Alberto Biondi

Determinants of surgical morbidity in gastric cancer treatment

BACKGROUND The occurrence of early surgical complications after gastrectomy as a treatment for gastric cancer has been reported to have a negative impact on longterm survival. The aim of this study was to identify treatment-related factors that can predict morbidity and mortality in patients undergoing operations for gastric cancer. STUDY DESIGN The charts of 388 patients who underwent different operations for gastric cancer at A Gemelli General Hospital, Catholic University of Rome, Italy, between January 1992 and April 2007, were reviewed. Patients were grouped according to the type of surgical treatment performed. The study end points were postoperative morbidity, mortality, and the length of hospital stay after surgery. RESULTS Overall morbidity and mortality rates were 16.2% (63 patients) and 2.3% (9 patients), respectively. Overall morbidity rates were higher in patients more than 64 years of age, when a gastric tumor was resected along with the spleen, and when an extended lymphadenectomy was performed. Patients older than 64 years had longer postoperative hospital stays, and Roux-en-Y gastrojejunostomy was predictive of a shorter stay. Mortality was not influenced by any surgically related factors. CONCLUSIONS Age, splenectomy, and extended lymphadenectomy were independently associated with the development of complications after gastric cancer operations. After subtotal gastrectomy, Roux-en-Y gastrojejunostomy was associated with a shorter postoperative length of stay than conventional Billroth I and Billroth II reconstructions.

Seventh Edition of TNM Classification for Gastric Cancer

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a “U” are those for which no compensation was received; those relationships marked with a “C” were compensated. For a detailed description of the disclosure categories, or for more information about ASCO’s conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors. Employment or Leadership Position: None Consultant or Advisory Role: Howard I. Scher, Novacea (U) Stock Ownership: None Honoraria: None Research Funding: None Expert Testimony: None Other Remuneration: None REFERENCES 1. Beer TM, Ryan CW, Venner PM, et al: Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: A report from the ASCENT Investigators. J Clin Oncol 25:669-674, 2007 2. Scher HI, Jia X, Chi K, et al: Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. J Clin Oncol 29:2191-2198, 2011 3. Fink M: Febrile neutropenia and infection in the ASCENT studies. J Clin Oncol 29:4337, 2011 4. Tannock IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502-1512, 2004 5. Fink M: Vitamin D deficiency is a cofactor of chemotherapy-induced mucocutaneous toxicity and dysgeusia. J Clin Oncol 29:e81-e82, 2011

Prognostic implications of the lymph node count after neoadjuvant treatment for rectal cancer

The aim of this study was to investigate the effect of neoadjuvant chemoradiotherapy on the lymph node yield of rectal cancer surgery.

Surgical treatment of ulcerative colitis in the biologic therapy era

Recently introduced in the treatment algorithms and guidelines for the treatment of ulcerative colitis, biological therapy is an effective treatment option for patients with an acute severe flare not responsive to conventional treatments and for patients with steroid dependent disease. The reduction in hospitalization and surgical intervention for patients affected by ulcerative colitis after the introduction of biologic treatment remains to be proven. Furthermore, these agents seem to be associated with increase in cost of treatment and risk for serious postoperative complications. Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice in ulcerative colitis patients. Surgery is traditionally recommended as salvage therapy when medical management fails, and, despite advances in medical therapy, colectomy rates remain unchanged between 20% and 30%. To overcome the reported increase in postoperative complications in patients on biologic therapies, several surgical strategies have been developed to maintain long-term pouch failure rate around 10%, as previously reported. Surgical staging along with the development of minimally invasive surgery are among the most promising advances in this field.

A case-control study on the effect of Apolipoprotein E genotypes on gastric cancer risk and progression

BackgroundApolipoprotein E (ApoE) is a multifunctional protein playing both a key role in the metabolism of cholesterol and triglycerides, and in tissue repair and inflammation. The ApoE gene (19q13.2) has three major isoforms encoded by ε2, ε3 and ε4 alleles with the ε4 allele associated with hypercholesterolemia and the ε2 allele with the opposite effect. An inverse relationship between cholesterol levels and gastric cancer (GC) has been previously reported, although the relationship between apoE genotypes and GC has not been explored so far.MethodsOne hundred and fifty-six gastric cancer cases and 444 hospital controls were genotyped for apoE polymorphism (ε2, ε3, ε4 alleles). The relationship between GC and putative risk factors was measured using the adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) from logistic regression analysis. A gene-environment interaction analysis was performed. The effect of the apoE genotypes on survival from GC was explored by a Kaplan–Meier analysis and Cox proportional hazard regression model.ResultsSubjects carrying at least one apoE ε2 allele have a significant 60% decrease of GC risk (OR=0.40, 95% CI: 0.19 – 0.84) compared with ε3 homozygotes. No significant interaction emerged between the ε4 or ε2 allele and environmental exposures, nor ε2 or ε4 alleles affected the median survival times, even after correcting for age, gender and stadium.ConclusionsOur study reports for the first time a protective effect of the ε2 allele against GC, that might be partly attributed to the higher antioxidant properties of ε2 compared with the ε3 or ε4 alleles. Given the study’s sample size, further studies are required to confirm our findings.

Follow-up: the evidence.

There is currently no consensus on the best strategy for the follow-up of patients who have undergone surgical treatment with curative intent for gastric cancer. The wide variation in recommendations for surveillance among international experts and hospital schedules clearly reflects a lack of an established body of evidence on this subject. Consequently, most of the international guidelines aimed at early detection of disease recurrence gloss over details concerning the mode, duration, and intensity of surveillance since they cannot be based on an acceptable grade of recommendation. Very few report anything other than the detection of recurrences or death as the primary endpoints, and, given the poor survival of patients with recurrent gastric cancer, the prognostic effect of early detection seems doubtful. In recent years, an increasing focus on evidence-based medicine, which has coincided with a growing concern about costs and efficiency in medicine, has caused a reevaluation of most surveillance practices. In this paper, we review and discuss the current body of evidence and follow-up practices after curative resection of gastric cancer.

PDGFRA-mutant syndrome.

Germline PDGFRA mutations cause multiple heterogeneous gastrointestinal mesenchymal tumors. In its familial form this disease, which was formerly termed intestinal neurofibromatosis/neurofibromatosis 3b (INF/NF3b), has been included among familial gastrointestinal stromal tumors (GISTs) because of its genotype, described when GIST was the only known PDGFRA-mutant gastrointestinal tumor. Shortly afterwards, however, inflammatory fibroid polyps also revealed PDGFRA mutations. Subsequently, gastrointestinal CD34+ ‘fibrous tumors’ of uncertain classification were described in a germline PDGFRA-mutant context. Our aim was to characterize the syndrome produced by germline PDGFRA mutations and establish diagnostic criteria and management strategies for this hitherto puzzling disease. We studied a kindred displaying multiple gastrointestinal mesenchymal tumors, comparing it with published families/individuals with possible analogous conditions. We identified a novel inherited PDGFRA mutation (P653L), constituting the third reported example of familial PDGFRA mutation. In adult mutants we detected inflammatory fibroid polyps, gastric GISTs and gastrointestinal fibrous tumors of uncertain nosology. We demonstrate that the syndrome formerly defined as INF/NF3b (exemplified by the family reported herein) is simplistically considered a form of familial GIST, because inflammatory fibroid polyps often prevail. Fibrous tumors appear variants of inflammatory fibroid polyps. ‘INF/NF3b’ and ‘familial GIST’ are misleading terms which we propose changing to ‘PDGFRA-mutant syndrome’. In this condition, unlike KIT-dependent familial GIST syndromes, if present, GISTs are stomach-restricted and diffuse Cajal cell hyperplasia is not observed. This restriction of GISTs to the stomach in PDGFRA-mutant syndrome: (i) focuses oncological concern on gastric masses, as inflammatory fibroid polyps are benign; (ii) supports a selective role of gastric environment for PDGFRA mutations to elicit GISTs, justifying the known predilection for stomach of sporadic PDGFRA-mutant GISTs. An awareness that inflammatory fibroid polyps, relatively common among gastrointestinal mesenchymal tumors, may be the prevailing tumor in PDGFRA-mutant syndrome could eventually reveal an unsuspected prevalence of this condition.

Prognostic factors and outcomes in Italian patients undergoing curative gastric cancer surgery

BACKGROUND Survival of patients after curative surgical resection for gastric cancer (GC) remains poor, thus emphasizing the need for better definition of prognostic factors to improve the long-term course of disease. METHODS From 1999 to 2009, 110 patients had curative-intent gastrectomy for adenocarcinoma. Clinicopathological features, Helicobacter pylori infection, dietary habits and lifestyle, and the presence of proinflammatory gene polymorphisms were evaluated. RESULTS At the end of follow-up, 55 deaths had occurred, 48 of them due to GC, whereas the median overall survival (OS) and disease-free survival (DFS) were 62 and 51 months, respectively. From the Kaplan-Meier analysis and log-rank test, statistically significant differences in OS and DFS were found for tumor site (only for DFS), tumor size, lymph node metastasis ratio (NR), and tumor-node-metastasis stage, but not for age, comorbidity, H. pylori infection, cigarette smoking, and IL1B or TNFA polymorphisms. Multivariable Cox regression analysis revealed NR was an independent prognostic factor for OS and DFS. Cardia tumor and patient age 65 years or older were also independent prognostic factors for OS and DFS. CONCLUSIONS Tumor-related factors remain strongest predictors of survival in GC patients after surgery. Particularly, NR was an effective feature in identifying patients at high risk for adverse outcome.

Neo-adjuvant chemo(radio)therapy in gastric cancer: Current status and future perspectives

In the last 20 years, several clinical trials on neoadjuvant chemotherapy and chemo-radiotherapy as a therapeutic approach for locally advanced gastric cancer have been performed. Even if more data are necessary to define the roles of these approaches, the results of preoperative treatments in the combined treatment of gastric adenocarcinoma are encouraging because this approach has led to a higher rate of curative surgical resection. Owing to the results of most recent randomized phase III studies, neoadjuvant chemotherapy for locally advanced resectable gastric cancer has satisfied the determination of level I evidence. Remaining concerns pertain to the choice of the optimal therapy regimen, strict patient selection by accurate pre-operative staging, standardization of surgical procedures, and valid criteria for response evaluation. New well-designed trials will be necessary to find the best therapeutic approach in pre-operative settings and the best way to combine old-generation chemotherapeutic drugs with new-generation molecules.

cDNA-Microarray Analysis as a New Tool to Predict Lymph Node Metastasis in Gastric Cancer

BackgroundThe aim of the present study was to investigate whether microarray gene expression analysis can be used to predict lymph node status in gastric cancer.MethodsTwenty-nine patients undergoing gastrectomy for cancer were enrolled and subdivided according to the pathologic nodal involvement of their disease (N+ vs N0). Molecular profiling was performed by cDNA microarray on tumor tissue and healthy mucosa. Data were processed to identify differently expressed genes. Selected genes were categorized with gene ontology.ResultsCompared to healthy gastric mucosa, 52 genes were differently expressed in N+ patients, and 50 genes in N0 patients. Forty-five genes were similarly regulated in N+ and N0 patients, whereas 12 genes were differently expressed between N+ and N0 patients. Seven genes were exclusively expressed in N+ patients: Egr-1 was upregulated; Claudin-18, AKR1C2, Cathepsin E, CA II, TFF 1, and progastricsin were downregulated. Five genes were exclusively expressed in N0 patients: Complement C5 receptor 1, PLA2/VII, and MMP- 9 were upregulated; MAO-A and ID-4 were downregulated.ConclusionsMicroarray analysis could be a valuable tool to identify genes associated with lymph node metastasis in gastric cancer. This technique could improve the selection of patients with locally advanced disease who are candidates for extended lymph node dissection, multimodal treatment options, or alternative therapeutic strategies.