Effect of preoperative chemoradiotherapy on outcome of patients with locally advanced esophagogastric junction adenocarcinoma-a pilot study.

BACKGROUND: To date, few studies of preoperative chemotherapy or chemoradiotherapy (crt) in gastroesophageal junction (gej) cancer have been statistically powered; indeed, gej tumours have thus far been grouped with esophageal or gastric cancer in phase iii trials, thereby generating conflicting results. METHODS: We studied 41 patients affected by locally advanced Siewert type i and ii gej adenocarcinoma who were treated with a neoadjuvant crt regimen [folfox4 (leucovorin-5-fluorouracil-oxaliplatin) for 4 cycles, and concurrent computed tomography-based three-dimensional conformal radiotherapy delivered using 5 daily fractions of 1.8 Gy per week for a total dose of 45 Gy], followed by surgery. Completeness of tumour resection (performed approximately 6 weeks after completion of crt), clinical and pathologic response rates, and safety and outcome of the treatment were the main endpoints of the study. RESULTS: All 41 patients completed preoperative treatment. Combined therapy was well tolerated, with no treatment-related deaths. Dose reduction was necessary in 8 patients (19.5%). After crt, 78% of the patients showed a partial clinical response, 17% were stable, and 5% experienced disease progression. Pathology examination of surgical specimens demonstrated a 10% complete response rate. The median and mean survival times were 26 and 36 months respectively (95% confidence interval: 14 to 37 months and 30 to 41 months respectively). On multivariate analysis, TNM staging and clinical response were demonstrated to be the only independent variables related to long-term survival. CONCLUSIONS: In our experience, preoperative chemoradiotherapy with folfox4 is feasible in locally advanced gej adenocarcinoma, but shows mild efficacy, as suggested by the low rate of pathologic complete response.

Moderate alcohol consumption predicts long-term mortality in elderly subjects with chronic heart failure.

OBJECTIVE: Moderate alcohol consumption is related to a reduction of mortality. However, this phenomenon is not well established in the elderly, especially in the presence of chronic heart failure (CHF). The aim of the study was to verify the effect of moderate alcohol consumption on 12-year mortality in elderly community-dwelling with and without CHF. SETTINGS: community-dwelling from 5 regions of Italy. PARTICIPANTS: A cohort of 1332 subjects aged 65 and older. MEASUREMENT: Mortality after 12-year follow-up in elderly subjects (≥65 years old) with and without CHF was studied. Moderate alcohol consumption was considered ≤250 ml/day (drinkers). RESULTS: In the absence of CHF (n=947), mortality was 42.2% in drinkers vs. 53.7% in non-drinker elderly subjects (p=0.021). In contrast, in the presence of CHF (n=117), mortality was 86.5% in drinkers vs. 69.7% in non-drinker elderly subjects (p=0.004). Accordingly, Cox regression analysis shows that a moderate alcohol consumption is protective of mortality in the absence (HR=0.79; CI 95% 0.66-0.95; p<0.01) but it is predictive of mortality in the presence of CHF (HR=1.29; CI 95% 1.05-1.97; p<0.05). CONCLUSIONS: Our data demonstrates that moderate alcohol consumption is associated with an increased long-term mortality risk in the elderly in the presence of CHF.

Complete response to preoperative chemoradiation and survival in esophageal cancer: a pooled analysis of three single-institution phase II trials.

This pooled analysis was performed using individual patient data from three phase II trials that included on the whole 113 esophageal cancer treated preoperatively with chemoradiotherapy (CRT), in order to analyze the efficacy and survival outcomes according to the achievement of the pathologic complete response (pCR). Thirty-nine patients were treated with 5-fluorouracil/cisplatin and RT (40 Gy), 33 patients received paclitaxel/cisplatin weekly during weeks 1-6 with and RT (46 Gy), 41 patients were treated with induction bio-chemotherapy with cetuximab and FOLFOX-4 followed by concomitant cetuximab and RT of 50.4 Gy. One hundred and two out of 113 resected patients were included in the survival analysis. The median overall survival (OS) time for the whole population was 21.5 months. The 12, 24, and 36 months OS rates were 85.4, 45.2, and 33%, respectively. The difference in survival probability between patients with pCR and patients with partial response or stable disease after treatment was significant (P= 0.0002, hazard ratios = 0.21, 95% CI 0.18-0.60). On multivariate analysis, the pathologic response and histology were the only covariates independently associated with OS (P= 0.0157 and P= 0.0212, respectively). In our series, complete responder patients had a significant longer survival probability after treatment when compared to patients with partial response or stable disease.

A multicenter phase II study of induction chemotherapy with FOLFOX-4 and cetuximab followed by radiation and cetuximab in locally advanced oesophageal cancer.

BACKGROUND: Preoperative chemoradiotherapy (CRT) improves the survival of patients with oesophageal cancer when compared with surgery alone. METHODS: We conducted a phase II, multicenter trial of FOLFOX-4 and cetuximab in patients with locally advanced oesophageal cancer (LAEC) followed by daily radiotherapy (180 cGy fractions to 5040 cGy) with concurrent weekly cetuximab. Cytokines levels potentially related to cetuximab efficacy were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, at week 8 and at week 17. Primary end point was complete pathological response rate (pCR). RESULTS: In all, 41 patients were enroled. Among 30 patients who underwent surgery, a pCR was observed in 8 patients corresponding to a rate of 27%. The most frequent grade 3/4 toxicity was skin (30%) and neutropenia (30%). The 36-month survival rates were 85 and 52% in patients with pathological CR or PR vs 38 and 33% in patients with SD or PD. CONCLUSIONS: Incorporating cetuximab into a preoperative regimen for LAEC is feasible; no correlation between cytokines changes and patient outcome was observed. Positron emission tomography/computed tomography study even if influenced by the small number of patients appears to be able to predict patients outcome both as early and late metabolic response.

PUFA for human health: diet or supplementation?

Large doses of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are used to treat several diseases including hypertriglyceridemia in humans. Modest levels of EPA and DHA may be obtained from food, particularly from fatty fish. This review presents the literature examining the differences between omega-3 fatty acid dietary supplementation and prescribed omega-3-acid ethyl esters (P-OM3). Reports published between 1995 and 2007 containing sources, recommended intake, and differences in the various formulations of omega-3 fatty acids were sought in PubMed and the Food and Drug Administration (FDA) Websites. However, lack of head-to-head clinical trials using both P-OM3 and dietary-supplement omega-3 fatty acids is the greatest limitation of this review. Although many kinds of omega-3 fatty acid dietary supplements are available, the efficacy, quality, and safety of these products are questionable because they are beyond any pharmaceutical control. Thus, P-OM3 is the only FDA approved omega-3 fatty acid product which is available in the United States as an adjunct to diet to improve human health.

Lithiasis and risk factors.

Nephrolithiasis is a worldwide disease with high clinical and economic costs. The increasing incidence in industrialized countries seems to be related to several risk factors, which are partly inherited and partly acquired. Although risk factors in urolithiasis are still under discussion, their identification would provide a notable gain for the patient in terms of stone episodes, and for the health service in terms of costs. This article presents an easy classification of risk factors based on clinical background.

Neo-adjuvant and adjuvant chemotherapy of gastric cancer.

Gastric cancer is still a major health problem and a leading cause of cancer mortality despite a worldwide decline in incidence. Surgery is the primary curative treatment of locoregional gastric cancer. In Western countries, however, at the time of resection, most patients are expected to have regional lymph node involvement with poor prognostic implications. To improve these results, different trials have been carried out in the adjuvant or neo-adjuvant setting. Many phase III trials of adjuvant therapy have been conducted; however, postoperative treatment modalities have not proven to be superior to postsurgical observation alone. Therefore, at present the routine use of adjuvant therapy should be regarded as an investigational approach. Improved clinical trial designs with standardized surgical techniques and the incorporation of newer active drugs are needed. On the contrary, neo-adjuvant chemotherapy has shown promising results as suggested by the final results of UK Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial.

Chemoradiotherapy as adjuvant treatment of gastric cancer.

Historically, radiotherapy has been occasionally used in the treatment of gastric cancer. More recently, the results of INT-0116 trial have shown an improvement of disease-free and overall survival by chemoradiation with a significant impact on the management of this tumor. Based on these data, there has been an increasing interest in radiotherapy and its association with chemotherapy for patients with locoregional disease as a part of an adjuvant treatment after surgery in high-risk patients. However, many questions remain to evaluate; first of all the toxicity of this approach and its efficacy after adequate surgery.

Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer.

The recent successful development of monoclonal antibodies that target key components of biological pathways has expanded the armamentarium of treatment options for patients with colorectal cancer (CRC). In particular, the epidermal growth factor receptor (EGFR), a tyrosine kinase growth factor receptor involved in CRC development and progression, is exploited by the newest monoclonal antibody that is available for use in CRC patients. Cetuximab, the first chimeric monoclonal antibody, which has been generated against the EGFR, is currently registered in USA, Europe and worldwide, in combination with irinotecan in the treatment of metastatic CRC patients who have progressed on irinotecan containing chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of concomitant chemotherapy. Furthermore, a series of phase III clinical trials are currently evaluating the combination of cetuximab with standard chemotherapy regimens in the first-line treatment chemotherapy-naïve patients with metastatic CRC.

Adjuvant chemotherapy with epirubicin, leucovorin, 5-fluorouracil and etoposide regimen in resected gastric cancer patients: a randomized phase III trial by the Gruppo Oncologico Italia Meridionale (GOIM 9602 Study).

BACKGROUND: This randomized, multicenter, phase III trial evaluated the efficacy and safety of the combination of epirubicin, leucovorin, 5-fluorouracil and etoposide (ELFE regimen) as adjuvant therapy for radically resected gastric cancer patients. PATIENTS AND METHODS: From June 1996 to June 2001, 228 stage IB-IIIB gastric cancer patients were enrolled. All patients received a total or subtotal gastrectomy with at least a D1 lymphoadenectomy and were randomly assigned to receive surgery alone or surgery followed by chemotherapy. RESULTS: A total number of 630 cycles was delivered with a median number of 5. With a median follow-up of 60 months, the 5-year overall survival (OS) was 48% in the treatment arm and 43.5% in the control arm [hazard ratio (HR) 0.91; 95% confidence interval (CI) 0.69-1.21; P = 0.610); the 5-year disease-free survival (DFS) was 44% in the treatment arm and 39% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.305). In node-positive patients, the 5-year OS was 41% in the treatment arm and 34% in the control arm (HR 0.84; 95% CI 0.69-1.01; P = 0.068), while the 5-year DFS was 39% in the treatment arm and 31% in the control arm (HR 0.88; 95% CI 0.78-0.91; P = 0.051). The most common grade 3-4 toxic effects according to World Health Organization criteria were hematological and gastrointestinal. CONCLUSIONS: In radically resected gastric cancer patients, adjuvant chemotherapy with ELFE regimen does not improve OS over surgery alone.

Weekly docetaxel and capecitabine is not effective in the treatment of advanced gastric cancer: a phase II study.

BACKGROUND: Capecitabine and docetaxel have demonstrated preclinical antitumor synergy and activity in advanced gastric cancer. We assessed the clinical activity and the toxicity of weekly docetaxel in combination with capecitabine in untreated patients with advanced gastric cancer. PATIENTS AND METHODS: A total of 38 patients were treated with docetaxel 36 mg/m2 on days 1, 8, and 15 i.v., plus capecitabine, 625 mg/m2 bid per os on days 5 to 18 repeated every 4 weeks. RESULTS: All patients were assessable for response to treatment and for toxicity. Major responses were observed in eight patients (21%), with three patients achieving a CR (7.8%) and five showing a PR (13%). The median time to progression was 5.4 months and the overall survival was 7.7 months. The safety profile of this schedule was acceptable with a low rate of myelossuppression, diarrhoea and hand-foot syndrome. CONCLUSIONS: The combination of docetaxel and capecitabine at the doses and schedule investigated in this study is safe, but does not show significant activity in untreated patients with advanced gastric cancer.

Feasibility of primary inguinal hernia repair with a new mesh.

BACKGROUND: The purpose of this study was to evaluate the feasibility of primary inguinal repair with open tension-free and sutureless technique using a new polypropylene "patch and plug system" (Prolene 3D patch), and the quality of the treatment in terms of reduction of postoperative discomfort. METHODS: Fifty-six consecutive patients, mean age 54.5+/-11.2 years, with primary unilateral uncomplicated inguinal hernia, were treated in a day-surgery setting. Collected data included: pain scores at 24 hours, 72 hours, and 7, 15, and 30 days after operation, analgesic medications, return to work and to heavy house and/or moderate sporting activities, and quality of life as measured by Short Form 36 health survey questionnaire (SF-36) before the operation and at 6 months follow-up. RESULTS: Postoperative pain was low: the mean visual analog scale (VAS) scores were 2.8 at 24 h, 1.8 at 72 h, and 0.9, 0.3, and 0.04 at 7, 15, and 30 days, respectively. Analgesic drugs were not used by 66.0% (n=37) of the patients. The mean global time to return to work and to heavy activities was 9.9+/-4.6 and 14.6+/-7.0, days, respectively. Patient satisfaction showed a significant improvement in all SF-36 domain scores at 6 months follow-up (P<0.001). There were no major complications, recurrences, or mortality. CONCLUSIONS: The new mesh seems to satisfy all requirements of a feasible, reliable, and effective device for repairing primary inguinal hernia with high patient comfort.

Frailty predicts long-term mortality in elderly subjects with chronic heart failure.

BACKGROUND: The elderly are characterized by a high prevalence of chronic heart failure (CHF) and frailty, which is a complex interaction of physical, psychological and social impairment. This study aimed to examine the predictive role of frailty on long-term mortality in elderly subjects with CHF. MATERIALS AND METHODS: The study assessed long-term mortality after 12-year follow up in 120 subjects with CHF and 1139 subjects without CHF, selected in 1992, from a random sample of the elderly population in the Campania region of Italy. Frailty was assessed according to a 'Frailty Staging System'. RESULTS: Subjects with CHF were prevalently female (60%) and older than 75 years (mean 75.9 +/- 6.7); subjects without CHF were prevalently female (56.4%) and younger than 75 years (mean 74.0 +/- 6.3). In subjects with and without CHF stratified into classes of frailty there was a statistically significant increase in age, comorbidity, disability and low social support, and a decrease in MMSE score. Moreover, death progressively increased more with frailty in subjects (70.0% to 94.4%, P < 0.03) than in those without (43.8.% to 88.3%, P < 0.0001) CHF. The Kaplan-Meier analysis shows that at 9 years the probability of survival progressively decreased as frailty increased (45.5% to 0%) in subjects with CHF and from 62.8% to 25.9% in subjects without CHF. The Cox regression analysis indicated that frailty is predictive of mortality in the multivariate model adjusted for several variables including sex and age in subjects with and without CHF. Moreover, the analysis showed that frailty is more predictive of mortality in elderly subjects with CHF when it was analyzed either as continuous (1.48 vs. 1.36) or as a dummy (3 vs. 1 = 1.62 vs. 1.24) variable. CONCLUSIONS: Thus mortality among elderly subjects with or without CHF increases with frailty. Moreover, frailty is more predictive of long-term mortality in elderly subjects with than in those without CHF. Hence, frailty represents a new independent variable for predicting long-term mortality in elderly subjects with CHF.

A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients.

The aim of the study was to assess the toxicity and the clinical activity of biweekly oxaliplatin in combination with infusional 5-fluorouracil (5-FU) and folinic acid (FA) administered every 2 weeks (FOLFOX-4 regimen) in patients with advanced gastric cancer (AGC). A total of 61 previously untreated AGC patients were treated with oxaliplatin 85 mg m(-2) on day 1, FA 200 mg m(-2) as a 2 h infusion followed by bolus 5-FU 400 mg m(-2) and a 22 h infusion of 5-FU 600 mg m(-2), repeated for 2 consecutive days every 2 weeks. All patients were assessable for toxicity and response to treatment. Four (7%) complete responses and 19 partial responses were observed (overall response rate, 38%). Stable disease was observed in 22 (36%) patients, with progressive disease in the other six (10%) patients. Median time to progression (TTP) and median overall survival (OS) were 7.1 and 11.2 months, respectively. National Cancer Institute Common Toxicity Criteria grade 3 and 4 haematologic toxicities were neutropenia, anaemia and thrombocytopenia in 36, 10 and 5% of the patients, respectively. Grade 3 peripheral neuropathy was recorded in three (5%) patients. FOLFOX-4 is an active and well-tolerated chemotherapy. Response rate (RR), TTP and OS were comparable with those of other oxaliplatin-based regimens, suggesting a role for this combination in gastric cancer.

Tandem action of exercise training and food restriction completely preserves ischemic preconditioning in the aging heart.

Ischemic preconditioning (IP) has been proposed as an endogenous form of protection against ischemia reperfusion injury. IP, however, does not prevent post-ischemic dysfunction in the aging heart but may be partially corrected by exercise training and food restriction. We investigated the role of exercise training combined with food restriction on restoring IP in the aging heart. Effects of IP against ischemia-reperfusion injury in isolated hearts from adult (A, 6 months old), sedentary 'ad libitum' fed (SL), trained ad libitum fed (TL), sedentary food-restricted (SR), trained- and food-restricted senescent rats (TR) (24 months old) were investigated. Norepinephrine release in coronary effluent was determined by high performance liquid cromatography. IP significantly improved final recovery of percent developed pressure in hearts from A (p<0.01) but not in those from SL (p=NS) vs unconditioned controls. Developed pressure recovery was partial in hearts from TL and SR (64.3 and 67.3%, respectively; p<0.05 vs controls) but it was total in those from TR (82.3%, p=NS vs A; p<0.05 vs hearts from TL and SR). Similarly, IP determined a similar increase of norepinephrine release in A (p<0.001) and in TR (p<0.001, p=NS vs adult). IP was abolished by depletion of myocardial norepinephrine stores by reserpine in all groups. Thus, IP reduces post-ischemic dysfunction in A but not in SL. Moreover, IP was preserved partially in TR and SR and totally in TR. Complete IP maybe due to full restoration of norepinephrine release in response to IP stimulus.

Myxopapillary ependymoma of the ischioanal fossa.

Ependymomas outside the confines of the cranium and spinal cord are rare. Direct extension into the soft tissues of the sacrococcygeal area may occur from a primary ependymoma of the spinal cord, cauda equina or filum terminale. Alternatively they may occur as a primary pre-sacral, pelvic and abdominal tumour, or as a primary tumour of the skin and subcutaneous tissue of the sacrococcygeal area without any demonstrable connection with the spinal cord. The Authors report a case of myxopapillary ependymoma of the ischioanal fossa, demonstrated by MRI. To our knowledge, our case is the first lesion reported at this site.

True tail dorsal-lumbar: malformation or ancestral remaining?

The case of a healthy newborn presenting a dorsal-lumbar cutaneous appendage is reported. The appendage was excised by ligature. This appendage was not associated with dysraphism or other malformations. It was analysed histologically and then defined as a so called true tail. Although it was been expressed a lot of hypotheses, the etiology of this finding remains disputed. The embryology of malformation and its non identification between known-syndromes is showed. The difference between true tails and not-true tails is discussed. The conclusion is drawn that for its clinical and histological aspect this malformation may be included in true tails.

Hemodynamic and pulmonary changes during open, carbon dioxide pneumoperitoneum and abdominal wall-lifting cholecystectomy. A prospective, randomized study.

BACKGROUND: Carbon dioxide (CO2) pneumoperitoneum effects are still controversial. The aim of this study was to investigate cardiopulmonary changes in patients subjected to different surgical procedures for cholecystectomy. METHODS: In this study, 15 patients were assigned randomly to three groups according to the surgical procedure to be used: open cholecystectomy (OC), CO2 pneumoperitoneum cholecystectomy (PP), and laparoscopic gasless cholecystectomy (abdominal wall lifting [AWL]), respectively. A pulmonary artery catheter was used for hemodynamic monitoring in all patients. A subcutaneous multiplanar device (Laparo Tenser) was used for abdominal wall lifting. To avoid misinterpretation of results, conventional anesthesia was performed with all parameters, and the position of the patients held fixed throughout surgery. The following parameters were analyzed: mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP), systemic vascular resistances index (SVRI), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistances index (PVRI), peak inspiratory pressure (PIP), end-tidal CO2 pressure (ETCO)2, CO2 arterial pressure (PaCO2), and arterial pH. RESULTS: All the operations were completed successfully. The Laparo Tenser allowed good exposition of the surgical field. A slight impairment of the cardiopulmonary functions, with reduction of SVRI, MAP, and CI and elevation of pulmonary pressures and vascular resistance, followed induction of anesthesia. However, these effects tended to normalize in the OC and AWL groups over time. In contrast, CO2 insufflation produced a complex hemodynamic and pulmonary syndrome resulting in increased right- and left side filling pressures, significant cardiac index reduction, derangement of the respiratory mechanics, and respiratory acidosis. All of these effects normalized after desufflation. CONCLUSIONS: Cardiopulmonary adverse effects of general anesthesia were significant but transitory and normalized during surgery. Carbon dioxide pneumoperitoneum caused a significant impairment in cardiopulmonary functions. In high-risk patients, gasless laparoscopy may be preferred for reliability and absence of cardiopulmonary alterations.

[Ectopic thyroid: report of a case]. / Tiroide ectopica: a proposito di un caso clinico.

The development of thyroid tissue can occur in any moment of the migration of the thyroid along the thyroglossal duct from the tongue, resulting in lingual (at tongue base), sublingual (below the tongue), prelaryngeal (in front of the larynx), and substernal (in the mediastinum) ectopy. Thyroglossal duct cyst is the most common type of clinical abnormality related to thyroid ectopy. Surgical removal of such ectopic tissue is justified since some Authors describe thyroid cancer arising from aberrant thyroid tissue. The Authors report a case of thyroid ectopy in a patient who underwent 20 years before a left thyroid resection with isthmectomy; during the operation the surgeon described a hypertrophic pyramidal lobe which was left in situ and the patients did not receive any hormone suppressing therapy.