intense induction regimen with paclitaxel and high-dose hyperfractionated radiotherapy to maximize complete response rates. METHODS: Forty patients with esophageal cancer were treated in a phase I and II trial of induction chemotherapy (cisplatin, 5-fluorouracil, and paclitaxel) at three dosage levels (75, 125, and 100 mg/m2) and concurrent hyperfractionated radiotherapy (45 Gy to the mediastinum, 58.5 Gy to the tumor). The mean age was 62 years, and 32 patients (80%) had adenocarcinoma. Twenty-eight of 40 (70%) patients had locally advanced tumors (T3, or stage IIB or greater). RESULTS: The average hospitalization for induction treatment was 17 days. Toxicity was substantial, with esophagitis necessitating nutritional support the most common complication. The maximum tolerated dose of paclitaxel was 100 mg/m2. Two patients died during induction treatment. Thirty-six patients (90%) underwent resection. The median length of stay was 10 days, and two patients died after the operation. Fourteen of 36 patients (39%) had a pathologic complete response. Patients who received all prescribed chemotherapy had a higher pathologic complete response rate (50%) than did patients who required dose reduction (17%; p = 0.076). The 2-year survival rate was 61% (95% CI 35% to 86%) with a median follow-up of 11.9 months. CONCLUSIONS: Paclitaxel at a dose of 100 mg/m2 appears to have acceptable toxicity. The high pathologic complete response rate in this regimen is encouraging, but it is associated with substantial toxicity. The toxicity of this regimen is not acceptable and will require substantial reduction in the radiation component. Survival data are too short-term to confirm enhanced survival.     

Chemotherapy, biologics, and chemoprevention as systemic therapies for head and neck cancer

The role of chemotherapy in the management of patients with head and neck carcinoma is actively being investigated. Currently, chemotherapy is considered the standard of care for patients with recurrent or metastatic disease. Several single-agent and combination regimens have been used, demonstrating a partial response rate of 30% or less. The role of chemotherapy in the neo-adjuvant and adjuvant setting is less clearly defined. Concomitant chemoradiotherapy and rapid sequence alternating combined therapy have demonstrated a survival advantage in randomized trials. The degree of toxicities associated with these regimens, however, currently limits their use to clinical trials. Biologic therapy has been evaluated neo-adjuvantly and in recurrent and metastatic disease. Additional trials are needed before definitive conclusions can be made regarding its effectiveness and indications. The role of chemoprevention is rapidly expanding, with new agents and combinations currently in clinical trials.     

Chemotherapy of metastatic endometrial cancer

Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive disease of carbohydrate metabolism. HFI patients are deficient in aldolase B, the isozyme expressed in fructose-metabolizing tissues. The eight protein coding exons, including splicing signals, of the aldolase B gene from one American HFI patient were amplified by the polymerase chain reaction (PCR). Single-strand conformational polymorphism (SSCP) analysis and direct sequence determination were applied to the amplified fragments. The mutations in the patient's alleles were identified as a nonsense mutation (R59op) in exon 3 and a missense mutation (C134R) in exon 5. These mutations were confirmed by sequence determination of cloned PCR-amplified exons 3 and 5 from the patient. Allele specific oligonucleotide (ASO) hybridizations of amplified exons 3 and 5 showed the Mendelian inheritance of both mutations. Site-directed mutagenesis was used to generate an expression plasmid for the C134R mutation, and the mutant enzyme was expressed in bacteria. Assays of partially purified enzyme preparations showed that this missense mutation results in an apparently unstable enzyme that retains partial activity. This is the first evidence for a partially active aldolase B from an HFI individual with an identified mutation, and supports the hypothesis that adequate gluconeogenesis/glycolysis is maintained in HFI patients by the presence of partially active enzymes.     

Primary cell culture of esophageal cancer as an indicator of biological malignancy

The predictability of the monolayer culture patterning of primary cell culture as an indicator of biological malignancy was described. The prognosis of patients whose cancer cells could grow in monolayer epithelial pattern were significantly lower than that of the "no tumor growth" group. Multivariate analysis indicated that monolayer culture status best correlated with a mortality rate nearly equivalent to the number of lymph node metastasis, and Akaike's information criterion revealed that monolayer epithelial growth is a predictive factor of hematogenous recurrence. The relation of oncogenes and suppressor genes to cell culture was also described. Monolayer epithelial growth may be indicative of such general characteristics as adhesion, motility, invasion and reproduction of cancer cells.     

Surgical management of late esophageal perforation

A simple and rapid high-performance capillary electrophoresis (HPCE) method for the determination of 2-mercaptopyridine-1-oxide (pyrithione) was developed. After addition of ethylenediaminetetraacetic acid (EDTA), pyrithione was determined in the form of the free anion using 50 mM borate (pH 9.2) as background electrolyte and was detected at 244 nm with a limit of detection (LOD) of 0.636 ppm (S/N = 3). The method was used to check the purity of pyrithione preparations and for the determination of pyrithione in shampoo.     

Endoscopic therapy of esophageal cancer

In the management of esophageal cancer, endoscopy has evolved from a tool used to provide biopsy confirmation of suspected tumor to an integral part of the staging and ongoing treatment of patients. Endoscopic ultrasound is currently the most accurate means for T and N staging. Improved endoscopic techniques like dye staining and aggressive biopsy protocols can identify very early stage tumors in high-risk groups and allow curative surgery. Patients with early-stage tumors who are not surgical candidates can also be treated with endoscopic mucosectomy, photodynamic therapy, or Nd:YAG laser and still have a chance of long-term cure. Palliation of advanced tumors remains the major role of endoscopy in patients with esophageal cancer. A variety of techniques have proven effective over the years, including dilatation, laser, and rigid prostheses. Newer developments like bipolar probes, injection therapy, photodynamic therapy, and brachytherapy offer potential applications. The development and continuing improvements in both coated and uncoated expandable metal stents have been perhaps the greatest recent advance in endoscopic palliation of malignant dysphagia and esophagorespiratory fistulas. With the increasing array of endoscopic treatments and palliative techniques, emphasis must be placed on considering functional status; tumor characteristics like stage, location, and shape; patient wishes; and local expertise in tailoring treatment plans for each situation.     

The etiopathogenesis of esophageal cancer

Cancer of the oesophagus is a challenging clinical problem. Overall survival is poor, but patients who present early are eminently curable. Most cancers of the middle and upper oesophagus are squamous cell carcinoma. Adenocarcinoma is the most common cancer of the third of the oesophagus; this is not surprising when the usual distribution of Barrett's mucosa is considered. The geographical variation in the prevalence of oesophagus cancer is important. In most parts of the world, alcohol consumption and tobacco usage are the principal risk factors. Other risk factors have been identified in "the high-risk areas": a diet high in nitrosamines, deficient in trace elements, in vitamins (C.A, E) and the hereditary conditions like: Barrett's oesophagus, achalasia, caustic strictures.     

食管癌全程三维适形放疗后程加速超分割的疗效观察

Objective:The aim of the study was to evaluate the therapeutic effect and safety of whole-course three-dimen-sional conformal radiotherapy (3DCRT) combined with late-course accelerated hyperfractionated radiotherapy (LCAFR) on patients with esophageal carcinoma.Methods:one hundred and one patients with esophageal carcinoma were divided into two groups.Observing group (49 cases) were treated by whole-course 3DCRT.Patients in control group (52 cases) were treated by conventional radiotherapy.Clinical efficiencies and radiation toxicities were compared between two groups.Re-sults:The side effects including radiation esophagitis (63.2%) and tracheitis (49.0%) decreased in observing group,but there was no significant difference between two groups (69.2% and 55.7% in controls).The 1-,2- and 3-year tumor local control rates and overall survival rates in the observing group were significantly improved compared with the control group,being respectively 87.8%,75.5%,63.3% vs 71.2%,55.8%,42.3% and 85.7%,71.4%,46.7% vs 69.2%,51.9%,26.9% (all P < 0.05).Conclusion:The therapeutic effect of whole-course 3DCRT combined with LCAFR for esophageal carcinomas is superior to conventional radiotherapy.     

Pre-operative chemotherapy and radiotherapy in breast cancer

Primary systemic treatment of breast cancer with cytotoxics yields a high response rate and allows conservative surgical procedures in bulky tumours. In order to maximise local control of disease, two innovations were introduced in a pilot study. The first was to identify the good responders after three cycles of chemotherapy and to treat them with three additional cycles. The second was to also give this group of patients a full dose of radiotherapy before surgery with the aim of verifying the rate of pathological complete remissions in view of a possible treatment of breast primary with chemoradiotherapy only. Patients were treated with doxorubicin 60 mg/m2 and cyclophosphamide, 600 mg/m2 both intravenously on day 1, every 21 days for three courses. Partial or complete responders received three more courses followed by radiotherapy (50 Gy plus a 10 Gy boost). The others underwent immediate surgery. A total of 32 patients (median age, 50 years; range 28-69 years); performance status, 0-1; T2 22, T3 8, T4 2) were enrolled and were evaluable for response and side-effects. 9 patients had only three cycles of chemotherapy due to absence of response and 23 patients had six cycles of chemotherapy. Overall, 7 patients had a complete remission, 16 a partial remission and 9 had stable disease, for an overall response rate of 72% (95% confidence interval 53-86%). In the group of patients that completed the programme, two complete pathological remissions were observed and 5 patients had only microfoci of tumour. No toxic death or grade III-IV toxicities were observed. Mild or moderate side-effects included mucositis, nausea/vomiting and leucopenia. In conclusion, our results indicate that the addition of radiotherapy to pre-operative chemotherapy did not significantly enhance the incidence of pathological complete remissions. New primary treatment approaches should be explored in this subset of patients in order to improve outcome.