Lycopodium similiaplex-induced acute hepatitis: a case report.

A 46-year-old woman was admitted to our department with symptoms of nausea, anorexia and asthenia. Serum alanine aminotransferase and aspartate aminotransferase levels were increased; all serological tests for viral hepatitis and autoimmune disorders were negative. She had taken Lycopodium similiaplex solution as sedative for the previous 8 weeks, whose two constituents, Lycopodium serratum and Chelidonium majus, are found to be potentially toxic. After discontinuing L. similiaplex use, liver values returned to normal and she was asymptomatic. The diagnosis was definitively confirmed by liver biopsy; on the basis of the histological specimen, a hypersensitivity reaction was hypothesized as a possible pathogenic mechanism. Hepatotoxicity of phytotherapy has already been described, although so far, the true incidence and the pathogenic mechanisms are largely unknown. It is important to increase awareness of both clinicians and patients about the potential dangers of herbal remedies; surveillance systems and quality control of these products are necessary.

Correlation between magnetic resonance imaging and histopathological tumor response after neoadjuvant chemotherapy in breast cancer.

AIM: To evaluate the accuracy of magnetic resonance imaging in assessing tumor response following neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIALS AND METHODS: Twenty-six patients entered a phase II study of neoadjuvant chemotherapy, undergoing bilateral breast magnetic resonance imaging before therapy and before surgery. Tumor response was classified using RECIST criteria, using tumor size at magnetic resonance imaging. The latter was then compared to residue found at histopathological examination. RESULTS: Magnetic resonance imaging showed 6 (23%) complete responses, 17 (65%) partial responses, 3 (11.5%) disease stabilizations and no disease progressions. Twenty-three tumors (88.5%) were considered responsive and 3 (11.5%) unresponsive. Pathological tumor response was: 6 complete responses (23%), 17 partial responses (65%), 2 stable disease (8%), 1 progression (4%). When results of the preoperative magnetic resonance imaging were compared to pathological tumor response, magnetic resonance imaging overestimated tumor size in 12 cases (46%) and underestimated it in 9 (35%). However, preoperative magnetic resonance imaging failed to detect invasive tumor in 2 false-negative cases (8%), 1 of which was multifocal. Mastectomy was performed in 12 cases: 1 case of disease progression even though the neoplasm appeared smaller at magnetic resonance imaging, 3 cases with stable disease, and 4 cases with T3 or T4 disease. The 9th patient was T2N2 with initial retroareolar disease and negative magnetic resonance imaging after chemotherapy. The 10th patient, affected by lobular cancer, was in partial remission but was T3N1. The 11th patient was 57 years old but was not interested in conservative surgery. The 12th patient requested bilateral prophylactic mastectomy due to her positive family history of breast cancer. CONCLUSIONS: Magnetic resonance imaging of the breast allowed conservative surgery in 54% of the patients. This low value is primarily due to overestimation of tumor size, with a negative predictive value of 67% in our population. However, surgeons were able to choose conservative surgery with relative safety in cases of small residual disease.

Sentinel lymph node metastasis from mammary ductal carcinoma in situ with microinvasion.

Axillary lymph node dissection (ALND) in patients with ductal carcinoma in situ with microinvasion (DCISM) of the breast was controversial, because of the relevant morbidity incurred by the procedure and the low incidence of axillary involvement. The introduction of the sentinel lymph node (SLN) biopsy as a minimally invasive procedure for axillary staging has prompted new interest in this issue. However, as DCISM is a rare type of cancer, data on the incidence of SLN metastasis are scarce. The aim of the present paper was therefore to assess the prevalence of SLN metastasis in a multi-institutional series of DCISM patients, in order to ascertain whether SLN biopsy might be justified as a standard procedure in the presence of microinvasive cancer. Between 1999 and 2004, 43 patients with a diagnosis of DCISM underwent SLN biopsy. Microinvasion was defined as one or more foci of invasion beyond the basal membrane, none exceeding 1mm. SLNs were examined following haematoxylin-eosin and immunohistochemical staining. SLN metastases were found in four out of 43 cases (9.3%). In one patient, SLN contained only micrometastasis. All four patients with positive SLN underwent complete ALND and in all these cases further metastatic axillary nodes were found. In conclusion, given the relevant incidence of nodal metastases and the low morbidity of the procedure, we believe that SLN biopsy should be considered in all patients with a diagnosis of DCISM. In cases of SLN involvement, even if micrometastatic, our policy is to perform a complete ALND.

Prognosis of gastrointestinal stromal tumors.

BACKGROUND/AIMS: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors (GIMT) of the gut. The aim of this retrospective study is to correlate the histological risk factors with the survival of our patients operated for GIST. METHODOLOGY: In our department, from 1980 to October 2003, 15 patients were operated for GIST. Their mean age was 58 years old and 8 of them were males; 10 (67%) were localized in the stomach and 5 (33%) in the small bowel. In 7 cases liver metastases were present at laparotomy and 4 of them also had peritoneal diffusion. We performed immunohistochemistry for c-Kit, SMA and S100p. Mitotic index (MI) and size neoplasm were the main pathological criteria for malignity. The patients with c-kit (CD117) positive neoplasms were divided according to NIH Consensus Conference risk class, MI, tumor size, localization, SMA or S100p presence, liver metastasis and peritoneal metastasis to compare the different 5-year survival rates. Survival analysis was performed using Kaplan-Meier method and log-rank test and a p < 0.05 was considered as significant. RESULTS: Global survival rate after 5 years was 40% and the mortality was, in all cases, due to GIST. In our experience gender, age, tumor size, localization and S100p positivity did not play any role in predicting the prognosis of GIST. On the contrary high MI and SMA positivity are significantly associated to a lower survival rate (33% vs. 86% and 39% vs. 100% at 5 years, respectively). Finally patients with metastases at laparotomy have a significantly lower 5-year survival rate (hepatic 29% vs. 100%, hepatic and peritoneal 25% us. 78%). CONCLUSIONS: In our experience high MI and in some cases SMA expression can be considered assessed risk factors. On the other hand, criteria of benign behavior did not completely predict the long-term clinical outcome.

Peritoneal mesothelioma: a review.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare aggressive tumor of the peritoneum, regarded as a universally fatal disease. It is poorly described and the knowledge of its natural history is very limited. Occupational and environmental asbestos exposure still remains a public health problem around the world. The incidence has increased in the past 2 decades. Only 20% to 33% of all mesotheliomas arise from the peritoneum itself; the pleura is the most common site of origin.

Epidermal growth factor receptor (EGFR): mutational and protein expression analysis in gastric cancer.

BACKGROUND: Since specific epidermal growth factor receptor (EGFR) somatic mutations have been demonstrated to influence the response to anti-EGFR therapy in non-small cell lung cancer, EGFR gene mutational analysis of different types of neoplasm is under investigation. PATIENTS AND METHODS: EGFR protein expression and gene mutations in exons 18, 19 and 21 were investigated in 49 gastric adenocarcinomas. RESULTS: no specific EGFR gene mutations were detected, while EGFR positive staining was detected in 6% of the cases. CONCLUSION: Our findings indicate that in gastric adenocarcinoma, specific EGFR gene mutations are very rare or absent and the rate of EGFR protein expression is low.

Role of axillary sentinel lymph node biopsy in patients with pure ductal carcinoma in situ of the breast.

BACKGROUND: Sentinel lymph node (SLN) biopsy is an effective tool for axillary staging in patients with invasive breast cancer. This procedure has been recently proposed as part of the treatment for patients with ductal carcinoma in situ (DCIS), because cases of undetected invasive foci and nodal metastases occasionally occur. However, the indications for SLN biopsy in DCIS patients are controversial. The aim of the present study was therefore to assess the incidence of SLN metastases in a series of patients with a diagnosis of pure DCIS. METHODS: A retrospective evaluation was made of a series of 102 patients who underwent SLN biopsy, and had a final histologic diagnosis of pure DCIS. Patients with microinvasion were excluded from the analysis. The patients were operated on in five Institutions between 1999 and 2004. Subdermal or subareolar injection of 30-50 MBq of 99 m-Tc colloidal albumin was used for SLN identification. All sentinel nodes were evaluated with serial sectioning, haematoxylin and eosin staining, and immunohistochemical analysis for cytocheratin. RESULTS: Only one patient (0.98%) was SLN positive. The primary tumour was a small micropapillary intermediate-grade DCIS and the SLN harboured a micrometastasis. At pathologic revision of the specimen, no detectable focus of microinvasion was found. CONCLUSION: Our findings indicate that SLN metastases in pure DCIS are a very rare occurrence. SLN biopsy should not therefore be routinely performed in patients who undergo resection for DCIS. SLN mapping can be performed, as a second operation, in cases in which an invasive component is identified in the specimen. Only DCIS patients who require a mastectomy should have SLN biopsy performed at the time of breast operation, since in these cases subsequent node mapping is not feasible.

Postmortem distribution of sildenafil in histological material.

This study reports results of the detection and quantitation of sildenafil (Viagra) in biological fluids and tissues and its stability in fixed tissues and formalin solutions in which the tissues were fixed. Toxicological analyses were performed on samples from a 60-year-old man who died of acute heart failure due to myocardiosclerosis. Sildenafil pills were found in his pocket. At the time of autopsy, sildenafil was found in body fluids and tissues (blood 0.04 mg/L, bile 0.99 mg/L, gastric contents 6.84 mg/L, urine 9.60 mg/L, brain 6.43 mg/kg, heart 6.10 mg/kg, kidney 4.28 mg/kg, liver 5.46 mg/kg, lung 5.38 mg/kg, spleen 1.38 mg/kg). Tissue samples were preserved in formalin solutions for four weeks. Analyses of formalin-fixed tissues and formalin solutions in which the same tissues had been preserved allowed the detection and quantitation of sildenafil (brain 2.20 mg/kg, formalin from brain 4.01 mg/L; heart 1.46 mg/kg, formalin from heart 4.41 mg/L; kidney 0.98 mg/kg, formalin from kidney 3.19 mg/L; liver 2.19 mg/kg, formalin from liver 3.21 mg/L; lung 1.02 mg/kg, formalin from lung 4.18 mg/L; spleen 0.28 mg/kg, formalin from spleen 0.94 mg/L). Results indicate that sildenafil has good stability in biological specimens subjected to chemical fixation.

Simultaneous detection and quantitation of morphine, 6-acetylmorphine, and cocaine in toenails: comparison with hair analysis.

This study describes the results of the simultaneous detection and quantitation of morphine, 6-acetylmorphine, and cocaine in toenail and hair samples obtained from 18 forensic autopsies of drug abusers who had died in various manners. After external decontamination, each specimen was submitted to hot acid hydrolysis (1 mL of HCl 37%) in the presence of internal standards, followed by liquid-liquid and solid-phase extraction techniques. The extracts were then derivatized with propionic anhydride and analyzed by gas chromatography-mass spectrometry, operating in the selected ion monitoring mode. The limit of quantitation for all analytes was 0.5 ng on column. Results showed that both cocaine and morphine are more concentrated in toenails than in hair. Mean concentrations were 0.99 ng/mg (toenails) versus 0.48 ng/mg (hair) for cocaine and 1.27 ng/mg (toenails) versus 0.79 ng/mg (hair) for morphine. Distribution of 6-acetylmorphine showed no significant variations between the two (mean concentrations 0.46 ng/mg vs. 0.50 ng/mg in hair).

Intraoperative hand-held imaging γ-camera for sentinel node detection in patients with breast cancer: feasibility evaluation and preliminary experience on 16 patients.

PURPOSE: This study aimed to assess the feasibility and potential usefulness of a new intraoperative portable high-resolution imaging γ-camera for the localization of sentinel lymph node in patients with breast cancer. METHODS: Sixteen T1 to T2 breast cancer female patients were evaluated (mean age, 62 years) with preoperative lymphoscintigraphy, acquired 30 minutes after intradermal injection of 60 to 70 MBq (1.6-1.9 mCi) of (99m)Tc-nanocolloids in saline volumes of 0.1 to 0.2 mL. Surgery took place the day after (18-20 hours after tracer injection). For intraoperative sentinel lymph node localization, a traditional γ-probe was used by the surgeon. Moreover, a portable imaging γ-camera was used by the nuclear physician who was present in the operating room. RESULTS: The portable imaging γ-camera showed very high spatial resolution (2.4 mm) in the 4.4 × 4.4 cm(2) FOV, with a good sensitivity of 180 cps/MBq at a Plexiglas depth of 1 cm. In 11 patients, lymphoscintigraphy, γ-probe, and imaging γ-camera depicted the same number of radioactive lymph nodes (17 nodes; 5 of which were metastatic and detected in 6 different patients). In 6 patients, the portable imaging γ-camera detected 1 node more than lymphoscintigraphy (in total, 5 nodes more), one of which was metastatic (the only one metastatic in that patient). CONCLUSIONS: Our preliminary results showed that a portable high-resolution hand-held imaging γ-camera is a feasible, not time-consuming, noninvasive procedure in intraoperative sentinel node localization, offering extra confidence to the surgeon. In our hands, it was a very useful auxiliary imaging tool especially in the identification of nodes located deep in the axilla, which are difficult to detect at the preoperative lymphoscintigraphy. Additional multicenter studies involving a greater number of patients are necessary to confirm these promising data.

A web-based pilot study of inter-pathologist reproducibility using the ISHLT 2004 working formulation for biopsy diagnosis of cardiac allograft rejection: the European experience.

BACKGROUND: The aim of this study was to assess, at the European level and using digital technology, the inter-pathologist reproducibility of the ISHLT 2004 system and to compare it with the 1990 system We also assessed the reproducibility of the morphologic criteria for diagnosis of antibody-mediated rejection detailed in the 2004 grading system. METHODS: The hematoxylin-eosin-stained sections of 20 sets of endomyocardial biopsies were pre-selected and graded by two pathologists (A.A. and M.B.) and digitized using a telepathology digital pathology system (Aperio ImageScope System; for details refer to http://aperio.com/). Their diagnoses were considered the index diagnoses, which covered all grades of acute cellular rejection (ACR), early ischemic lesions, Quilty lesions, late ischemic lesions and (in the 2005 system) antibody-mediated rejection (AMR). Eighteen pathologists from 16 heart transplant centers in 7 European countries participated in the study. Inter-observer reproducibility was assessed using Fleiss's kappa and Krippendorff's alpha statistics. RESULTS: The combined kappa value of all grades diagnosed by all 18 pathologists was 0.31 for the 1990 grading system and 0.39 for the 2005 grading system, with alpha statistics at 0.57 and 0.55, respectively. Kappa values by grade for 1990/2005, respectively, were: 0 = 0.52/0.51; 1A/1R = 0.24/0.36; 1B = 0.15; 2 = 0.13; 3A/2R = 0.29/0.29; 3B/3R = 0.13/0.23; and 4 = 0.18. For the 2 cases of AMR, 6 of 18 pathologists correctly suspected AMR on the hematoxylin-eosin slides, whereas, in each of 17 of the 18 AMR-negative cases a small percentage of pathologists (range 5% to 33%) overinterpreted the findings as suggestive for AMR. CONCLUSIONS: Reproducibility studies of cardiac biopsies by pathologists in different centers at the international level were feasible using digitized slides rather than conventional histology glass slides. There was a small improvement in interobserver agreement between pathologists of different European centers when moving from the 1990 ISHLT classification to the "new" 2005 ISHLT classification. Morphologic suspicion of AMR in the 2004 system on hematoxylin-eosin-stained slides only was poor, highlighting the need for better standardization of morphologic criteria for AMR. Ongoing educational programs are needed to ensure standardization of diagnosis of both acute cellular and antibody-mediated rejection.

Gastrointestinal stromal tumors: report of an audit and review of the literature.

Gastrointestinal stromal tumors (GISTs), tumors characterized by c-KIT mutations, are the most frequent mesenchymal tumors of the digestive tract. The stomach is the most commonly involved site. Localization, size and mitotic rate are reliable predictors of survival and the two milestones of GISTs treatment are surgery and imatinib. This article is aimed to report the data of an audit, carried out on the morphological and clinical aspects of the disease and to review the present knowledge on GISTs. A total of 172 patients with GISTs (M : F=1 : 1; mean age 65 years) were recruited. The stomach was the most frequently involved site. In 50% of the cases the tumor was smaller than 5 cm, whereas major symptoms were observed in 43% of the cases. Predictors of progressive disease were present only in a small percentage of cases but the disease was in the metastatic phase in over 25% of the cases at diagnosis. Familial aggregation was rare but a consistent share of the patients (21%) had other synchronous or metachronous cancers. The most frequent mutations were in-frame deletions and point mutations of c-KIT exon 11. This report confirms in part the available data on GIST in a consecutive series of patients recruited in Italy and shows that only large collaborative multicenter studies provide data sound enough to enable making reasonable clinical and therapeutic choices, and suggests that, as a measure of secondary prevention, a diagnostic definition should be obtained in all submucosal lesions of the GI tract and that GIST patients should be screened for second tumors.

Organizational model for a telepathology system.

The technological development of telemedicine has performed important progress, assuming a diagnostic relief role inside of the processes. Among the fields in fast evolution, telepathology is placed among those of greater interest. Up to some years ago, telepathology allowed us to observe at a distance and in real time, histological or cytological slides through the Internet, using a motorized microscope (dynamic telepathology). Currently, telepathology has completed an important step in ahead being possible to digitize completely a slide and to store it. This allows observation of the whole surface of histological or cytological slides remotely with a customary PC, without human intervention (virtual slide). The described systems have exclusive characteristics, so that a "hybrid system" supporting both technologies, turns out to be the best solution applicable in a wide range program. In order to realize the theoretical aspects previously described, we report an organizational model practicable and applicable to a territory in which three hospitals operate. An essential prerequisite in order to arrange an efficient telepathology system turns out to be one structured data transmission network, equipped with elevated guaranteed bandwidth, and one consolidated experience in the registration and management of digital images.

Role of resection margins in patients treated with breast conservation surgery.

BACKGROUND: After breast conservation therapy (BCT), margin status is routinely evaluated to select patients who need reexcision. The aim of this study was to investigate how margin status and other clinicopathologic factors correlate with the presence of residual tumor at reexcision. METHODS: A series of 431 breast cancer patients who underwent BCT followed by reexcision were considered because they had positive or close (< or =3 mm) margins. At univariate and multivariate analysis the frequency of residual tumor in the reexcision specimens was associated with the status and width of resection margins and with a series of other clinicopathologic factors. RESULTS: Of the 382 evaluable patients, 253 had positive and 129 close margins. Residual tumor was found at reexcision in 51.8% positive-margin patients and 34.1% close-margin patients (P = .001). In the latter group tumor-margin distance (range, 0.08 to 3 mm) was not associated with the incidence of residual tumor (P = .134). On univariate analysis age < or =45 years (P = .006), intraductal histotype (P = .005), size > 2 cm (P = .010), positive axillary nodes (P = .031), and timing of reexcision (P = .044) were significantly associated with a higher frequency of residual tumor. All these factors, except tumor size, maintained a significant predictive value on multivariate analysis. CONCLUSIONS: In the presence of positive margins, relevant residual disease cannot be ruled out and further surgery is indicated. Close margins do not mandate reexcision because they may indicate either that the tumor has been radically excised or the presence of residual foci of a multifocal tumor, which are usually effectively treated by radiotherapy.

True solitary pancreatic cyst in an adult: report of a case.

The differential diagnosis of cystic neoformations in the pancreas is challenging. We report a case of a true solitary cyst of the pancreas in a 26-year old woman. Abdominal magnetic resonance imaging and computed tomography showed a unilocular neoformation in the head of the pancreas, without obstruction of Wirsung's duct. We excised the cyst and performed Roux-en-Y loop pancreaticojejunostomy, but the patient suffered recurrent acute pancreatitis from Wirsung's duct stenosis. Thus, a new Roux-en-Y loop pancreaticojejunostomy was successfully done 6 months later. Histologically, the cyst was lined by cuboidal epithelium, immunohistochemically positive to anti-carbohydrate antigen 19-9 antibodies. To our knowledge, only 11 cases of solitary true cyst of the pancreas in adults have been reported, so the characteristics of this unusual entity are not well known. We propose a scheme for the differential diagnosis of cystic neoformations of the pancreas, starting from the histopathological definition of a true solitary cyst.

Ratio between metastatic and examined lymph nodes is an independent prognostic factor after D2 resection for gastric cancer: analysis of a large European monoinstitutional experience.

BACKGROUND: In view of the lack of consensus on the level and number of lymph nodes to be examined for accurate staging of patients with gastric cancer, our aim was to evaluate the prognostic significance of lymph node status in a large European monoinstitutional experience. METHODS: A review was made of our prospective database from 1980 to 2000, when 314 of 445 patients operated for gastric adenocarcinoma underwent radical resection (R0) with D2 lymphadenectomy. Survival was determined by the Kaplan-Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression. RESULTS: In 277 evaluable patients, 5-year survival was 57% (median follow-up, 48 months; range, 2-251). A total of 7668 lymph nodes were examined (median, 27; range, 11-62). The 5-year survivals according to the metastatic/examined lymph nodes ratio (N ratio) were 14%, 50%, 61%, and 82% in the group of patients with N ratio >25%, 11%-25%, 1%-10%, and 0%, respectively (P <.0001). At multivariate analysis, the N ratio was the best single independent prognostic factor (P =.000). CONCLUSIONS: After R0 resection for gastric cancer, the N ratio is a potent prognostic factor. It should therefore be considered in the clinical decision making process.

Low level of p27(Kip1) protein expression in gastric adenocarcinoma is associated with disease progression and poor outcome.

BACKGROUND AND OBJECTIVES: Low tumor expression of the p27(Kip1) protein, which is involved in cell cycle control and apoptosis, is considered a negative prognostic factor in different types of cancer. The aim of this study was to evaluate the clinical and pathological significance of low p27(Kip1) protein expression in patients who had undergone resection for gastric adenocarcinoma. METHODS: p27(Kip1) protein was studied by immunohistochemistry in formalin-fixed tumor sections from 95 patients who underwent resection for gastric adenocarcinoma between 1991 and 1996. Based on the median value of protein expression, p27(Kip1) protein expression was classified as low or high. RESULTS: Low p27(Kip1) protein expression was significantly associated with tumor de-differentiation, increased penetration through the gastric wall, lymph node metastasis, and advanced tumor stage. In the group of 84 patients who underwent curative surgery, 5-year survival was 74% in cases with high p27(Kip1) protein expression and 38% in those with low p27(Kip1) protein expression (P < 0.001). At multivariate analysis, low p27(Kip1) protein expression was an independent negative prognostic factor for survival (RR = 3.671; P = 0.004). CONCLUSIONS: In gastric adenocarcinoma, low p27(Kip1) protein expression is associated with poorly differentiated and advanced tumors and is a negative prognostic factor of potential clinical value.

Gastrointestinal stromal tumors: from a surgical to a molecular approach.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. These tumors span a wide clinical spectrum from benign to malignant and have long been recognized for their nearly absolute resistance to chemotherapy and radiation treatment. We reviewed the worldwide experience on GIST diagnosis, prognosis and treatment and describe our own series. PubMed was searched for references using the terms gastrointestinal stromal tumor, GIST and gastrointestinal sarcoma. Recent reports were given emphasis because GIST is a novel clinical entity and older published work on gastrointestinal sarcomas might be contaminated with other histologic tumor types. At present, surgery is the standard treatment for primary resectable GIST. To increase the activity of conventional chemotherapeutic agents, locoregional therapies are being implemented in the clinical setting. A major breakthrough is the development of a new class of anticancer agents targeting tumor-specific molecular abnormalities. Preliminary results on administration of imatinib mesylate, a signal transduction inhibitor, are particularly encouraging, showing potent activity of this drug against metastatic GIST. Molecular targeting of the critical pathogenetic mechanism underlying GIST might not only revolutionize the strategy to treat locally advanced and metastatic GIST but also improve disease control after macroscopically radical surgery.

Lymphadenectomy in patients with gastric cancer. A critical review.

BACKGROUND: Surgical resection is still the main treatment for patients with gastric cancer. However, while surgical procedures for the treatment of the primary tumor have been standardized, there has been no worldwide consensus as yet on the extent of lymphadenectomy. The aim of the present study was therefore to evaluate the outcome following extended lymphadenectomy, and the prognostic significance of lymph node status, in a group of patients who underwent radical resection for gastric cancer. METHODS: Among 445 consecutive patients operated on for gastric adenocarcinoma between 1980 and 2000 at Clinica Chirurgica II of the Padua University, 314 underwent radical resection (R0). A D2 lymphadenectomy was performed in 293/314 cases (93.3%), and a D1 in 21/314 (6.7%). The rate of postoperative morbidity was 22% (69/314 patients), and the postoperative mortality (within 30 days of surgery), 4.1% (13/314 patients). Survival was determined using the Kaplan Meier method and differences were assessed by the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model in forward stepwise regression. RESULTS: Of 301 valuable patients, a total of 7991 lymph nodes were examined (mean, 27.18; range, 9-62) and the total number of metastatic lymph nodes was 1343 (mean, 4.5; range, 1-47). After a median follow-up of 49 months (range, 2-251), the overall 5-year survival was 57%. At multivariate analysis of all 301 patients, factors retained were depth of invasion (P < 0.001), age (P = 0.027), number of lymph node metastasis (P = 0.029), and metastatic/examined lymph node ratio (P < 0.0001). CONCLUSIONS: D2 dissection can be performed without incurring high mortality and morbidity rates. At least 15 lymph nodes must be removed to achieve an accurate disease staging. As confirmed at multivariate analysis, a metastatic/examined lymph node ratio greater than 25% is an independent negative prognostic factor.