Assessing the Prevalence of Male Obesity-Associated Gonadal Dysfunction in Severe Obesity: A Focus on the Impact of Bariatric Surgery and Surgical Approaches.

PURPOSE: Obesity is an important risk factor for secondary hypogonadism in men. Several studies evaluated the impact of bariatric surgery on gonadal function in men, proving an improvement in testosterone levels, without yet a global consensus on the impact of different surgical approaches. Objectives of the study are: to estimate the prevalence of obesity-associated gonadal dysfunction among men with severe obesity; to evaluate the response to bariatric surgery in terms of resolution of this condition, distinguishing between restrictive and restrictive-malabsorptive surgery. METHODS: We conducted a retrospective evaluation of 413 males with severe obesity (BMI 44.7 ± 8.3 kg/m2). A subgroup of them (61.7%) underwent bariatric surgery. Anthropometric assessment (weight, BMI, waist and hip circumference), metabolic (glyco-lipidic asset and urate) and hormonal (morning gonadotropin and total testosterone) assessments were carried out at baseline and 3-6 months post-surgery. RESULTS: Using a TT threshold of 2.64 ng/ml, 256 out of 413 (62%) patients were categorized as having biochemical hypogonadism. At multivariate analysis, the only parameter significantly associated with biochemical hypogonadism, was BMI value (p = 0.001). At 3-6 months after surgery, during the acute weight loss phase, only 20.1% of patients still had biochemical hypogonadism. At multivariate analysis, which included age, presurgical BMI, pre-surgical TT, surgical approach and %EWL, presurgical TT levels (p = 0.0004), %EWL (p = 0.04), and mixed restrictive-malabsorptive surgery (p = 0.01), were independently associated with the recovery of gonadal function. CONCLUSIONS: The results of this study underscore the potential reversibility of obesity-associated gonadal dysfunction through bariatric surgery, highlighting the importance of considering surgical approach.

Normalization of Spexin Levels in Patients with Obesity Submitted to Bariatric Surgery.

PURPOSE: Spexin is expressed by white fat tissue and other endocrine organs. A negative correlation between spexin and gluco-lipidic metabolism, energy homeostasis, and food intake has been reported. The objectives of this study are (1) to compare spexin levels between patients with obesity (study group) and normal-weight subjects (control group); (2) to evaluate spexin levels after bariatric surgery; and (3) to identify a correlation between spexin and weight loss/metabolic profile of patients with obesity. MATERIALS AND METHODS: We examined 53 patients with obesity (mean BMI 48.5 ± 9.4 kg/m2) who underwent bariatric surgery, compared to 55 normal-weight subjects. Serum spexin levels were assessed at baseline (study and control group) and at 3 and 6 months after surgery in patients with obesity. RESULTS: Spexin at baseline was significantly lower in the study group (p < 0.0001). At 3 and 6 months after bariatric surgery, spexin significantly increased compared to pre-surgical levels (p < 0.001) reaching control group levels (p = 0.08) at 6 months. In patients with obesity, pre-surgical spexin was similar in patients with and without comorbidities. No correlation between spexin and C-reactive protein (p = 0.8) and HOMA index (p = 0.5) was found. A significant negative correlation between age and pre-surgical spexin was observed (p = 0.03). At multivariable analysis, no correlation between Δ spexin and pre-surgery BMI, HOMA index, age, and 6-month TWL% was found. CONCLUSION: This study demonstrates that patients with obesity have significantly lower spexin levels than healthy subjects. After surgery, spexin levels of the study group become similar to those observed in the normal-weight group.

New specific skeletal muscle mass index cut-offs for the assessment of sarcopenia in patients with severe obesity.

Introduction: Bioelectrical impedance analysis (BIA) is the most used tool in clinical practice to evaluate body composition in patients with obesity. The skeletal muscle index (SMI) defined by BIA has been proposed for the identification of sarcopenia, but there are currently no univocal cutoffs for this condition. In this study, we aimed: 1) to determine the prevalence of sarcopenia in patients with severe obesity using the current cutoffs of SMI; 2) to define new specific cutoffs; 3) to validate the new cutoffs; and 4) to re-determine the prevalence of sarcopenia. Methods: A total of 300 patients, 74% women and 26% men (mean age = 42.6 ±; 9 years), with morbid obesity (mean BMI = 46.7 ±; 6.5 kg/m2) followed by the Unit of Endocrinology from January 2014 to December 2020 were retrospectively evaluated. SMI was calculated as the skeletal muscle mass normalized for squared height through the BIA equation by Janssen et al. Results: The prevalence of sarcopenic obesity calculated using the cutoff points reported by De Rosa et al. (7.3 kg/h2 for women and 9.5 kg/h2 for men) was 2.3%. The prevalence of sarcopenia was calculated using the new cutoffs: with the cutoff obtained from the standard deviation method (8.2 kg/h2 for women and 10.2 kg/h2 for men), a prevalence of 14.7% was observed, whereas the prevalence reached 47.6% when using the cutoff calculated through the K-means unsupervised cluster (9.2 kg/h2 for women and 11.3 kg/h2 for men). The new cutoffs were validated with a second sample consisting of 300 patients with morbid obesity (BMI = 44.9 ±; 6.7 kg/m2): the rate of sarcopenic patients was still higher than that observed in the training cohort (56%). After the matching procedure (by BMI and age), the rates of sarcopenic patients were similar in both groups (50.2% in the validation group and 53% in the training group, p = 0.6). Conclusion: The new cutoffs calculated with cluster analysis could better identify sarcopenia in morbidly obese patients. However, further studies are needed to validate these cutoffs in different patient cohorts.

Type 2 deiodinase p.Thr92Ala polymorphism does not affect the severity of obesity and weight loss after bariatric surgery.

A single nucleotide polymorphism in the Type 2 deiodinase (DIO2) gene (p.Thr92Ala) was found to be associated with hypertension, type 2 diabetes mellitus (T2DM), insulin resistance, and body mass index (BMI). We retrospectively evaluated 182 patients to assess whether the DIO2 p.Thr92Ala was associated with severe obesity and response to bariatric surgery. Genomic DNA was extracted from peripheral blood leukocytes before surgery. Glycemic control parameters, cardiometabolic risk biomarkers (waist circumference, lipid assessment and blood pressure) and hormonal parameters were assessed at baseline and after surgery. Based on genotype evaluation, 78/182 (42.9%) patients were homozygous wild-type (Thr/Thr), 83/182 (45.6%) heterozygous (Thr/Ala), and 21/182 (11.5%) rare homozygous (Ala/Ala). Age at the time of the first evaluation in our Unit was significantly lower in patients with DIO2 p.Thr92Ala. No significant association was observed between DIO2 p.Thr92Ala and BMI, excess weight, waist circumference, Homa Index. The prevalence of comorbidities was not associated with allele distribution except for hypertension that was more frequent in wild-type patients (p = 0.03). After bariatric surgery, excess weight loss (EWL) % and remission from comorbidities occurred without differences according to genotypes. DIO2 p.Thr92Ala does not affect the severity of obesity and its complications, but it seems to determine an earlier onset of morbid obesity. The presence of polymorphism seems not to impact on the response to bariatric surgery, both in terms of weight loss and remission of comorbidities.

Follow-up after bariatric surgery: is it time to tailor it? Analysis of early predictive factors of 3-year weight loss predictors of unsuccess in bariatric patients.

Bariatric surgery (BS) is the most effective treatment strategy for obesity. Nevertheless, a subset of patients does not reach a successful weight loss or experience long-term weight regain. Conflicting evidence exists regarding predictors of BS outcomes. We aimed to define the early factors linked to 3 year unsuccessful weight loss in order to promote a tailored close follow-up. We enrolled 443 patients who underwent BS from January 2014 to December 2018 with a 3 year follow-up. An unsuccessful BS outcome was defined as a percentage of total weight loss (%TWL) < 20. We compared the characteristics between successful and unsuccessful patients in order to identify predictor factors of unsuccess after surgery. We found that the proportion of patients with unsuccessful weight loss progressively increased from one to three years after BS. In a multiple regression model, only 1 month %TWL and sleeve gastrectomy (SG) were significantly associated with 3 year unsuccessful weight loss. We stratified our cohort in four groups according to the risk of BS unsuccess, in terms of 1 month %TWL and type of surgery (SG vs gastric bypass). Interestingly, groups showed a significant difference in terms of %TWL at each follow-up point. Patients submitted to SG with lower 1 month %TWL must be considered at higher risk of future weight regain; consequently, they require a tailored and closer follow-up.

Controlling Nutritional Status (CONUT) Score and Micronutrient Deficiency in Bariatric Patients: Midterm Outcomes of Roux-en-Y Gastric Bypass Versus One Anastomosis Gastric Bypass/Mini Gastric Bypass.

BACKGROUND: Two of the most common bariatric procedures performed worldwide are Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB). Comparative data regarding nutritional status are lacking and no previous study focus on malnutrition according to a validated score. METHODS: Retrospective data from a single institution were reviewed. Anthropometric variables and nutritional data were assessed. The primary aim was to analyze and compare the nutritional status before and 3 years after RYGB vs OAGB using the controlling nutritional status (CONUT) score. The incidence of micronutrient deficiency and the remission of comorbidities in each group were defined as secondary outcomes. RESULTS: Fifty-seven patients in each arm were enrolled. A 3-year mild malnutrition (CONUT score 2-3) was found in 38% and 37.05% in the RYGB and OAGB groups, respectively (p > 0.05). In terms of percentage of total weight loss (%TWL) and percentage of adjustable weight loss (%AWL), no differences were found between OAGB and RYGB groups. OAGB and RYGB patients had similar vitamin deficiencies. Anemia, hypoproteinemia, hypoalbuminemia, and hypocalcemia were comparable between groups. At 3-year follow-up, total protein and albumin values were similar between arms while prealbumin deficit was more frequent after OAGB than after RYGB. The rate of type 2 diabetes (87.5% in OAGB and 92% in RYGB), arterial hypertension (51.6% in OAGB and 58.3% in RYGB), and dyslipidemia (69.7% in OAGB and 78.6% in RYGB) remission was not significantly different between the two groups. CONCLUSIONS: Postoperative CONUT score, micronutrient deficiency, comorbidity remission, and improvement of anthropometric parameters 3 years postoperatively were comparable between RYGB and OAGB groups.

The impact of CPT1B rs470117, LEPR rs1137101 and BDNF rs6265 polymorphisms on the risk of developing obesity in an Italian population.

OBJECTIVE: This study aimed to analyze 11 single nucleotide polymorphisms (SNPs) belonging to 9 genes involved in metabolic pathways (BDNF rs6265; PNPLA3 rs2294918 and rs2076212; CIDEA rs11545881; NTRK2 rs2289658; ALOX12 rs1126667; ALOX12B rs2304908; LEPR rs1137101; CPT1B rs470117 and rs8142477; rs2305507 CPT1A) in obese patients and controls. METHODS: Polymorphisms were analyzed in 300 severe obese patients undergoing bariatric surgery (body mass index >30 kg/m2) and 404 control subjects in order to evaluate their association with obesity and clinical variables. RESULTS: Our findings showed significant differences for the allelic distributions of CPT1B rs470117 and LEPR rs11371010 in obese subjects compared to controls. The BDNF rs6265 correlates with obesity only when associated with the other two SNPs. In particular, for CPT1B rs470117 and LEPR rs1137101, the rare allele was associated with a reduced risk of developing the obese phenotype, whereas the simultaneous presence of the common C allele for rs470117 and A allele for rs1137101 was more frequent in obese patients (p = 0.002, OR = 1.417). A significant association between CPT1B rs470117 and steatosis was found. Moreover, we observed that by associating the rare allele T of the BDNF rs6265 with the most common alleles of the SNPs CPT1B rs470117 and LEPR rs1137101, the combination of T-C-A alleles was associated with a higher risk of developing an obese phenotype (p = 0.001, OR = 1.6679). CONCLUSIONS: Our results suggest that SNPs CPT1B rs470117 and LEPR rs1137101 taken individually and in association with BDNF rs6265 may be involved in an increased risk of developing obese phenotype in an Italian cohort.

[Transanal haemorridal dearterialisation: personal experience]. / Emorroidectomia con tecnica THD (transanal haemorroidal dearterialization) nostra esperienza.

Transanal haemorroidal dearterialisation (THD) is a nonexcisional surgical technique for the treatment of piles, consisting in the ligation of the distal branches of the superior rectal artery, resulting in a reduction of blood flow and decongestion of the haemorroidal plexus. THD for 2 degrees and 3 degrees degree haemorroids is highly effective and painless. There are few complications and the technique can be performed as a day case.

Cardiovascular Benefits and Lipid Profile Changes 5 Years After Bariatric Surgery: A Comparative Study Between Sleeve Gastrectomy and Roux-en-Y Gastric Bypass.

INTRODUCTION: Visceral adipose tissue has been linked with cardiovascular events. Visceral adiposity index (VAI) is a routinely applicable tool for evaluation of visceral adipose dysfunction and linked to 10 year-cardiovascular risk. No previous studies have evaluated the changes over time of the VAI in patients who underwent different types of bariatric surgery. MATERIALS AND METHODS: We reviewed data of 42 patients who underwent laparoscopic sleeve gastrectomy (LSG) and 61 patients who underwent laparoscopic Roux-en-Y gastric bypass (LRYGB). VAI, lipid profile, and several anthropometric variables were measured before and after 5 years following surgery. RESULTS: During the studied time period, the BMI was similar between LSG and LRYGB patients (34.1 vs 31.6; p = 0.191), but the percentage of total weight loss (%TWL) for LRYGB was significantly higher than LSG (31.3% vs 23.0%; p < 0.001). LRYGB patients had a significant improvement of all lipid parameters evaluated over time, while LSG patients experienced only a reduction in triglycerides (TG) levels and an increase in HDL cholesterol (HDL-C). VAI values were similar in the two groups at baseline as well at the last follow-up point (5-year VAI, LSG: 0.93, RYGB: 0.93; p = 0.951). At multivariate regression analysis, 5-year-%TWL was the only independent predictor of a greater amount of VAI reduction over time. CONCLUSION: Bariatric surgery, independent of the type of surgical procedure, decreases the cardiovascular disease (CVD) risks due to weight loss and improvement of lipid parameters. VAI could be a useful tool to better identify eligible patients for bariatric surgery and to determine the success of surgery.

[Radiation proctitis: description of two cases refractory to pharmacological treatment]. / La proctite attinica: descrizione di due casi refrattari al trattamento farmacologico.

Radiation proctitis, is a relatively frequent complication resulting from the direct or collateral irradiation of the rectum in radiotherapy treatment for genito-urinary or anorectal malignancies. The main symptoms are diarrhoea, tenesmus, proctorrhagia, anal pain, mucorrhoea and faecal incontinence. The evolution of chronic radiation proctitis requires treatment for related anaemia, anal incontinence and micturition disorders. The approach and type of treatment depend on the severity of the symptoms and on the endoscopic aspect, in relation to the response to previous medical therapy performed. In our experience, endoscopic treatment is the best choice in the presence of ongoing bleeding and the possible development of severe anaemia. The surgical option is mandatory in patients at high risk of sepsis, requiring a faecal diversion constructed using the Hartmann technique. We report two cases, observed during the last two years, one treated with endoscopic bipolar coagulation and the other with a double urinary and faecal diversion.

[Malignant degeneration of chronic pilonidal cyst. Case report]. / Degenerazione maligna di una cisti pilonidale. Caso clinico.

This report describes the case of a patient with a chronic pilonidal cyst developed squamous cell carcinoma. The case was treated with primary radical excision, followed adjuvant radiation and chemiotherapy. Recurrence following such treatment was high and prognosis poor compared with non melanoma skin cancer.

Conversion from laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) to one anastomosis gastric bypass (OAGB): preliminary data from a multicenter retrospective study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is the most commonly performed bariatric procedure, while laparoscopic adjustable gastric banding (LAGB) has been for a decade one of the most popular interventions for weight loss. After LSG and LAGB, some patients may require a second surgery due to weight regain or late complications. One anastomosis gastric bypass (OAGB) is a promising bariatric procedure, which provides effective long-term weight loss and has a favorable effect on type 2 diabetes. OBJECTIVES: To retrospectively analyze data from 10 Italian centers on conversion from LAGB and LSG to OAGB. SETTING: High-volume centers for bariatric surgery. METHODS: Prospectively collected data from 10 high-volume centers were retrospectively reviewed. Body mass index (BMI), percentage of excess BMI loss, reasons for redo, remission from co-morbidities (hypertension, diabetes, gastroesophageal reflux, and dyslipidemia), and major complications were recorded. RESULTS: Three hundred patients were included in the study; 196 patients underwent conversion from LAGB to OAGB and 104 were converted from LSG. BMI was 45.1 ± 7 kg/m2 at the time of first intervention, 41.8 ± 6.3 kg/m2 at redo time, and 30.5 ± 5.5 kg/m2 at last follow-up appointment. Mean percentage of excess BMI loss was 13.2 ± 28.2 at conversion and 73.4 ± 27.5 after OAGB. Remission rates from hypertension, diabetes, gastroesophageal reflux, and dyslipidemia were 40%, 62.5%, 58.7% and 52%, respectively. Mean follow-up was 20.8 (range, 6-156) months and overall complications rate was 8.6%. CONCLUSION: Our data show that OAGB is a safe and effective revisional procedure after failed restrictive bariatric surgery.

[Treatment of liver metastases from colorectal carcinoma: our experience]. / Trattamento delle metastasi epatiche da carcinoma colorettale: nostra esperienza.

The latest hepatic surgical strategies enable liver resections to be performed on a larger number of patients, improving the survival rate. Moreover, the contribution of radiological techniques and chemotherapy to surgery has led to the multidisciplinary management of patients suffering from liver metastases, involving surgeons, radiologists and oncologists. If surgical treatment is not considered curative, it is appropriate to advise alternative strategies in order to down-stage the disease and make it resectable.

[Stapled transanal rectal resection (STARR) in the treatment of rectocele: personal experience]. / La S.T.A.R.R. nel trattamento del rettocele. Esperienza personale.

Rectocele is an organic cause of chronic constipation, with a prevalence ranging from 8.95% to 12% in Europe and United States. Necessarily, the approach for rectocele repair is a surgical operation. Stapled transanal rectal resection (STARR) is safe and effective in the treatment of obstructed defecation syndrome. The authors' experience suggests that the surgical operation needs to be combined to rehabilitation exercises, before and after the surgical treatment, in order to strengthen the muscles of the pelvic pavement. From January 2005 to January 2007, 20 patients with outlet obstruction underwent STARR. Patients were selected for operation based on a strict diagnostic protocol: anamnesis, clinical examination, coloproctological and urogynaecological examinations, defecography, anorectal manometry, transrectal ultrasonography and peritoneal electromyography. The therapeutic protocol consists of 3 parts: phase I: rehabilitation of the pelvic pavement; phase II: surgical operation; III phase: post-surgical rehabilitation of the pelvic pavement; The clinical result was classified into: excellent (6 patients), when all constipation symptoms disappeared, good (11 patients), when patient has 1 or 2 obstructed defecation episodes treated with a laxative, fairly good (2 patients), more than 2 episodes, and poor (1 patient), when surgical operation doesn't improve any of the symptoms. Our results, confirmed by the literature, suggest that Longo's technique should be considered as gold standard for rectocele treatment.

[Urachus' carcinoma: a case report]. / Carcinoma dell'uraco. Case report.

Urachus' carcinoma represents a rare oncologic disease with an unfavourable prognosis due to the usual delay of correct diagnosis for its anatomical localization. Its surgical treatment varies from radical cystectomy to segmentary resection of the bladder with pelvic lymphadenectomy. We report a case occurred in a ninety years old female, in which the diagnosis was achieved only at laparotomy. The patient was submitted to surgery with the only generic diagnosis of "lower abdominal mass", and treated with segmentary resection.

Bariatric Surgery Reduces Serum Anti-mullerian Hormone Levels in Obese Women With and Without Polycystic Ovarian Syndrome.

PURPOSE: Obesity in fertile women has negative effect on fertility. Anti-mullerian hormone (AMH) represents a good index of fertility, and it is considered a marker of ovarian reserve and of polycystic ovarian syndrome (PCOS) gravity. Previous studies evaluated the relationship between obesity and AMH with contradictory results. The aim of the study was to investigate the relationship between obesity and AMH and the changes of AMH in obese women in reproductive age submitted to bariatric surgery. MATERIALS AND METHODS: Fifty-five obese patients between 18 and 39 years with (29 patients) and without PCOS (26 patients) were compared with a control group of normal weight women with (24 patients) and without PCOS (19 patients). Fourteen obese women with PCOS and 18 without PCOS underwent to bariatric surgery. Serum AMH, testosterone, androstenedione, and DHEAS were performed in all patients before and 1 year after surgical intervention. RESULTS: AMH was significantly higher in the PCOS groups (p < 0.001), both in obese (5.84 ± 3.94 ng/ml) and non-obese women (7.35 ± 4.39 ng/ml). AMH was positively related to testosterone (p < 0.0001), androstenedione (p = 0.0005), and DHEAS (p = 0.003). After bariatric surgery, AMH levels were reduced in the both PCOS (p = 0.02) and non-PCOS group (p = 0.04). CONCLUSIONS: AMH levels are elevated in PCOS patients regardless of the body weight. Bariatric surgery is effective in the normalization of AMH levels (a possible indirect marker of better fertility) only in obese patients with PCOS.

[Management of patients with non-functioning gastroentero-pancreatic neuroendocrine tumours]. / Management di un paziente portatore di neoplasia neuroendocrina non fiunzionante del tratto gastro-entero-pancreatico (GEP).

The Authors examine the feasibility of diagnosing non-functioning gastroentero-pancreatic neuroendocrine tumours preoperatively or intraoperatively, with particular reference to laboratory examinations and octreoscan scintigraphy, which are capable of conditioning the surgical treatment and subsequent follow-up. Of the 4 cases reported here: three presented multiple intestinal localizations, and in only one case the origin of the primitive carcinoma was undefined. The suspicion of a non-functioning neuroendocrine tumour must be considered when yellowish or ochre-coloured intestinal lesions are found intraoperatively. Determination of specific markers and octreoscan scintigraphy must be performed without awaiting histological confirmation. Surgery plays a fundamental role in the debulking of these carcinomas. However, medical therapy with the aid of specific laboratory examinations and octreoscan scintigraphy may improve the long-term survival.

Is sleeve gastrectomy a therapeutic procedure for all obese patients?

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a worldwide surgical procedure for morbid obesity. However patients selection is still anecdotal. The aim of this study is to analyse clinical and anthropometric parameters correlated with LSG and to check the validity of this procedure for different categories of obese patients. METHODS: Two-hundred one consecutive patients were submitted to LSG as a primary bariatric procedure between 2008 and 2014. One year follow-up was completed in 159 patients. Smaller groups of patients completed 2 and 3 years follow-up (78, 46 patients respectively). Median preoperative body mass index (BMI) was 45.4 kg/m2 (range: 34.8-73.8); 135 patients (80%) had one or more comorbidities. Potential correlations between age, gender, preoperative BMI, preoperative excess weight, early excess weight loss (EWL) and 1 and 3 year-EWL were investigated. RESULTS: All procedures were regularly completed with laparoscopic approach without conversion to laparotomy. Postoperative complications occurred in six patients (3.7%); no postoperative mortality was observed. Median one-year BMI and EWL were 32.8 kg/m2 and 55.34%, respectively. Three year-EWL was significantly influenced by age, and early EWL. A complete normalization of glycemic levels after the three-year follow-up was also observed in high percentage of diabetic patients. In patients with preoperative BMI>50 kg/m2 we observed most failure cases in terms of EWL and the worst metabolic results. CONCLUSIONS: Our experience indicates that LSG is a safe procedure with satisfactory three-year late weight loss in patients with preoperative BMI <50 kg/m2. Promising results, in terms of improvements of comorbidities, were also observed. These results make LSG one of the most attractive first stage surgical procedure for morbid obesity.

Gemcitabine (GEM) plus oxaliplatin, folinic acid, and 5-fluorouracil (FOLFOX-4) in patients with advanced gastric cancer.

BACKGROUND AND AIMS: oxaliplatin in combination with folinic acid (FA) and infusional 5-fluorouracil (5-FU) has shown significant anti-tumor activity in gastric cancer patients (FOLFOX). Previous studies have shown that gemcitabine (GEM), a new fluorinated anti-metabolite, enhances the individual anti-tumor activity of either 5-FU or oxaliplatin. We have therefore designed a multi-center phase II trial in order to test a novel GEM+FOLFOX-4 regimen in patients with metastatic gastric cancer. METHODS: we enrolled 36 patients, 28 males and 8 females, with an average age of 64.4 years (range 37-78), who received bi-weekly treatment with GEM (1,000 mg/m2 on day 1), levo-FA (100 mg/m2 on days 1 and 2), a 5-FU (400 mg/m2) bolus injection followed by 22-h continuous infusion (800 mg/m2) on days 1 and 2, and oxaliplatin 85 mg/m2 in a 4-6 h intravenous (i.v.) infusion before the second FUFA administration on day 2. RESULTS: the most frequent side effect was grade 1-2 hematological toxicity and late sensorial neurotoxicity. Two patients developed hypersensitivity to oxaliplatin while another developed an aseptic eosinophilic pneumonitis. Two patients refused to continue the treatment after two cycles of chemotherapy and were lost at the follow-up. Among the remaining 34 patients four achieved a complete response, 15 a partial response, 12 had a stable disease and three progressed. CONCLUSIONS: these results may grant the rationale to evaluate this multi-drug combination in randomized phase III trials in advanced gastric cancer.