Giovanni de Manzoni

The ratio between metastatic and examined lymph nodes (N ratio) is an independent prognostic factor in gastric cancer regardless of the type of lymphadenectomy: results from an Italian multicentric study in 1853 patients.

Purpose:To investigate whether the ratio between metastatic and examined lymph nodes (N ratio) is a better prognostic factor as compared with traditional staging systems in patients with gastric cancer regardless of the extension of lymph node dissection. Patients & Methods:We retrospectively reviewed the data of 1853 patients who underwent radical resection for gastric carcinoma at 6 Italian centers. Patients with >15 (group 1, n = 1421) and those with ≤15 (group 2, n = 432) lymph nodes examined were separately analyzed. N ratio categories (N ratio 0, 0%; N ratio 1, 1%–9%; N ratio 2, 10%–25%; N ratio 3, >25%) were determined by the best cut-off approach. Results:After a median follow-up of 45.5 months (range, 4–182 months), the 5-year overall survival of N0, N1, and N2 patients of group 1 versus group 2 was 83.4% versus 74.2% (P = 0.0026), 54.3% versus 44.3% (P = 0.018), and 32.7% versus 14.7% (P = 0.004), respectively, suggesting that a low number of excised lymph nodes can lead to the understaging of patients. N ratio identified subsets of patients with significantly different survival rates within N1 and N2 stages in both groups. At multivariate analysis, the N ratio (but not N stage) was retained as an independent prognostic factor both in group 1 and group 2 (HR for N ratio 1, N ratio 2, and N ratio 3 = 1.67, 2.96, and 6.59, and 1.56, 2.68, and 4.28, respectively). In our series, the implementation of N ratio led to the identification of subgroups of patients prognostically more homogeneous than those classified by the TNM system. Conclusion:N ratio is a simple and reproducible prognostic tool that can stratify patients with gastric cancer also in case of limited lymph node dissection. These data may represent the rational for improving the prognostic power of current UICC TNM staging system and ultimately the selection of patients who may most benefit from adjuvant treatments.

Prediction of Recurrence After Radical Surgery for Gastric Cancer: A Scoring System Obtained From a Prospective Multicenter Study

Objective:The aim of this prospective multicenter study was to define a scoring system for the prediction of tumor recurrence after potentially curative surgery for gastric cancer. Summary Background Data:The estimation of the risk of recurrence in individual patient may be relevant in clinical practice, to apply adjuvant therapies after surgery, and plan an adequate follow-up program. Only a few studies, most of which were retrospective or performed on a limited number of patients, have developed a prognostic score in patients with gastric cancer. Methods:A total of 536 patients who underwent UICC R0 resection between 1988 and 1998 at 3 surgical departments in Italy were considered. All patients were followed up using a standard protocol after discharge from the hospital. The mean follow-up period was 56 ± 44 months, and 94 ± 29 months for surviving patients. The scoring system was calculated on the basis of a logistic regression model, where the presence of the recurrence was the dependent variable, and clinicopathologic variables were the covariates. Results:Recurrence occurred in 272 of 536 patients (50.7%). The scoring system for the prediction of the risk in individual cases gave values ranging from 1.4 to 99.9; the model distributed most cases in the extremes of the range. The risk of recurrence increased remarkably with score values; it was only 5% in patients with a score below 10, up to 95.4% in patients with a score of 91 to 100. No recurrence was observed in 43 patients with a score below 4, whereas all of the 56 patients with a score over 97 presented a recurrence. The model correctly predicted recurrence in 227 of 272 patients (sensitivity, 83.5%), whereas the absence of recurrence was correctly predicted in 214 of 264 patients (specificity, 81.1%); the overall accuracy was 82.2%. Prognostic score was clearly superior to UICC tumor stage in predicting recurrence. The high effectiveness of the score was confirmed in preliminary data of a validation study. Conclusions:The scoring system obtained with a regression model on the basis of our follow-up data is useful for defining subgroups of patients at a very low or very high risk of tumor recurrence after radical surgery for gastric cancer. Final results of the validation study are essential for a clinical application of the model.

LAPAROSCOPIC CHOLECYSTECTOMY FOR SEVERE ACUTE CHOLECYSTITIS. A META-ANALYSIS OF RESULTS

ObjectiveThe aim of this review was to evaluate surgical outcomes of laparoscopic cholecystectomy for gangrenous and empyematous acute cholecystitis defined as severe acute cholecystitis.BackgroundIt is not known to what extent surgical outcomes of laparoscopic cholecystectomy for severe acute cholecystitis differ from those for the nonsevere acute form, making it questionable whether urgent laparoscopic cholecystectomy is the best approach even in severe acute cases.MethodsLiterature searches were conducted to identify: (1) comparative studies which reported laparoscopic surgical outcomes separately for severe acute and nonsevere acute cholecystitis; (2) studies comparing such an approach with open cholecystectomy, subtotal laparoscopic cholecystectomy or cholecystostomy in severe acute cholecystitis. Results were pooled by standard meta-analytic techniques.ResultsSeven studies with a total of 1,408 patients undergoing laparoscopic cholecystectomy were found. The risks of conversion (RR 3.2, 95% CI 2.5 to 4.2) and overall postoperative complications (RR 1.6, 95% CI 1.2–2.2) were significantly higher in severe acute cholecystitis with respect to the nonsevere acute forms. However, no difference was detected as regards to local postoperative complications. No studies comparing open cholecystectomy or cholecystostomy with urgent laparoscopy were found.ConclusionA lower feasibility of laparoscopic cholecystectomy has been found for severe cholecystitis. A lower threshold of conversion is recommended since this may allow to reduce local postoperative complications. Literature data lack valuable comparative studies with other treatment modalities, which therefore need to be investigated.

Different Patterns of Recurrence in Gastric Cancer Depending on Lauren’s Histological Type: Longitudinal Study

AbstractThe aim of this multicenter longitudinal study was to evaluate the pattern of recurrence in patients submitted to potentially curative surgery for intestinal-type and diffuse-type gastric cancer. The study included 412 patients surgically treated at three Italian surgical departments, subdivided into 273 intestinal-type cases (group A) and 139 diffuse-type cases (group B). Recurrence of disease was found in 41% of group A cases and 65% of group B cases (p <0.0001). The incidence of locoregional, hematogenous, and peritoneal recurrence was 20%, 19%, and 9% in group A, and 27%, 16%, and 34% in group B, respectively; the difference between the two groups was statistically significant for peritoneal recurrence (p <0.0001). Multivariate analysis identified as prognostic variables lymph node status, depth of invasion, extent of lymphadenectomy, advanced age, and male gender in group A; depth of invasion, extent of lymphadenectomy, tumor size, and lymph node status, in group B. Whereas in group A the incidence of peritoneal recurrence was limited in all subgroups examined, in group B very high rates were observed in cases with infiltration of the serosa, involvement of second-level lymph nodes, or large tumor size. The notable difference in the risk of peritoneal recurrence between the intestinal and diffuse types should be taken into consideration in the therapeutic approach to gastric cancer.

Endoscopic ultrasonography in the staging of esophageal carcinoma after preoperative radiotherapy and chemotherapy

BACKGROUND In past years multimodal neoadjuvant treatment for carcinoma of the esophagus has been used with increased frequency. Staging of the neoplasm still remains fundamental in evaluating the response to therapy and in planning operation. The aim of the present study was to assess the accuracy of endoscopic ultrasonography (EUS) in a group of patients with squamous cell carcinoma of the thoracic esophagus after undergoing radiotherapy and chemotherapy. METHODS Among a group of 111 patients with squamous cell carcinoma of the thoracic esophagus and treated with preoperative radiotherapy and chemotherapy, 87 were operated. In these patients it was possible to compare the results of EUS, with regard to depth of invasion of esophageal wall (T) and lymph node involvement (N), with the results of operation and histopathologic study. RESULTS Feasibility of EUS before and after neoadjuvant treatment was 71.2% and 83.9%, respectively. The overall accuracy of EUS regarding the wall invasion was 47.9%. The more frequent error was overstaging, especially in patients with complete response and in patients with minimal residual disease. In the assessment of lymph node involvement, EUS showed an overall accuracy of 71.2% with a moderate kappa value. Sensitivity for N1 and NO was 73.7% and 68.6%, respectively. CONCLUSIONS Endoscopic ultrasonography was feasible in most patients after preoperative radiotherapy and chemotherapy, but our study documented a worsening of accuracy of EUS in the evaluation of T attributable to the confounding presence of radiation fibrosis and soft tissue reaction after radiotherapy and chemotherapy.

Survival benefit of extended D2 lymphadenectomy in gastric cancer with involvement of second level lymph nodes: A longitudinal multicenter study

BackgroundThe survival benefit of extended lymphadenectomy in the surgical treatment of gastric cancer is still being debated. The aim of this longitudinal multicenter study was to evaluate long-term survival in a group of patients with involvement of second level lymph nodes, which would not have been removed in the case of a limited lymphadenectomy. Results were compared with those in patients with involvement of first level lymph nodes.MethodsBetween 1991 and 1997, 451 patients with primary gastric cancer underwent curative resection with extended lymphadenectomy at three surgical departments in Italy according to the rules of the Japanese Research Society for Gastric Cancer.ResultsIn 451 cases treated by extended lymphadenectomy, morbidity and mortality rates were 17.1% and 2%, respectively. In 126 patients (27.9%) (group A), metastases were found in lymph node stations 7 to 12; 109 patients (24.2%) had metastases confined to the first level (group B). Lymph node stations 7 and 8 showed the highest incidence of metastases in the second level (17.1% and 12.4%, respectively). A significant difference in 5-year survival was observed between group A and group B (32% vs. 54%;P=.0005). This difference disappeared when cases were stratified according to the number of positive lymph nodes. By multivariate analysis, only the number of positive lymph nodes (relative risk, 1.8;P<.0001) and the depth of invasion (relative risk. 2.1;P<.0001), but not the level of involved nodes, showed to be independent predictors of poor prognosis.ConclusionsJapanese-type extended lymphadenectomy yields low morbidity and mortality rates if performed in specialized centers. This procedure could provide a good probability of long-term survival, even for patients with involvement of regional lymph nodes.

Pleomorphic carcinomas of the lung show a selective distribution of gene products involved in cell differentiation, cell cycle control, tumor growth, and tumor cell motility: a clinicopathologic and immunohistochemical study of 31 cases.

We investigated 31 cases of pleomorphic carcinomas of the lung, with a double component of neoplastic epithelial cells and of spindle and/or giant cells. To correlate the morphologic diversity of these two cell components with their immunophenotype, we evaluated the expression of several gene products involved in cell differentiation (cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, vimentin, S-100 protein, smooth muscle actin, desmin), cell cycle control and apoptosis (p53, p21Waf1, p27Kip1, FHIT), tumor growth (proliferative fraction, assessed by Ki-67 antigen, and microvascular density, assessed by CD34 immunostaining), and tumor cell motility (fascin). We found the epithelial component to be significantly more immunoreactive for cytokeratins, epithelial membrane antigen, carcinoembryonic antigen, cell cycle inhibitors p21Waf1, p27Kip1 and tumor suppressor gene FHIT, whereas the sarcomatoid component, independent of tumor stage and size, was more immunoreactive for vimentin, fascin, and microvascular density. Accordingly, we suggest a model of tumorigenesis whereby the mesenchymal phenotype of pleomorphic cells is likely induced by the selective activation and segregation of several molecules involved in cell differentiation, cell cycle control, and tumor cell growth and motility. Whether pleomorphic carcinomas of the lung are tumors with a dismal prognosis still remains an unsettled issue. In our series, however, stage I pleomorphic carcinomas have the same clinical behavior as ordinary non-small cell lung cancer, and only a high proliferative index (Ki-67 labeling index >35%) is associated with a worse prognosis in these tumors.

Independent value of fascin immunoreactivity for predicting lymph node metastases in typical and atypical pulmonary carcinoids

Immunoreactivity for fascin, an actin-bundling protein related to cell motility, has been reported in breast, ovary, pancreas, skin, and non-small cell carcinomas, and associated with more advanced disease stage and poorer prognosis. Data on pulmonary neuroendocrine (NE) tumors, however, are lacking. We evaluated the expression of fascin by immunohistochemistry--using two different monoclonal antibodies--in surgical specimens of pulmonary NE tumors of all the diverse histological types from 128 consecutive patients recruited between 1987 and 2001, and investigated its relationship with the presence of lymph node metastases. Overall, fascin immunoreactivity was detected in 5% of 38 typical carcinoids (TC), 35% of 23 atypical carcinoids (AC), 83% of 40 large-cell neuroendocrine carcinomas (LCNEC), and 100% of 27 small-cell lung carcinomas (SCLC) (P<0.001), Normal NE cells or hyperplastic NE tumorlets were consistently unreactive. No statistically significant differences in fascin immunoreactivity were found between the two antibodies. In TC and AC but not high-grade NE tumors, fascin immunoreactivity closely correlated with the occurrence of lymph node metastases, the pN class and the number of involved lymph nodes (P<0.001). It was also significantly associated with an increased proliferative activity (Ki-67 labeling index >5%) (P=0.020), and with either down-regulation or altered subcellular compartmentalization of E-cadherin (P<0.001) and CD99 (P=0.030), two cell adhesion complexes in pulmonary NE tumors. At multivariate analysis, only fascin emerged as an independent predictor of lymph node metastases in this tumor group (HR 30.28; 95% confidence intervals: 1.59-574.49; P=0.023). This study indicates that fascin immunoreactivity may identify subsets of pulmonary carcinoid patients with different metastatic potential to regional lymph nodes. Targeting the fascin pathway could be a novel therapeutic strategy of pulmonary carcinoids.

Prognostic implications of neuroendocrine differentiation and hormone production in patients with Stage I nonsmall cell lung carcinoma

Approximately 10–20% of nonsmall cell lung carcinomas (NSCLC) show neuroendocrine (NE) differentiation, as evaluated by panendocrine markers or ultrastructural evidence of dense‐core secretory granules. However, little is known regarding the prevalence and clinical implications of NE differentiation in patients with Stage I NSCLC.

Treatment of Peritoneal Carcinomatosis by Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemoperfusion (IHCP): Postoperative Outcome and Risk Factors for Morbidity

BackgroundCytoreductive surgery with limited or extended peritonectomy associated with intraperitoneal hyperthermic chemoperfusion (IHCP) has been proposed for treatment of peritoneal carcinomatosis (PC) from abdominal neoplasms.MethodsFifty-nine patients with PC from abdominal neoplasms underwent 61 treatments using this technique from January 2000 to August 2005. Surgical debulking, completed by partial or total peritonectomy, was performed in most cases. In 16 patients with positive peritoneal cytology without macroscopic peritoneal disease, IHCP was performed in order to prevent peritoneal recurrence. IHCP was carried out throughout the abdominopelvic cavity for 60 minutes using a closed abdomen technique. Intra-abdominal temperature ranged between 41°C and 43°C; mitomycin C (25 mg/mq) and cisplatin (100 mg/mq) were the anticancer drugs generally used, and they were administered with a flow rate of 700–800 ml/minute.ResultsMean hospital stay was 13 ± 7 (range 7–49) days. Postoperative complications occurred in 27 patients (44.3%); of these, major morbidity was observed in 17 (27.9%). The most frequent complications were wound infection (9 cases), grade 2 or greater hematological toxicity (5 cases), intestinal fistula (5 cases), and pleural effusion requiring drainage (5 cases). Reoperation was necessary in 5 patients (8.2%). One patient with multiorgan failure died in the postoperative period (mortality rate: 1.6%). Multivariate analysis of several variables identified completeness of cancer resection (CCR-2/3 vs. CCR-0/1, relative risk: 9.27) and age (relative risk: 1.06 per year) as independent predictors of postoperative morbidity. Preliminary follow-up data indicate that survival probability may be high in patients with ovarian or colorectal cancer and low in patients with gastric cancer.ConclusionsIHCP combined with cytoreductive surgery involves a high risk of morbidity, but postoperative complications could be resolved favorably in most cases with correct patient selection and adequate postoperative care. Tumor residual and advanced age significantly increase the risk of morbidity after this procedure.