Anna Maria Minicozzi

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.

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.

A multicentric Western analysis of prognostic factors in advanced, node-negative gastric cancer patients

Background:The presence of lymph node metastasis is one of the most important prognostic factors in patients with gastric carcinoma. Node-negative patients have a better outcome, nevertheless a subgroup of them experience disease recurrence. Aim:To analyze the clinicopathological characteristics of lymph node-negative advanced gastric carcinoma patients submitted to gastrectomy and D2 lymphadenectomy with a retrieved number of nodes greater than 15, after an actual follow-up of almost 5 years, and to evaluate outcome indicators. Study Design:The records of 301 patients who underwent curative gastrectomy for gastric carcinoma and were adequately staged as N0 between 1992 and 2002 were retrospectively analyzed from the prospectively collected database of 7 centers participating to the Italian Research Group for Gastric Cancer. Results:Disease-specific and disease-free survival after 3, 5, and 10 years were 90.4%, 86.1%, 75.9%, and 72.1%, 57.3%, 57.3%, respectively. Mortality was 1.7%. The factors associated with a better disease-free survival at univariate analysis were age <60, T2 tumors, distal location, intestinal histotype, and number of retrieved nodes >25; depth of infiltration and histotype were the only 2 independent predictors of 5-year recurrence-free survival at multivariate analysis. Conclusion:These parameters must be considered to stratify node-negative gastric cancer patients for an adjuvant treatment and follow-up scheduling. Survival was similar to that previously reported by Eastern Centers. Lymphadenectomy is suggested to be effective, and retrieval of more than 25 nodes may be warranted.

The role of resistin in colorectal cancer

BACKGROUND To date the role of resistin in colorectal cancer (CRC) is far from being elucidated. The aim of this study was to investigate the association between serum resistin levels and CRC in relation to known risk/protective factors including anthropometric, metabolic, inflammatory parameters as well as lifestyle individual characteristics. METHODS 40 CRC patients and 40 controls were enrolled. Body weight, height, waist circumference and blood pressure were recorded. Fasting plasma glucose, lipids, C-reactive protein (CRP) and resistin levels were measured. Metabolic Syndrome (MS) was defined according to the harmonized definition. RESULTS Resistin levels were significantly higher in CRC patients than in controls (p=0.028) and gradually increased with tumor stage progression (p=0.042). A high resistin level was statistically significant determinant of CRC after adjusting for age, sex, body mass index and lifestyle parameters (p=0.029). Resistin showed a strong association with CRP levels (p ≤ 0.0001). In stepwise regression analysis CRP remained the only independent predictor of both resistin levels (p=0.001) and CRC risk (p=0.021). CONCLUSIONS These results clarify the nature of the association between resistin and CRC risk suggesting that the proinflammatory state of cancer, rather than the clinical diagnosis of CRC itself or its link with obesity and MS, may govern this association.

Perianal Paget's disease: presentation of six cases and literature review

PurposeExtramammary Paget’s disease (EMPD) is frequently associated with adnexal or visceral synchronous or metachronous malignancies. Our purpose was to evaluate, retrospectively, the results obtained in six cases of EMPD and to review the literature.MethodsSix patients with the perianal Paget’s disease had been treated in our division between March 1996 and December 2006. In three cases, the disease was confined in the epidermis; in one case, there was a microinvasion of the dermis, while in another one the dermis was infiltrated. The last case was associated to a low rectal adenocarcinoma. All patients underwent wide perianal excision and reconstruction with skin graft. We performed a transanal resection of the rectal adenocarcinoma. A review of the literature from 1990 to 2008 revealed 193 cases of perianal EMPD, 112 were intraepithelial/intradermal while 81 were associated with malignancies. Anorectal adenocarcinoma was already existing in two cases, synchronous in 48, and subsequent to diagnosis in 11.ResultsIn three cases, the disease recurred locally, but no patient developed metastatic spread. Five patients survived and are free of disease. The review of the literature allows a clear identification of the primitive EMPD and the form associated to anorectal adenocarcinoma and little information about cases associated with synchronous adnexal adenocarcinoma. The Paget’s disease can relapse after radical surgery and has a capacity of metastatic spread.ConclusionsUp to now, no clear guidelines have been established for the diagnosis of EMPD. The association with synchronous or metachronous carcinomas imposes a long-term follow-up with frequent clinical, radiological, and endoscopical controls.

Lymph Node Involvement in Gastric Cancer for Different Tumor Sites and T Stage

BackgroundThe aim of lymphadenectomy is to clear all the metastatic nodes achieving a complete removal of the tumor; nevertheless, its role in gastric cancer has been very much debated.Materials and methodsThe frequency of node metastasis in each lymphatic station according to the International Gastric Cancer Association, was studied in 545 patients who underwent D2 or D3 lymphadenectomy from June 1988 to December 2002.ResultsUpper third early cancers have shown an involvement of N2 celiac nodes in 25%. In advanced cancers, there was a high frequency of metastasis in the right gastroepiploic (from 10% in T2 to 50% in T4) and in the paraaortic nodes (26% in T2, 32% in T3, 38 % in T4). N3 left paracardial nodes involvement was observed in an important share of middle third tumors (17% in T3, 36% in T4). Splenic hilum nodes metastasis were common in T3 and T4 cancers located in the upper (39%) and middle (17%) stomach. N2 nodal involvement was frequent in lower third advanced cancers. Metastasis in M left paracardial and short gastric nodes were observed in a small percentage of cases.ConclusionGiven the nodal diffusion in our gastric cancer patients, extended lymphadenectomy is still a rationale to obtain radical resection.

18F-FDG-PET/CT in patients with breast cancer and rising Ca 15-3 with negative conventional imaging: A multicentre study

OBJECTIVES Breast cancer is the second cause of death in women in Europe and North America. The mortality of this disease can be reduced with effective therapy and regular follow up to detect early recurrence. Tumor markers are sensitive in detecting recurrent or residual disease but imaging is required to customize the therapeutic option. Rising tumor markers and negative conventional imaging (US, X-mammography, CT and MR) poses a management problem. Our aim is to assess the role of 18F-FDG-PET/CT in the management of post-therapy patients with rising markers but negative conventional imaging. MATERIALS AND METHODS In the period from January 2008 to September 2009, 89 female patients with breast cancer who developed post-therapy rising markers (serum Ca 15-3 levels=64.8±16.3 U/mL) but negative clinical examination and conventional imaging were investigated with 18F-FDG-PET/CT. RESULTS Tumor deposits were detected in 40/89 patients in chest wall, internal mammary nodes, lungs, liver and skeleton. The mean SUVmax value calculated in these lesions was 6.6±1.7 (range 3.1-12.8). In 23/40 patients solitary small lesion were amenable to radical therapy. In 7 out of these 23 patients a complete disease remission lasting more than 1 year was observed. CONCLUSIONS 18F-FDG-PET/CT may have a potential role in asymptomatic patients with rising markers and negative conventional imaging. Our findings agree with other studies in promoting regular investigations such as tumor markers and 18F-FDG-PET/CT rather than awaiting the developments of physical symptoms as suggested by current guidelines since the timely detection of early recurrence may have a major impact on therapy and survival.

Response to induction therapy in oesophageal and cardia carcinoma using Mandard tumour regression grade or size of residual foci.

Tumour regression grade (TRG) is used to evaluate responses to induction therapy in cancer of the oesophagus or cardia. This study aimed to determine whether inclusion of node category could improve the prognostic accuracy provided by TRG, and explore the prognostic value of an alternative classification based on size of residual foci and node category.

Epigenetic alteration: new insights moving from tissue to plasma – the example of PCDH10 promoter methylation in colorectal cancer

Background:Tumour-released DNA in blood represents a promising biomarker for cancer detection. Although epigenetic alterations such as aberrant promoter methylation represent an appealing perspective, the discordance existing between frequencies of alterations found in DNA extracted from tumour tissue and cell-free DNA (cfDNA) has challenged their practical clinical application. With the aim to explain this bias of agreement, we investigated whether protocadherin 10 (PCDH10) promoter methylation in tissue was associated with methylation pattern in matched cfDNA isolated from plasma of patients with colorectal cancer (CRC), and whether the strength of concordance may depend on levels of cfDNA, integrity index, as well as on different clinical–pathological features.Methods:A quantitative methylation-specific PCR was used to analyse a selected CpG site in the PCDH10 promoter of 67 tumour tissues, paired normal mucosae, and matched plasma samples. The cfDNA integrity index and cfDNA concentration were assessed using a real-time PCR assay.Results:The PCDH10 promoter methylation was detected in 63 out of 67 (94.0%) surgically resected colorectal tumours and in 42 out of 67 (62.7%) plasma samples. The median methylation rate in tumour tissues and plasma samples was 43.5% (6.3–97.8%) and 5.9% (0–80.9%), respectively. There was a significant correlation between PCDH10 methylation in cfDNA and tumour tissue in patients with early CRC (P<0.0001). The ratio between plasma and tissue methylation rate increases with increasing cfDNA integrity index in early-stage cancers (P=0.0299) and with absolute cfDNA concentration in advanced cancers (P=0.0234).Conclusion:Our findings provide new insight into biological aspects modulating the concordance between tissues and plasma methylation profiles.

Real-time polymerase chain reaction quantification of free DNA in serum of patients with polyps and colorectal cancers

Abstract Background: Colorectal cancer (CRC) is one of the most frequent causes of cancer related deaths worldwide. Recently, the use of cell-free DNA as diagnostic tools to identify cancer has been investigated. The aim of this work was to assess whether circulating DNA could be considered a useful marker for detection of early stage CRC and polyps. Methods: A total of 118 patients with CRC were included in the study along with 49 patients with colorectal polyps and 26 control subjects. Cell-free DNA was quantified using a real-time TaqMan-polymerase chain reaction assay. Non-parametric tests (Mann-Whitney test and Spearman correlation) were utilized for statistical analysis. Results: Serum DNA concentrations were significantly higher in CRC patients and patients with polyps (median value 105.0 ng/mL and 40.0 ng/mL) compared with controls (median value 14.0 ng/mL; p<0.05). Although carcinoembryonic antigen was above the cut-off in only 13/66 (19.7%) patients with early stage CRC, serum free DNA showed values above the threshold identified using receiver operator characteristic (ROC) curve analysis in 53/66 (80.3%) patients. Conclusions: Our data confirm that serum DNA concentrations are significantly increased in CRC patients with early stage disease and in patients with polyps. This marker might be useful for identifying high-risk individuals. Clin Chem Lab Med 2010;48:1665–8.