Angelo Nespoli

Lymphocyte counts independently predict overall survival in advanced cancer patients: a biomarker for IL-2 immunotherapy.

Interleukin-2 (IL-2) targets cells bearing IL-2 receptors and induces different degrees of lymphocytosis. This study retrospectively evaluated whether lymphocytosis, in addition to clinical characteristics at baseline and to tumor objective response, may predict overall survival in metastatic renal cell carcinoma patients who received IL-2 subcutaneously (s.c.). Overall survival, clinical characteristics, tumor response, and total lymphocyte count at baseline and during the first treatment cycle of 266 advanced renal cell cancer patients, treated with 1 of 4 different first-line s.c. IL-2-based protocols, were studied using the Cox multivariate analysis. Median IL-2 cumulative dose and length of treatment (±SD) were 232 ± 282 × 106/m2 in 7 ± 5.9 weeks, respectively. Median overall survival (os) was 13.1 months (range 0.7–86.9+) in all. Tumor outcome consisted of: 9 CR (3%) (os = NR); 35 PR (13%) (os = 19.7 months.); 117 SD (44%) (os = 15.1 months); 105 PD (39%) (os = 6.4 months). Median lymphocyte counts were 1400/mm3 at baseline (25th–75th, 900–1900/mm3) and 3600/mm3 as a maximum value (25th–75th, 2600–4800/mm3). Death risk significantly decreased by 11% for each 1,000 lymphocytes/mm3 (RR 0.89; 95% CI 0.82–0.97), after correcting for clinical characteristics (PS ECOG 0 versus ≥1, time from primary diagnosis ≥2 years versus <2 years, number of metastatic sites 1 versus >1) and tumor response (CR, PR). A two-step bootstrapping procedure confirmed such predictive performance. Lymphocyte count monitoring represents a biomarker of the host response to subcutaneous IL-2 treatment useful for multimodal clinical assessment, as it predicts overall survival in advanced cancer patients independently from tumor response and from main clinical characteristics.

CORRELATION BETWEEN POSTOPERATIVE INFECTIONS AND LONG-TERM SURVIVAL AFTER COLORECTAL RESECTION FOR CANCER

Introduction Predicting long-term survival and cancer recurrence in patients with colorectal cancer is difficult because of the many factors that may affect the prognosis. This study investigated the prognostic significance of postoperative infections for patient outcome. Methods From an electronic database we selected 192 patients undergoing elective radical surgery for Dukes’ stage B and C colorectal adenocarcinoma. The five-year survival rates were analyzed by the Kaplan-Meier method. Univariate and multivariate analyses were carried out to evaluate the potential prognostic variables using the Cox proportional hazard model. Results Forty-three patients developed deep incisional or organ/space surgical site infections, while the remaining 149 were complication free. The two groups were comparable for baseline, surgical and histopathological characteristics. At univariate analysis, Dukes’ stage and infections were negative prognostic factors, while peritumoral infiltration of lymphocytes and eosinophils and fibrotic tissue appeared as protective variables. However, multivariate analysis showed that only Dukes’ stage (P = 0.048) and occurrence of postoperative infectious complications (P = 0.011) were independently associated with outcome. In patients with infectious complications, the survival rate was significantly lower than in patients without infections (log-rank = 0.0004). Conclusions The present results suggest the importance of evaluating other variables besides tumor stage in the prediction of long-term outcome. In prognostic studies more attention should be paid to postoperative infections.

Surgical treatment of liver metastases of gastric cancer: is local treatment in a systemic disease worthwhile?

OBJECTIVES The prognosis of patients with liver metastases of gastric cancer (LMGC) is dismal, but little is known about prognostic factors in these patients; thus justification for surgical resection is still controversial. The purpose of this study was to review recent outcomes of hepatectomy for LMGC and to determine which patients represent suitable candidates for surgery by assessing surgical results and clinicopathologic features. METHODS Outcomes in 21 patients with LMGC who underwent hepatectomy between 1998 and 2007 were assessed. Isolated metastases and potential to perform a curative resection were requisite indi-cations for surgery. Surgical outcome and clinicopathologic features of the hepatic metastases were analysed. RESULTS Overall 1-, 3- and 5-year survival rates after hepatic resection were 68%, 31% and 19%, respectively; three patients survived for >5 years without recurrence. Univariate analysis revealed a solitary metastasis, negative margin (R0) resection and the presence of a peritumoral fibrous capsule as significant favourable prognostic factors. These characteristics were present in all of the three patients who survived for >5 years. CONCLUSIONS Solitary metastases from gastric cancer should be treated surgically and confer a better prognosis. Surgical resection should provide microscopically negative margins (R0). A new prognostic factor, the presence of a pseudocapsule, may be associated with improved prognosis.

Bleeding in Hepatic Surgery: Sorting through Methods to Prevent It

Liver resections are demanding operations which can have life threatening complications although they are performed by experienced liver surgeons. The parameter “Blood Loss” has a central role in liver surgery, and different strategies to minimize it are a key to improve results. Moreover, recently, new technologies are applied in the field of liver surgery, having one goal: safer and easier liver operations. The aim of this paper is to review the different principal solutions to the problem of blood loss in hepatic surgery, focusing on technical aspects of new devices.

Single-incision versus standard multiple-incision laparoscopic cholecystectomy: a meta-analysis of experimental and observational studies.

Objective. The advantages of single-incision surgery for the treatment of gallstone disease is debated. Previous meta-analyses comparing single-incision laparoscopic cholecystectomy (SILC) and standard laparoscopic multiport cholecystectomy (SLMC) included few and underpowered trials. To overcome this limitation, we performed a meta-analysis of randomized and nonrandomized studies. Methods. A MEDLINE, EMBASE, and Cochrane Library literature search of studies published in and comparing SILC with SLMC was performed. The primary outcome was safety of SILC as measured by the overall rate of postoperative complications and biliary spillage. Feasibility was another primary outcome as measured by the conversion and operative time. Postoperative pain, length of hospital stay, perioperative blood loss, time to return to normal activity, and cosmetic satisfaction were secondary outcomes. Results. We identified 43 studies of which 30 were observational reports and 13 experimental trials, for a total of 7489 patients (2090 SILC and 5389 SLMC). The overall rate of complications was comparable between groups (relative risk [RR] = 1.08; 95% CI = 0.87-1.35; P = .46), as were the rates of biliary spillage (RR = 1.16; 95% CI = 0.73-1.84; P = .53) and conversion rate (RR = 0.88; 95% CI = 0.53-1.46; P = .62). Operative time was in favor of SLMC (weighted mean difference = 0.73; 95% CI = 0.67-0.79; P < .0001). Secondary outcomes favored SILC, but with marginal advantages. Conclusions. SILC is a feasible technique but without any significant advantage over SLMC for relevant end points. Although secondary outcomes favored SILC, the small magnitude of the advantage and the low quality of assessment methods question the clinical significance of these benefits.

Skin antisepsis with chlorhexidine versus iodine for the prevention of surgical site infection: A systematic review and meta-analysis

HighlightsSurgical site infection is one of the most frequent health care–associated infections.It is not clear if one antiseptic is better than any other prior to surgery.A review of literature shows results in favor of chlorhexidine. Background: Surgical site infection (SSI) is one of the most frequent health care–associated infections. One of the practices to reduce their incidence is preoperative skin antisepsis. Two of the most commonly active components used are chlorhexidine gluconate and povidone iodine. Of 3 reviews conducted between 2010 and 2012 comparing antiseptics, 2 were in favor of chlorhexidine; however, the latest was unable to draw conclusions. Purpose: To verify whether recent evidence supports the hypothesis that chlorhexidine in preoperative antisepsis is more efficient than other antiseptics in reducing SSI rates. Procedures: We conducted a systematic review from 2000‐2014 in all languages. The primary end point was SSI incidence and secondary skin bacterial colonization. Results: Nineteen studies were included. Meta‐analysis were conducted for comparable studies for both outcomes. The results of the meta‐analysis, including all of the studies in which chlorhexidine was compared with iodophor, were in favor of chlorhexidine for both SSI incidence (risk ratio [RR], 0.70; 95% confidence interval [CI], 0.52‐0.92) and bacterial skin colonization (RR, 0.45; 95% CI, 0.36‐0.55). Conclusions: There is moderate‐quality evidence supporting the use of chlorhexidine for preoperative skin antisepsis and high‐quality evidence that the use of chlorhexidine is associated with fewer positive skin cultures. Further rigorous trials will be welcomed to attain stronger evidence as to the best antiseptic to be used before surgery.

The History of Surgical Infections

The practice of medicine is a life-long learning process, which is based necessarily on knowledge of the past. To understand and set forth the history of surgery is to comprehend better the discipline’s present and anticipate its future, because there is absolutely no way to separate today’s surgery from the experiences of all the surgeons who have preceded us. Moreover, we believe that to study the past of our profession is fun, illuminating, humbling, and enormously useful even in this era of ever-increasing specialization. We have tried to approach the important topic of the history of surgical infections by illustrating, through the centuries, the development of medical cognition and the contribution of great personalities (e.g., physicians, surgeons, and microbiologists). In our travels through past decades, the beginnings of surgery can be traced directly from Adam and Eve, who were given birth by God in the week of Creation, as described in the first book of the Holy Bible. According to Genesis, God, having made man from dust, decided to create woman so that Adam would have another with whom he could share his life and would not be alone:

Effect of oral mesalamine on inflammatory response in acute uncomplicated diverticulitis

AIM To evaluate the impact of mesalamine administration on inflammatory response in acute uncomplicated diverticulitis. METHODS We conducted a single centre retrospective cohort study on patients admitted to our surgical department between January 2012 and May 2014 with a computed tomography -confirmed diagnosis of acute uncomplicated diverticulitis. A total of 50 patients were included in the analysis, 20 (study group) had received 3.2 g/d of mesalamine starting from the day of admission in addition to the usual standard treatment, 30 (control group) had received standard therapy alone. Data was retrieved from a prospective database. Our primary study endpoints were: C reactive protein mean levels over time and their variation from baseline (ΔCRP) over the first three days of treatment. Secondary end points included: mean white blood cell and neutrophile count over time, time before regaining of regular bowel movements (passing of stools), time before reintroduction of food intake, intensity of lower abdominal pain over time, analgesic consumption and length of hospital stay. RESULTS Patients characteristics and inflammatory parameters were similar at baseline in the two groups. The evaluation of CRP levels over time showed, in treated patients, a distinct trend towards a faster decrease compared to controls. This difference approached statistical significance on day 2 (mean CRP 6.0 +/- 4.2 mg/dL and 10.0 +/- 6.7 mg/dL respectively in study group vs controls, P = 0.055). ΔCRP evaluation evidenced a significantly greater increment of this inflammatory marker in the control group on day 1 (P = 0.03). A similar trend towards a faster resolution of inflammation was observed evaluating the total white blood cell count. Neutrophile levels were significantly lower in treated patients on day 2 and on day 3 (P < 0.05 for both comparisons). Mesalamine administration was also associated with an earlier reintroduction of food intake (median 1.5 d and 3 d, study group vs controls respectively, P < 0.001) and with a shorter hospital stay (median 5 d and 5.5 d, study group vs controls respectively, P = 0.03). CONCLUSION Despite its limitations, this study suggests that mesalamine may allow for a faster recovery and for a reduction of inflammatory response in acute uncomplicated diverticulitis.

Erratum: Corrigendum: Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells

Corrigendum: Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells

Erratum : Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells (Nature Immunology (2005) 6 (507-514))

Corrigendum: Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells