Outpatient management of proctologic disease. Which techniques for local anesthesia? The experience of a single center.

INTRODUCTION: Since 1899 outpatient management of surgical patients had been increasing, becoming the best option when possible. In 1988 was described the first experience of outpatient management of proctologic disease. Advances in local anesthesia techniques have improved the outpatient approach to surgical disease, particularly in patients with proctological diseases. METHODS: From 2010 to 2016, 1160 patients who needed surgery for proctologic disease have been recruited: 239 hemorrhoidectomies using the variant of Milligan Morgan technique described by Phillips, 45 trans-anal hemorrhoidal DE-arterialization (THD), 315 sphincterotomies, 12 anal polypectomies, 230 loop seton positions, 65 cone-like fistulectomies and 254 fistulotomies for perianal fistulas. In 329 cases, we used the posterior perineal block, 603 local perineal blocks, and 228 tumescent anesthesia. RESULTS: On a total of 1160 procedure failure rate was of 4.7% (55 cases). Urinary retention (69% 38 cases); bleeding 18% (10 cases), uncontrolled pain 12% of cases (7 cases). The chi-square test demonstrates (p<0.01) that the failure rate of the three types of anesthesia is very different with high statistical significance. The failure rate in patient underwent Posterior Perineal Block was 27/329 cases (8.2%), 8/228 (3.5%) in patients who underwent Tumescent Anesthesia and 20/603 (3.3%) in who underwent Local Perineal Block. CONCLUSIONS: Outpatient protocols represent the most common approach to minor proctologic disease that needs a good local block, with a good analgesic and sedative assistance, the different local block seems to be the same concerning the pain control, but presents some little, not relevant difference concerning urinary retention rate.

Benign multicystic mesothelioma: a case report of recurrent disease in a young adult with familiarity for renal cell carcinoma.

Benign multi-cystic peritoneal mesothelioma (BMCM) is a very rare disease (about 150 cases observed). The aetiology is currently little-known, and the data collected, without having achieved conclusive re sults, identify two possible causes: neoplastic and reactive inflammatory. This case report refers to a recidivism of BCMC in a patient whose brother, few months before, underwent a left nephrectomy and right renal Radio Frequency Termo Ablation (RFTA) for bilateral papillary renal cell carcinoma. For the recurring trend, the onset in a male young patient without chronic inflammatory diseases evidence, the presence of a first degree relative with a rare carcinoma we supposed a neoplastic aetiology. The available literature suggests that both tumours (BCMC and renal cell carcinoma) are susceptible to oestrogens. This biomolecular mechanism could represent a valid antipathogenic hypothesis.

Use of the KSVM-based system for the definition, validation and identification of the incisional hernia recurrence risk factors.

BACKGROUND: Incisional hernia is one of the most common complications after abdominal surgery with an incidence rate of 11 to 20% post laparotomy. Many different factors can be considered as risk factors of incisional hernia recurrence. The aim of this study is to confirm and to validate the incisional hernia recurrence risk factors and to identify and to validate new ones. METHODS: In the period from July 2007 to July 2017, 154 patients were selected and subjected to incisional hernia repair. The surgical operations were conducted under general anaesthesia. Patients received antibiotic prophylaxis when indicated, according to the hospital prophylaxis scheme. Inclusion criteria of the study were single operator case studies and open laparotomy for incisional hernia repair. The statistical analysis proposed to identify and to verify the risk factors for recurrence of incisional hernia is the Support Vector Machine (SVM). The analysis was conducted verifying 34 risk factors. RESULTS: The data analysis confirmed the known correlations showed in the international literature with a greater incidence of comorbidities such as diabetes 37%, dyslipidaemia and hypercholesterolemia with a cumulative incidence of 16%; tobacco smoke - by combining categories smokers and ex-smokers - reach 46%, COPD 16% and hypertension 51%. CONCLUSIONS: The analysis of the data therefore confirmed the correlations showed in the international literature. A KSVM-based system to classify incisional hernia recurrence has been presented. The type of prosthesis and the site of its implant also play a significant role in the development of the recurrence. Sensitivity (86,25%), Specificity (87,14%), Negative Predictive Value (84,72%), Precision (88,46%), Accuracy (86,67%), and Error (13,33%) scores obtained using the proposed technique highlight the validity for the relapse's classification methodology.

Mapping the centers performing endocrine neck surgery in Italy.

BACKGROUND: Quality of care and provider's experience seem to be strictly connected in any field of surgery. Aim of this study is to identify a method to classify the centers on the basis of the number of thyroidectomies and parathyroidectomies performed. METHODS: We listed 666 centers performing endocrine neck surgery in 2015, from the database of the Italian Health Ministry. We performed a descriptive statistic analysis with a dedicated software. We identified the outliers, according to a previous literature review, in those centers performing >1000 and < 10 thyroidectomies, >100 and < 3 parathyroidectomies and we excluded them to our analysis. The remaining centers were grouped in a box-plot. Third quartile, median, procedures performed/3rd quartile value ratio (Standardized Hospitalization Ratio, SHR, superior cut-off), Romamedian/3rd quartile values ratio (inferior cut-off) were calculated. These centers were charted in a bar graph and three zones were identified: "excellence" (SHR>1.1), "SHR", "alert" (between the two cut-offs) and "risk" (under the lower cut-off). RESULTS: 35743 thyroidectomies and 2306 parathyroidectomies were performed in Italy in 2015. After the outliers' exclusion, 407 and 157 centers performing respectively thyroidectomies and parathyroidectomies were analysed. A median value of respectively 37 thyroidectomies and 6 parathyroidectomies, and a 3rd quartile cut-off of respectively 85 and 12 were calculated. Concerning all the 666 centers, we found: 95 excellence centers for thyroidectomy and 33 for parathyroidectomy, respectively 18 and 17 falling into superior cut-off line, 100 and 29 in the alert zone, 453 and 587 in the risk zone. CONCLUSIONS: Our method, according to the literature data, highlighted a number of thyroidectomies and parathyroidectomies performed in low volume centers. Looking for an optimization in health organization, we can consider some measures such as a net of tutorship of the "alert" hospitals by the excellence ones and a discouragement of the "risk" hospitals in performing endocrine neck surgery.

Fibrin sealant agents: clinical application of TachoSil® in abdominal surgery. Six years experience in an emergency surgery department and review of the literature.

BACKGROUND: The success of every surgical procedure depends on an appropriate hemostatis. Topical haemostatic agents, like fibrin sealants, are an option for providing haemostasis and may be particularly useful for complex injuries. AIM: The aim of the study is to evaluate the use of TachoSil® in abdominal surgery and its benefits to prevent bleedings, and to establish its fields of use. METHODS: A retrospective observational study was performed on 308 patients underwent to emergency surgery with TachoSil®'s application into our department between January 2012 and March 2018. RESULTS: After the application of the hemostatic device there have been no haemorrhagic complications that have needed a second surgical intervention. Most frequently use of TachoSil® was in the gallbladder bed after cholecystectomy for an acute cholecystitis. CONCLUSIONS: Our experience, supported by other reports in the literature, suggests the use of TachoSil® may provide an effective option in helping to control bleedings.

Thyroid neoplasms: surgical and cyto-histopathological connections on a six year cases study.

OBJECTIVE: This study aims to evaluate the percentage of cyto-histologic correlation in patients with a thyroid disease documented through clinical-instrumental, cytological (FNAB), histological and surgical examinations. The purpose of this study is also to determine the percentage of disease incidence and evaluating any surgical indication in relation to biological behavior (benign, malignant or indeterminate lesions, occult carcinomas), sex, and age. BACKGROUND: Almost all of thyroid neoplasms is manifested through thyroid nodule. Therefore, clinical evidence of the thyroid nodule analysis is primarily related to the need to exclude malignant pathology or carcinoma of the thyroid, present in 4-6.5% of cases. PATIENTS AND METHODS: The trial was conducted analyzing the data including cytological and histology thyroid reports recorded from 1 March 2010 to 1 March 2016, for a total of 5,956 reports. To determine the cyto-histological correlations, have been considered eligible all patients of both sexes, that have performed at least one cytologic exam followed by an histologic exam. Thus, the total number of the cases studied is 554 cases. RESULTS: Cyto-histologic compliance was 93% with a diagnostic accuracy of 4% higher than the literature examined. CONCLUSIONS: The results thus obtained show, furthermore, that there is a non-negligible percentage of thyroid disease with malignant biological behavior and involvement of male individuals. Therefore, the execution of the FNAB is of utmost importance for the purpose of a correct surgical indication.

P-POSSUM score: a prognostic instrument for postoperative complications in Crohn's disease.

AIM: The purpose of this work is to demonstrate the correlation between the p-POSSUM score and the severity of Crohn's Disease (CD) postoperative complications, evaluated by using the Clavien-Dindo score. PATIENTS AND METHODS: We have selected data of 22 patients (11 males, 11 females) that had been recovered in the Operative Unit of General Surgery of the University of Palermo General Hospital and undergone surgery for CD from 2010 to 2017. RESULTS: Patients who underwent surgery for complicated CD was divided in three different group on the base of Clavien Dindo score, C1 (Clavien-Dindo ≤ 1), C2 (Clavien Dindo = 2), and C3 (Clavien Dindo ≥ 3). ANOVA one way statistic analysis was used to investigate the presence of statistic difference in the mean of p-POSSUM operative score between the three groups of patients who underwent surgery for complicated CD. Results show that the severity of postoperative complication after surgery for complicated CD is related to the value of p-POSSUM score (p = 0,004965). CONCLUSIONS: This study clearly demonstrates a statistic correlation between p-POSSUM operative score and the risk of occurrence of severe postoperative complications in patients with Crohn's disease that had been undergone to surgical procedures of resection with ileostomy and percutaneous drainage.

23-hour observation endocrine neck surgery: lessons learned from a case series of over 1700 patients.

Although the surgical procedures concerning the thyroid and the parathyroid glands are considered safe, the possible occurrence of complications (mainly hematoma and hypocalcemia) limit the short stay surgery. At our institution a 23-hour-surgery with overnight hospital stay for endocrine neck surgical procedures was introduced since 2004. The present case series analyses the institutional results. Over 1913 endocrine neck surgery procedures, 1730 patients (90,2%) were managed according to this model. Among these patients, 92 suffered from hypocalcemia, 12 from airways obstruction due to the hematoma, 5 from bilateral nerve palsy. 15 more patients had unpredictable general disease compromising the short-stay surgery management. The goal of the discharge after 23 hours was achieved in 92,8% of cases with a mean hospital stay of 1,1days. The 23-hour observation with an overnight surgery is feasible and safe if the correct indications are observed. A considerable volume of specific activity is needed.

The non-surgical management for hemorrhoidal disease. A systematic review.

The non-surgical treatments for hemorrhoids are cost and time-saving techniques usually performed in patients suffering early hemorrhoidal disease. The most used are rubber band ligation (RBL), injection sclerotherapy (IS), and infrared coagulation (IRC). We performed a systematic review in order to evaluate: do these procedures really help to avoid further more aggressive treatments? What are the common harms? What are the rare harms? How many recurrences there are? A total of 21 RCTs were included in this review: 12 on RBL, 4 on IRC and 5 on IS. In RBL bleeding stops in up to 90% and III degree hemorrhoids improves in 78%-83.8%. IV degree prolapse should have a more invasive treatment. The commonest complications are bleeding and pain (8-80%). IRC related improvement is 78%, 51% and 22% for I, II and III degree. Post-operative pain occurs in 15-100% and post-operative bleeding ranges from 15% to 44%. Recurrence rate is 13% at a three months follow-up. IS brings to the resolution of prolapse in 90%-100% of II degree and allows good results for III degree even if reported only by case series. The post-procedural pain is 36%-49%. Bleeding is a very rare harm. Even if not definitive, these treatments could be an alternative for mild symptomatic patients after a clear explanation of recurrence rates and possible complications.

Laparoscopic ileocecal resection in acute and chronic presentations of Crohn's disease. A single center experience.

INTRODUCTION: The terminal ileum is the most involved tract in Crohn's disease. The obstruction in this location is the most frequent complication. Acute or chronic presentations can occur. Surgery finds a role in the management of chronic strictures and in acute clinical presentations with complications not improving with conservative therapy. PATIENTS AND METHODS: We investigate the outcome of patients with obstruction of the ileo-cecal bowel tract laparoscopically managed. It was analyzed the average operative time (OT), the conversion rate and the occurrence of re-operation due to surgical complications. RESULTS: 21 patients underwent an ileocecal resection for complicated Crohn's disease between January 2013 and December 2014. The admissions were performed in emergency in 42% of patients. The preintervention hospital stay was 5.8 (Sd 6.23). The mean operative time was 154 min (Sd 41). 28% of the procedures were converted to open surgery. The average hospital stay was 10 days (Sd 5) in uncomplicated patients. The morbidity rate was 28%. In 19% of cases a re-intervention was needed due to anastomotic leakage (3pts) and one hemoperitoneum for bleeding from the suture line. DISCUSSION: Laparoscopy seems an affordable technique in the management of obstructive pattern of Crohn's disease. It should be the preferable approach in young patients that probably will be submitted to subsequent surgery for the same disease; in fact, the reduced adhesions formation provided by the less bowel manipulation make easy the subsequent access. Older patients had usually more post-operative morbidity and mortality mostly due to pre-existing conditions; if possible in these patients the treatment should be medical.

An investigation of bedside laparoscopy in the ICU for cases of non-occlusive mesenteric ischemia.

BACKGROUND: Acute mesenteric ischemia is a rare affection with high related mortality. NOMI presents the most important diagnostic problems and is related with the higher risk of white laparotomy. This study wants to give a contribution for the validation of laparoscopic approach in case of NOMI. METHODS: Thirty-two consecutive patients were admitted in last 10 years in ICU of Paolo Giaccone University Hospital of Palermo for AMI. Diagnosis was obtained by multislice CT and selective angiography was done if clinical conditions were permissive. If necrosis was already present or suspected, surgical approach was done. Endovascular or surgical embolectomy was performed when necessary. Twenty NOMI patients underwent medical treatment performing laparoscopy 24 h later to verify the evolution of AMI. A three-port technique was used. In all patients we performed a bed side procedure 48-72 h later in both non-resected and resected group. RESULTS: In 14 up 20 case of NOMI the disease was extended throughout the splanchnic district, in 6 patients it involved the ileum and the colon; after a first look, only 6 patients underwent resection. One patient died 35 h after diagnosis of NOMI. The second look, 48 h later, demonstrated 4 infarction recurrences in the group of resected patients and onset signs of necrosis in 5 patients of non-resected group. A total of 15 resections were performed on 11 patients. Mortality rate was 6/20-30% but it was much higher in resected group (5/11-45,5%). Non-therapeutic laparotomy was avoided in 9/20 patients and in this group mortality rate was 1/9-11%. No morbidity was recorded related to laparoscopic procedure. CONCLUSIONS: Laparoscopy could be a feasible and safety surgical approach for management of patient with NOMI. Our retrospective study demonstrates that laparoscopy don't increase morbidity, reduce mortality avoiding non-therapeutic laparotomy.

Bowel perforation in Crohn's Disease: correlation between CDAI and Clavien-Dindo scores.

BACKGROUND: Many studies have elaborated different kind of activity indices for Crohn's Disesase (CD) with the endpoint of univocally measure and evaluate the gravity of its lesions and symptoms. AIM: Purpose of this work is to study and define the correlation that runs between the preoperative score obtained at the Crohn's Disease Activity Index, the occurrence of postoperative complications that will require re-intervention and the severity of the postoperative lesions evaluated using the Clavien-Dindo score. PATIENTS AND METHODS: We have collected and analyzed data from 23 patients (12 males, 11 females) that in a period that spans from 2010 to 2016 had been recovered in our Operative Unit and then undergone surgical treatment for the perforative complications of the CD. RESULTS: The CDAI scores obtained for each patient and the data concerning their postoperative period have been analyzed using the ANOVA system. Results demonstrate the existence of a statistically signifying correlation (p = 0.0016) between the mean category's CDAI score and the Clavien-Dindo classification. CONCLUSIONS: Despite the small number of patients that had been recruited and analyzed in our study, it clearly shows a statistically signifying correlation between CDAI scores higher than 150 points and the risk of occurrence of severe postoperative complications in patients that had been subjected to surgical procedures for perforative or abscessual complications in Crohn's Disease.

Acute appendicitis: should the laparoscopic approach be proposed as the gold standard? Six-year experience in an Emergency Surgery Unit.

Acute appendicitis is common in an Emergency Surgery Unit. Although the laparoscopic approach is a method accepted for its treatment, no strong data are available for determining how many procedures must an experienced surgeon carry out for obtaining all the advantages of this technique and if this approach can become the gold standard in the activity of a general emergency unit with senior surgeons variously skilled on the basic laparoscopy. 142 patients that underwent appendectomy (90 laparoscopic, 52 conventional) for acute appendicitis were enrolled in this institutional retrospective cohort study. The surgeons were classified with a descriptor-based grading and divided in two groups regarding the skill. The only relevant result of our study was the significant reduction of conversion rate in case of laparoscopic approach. No strong differences were found concerning the duration of the procedure and the hospital stay between the two groups. The rate of complications were very low in both groups. In conclusion, the experienced surgeons can easily perform a laparoscopic approach independently from the specific skill in this approach.

Open versus laparoscopic approach in the treatment of abdominal emergencies in elderly population.

AIM: To evaluate the role of laparoscopy in the treatment of surgical emergency in old population. PATIENTS AND METHODS: Over-70 years-old patients submitted to emergency abdominal surgery from January 2013 to December 2014 were collected and grouped according to admission diagnoses. These accounted small bowel obstruction, colonic acute disease, appendicitis, ventral hernia, gastro-duodenal perforation, biliary disease. In each group it was analyzed the operation time (OT), the morbidity rate and the mortality rate comparing open and laparoscopic management using T-test and Chi-square test. RESULTS: 159 over 70-years-old patients underwent emergency surgery in the General and Emergency surgery Operative Unit (O.U.) of the Policlinic of Palermo. 75 patients were managed by a laparoscopic approach and 84 underwent traditional open emergency surgery. T-Test for OT and Chi-square test for morbidity rate and mortality rate showed no differences in small bowel emergencies (p=0,4; 0,250,9; p>0,95) and in gastro-duodenal perforation (p=0,9; p>0.9; p>0.95). In cholecystitis, laparoscopy group showed lower OT (T-Test: p= 0,0002) while Chi-square test for morbidity rate (0,1

Rectal bleeding and prolapse not always benign diseases rather anal cancer. The importance of a correct decision making since primary care.

Rectal bleeding is very common in general population with a prevalence of 10-20 %. Primary care physicians have to stratify patients basing on urgency and on the colo-rectal cancer risk and to conduct a decision making for the correct management. We report a case of a 61-years-old woman, complaining rectal bleeding and an anal mass attended to their family doctor who does a visit but without a digital rectal examination and diagnosed a hemorrhoidal prolapse suggesting medical therapy. For the persistence of symptoms she comes to our service from emergency attention. Inspection and digital rectal examination revealed an anal mass. CT scan was performed showing a large anal mass involving half anal circumference. Histologic samples showed an epithelial proliferation compatible with a squamous carcinoma. Oncological consult was requested and a chemo-radiotherapy treatment was proposed. This case report highlights the difficulty when physicians assess patients with anorectal complaints in differentiating anal cancer from benign disease, presumably because symptoms are similar. Primary care physicians must maintain a high index of suspicion of cancer in high-risk population. Sensitization of these colleagues is required since digital rectal examination is of inestimable value to verify the presence of a rectal or an anal mass.

Complication of endoscopic tattooing: a case report of covered perforation.

AIM: Laparoscopy is considered a good approach in treatment of colorectal neoplastic diseases; the endoscopic tattooing is then recommended (Evidence Level III and grade of recommendation A) to mark a lesion or a polypectomy site for intraoperative identification. We describe the case of perforation after tattoing treated conservatively. CASE REPORT: 63 years old woman, underwent colonoscopy for lipoma tattooing with India ink SPOT® solution kit and saline test. Immediately after the procedure the patient has been referred the appearance of colic epi-mesogastric pain and fever; Computed Tomography (CT) without MDC identified an irregular thickening of transverse colon with some microbubbles compatible with focal peritonitis. Initial paralytic ileus was present too. The blood count and metabolic panel examinations reveal a neutrophil leucocytosis (WBC: 11.000/mmc, 80% neutrophils). RESULTS: On the base of WSES sepsis severity score and recent literature patient was treated conservatively with total parenteral nutrition, and intravenous antibiotic therapy. After the resolution of fever and reactivation of peristalsis. The discharge occurred after six days with no early complications. CONCLUSION: India ink tattooing with SPOT® solution kit and saline test represent the first choice. It is a feasible technique although perforation is a possible complication. It may need an immediately surgical operation but in most cases a conservative management is a good and safe tool even if surgery may be attempted too.

Large retroperitoneal abscess extended to the inferior right limb secondary to a perforated ileal Crohn's disease: the importance of the multidisciplinary approach.

The typical complications of Crohn's disease concerns small and large bowel. The full thickness inflammation of the intestinal wall develops in strictures, fistulas and abdominal abscesses. Nowadays the most accepted therapeutic for intra-abdominal abscess option is antibiotic therapy and, in case of need, percutaneous drainage of the abscess. If the abscess passes through the pelvic foramen the abscess can involve the inferior limbs. We report a case a perforation of terminal ileum in Crohn's disease complicated by a large abscess of the right iliac fossa reaching the spaces between the anterior lateral muscles of the right thigh as far as the anterior lateral pre-tibial region. We discuss the diagnostic and therapeutic options in a multidisciplinary context.

Targeted therapies in hepatocellular carcinoma.

The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients are conflicting. To date various new target drugs are under developed and other biological treatments normally indicated in other malignancies are under investigation also for HCC. These strategies aim to target the different biological pathways implicated in HCC development and progression. The target drugs studied in HCC include anti-VEGF and anti-EGFR monoclonal antibodies, tyrosine kinase inhibitors and mTOR inhibitors. The most important challenge is represented by the best integration of these drugs with standard treatments to achieve improvement in overall survival and quality of life.

[An atypical bone metastasis of hepatocellular carcinoma: case report and review of the literature]. / Una metastasi ossea atipica in corso di epatocarcinoma: descrizione del caso clinico ed analisi della letteratura.

Bone metastases are a quite frequent complication of hepatocellular carcinoma (HCC). They are a substantial fraction (about 14-28%) of the metastatic locations of this neoplasm. Recent studies are indicative of the clinical usefulness of local therapy of HCC bone metastasis, expecially if they are single locations. The presence of a single bone metastasis does not seem to influence short term prognosis of the primary neoplasm and, furthermore, its treatment by radiation, chemio-embolization or surgery may obtain long-term pain control, without the side effects of analgesic drugs. Most frequently, bone metastases of HCC appear in the spine, femur, humerus or ribs. In the last years, some atypical locations, as jaws, gums and skull, were reported. In this paper, we report the case of a painful bone metastasis of HCC, localized at the second phalanx of the second finger of the right hand. To our knowledge, until now only two cases of HCC metastatic location at the bones of the hand have been reported. The lesion has been treated by surgical ablation, obtaining long-term pain remission and the withdrawal of the analgesic drugs. Few weeks later, another bone metastasis appeared, located at the second phalanx of the third finger of the same hand, indicating in this subject a peculiar "metastatic tropism".

Treatment of patients with advanced gastric carcinoma with a 5-fluorouracil-based or a cisplatin-based regimen: two parallel randomized phase II studies.

BACKGROUND: Although many drug combination therapies have been proposed, there is no standard therapy for patients with advanced gastric carcinoma. The superiority of combination therapy over monochemotherapy has not been demonstrated convincingly. To explore the role of monochemotherapy, the authors evaluated 5-fluorouracil (5-FU), modulated by 6S-leucovorin (6S-LV) and a cisplatin-containing regimen, which was comprised of epirubicin, etoposide, and cisplatin with the addition of the reversal agent lonidamine (EEP-L). METHODS: After stratification according to performance status (PS) and resection of the primary tumor, 72 patients with advanced gastric carcinoma were randomized to 2 parallel Phase II trials with 5-FU/6S-LV and EEP-L, respectively. Thirty-six patients in Study A received bolus 6S-LV, 100 mg/m2, followed by bolus 5-FU, 370 mg/m2, on Days 1-5 and 36 others in Study B received epirubicin, 30 mg/m2, on Days 1 and 5; etoposide, 100 mg/m2, on Days 1, 3, and 5; cisplatin, 30 mg/m2, on Days 2 and 4; and lonidamine, 150 mg/day. RESULTS: There were 6 partial responses (18.2%) (95% confidence interval [CI] +/- 13.2) in Study A and 7 partial responses (21.9%) (95% CI +/- 14.3) in Study B. Partial responses were more frequent in patients with resected tumors or with an Eastern Cooperative Oncology Group PS of 0-1. The median duration of response was 8.8 and 8.3 months, respectively, in Study A and Study B. The median survival reached 8 months in Study A and 9 months in Study B. In the whole population of patients survival was significantly higher in patients with a PS of 0-1 (P < 0.05). Patients with a PS of 0-1 and a resected tumor had the significantly longest survival both in EEP-L treated patients and in all evaluable patients in the two studies. The most frequent World Health Organization Grade 3-4 toxic effects were gastrointestinal in Study A and hematologic in Study B. No treatment-related death was observed. CONCLUSIONS: The efficacy of 5-FU, modulated with 6S-LV, is moderate in patients with advanced gastric carcinoma, similar to cisplatin-containing regimens. PS and other prognostic factors could influence the response rate, which does not appear to be a reliable parameter for evaluating the outcome of chemotherapy trials.