Is short-course radiotherapy and total neoadjuvant therapy the new standard of care in locally advanced rectal cancer? A sensitivity analysis of the RAPIDO clinical trial.

BACKGROUND: The results of the RAPIDO trial have been accepted as evidence in favour of short-course radiotherapy (SC-RT) followed by chemotherapy before total mesorectal excision in high-risk locally advanced rectal cancer. A noteworthy concern is that the RAPIDO trial did not ensure that all patients in the control arm received adjuvant chemotherapy. This may bias statistical estimates in favour of the experimental arm if adjuvant chemotherapy is active in rectal cancer. Moreover, the 5-year update revealed an increase in the risk of local relapse in the experimental arm. MATERIALS AND METHODS: We carried out sensitivity analyses to determine how plausible effects of adjuvant chemotherapy, adjusted by the proportion of patients in the standard arm receiving adjuvant treatment, would have influenced the observed treatment effect estimate of the RAPIDO trial. The most plausible values for the benefit of adjuvant chemotherapy were determined by Bayesian re-analysis of a prior meta-analysis. RESULTS: The meta-analysis suggested that oxaliplatin/fluorouracil-based adjuvant chemotherapy may improve disease-free survival (DFS) in rectal cancer although the signal is weak [hazard ratio (HR) 0.84, 95% credible interval, 0.57-1.15]; probability of benefit (HR <1) was 91.2%. In the sensitivity analysis, the HR for disease-related treatment failure would remain <1, thus favouring total neoadjuvant therapy (TNT), on most occasions, but the null hypothesis would not have been rejected in various credible settings. For the RAPIDO data to be consistent with the null effect, a moderate benefit of adjuvant chemotherapy (HR for DFS between 0.75 and 0.80) and 70%-80% of exposed participants would suffice. CONCLUSION: The decision to make adjuvant chemotherapy optional in the standard arm may have biased the results in favour of the experimental arm, in a scenario in which TNT does not offset the increase in local recurrences after SC-RT.

Strategies to develop radiomics and machine learning models for lung cancer stage and histology prediction using small data samples.

Predictive models based on radiomics and machine-learning (ML) need large and annotated datasets for training, often difficult to collect. We designed an operative pipeline for model training to exploit data already available to the scientific community. The aim of this work was to explore the capability of radiomic features in predicting tumor histology and stage in patients with non-small cell lung cancer (NSCLC). We analyzed the radiotherapy planning thoracic CT scans of a proprietary sample of 47 subjects (L-RT) and integrated this dataset with a publicly available set of 130 patients from the MAASTRO NSCLC collection (Lung1). We implemented intra- and inter-sample cross-validation strategies (CV) for evaluating the ML predictive model performances with not so large datasets. We carried out two classification tasks: histology classification (3 classes) and overall stage classification (two classes: stage I and II). In the first task, the best performance was obtained by a Random Forest classifier, once the analysis has been restricted to stage I and II tumors of the Lung1 and L-RT merged dataset (AUC = 0.72 ± 0.11). For the overall stage classification, the best results were obtained when training on Lung1 and testing of L-RT dataset (AUC = 0.72 ± 0.04 for Random Forest and AUC = 0.84 ± 0.03 for linear-kernel Support Vector Machine). According to the classification task to be accomplished and to the heterogeneity of the available dataset(s), different CV strategies have to be explored and compared to make a robust assessment of the potential of a predictive model based on radiomics and ML.

Randomized placebo-controlled phase II trial of high-dose melatonin mucoadhesive oral gel for the prevention and treatment of oral mucositis in patients with head and neck cancer undergoing radiation therapy concurrent with systemic treatment.

PURPOSE: The objective of this trial was to evaluate the safety and efficacy of melatonin oral gel mouthwashes in the prevention and treatment of oral mucositis (OM) in patients treated with concurrent radiation and systemic treatment for head and neck cancer. METHODS: Randomized, phase II, double-blind, placebo-controlled trial (1:1 ratio) of 3% melatonin oral gel mouthwashes vs. placebo, during IMRT (total dose ≥ 66 Gy) plus concurrent Q3W cisplatin or cetuximab. Primary endpoint: grade 3-4 OM or Severe Oral Mucositis (SOM) incidence by RTOG, NCI, and a composite RTOG-NCI scales. Secondary endpoints: SOM duration and grade 2-4 OM or Ulcerative Oral Mucositis (UOM) incidence and duration. RESULTS: Eighty-four patients were included in the study. Concurrent systemic treatments were cisplatin (n = 54; 64%) or cetuximab (n = 30; 36%). Compared with the placebo arm, RTOG-defined SOM incidence was numerically lower in the 3% melatonin oral gel arm (53 vs. 64%, P = 0.36). In patients treated with cisplatin, assessed by the RTOG-NCI composite scale, both SOM incidence (44 vs. 78%; P = 0.02) and median SOM duration (0 vs. 22 days; P = 0.022) were significantly reduced in the melatonin arm. Median UOM duration assessed by the RTOG-NCI scale was also significantly shorter in the melatonin arm (49 vs. 73 days; P = 0.014). Rate of adverse events and overall response rate were similar between the two arms. CONCLUSIONS: Treatment with melatonin oral gel showed a consistent trend to lower incidence and shorter SOM duration and shorter duration of UOM. These results warrant further investigation in phase III clinical trial.

Increased survival time or better quality of life? Trade-off between benefits and adverse events in the systemic treatment of cancer.

INTRODUCTION: Primary objective of the study was to assess the relative weighting between benefit in survival time (SV), benefit in quality of life (QoL) and willingness to experience adverse events (AEs), in patient preferences for chemotherapy treatment. MATERIALS AND METHODS: We included cancer patients with current or past systemic treatment of cancer (STC) as well as physicians placed as hypothetical patients. Participants filled a choice-based conjoint analysis questionnaire with 19 choices among three STC scenarios with variable amounts of benefit in SV or QoL and different types AEs. RESULTS: One hundred patients (50 on curative and 50 on palliative intention treatment) and 114 physicians (61 oncologists and 53 non-oncologists) were included and asked about their preferred chemotherapy treatment. The relative weighting (sum 100%) of SV-QoL-AEs for making the choice in the 100 patients was SV35%-CV33%-AEs31% what was not significantly different from a random distribution (Goodness of fit Chi square P = 0.91) just as it was not for both subgroups, palliative (SV37%-QoL29%-AEs34%; GoF Chi square P = 0.55) and curative (SV34%-QoL36%-AEs30%; GoF Chi square P = 0.73) treatment. The observed distribution in the group of 114 physicians (SV46%-QoL31%-AEs23%) was significantly different from a random distribution (GoF Chi square P = 0.018) just as it was for both subgroups, medical oncologists (SV48%-QoL29%-AEs23%; GoF Chi square P = 0.006) and non-medical oncologists (SV44%-QoL33%-AEs23%; GoF Chi square P = 0.04). CONCLUSIONS: The three attributes (SV, QoL, and AEs) are considered in the same way by cancer patients to make choices on their STC. On the contrary, when placed as hypothetical patients, physicians prefer for themselves those treatments that provide more SV.

Moderate hypofractionated helical tomotherapy for prostate cancer in a cohort of older patients: a mono-institutional report of toxicity and clinical outcomes.

PURPOSE OR OBJECTIVE: To evaluate toxicity and outcomes of moderately hypofractionated helical tomotherapy for the curative treatment of a cohort of patients aged ≥ 75 years with localized prostate cancer (PC). MATERIALS AND METHODS: From January 2013 to February 2017, 95 patients with median age 77 years (range 75-88) were treated for PC. 39% were low risk, 33% intermediate risk (IR), 28% high risk (HR). Median iPSA was 9.42 ng/ml (1.6-107). Androgen deprivation was prescribed according to NCCN recommendations. All patients received 70 Gy in 28 fractions to the prostate; 61.6 Gy were delivered to the seminal vesicles for IR; whole pelvis irradiation with a total dose of 50.4 Gy was added in the HR group. Toxicity evaluation was based on CTCAE V4.0 criteria, biochemical failure was defined following Phoenix criteria. Quality of Life was assessed with the EPIC-26 index. Overall survival and biochemical failure-free survival were analysed with Kaplan-Meier method. RESULTS: With a median follow-up of 36 months (range 24-73), acute and late toxicity were acceptable. No correlation between toxicity patterns and clinical or dosimetric parameter was registered. EPIC-26 showed a negligible difference in urinary and bowel function post-treatment that did not reach statistical significance. The 2- and 3-years OS were 93% and 87% with cancer specific survival of 97.9% and 96.2%. CONCLUSION: Moderate hypofractionated RT reported excellent outcomes in our cohort of older patients. Shorter schedules may be proposed regardless of chronological age facilitating the treatment compliance in the older population.

Role of ghrelin isoforms in the mitigation of hepatic inflammation, mitochondrial dysfunction, and endoplasmic reticulum stress after bariatric surgery in rats.

BACKGROUND/OBJECTIVES: Bariatric surgery improves nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), but the underlying mechanisms remain elusive. We evaluated the potential role of ghrelin isoforms in the amelioration of hepatic inflammation after sleeve gastrectomy and Roux-en-Y gastric bypass (RYGB). SUBJECTS/METHODS: Plasma ghrelin isoforms were measured in male Wistar rats (n = 129) subjected to surgical (sham operation, sleeve gastrectomy, or RYGB) or dietary interventions [fed ad libitum a normal (ND) or a high-fat diet (HFD) or pair-fed diet]. The effect of acylated and desacyl ghrelin on markers of inflammation, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in primary rat hepatocytes under palmitate-induced lipotoxic conditions was assessed. RESULTS: Plasma desacyl ghrelin was decreased after sleeve gastrectomy and RYGB, whereas the acylated/desacyl ghrelin ratio was augmented. Both surgeries diminished obesity-associated hepatic steatosis, CD68+- and apoptotic cells, proinflammatory JNK activation, and Crp, Tnf, and Il6 transcripts. Moreover, a postsurgical amelioration in the mitochondrial DNA content, oxidative phosphorylation (OXPHOS) complexes I and II, and ER stress markers was observed. Specifically, following bariatric surgery GRP78, spliced XBP-1, ATF4, and CHOP levels were reduced, as were phosphorylated eIF2α. Interestingly, acylated and desacyl ghrelin inhibited steatosis and inflammation of palmitate-treated hepatocytes in parallel to an upregulation of OXPHOS complexes II, III, and V, and a downregulation of ER stress transducers IRE1α, PERK, ATF6, their downstream effectors, ATF4 and CHOP, as well as chaperone GRP78. CONCLUSIONS: Our data suggest that the increased relative acylated ghrelin levels after bariatric surgery might contribute to mitigate obesity-associated hepatic inflammation, mitochondrial dysfunction, and ER stress.

Role of aquaporin-7 in ghrelin- and GLP-1-induced improvement of pancreatic ß-cell function after sleeve gastrectomy in obese rats.

BACKGROUND/OBJECTIVES: Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues as well as for pancreatic insulin secretion. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in ß-cells, and AQP12, an aquaporin related to pancreatic damage, in the improvement of pancreatic function and steatosis after sleeve gastrectomy in diet-induced obese rats. SUBJECTS/METHODS: Male Wistar obese rats (n=125) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by sleeve-gastrectomized animals) interventions. The tissue distribution and expression of AQPs in the rat pancreas were analyzed by real-time PCR, western blotting and immunohistochemistry. The effect of ghrelin isoforms and glucagon-like peptide 1 (GLP-1) on insulin secretion, triacylglycerol (TG) accumulation and AQP expression was determined in vitro in RIN-m5F ß-cells. RESULTS: Sleeve gastrectomy reduced pancreatic ß-cell apoptosis, steatosis and insulin secretion. Lower ghrelin and higher GLP-1 concentrations were also found after bariatric surgery. Acylated and desacyl ghrelin increased TG content, whereas GLP-1 increased insulin release in RIN-m5F ß-cells. Sleeve gastrectomy was associated with an upregulation of AQP7 together with a normalization of the increased AQP12 levels in the rat pancreas. Interestingly, ghrelin and GLP-1 repressed AQP7 and AQP12 expression in RIN-m5F ß-cells. AQP7 protein was negatively correlated with intracellular lipid accumulation in acylated ghrelin-treated cells and with insulin release in GLP-1-stimulated ß-cells. CONCLUSIONS: AQP7 upregulation in ß-cells after sleeve gastrectomy contributes, in part, to the improvement of pancreatic steatosis and insulin secretion by increasing intracellular glycerol used for insulin release triggered by GLP-1 rather than for ghrelin-induced TG biosynthesis.

Dissociation of body mass index, excess weight loss and body fat percentage trajectories after 3 years of gastric bypass: relationship with metabolic outcomes.

BACKGROUND/OBJECTIVES: Body weight, body mass index (BMI) and excess weight loss (EWL) are the most frequently used measures to analyse bariatric surgery outcomes. However, these measurements do not provide accurate information on body composition (BC) with body fat (BF), importantly determining the levels of cardiometabolic risk factors. Our aim was to analyse the evolution of BC after Roux-en-Y Gastric Bypass (RYGB) and its influence on the changes of cardiometabolic risk factors in comparison to BMI and EWL. SUBJECTS/METHODS: A group of 81 obese Caucasian patients (19 males/62 females) aged 44.9±1.3 years undergoing RYGB between January 2006 and December 2011 was prospectively followed up for a period of 3 years. BC was determined by air-displacement plethysmography. Visceral adiposity, physical activity and cardiometabolic risk factors were measured. RESULTS: BF was markedly (P<0.001) reduced after the first year, increasing progressively during the second and third years after RYGB, following a different trajectory than body weight, BMI and EWL that decreased up to the second year post surgery. Markers of glucose homeostasis decreased during the first month and continued to decrease during the first year (P<0.05), remaining stabilised or slightly increased between the second and third years following RYGB. However, markers of lipid metabolism decreased (P<0.05) markedly during the first 12 months, increasing thereafter in parallel to the changes observed in BC, with the exception of high-density lipoprotein-cholesterol, which increased progressively throughout the whole period analysed. CONCLUSIONS: The adverse switch in the changes in BC between the first and the second years after RYGB may underlie the changes observed in cardiometabolic risk factors. Tracking of adiposity during the follow-up of bariatric/metabolic surgery yields clinically relevant information to better identify patients in need of increased lifestyle advice or treatment intensification.

Baseline metabolic disturbances and the twenty-five years risk of incident cancer in a Mediterranean population.

BACKGROUND AND AIMS: Obesity is predictive of metabolic syndrome (metS), type 2 diabetes, cardiovascular (CV) disease and cancer. The aim of the study is to assess the risk of incident cancer connected to obesity and metS in a Mediterranean population characterized by a high prevalence of obesity. METHODS AND RESULTS: As many as 1133 subjects were enrolled in two phases and followed for 25 years (859 subjects) or 11 years (274 subjects) and incident cancer was registered in the follow-up period. Anthropometric measures and biochemical parameters were filed at baseline and evaluated as predictors of incident cancer by measuring hazards ratios (HR) using multivariate Cox parametric hazards models. Best predictive threshold for metabolic parameters and metS criteria were recalculated by ROC analysis. Fasting Blood Glucose >5.19 mmol/L [HR = 1.58 (1.0-2.4)] and the TG/HDL ratio (log10) (Males > 0.225, Females > 0.272) [HR = 2.44 (1.3-4.4)] resulted independent predictors of survival free of cancer with a clear additive effect together with age classes [45-65 years, HR = 2.47 (1.3-4.4), 65-75 years HR = 3.80 (2.0-7.1)] and male gender [HR = 2.07 (2.3-3.1)]. CONCLUSIONS: Metabolic disturbances are predictive of cancer in a 25 years follow-up of a Mediterranean population following a traditional Mediterranean diet. The high prevalence of obesity and metS and the observed underlying condition of insulin resistance expose this population to an increased risk of cardiovascular disease and cancer despite the healthy nutritional habits.

[Body weight- independent variations in HDL-cholesterol following gastric bypass]. / Las variaciones en cholesterol-HDL tras bypass gástrico proximal son independientes de la evolución ponderal.

BACKGROUND: Bariatric surgery has multiple beneficial effects on lipid profile in patients with morbid obesity. However, these changes can be attenuated by weight regain. This retrospective study was designed to assess the effects of gastric bypass(GBP) on different lipid fractions over a 6 year follow-up. PATIENTS AND METHODS: We studied 177 patients (135 women)with morbid obesity (BMI 44.2+0.4 kg/m2) aged 42.4+0.9 years before and 3, 6, 9, 12, 24, 36, 48, 60 and 72 months after laparoscopic proximal GBP. Anthropometry, body composition measurement (Bod-Pod) and fasting blood samples were taken in all evaluations to measure total cholesterol (TC),LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides(TG), glucose and insulin. RESULTS: GPB was followed by a significant BMI reduction (nadir BMI at 18 m 28.3+0.4 kg/m2 p<0,001) and fat mass decrease(p<0,001). Maximal percentage of excess BMI lost was 84.1%and that of body fat was 87% 18 months after GBP. These numbers decreased to 65.6% and 38.3% (p<0,005 vs nadir) respectively 72 months after the operation, indicating both weight and fat mass regain. TG and LDL-C values decreased 30% with respect to preoperative levels, while HDL-C increased 97%over initial values. This HDL-C increase was progressive even over the weight regain phase. Both TC/HDL-C and TG/HDL-Cratios normalized after GBP and values were sustained over the weight regain period until the end of the study. CONCLUSIONS: These results confirm the beneficial effects of GBP on all lipid fractions, which are maintained over 6 years of follow-up. Globally, the rise in HDL-C seems to be independent of weight or fat mass changes, since it increases even over the weight regain phase, so contributing to a reduction in the prevalence of dyslipidaemia and to cardiovascular risk reduction.

Bronchoscopy in sarcoidosis: union is strength.

Sarcoidosis is a benign disease of unknown etiology that is characterized by the formation of noncaseating epithelioid cell granulomas. Although a multisystemic disease, it primarily affects the lung and the lymphatic system of the body. When a histological diagnosis is required, bronchoscopy is frequently employed because allows tissue sampling from several anatomic sources, such as airways, lung parenchyma and hilar/mediastinal nodes. Transbronchial lung biopsies (TBLB), endobronchial biopsies (EBB) and conventional transbronchial needle aspiration (cTBNA) have long been the only bronchoscopic techniques to diagnose sarcoid granulomas, until the advent of endobronchial ultrasound guided needle aspiration (EBUS-TBNA). This technique shows excellent yield in sampling mediastinal adenopathies with a higher sensitivity than the conventional technique in sarcoidosis as well. Furthermore, non controlled studies, demonstrated its diagnostic superiority than EBB and TBLB in stages I (hilar adenopathies only) and II (hilar lymph nodes and parenchymal infiltrations) thoracic sarcoidosis. In a recent study, Gupta et al., randomized 130 patients with suspected stage I and II disease to undergo EBUS-TBNA or cTBNA in conjunction with transbronchial and endobronchial biopsies. The Authors demonstrated that the yield of cTBNA added to EBB and TBLB is similar to EBUS-TBNA plus transbronchial biopsies, although ultrasound guided transbronchial needle aspiration shows the best single diagnostic efficacy. In this review article we aimed to discuss the findings by Gupta in the context of medical literature, highlighting the importance of adding nodal aspirations (with or without ultrasound guidance) with bronchial and transbronchial samples to gain the optimal sensitivity in obtaining histological confirmation. We finally pointed out the need for future studies to evaluate the potential role of rapid on-site evaluation (ROSE) of needle aspirates in reducing additional sampling and related costs and complications.

Reduced hepatic aquaporin-9 and glycerol permeability are related to insulin resistance in non-alcoholic fatty liver disease.

BACKGROUND/OBJECTIVES: Glycerol represents an important metabolite for the control of lipid accumulation and hepatic gluconeogenesis. We investigated whether hepatic expression and functionality of aquaporin-9 (AQP9), a channel mediating glycerol influx into hepatocytes, is impaired in non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in the context of insulin resistance. SUBJECTS/METHODS: Liver biopsies were obtained from 66 morbid obese patients undergoing bariatric surgery (66% women, mean body mass index (BMI) 46.1±1.0 kg m(-2)) with available liver echography and pathology analysis of the biopsies in this cross-sectional study. Subjects were classified according to normoglycemia (NG), impaired glucose tolerance (IGT) or type 2 diabetes (T2D). Hepatic expression of AQP9 was analyzed by real-time PCR, western blotting and immunohistochemistry, while glycerol permeability (P(gly)) was measured by stopped-flow light scattering. RESULTS: AQP9 was the most abundantly (P<0.0001) expressed aquaglyceroporin in human liver (AQP9>>>AQP3>AQP7>AQP10). Obese patients with T2D showed increased plasma glycerol as well as lower P(gly) and hepatic AQP9 expression. The prevalence of NAFLD and NASH in T2D patients was 100 and 65%, respectively. Interestingly, AQP9 expression was decreased in patients with NAFLD and NASH as compared with those without hepatosteatosis, in direct relation to the degree of steatosis and lobular inflammation, being further reduced in insulin-resistant individuals. The association of AQP9 with insulin sensitivity was independent of BMI and age. Consistent with these data, fasting insulin and C-reactive protein contributed independently to 33.1% of the hepatic AQP9 mRNA expression variance after controlling for the effects of age and BMI. CONCLUSIONS: AQP9 downregulation together with the subsequent reduction in hepatic glycerol permeability in insulin-resistant states emerges as a compensatory mechanism whereby the liver counteracts further triacylglycerol accumulation within its parenchyma as well as reduces hepatic gluconeogenesis in patients with NAFLD.

The ghrelin O-acyltransferase-ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes.

AIMS/HYPOTHESIS: Proinflammatory and proapoptotic cytokines such as TNF-α are upregulated in human obesity. We evaluated the association between ghrelin isoforms (acylated and desacyl ghrelin) and TNF-α in obesity and obesity-associated type 2 diabetes, as well as the potential role of ghrelin in the control of apoptosis and autophagy in human adipocytes. METHODS: Plasma concentrations of the ghrelin isoforms and TNF-α were measured in 194 participants. Ghrelin and ghrelin O-acyltransferase (GOAT) levels were analysed by western-blot, immunohistochemistry and real-time PCR in 53 biopsies of human omental adipose tissue. We also determined the effect of acylated and desacyl ghrelin (10 to 1,000 pmol/l) on TNF-α-induced apoptosis and autophagy-related molecules in omental adipocytes. RESULTS: Circulating concentrations of acylated ghrelin and TNF-α were increased, whereas desacyl ghrelin levels were decreased in obesity-associated type 2 diabetes. Ghrelin and GOAT were produced in omental and subcutaneous adipose tissue. Visceral adipose tissue from obese patients with type 2 diabetes showed higher levels of GOAT, increased adipocyte apoptosis and increased expression of the autophagy-related genes ATG5, BECN1 and ATG7. In differentiating human omental adipocytes, incubation with acylated and desacyl ghrelin reduced TNF-α-induced activation of caspase-8 and caspase-3, and cell death. In addition, acylated ghrelin reduced the basal expression of the autophagy-related genes ATG5 and ATG7, while desacyl ghrelin inhibited the TNF-α-induced increase of ATG5, BECN1 and ATG7 expression. CONCLUSIONS/INTERPRETATION: Apoptosis and autophagy are upregulated in human visceral adipose tissue of patients with type 2 diabetes. Acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in human visceral adipocytes.

Short- and long-term changes in gastric morphology and histopathology following sleeve gastrectomy in diet-induced obese rats.

BACKGROUND: Sleeve gastrectomy (SG) has been used as a multipurpose surgical procedure for the treatment of morbid obesity. The aim of the study was to analyze gastric morphology and histology at two different time points after SG in rats. METHODS: Thirty-five male Wistar rats were fed ad libitum during 3 months on a high-fat diet to induce obesity. Subsequently, 25 diet-induced obese rats underwent either SG (n = 12) or a sham operation (n = 13). The remaining ten obese animals encompassed the nonoperated control group (Co). Four weeks postoperatively, 15 rats (n = 5 rats/experimental group) were sacrificed, while the remaining 20 rats were sacrificed after 16 weeks (animals/group; Co = 5, sham = 8, SG = 7) to compare the gastric morphological and histopathological changes over time. Body weight and food intake were regularly recorded. RESULTS: For both time periods, the Co groups exhibited the highest body weight, while the rats undergoing the SG showed the lowest weight gain (P < 0.05). Initially, significant differences (P < 0.005) in food intake relative to body weight were observed between the Co rats and animals undergoing surgery, which disappeared thereafter. The actual total stomach size after both experimental periods in the SG group was similar to that of non- and sham-operated rats mainly due to a forestomach enlargement, which was more pronounced after 16 weeks. Traits of gastritis cystica profunda characterized by gastric foveolae elongation with hyperplasia and cystic dilatation of the glands were observed in the residual stomachs of the sleeve-gastrectomized rats. These findings were mostly observed after 16 weeks of performing the SG, although they were also detected occasionally following 4 weeks postoperatively. No intestinal metaplasia was observed. CONCLUSION: After SG gastric macro- and microscopic changes with functional implications in both the short and long term take place.

Transthoracic oesophagectomy with lymphadenectomy in 100 oesophageal cancer patients: multidisciplinary approach.

OBJECTIVES Analysis of the results on the treatment of esophageal cancer by transthoracic esophagectomy by a multidisciplinary team of surgeons and oncologists. METHODS Between January 1990 and December 2009, 100 consecutive patients underwent transthoracic esophagectomy. Data were collected prospectively and clinical, pathological and histological features of the tumors were analyzed as well as the results of postoperative morbidity and mortality. RESULTS The average patient age was 55 years (range 31- 83 years). In 59 cases the tumor was located in the lower third and in 41 cases in the middle third. Forty-six patients had adenocarcinoma and 54 squamous cell carcinoma. In 54 cases radio-chemotherapy was planned preoperatively. Classifi cation according to pathological tumor stage was: stage 0 in 21 patients, stage I in 10 patients, stage IIa in 28, stage IIb in 9, stage III in 21 and stage IV in 11. The mean number of lymph nodes examined was 14 (range 0-28). Hospital mortality occurred in 4 cases and postoperative complications in 29 patients (33%). The most frequent postoperative complication was pulmonary complications in 17 cases. The average hospital stay was 15.2 days (range 10-40 days) CONCLUSIONS The results of esophageal cancer have been improved in recent years due to the formation of multidisciplinary teams in this pathology. In our study we have shown that the results obtained with the transthoracic technique for cancer of the esophagus are within the ranges reported in the literature for teams with high prevalence of the disease.

Morbidity, mortality, and pathological response in patients with gastric cancer preoperatively treated with chemotherapy or chemoradiotherapy.

BACKGROUND: Significant tumor downstaging has been achieved in patients with localized gastric adenocarcinoma by preoperative chemoradiotherapy (ChRT) or induction chemotherapy (Ch). However the influence of ChRT and Ch on postoperative outcomes has not yet been clarified, with very few studies examining this issue. We retrospectively analyzed the efficacy in terms of pathological response and early postoperative complications of two protocols of preoperative ChRT and Ch for locally advanced gastric cancer. METHODS: Between 2000 and 2008, 72 patients with operable locally advanced gastric cancer (cT3-4/N+) were treated with preoperative treatment: 1-patients receiving induction Ch or 2-neoadjuvant Ch followed by concurrent ChRT. Postoperative histopathological regression and surgical complications were investigated including variables related to patients, surgical variables, preoperative treatment, and tumor. RESULTS: There were no differences in the incidence of complications between the ChRT and Ch groups (30.9% vs. 33.3%). The most frequent complications were nonspecific surgical complications (pneumonia [12.5%] and infection from intravenous catheters [9.7%]). Risk factors for complications were high-body mass index (BMI > 25 kg/m(2) ) and extension of surgery to the pancreas and spleen. A major pathological response was observed in 33.3% of patients, being more frequent in the ChRT group (47.6% vs. 13.3%; χ(2) , P = 0.0024). CONCLUSIONS: Preoperative treatment with Ch or ChRT for locally advanced gastric cancer can be performed safely with an acceptable operative morbidity and low operative mortality rate with careful consideration of the added risk associated with BMI and surgical resection of the pancreas and spleen. Ch and ChRT is feasible and effective in terms of pathological response and R0 resection.