Fausto Rosa

Is malnutrition still a risk factor of postoperative complications in gastric cancer surgery

OBJECTIVE & AIMS The present study aimed at retrospectively evaluating the incidence of mortality and major and minor postoperative complications in patients who underwent surgery for gastric cancer between 2000 and 2006 stratified according to the preoperative percentage weight loss, serum albumin levels and body mass index (BMI). METHODS One hundred and ninety-six patients affected by gastric cancer admitted to the Division of Digestive Surgery of the Catholic University of Rome between January 2000 and December 2006 were considered eligible and were included in the study. According to the weight loss, patients were divided into three groups: (1) 0-5%; (2) 5.1-10%; (3) >10%. On the basis of serum albumin levels, were divided into three groups: (1) <3.0 g/dl; (2) 3.0-3.4 g/dl; (3) >3.5 g/dl. According to BMI, were divided into four groups: (1) <18.5 kg/m(2); (2) 18.5-24.9 kg/m(2); (3) 25.0-29.9 kg/m(2); (4) >30.0 kg/m(2). Postoperative complications and mortality were reported. Complications were classified by objective criteria as major or minor, and as infectious or non-infectious. RESULTS The postoperative mortality was 0%. Major infectious complications occurred in 20 patients (10.2%), major non-infectious in 18 (9.2%), minor infectious in 21 (10.7%), whereas minor non-infectious complications were absent. The rate of major infectious, major non-infectious and minor infectious postoperative complications was similar in patients with absent or light weight loss (8.8%, 8.8%, 10.6%, respectively), mild weight loss (15.3%, 11.5%, 9.6%, respectively), or severe weight loss (6.4%, 6.4%, 12.9%, respectively). Similarly, the rate of postoperative complications did not differ between patients with serum albumin <3.0 g/dl (10.8%, 8.1%, 8.1%, respectively); between 3.0 and 3.4 (8.8%, 13.3%, 17.7%, respectively) or > or =3.5 g/dl (10.5%, 7.9%, 8,7%, respectively). According to BMI, the rate of postoperative complications was: 11.7%, 5.8%, and 5.8% for BMI <18.5 kg/m(2); 9.4%, 8.2%, and 11.7% for BMI between 18.5 and 24.9 kg/m(2); 10.7%, 10.7%, and 9.2% for BMI between 25 and 29.9 kg/m(2); 10.3%, 10.3% and 13.7% for BMI >30 kg/m(2). Then, we evaluated the postoperative morbidity only in patients who underwent total gastrectomy or distal subtotal gastrectomy associated with extended lymphadenectomy. In this group of patients, the rate of postoperative complications was comparable in patients with 0-5% (8.8%, 7.7%, 10%, respectively), 5.1-10% (14.6%, 9.7%, 9.7%, respectively), and >10% (7.1%, 7.1%, 14.3%, respectively) weight loss. Also stratifying the patients according to the serum albumin levels, the rate of postoperative complications did not differ significantly (serum albumin <3.0 g/dl: 14.8%, 11.1%, 14.8%, respectively; serum albumin between 3.0 and 3.4 g/dl: 6.2%, 12.5%, 15.6%, respectively; serum albumin > or =3.5 g/dl: 10.4%, 5.8%, 7.0%, respectively). According to BMI, the rate of postoperative complications was: 7.6%, 0%, and 7.6% for BMI <18.5 kg/m(2); 9.5%, 9.5%, and 11.1% for BMI between 18.5 and 24.9 kg/m(2); 12.5%, 8.3%, and 10.4% for BMI between 25 and 29.9 kg/m(2); 9.5%, 9.5% and 9.5% for BMI >30 kg/m(2). CONCLUSION The present study suggests that weight loss and hypoalbuminemia are not associated with an increased risk of mortality and morbidity in patients who underwent surgery for gastric cancer. This study may represent a stimulus for further studies aiming at evaluating the actual role of malnutrition in the development of postoperative complications in major abdominal surgery.

Pancreatoduodenectomy for Tumors of Vater’s Ampulla: Report on 94 Consecutive Patients

Evaluation of prognostic factors of adenocarcinoma of Vater’s ampulla is still a matter of debate. The aim of this study was to evaluate retrospectively factors that influence early and long-term outcomes in a 20-year single-institution experience on ampullary carcinoma. A total of 94 consecutive patients with ampullary carcinoma or adenoma with severe dysplasia were managed from 1981 to 2002. Among them, 64 underwent pancreatoduodenectomy, and the remaining 30 submitted to surgical (n = 5) or endoscopic (n = 25) palliative treatment. Demographic, clinical, and pathologic data were collected, and a comparison was made between patients who did or did not undergo resection. Standard statistical analyses were carried out in an attempt to establish a correlation between clinical variables, intraoperative and pathologic factors, and survival in patients with resection. A total of 85 (90.4%) patients had potentially resectable lesions due to the extent of the tumor, but only 64 (68%) underwent curative resection. The surgical morbidity rate was 34.3%. Postoperative mortality was 9.3%, with no deaths among the 38 more recently treated patients. Median survivals were 9 and 54 months for nonresected and resected patients, respectively. The overall 5-year survival was 64.4% for patients undergoing pancreatoduodenectomy. Survival was found to be significantly affected by resection, tumor size, tumor grade, and tumor infiltration. Patients with negative lymph nodes show a trend toward longer survival. In a multivariate analysis, only the depth of tumor infiltration influenced patient survival.Pancreatoduodenectomy is the treatment of choice for ampullary carcinoma and adenomas with high-grade dysplasia, with a good chance of long-term survival. Surgical resection remains the most important factor influencing outcome.

Fatigue Is Associated With Serum Interleukin-6 Levels and Symptoms of Depression in Patients on Chronic Hemodialysis

CONTEXT Little is known about activated immune-inflammatory pathways and interleukin-6 (IL-6) in the development of fatigue and/or depression in patients with end-stage renal disease on chronic hemodialysis (HD). OBJECTIVES To evaluate the possible correlation between fatigue and serum levels of IL-6 in patients on chronic HD. METHODS One hundred HD patients were assessed for the presence of fatigue using the SF-36 Vitality subscale and were administered the Beck Depression Inventory (BDI), the Hamilton Anxiety Rating Scale (HARS), the Mini-Mental State Examination (MMSE), the activities of daily living (ADL), and the instrumental activities of daily living (IADL). We also calculated the time of recovery after hemodialysis (TIRD) and the number/severity of comorbidities using the Charlson Comorbidity Index (CCI). Laboratory parameters were measured as well as serum IL-6. RESULTS Forty-three patients constituted the fatigued group and 57 the nonfatigued group. Age, CCI, BDI, HARS, and TIRD were significantly higher in fatigued patients than in the nonfatigued patients. Conversely, the scores of ADL, IADL, and MMSE were significantly lower in fatigued than in nonfatigued patients. Serum IL-6 levels (pg/mL) were higher in the fatigued group (5.1 ± 3.4) than in the nonfatigued group (1.6 ± 1.5; P < 0.001); serum albumin and creatinine levels were significantly lower. Twenty-six patients (26%) had no symptoms of depression (BDI score <10), and 74 patients (74%) had symptoms of depression (BDI score >9). Patients with a BDI score >9 were older; had a higher CCI; a lower MMSE; a higher TIRD; lower serum albumin, creatinine, and urea levels; and higher serum IL-6 levels. The correlation analyses showed that the score of the SF-36 Vitality subscale was associated with age, dialytic age, TIRD, ADL, IADL, CCI, BDI, HARS, MMSE, serum urea, creatinine, albumin, and IL-6 levels. On multivariate general linear model analyses, with fatigue as the dependent variable and gender as a second factor, BDI and serum IL-6 levels were independently associated with the score of the SF-36 Vitality subscale. A canonical correlation analysis was performed including in the model fatigue, BDI, and biomarkers; the correlation was 0.679 (R(2) = 0.462). Fatigue, BDI, and IL-6 among biomarkers showed the strongest association with the underlying construct (standardized canonical coefficients = -0.989, 0.015, and 0.852, respectively), thus explaining a correlation of IL-6 with both depression and fatigue. CONCLUSION Fatigue was significantly associated with symptoms of depression and serum IL-6 levels in patients receiving chronic HD.

Mini Mental State Examination over time in chronic hemodialysis patients

OBJECTIVE Cognitive impairment is relatively common in end-stage renal disease patients on chronic hemodialysis, but the course of cognitive function deterioration in hemodialysis patients is essentially unknown. The present study aimed to evaluate if changes in Mini Mental State Examination (MMSE) over time in hemodialysis (HDP) and elderly (EP) patients differ significantly and determine the variables associated with such possible changes. METHODS In 80 HDP and 160 EP, the MMSE was assessed at baseline and after 1 year. Patients were stratified at baseline and at 1 year into three groups according to the MMSE: normal cognitive function >23; mild-moderate cognitive dysfunction: 18-23; severe cognitive dysfunction: <18. Univariate and multivariate analyses were performed to determine the variables associated with MMSE change over time RESULTS One-year median reduction of MMSE was greater in HDP (from 24 to 21) than in EP (from 26 to 25) (P<.0001). A higher percentage of HDP than EP switched from normal to mild-moderate or severe MMSE group (P<.0001). At baseline, MMSE was negatively correlated with hypertension (P=.013), angina (P=.007) and Beck Depression Inventory (P=.041) and positively correlated with education (P=.017) and male gender (P=.015). No factors were found to be significantly associated with change of MMSE between baseline and month 12 in HDP. CONCLUSION One-year MMSE reduction was greater in HDP that in EP. No factors were associated with MMSE reduction in HDP. However, it remains likely that cardiovascular comorbidities and low haemoglobin levels are related to such decline.

Multivisceral Resection for Locally Advanced Gastric Cancer: An Italian Multicenter Observational Study

IMPORTANCE The role of multivisceral resection, in the setting of locally advanced gastric cancer, is still debated. Previous studies have reported a higher risk for perioperative morbidity and mortality, with limited objective benefit in terms of survival. Conversely, recent studies have shown the feasibility of enlarged resections and the potential advantage of extended resection for clinical stage T4b gastric adenocarcinoma with good long-term results. OBJECTIVE To analyze the role of multivisceral resection for locally advanced gastric cancer with particular attention to the brief and long-term results and to the prognostic value of clinical and pathologic factors. DESIGN Prospective multicenter study using data from between January 1, 1995, and December 31, 2008. SETTINGS Seven Italian surgery centers. PATIENTS A total of 2208 patients underwent curative resections for gastric carcinoma at the centers. Among them, 206 patients presented with a clinical T4b carcinoma. One hundred twelve underwent a combined resection of the adjacent organs with a gastrectomy owing to suspicion or direct invasion of these organs by the gastric cancer. MAIN OUTCOMES AND MEASURES Clinical and pathologic variables were prospectively collected and the feasibility and efficacy of multivisceral resection for locally advanced clinical T4b gastric cancer were assessed. RESULTS Postoperative mortality and complication rates of patients who underwent a gastrectomy with a combined resection of the involved organs were 3.6% and 33.9%, respectively. Pathologic factors revealed that the nodal involvement was present in about 89.3% of patients and the mean (SD) number of pathologic lymph nodes was 14.8 (16.6). The overall 5-year survival rate was 27.2%. The completeness of resection and lymph node invasion represent independent prognostic parameters at multivariate analysis. CONCLUSIONS AND RELEVANCE Our study indicates that patients undergoing extended resections experience acceptable postoperative morbidity and mortality rates, and an en bloc multivisceral resection should be performed in patients when a complete resection can be realistically obtained and when lymph node metastasis is not evident.

CALPAIN activity is increased in skeletal muscle from gastric cancer patients with no or minimal weight loss

The influence of cancer on skeletal muscle calpain expression and activity in humans is poorly understood. We tested the hypothesis that calpain activity is increased in skeletal muscle from gastric cancer patients with no or <5% weight loss. Muscle biopsies were obtained from rectus abdominis muscle in 15 patients who underwent surgery for gastric cancer and had <5% weight loss and also in 15 control patients. Calpain activity was determined using a calpain‐specific substrate in the absence or presence of calcium. The expression of μ‐ and m‐calpain, calpastatin, atrogin‐1, and MuRF1 was determined by real‐time polymerase chain reaction. Calpain activity was increased by 70% in cancer patients compared with controls. There were no differences in mRNA levels for μ‐ and m‐calpain, calpastatin, atrogin‐1, or MuRF1 between control and cancer patients. Calpain activity may be increased in muscle from gastric cancer patients even before changes in molecular markers of muscle wasting and significant weight loss occur. Muscle Nerve, 2011

The Italian Research Group for Gastric Cancer (GIRCG) guidelines for gastric cancer staging and treatment: 2015

This article reports the guidelines for gastric cancer staging and treatment developed by the GIRCG, and contains comprehensive indications for clinical management, including radiological, endoscopic, surgical, pathological, and oncological paths.

Skeletal muscle in cancer cachexia: the ideal target of drug therapy

Cancer cachexia is a debilitating and life-threatening syndrome that accounts for at least 20% of deaths in neoplastic patients. Cancer cachexia significantly impairs quality of life and response to anti-neoplastic therapies, increasing morbidity and mortality of cancer patients. The loss of lean body mass is the main characteristic of cancer cachexia and the principal cause of function impairment, fatigue and respiratory complications. It is the result of an imbalance between protein synthesis and protein degradation, the mechanisms underlying such alteration being multiple and partially known. Current therapy of cancer cachexia continues to be extremely poor. However, in the last decade, the attention has focused just on the skeletal muscle, as a potential target of therapy, with the aim to discover drugs capable to inhibit the catabolic processes and to stimulate the anabolic pathways. The skeletal muscle has been faced at different levels such as the mediators (cytokines and tumor-derived factors), the receptors (TNF-alpha and androgen receptors), the proteolytic pathways (calpains and ubiquitin-proteasome), the intracellullar signalling pathways (NF-kB, AP-1, FOXO, PKR), and the negative modulators of muscle growth/hypertrophy (myostatin, GSK3-beta). Most of the drugs that have been tested have shown to be effective, at least in experimental models of cancer cachexia. It remains to define their safety, tolerance and efficacy in humans through large, adequate, clinical trials. However, the impression is that there is a light at the back of the tunnel.

Gastric linitis plastica: Which role for surgical resection?

BackgroundThe role of surgery for gastric linitis plastica (GLP) is questioned. This study aimed to analyze our experience in the surgical treatment of GLP with specific reference to the resectability rate, prognosis, and mode of recurrence.MethodsResults of surgery were analyzed in 102 patients with GLP.ResultsOf the 102 patients, 92 underwent surgical exploration, with resection performed in 60 cases. R2 resection was carried out in 20 patients and R1 in 12 patients, while the resection was considered potentially curative (R0) in 28 (27.5%). Overall, the median (95% confidence interval [CI]) survival time was 5.7 (3.7–7.5) months, with none of the patients alive at the end date of the study. For R0 patients the median (95% CI) survival time was 15.8 (11–20.7) months. The great majority of recurrences were intra-abdominal (peritoneal and/or locoregional), with a systemic component of the relapse that was rarely observed (5 cases).ConclusionsAfter primary surgery, GLP showed a poor prognosis without regard to the extent or type of resection. The failure of surgical treatment related mainly to the peritoneal spread of the disease. Specifically designed multimodality treatment protocols should be tested in this setting.

Retroperitoneal soft tissue sarcoma: prognostic factors and therapeutic approaches.

Aims and Background Retroperitoneal sarcomas are a rare group of malignant soft tissue tumors with a generally poor prognosis. The aim of the study was to assess clinical, pathological and treatment-related factors affecting prognosis in patients with retroperitoneal sarcomas. Methods and Study Design The hospital records of 73 patients who underwent surgical exploration at our unit for primary retroperitoneal sarcomas between 1984 and 2003 were reviewed. Factors influencing overall and disease-free survival were analyzed for all patients and for those who underwent complete surgical resection. Results The complete resectability rate was 69.8% (51/73). Operative mortality and morbidity rates were 2.7% and 21.9%, respectively. For patients who underwent complete resection, the 5-year survival rate was 58.3%, whereas it was 0% in cases of incomplete or no resection (P <0.001). Local recurrence rate was 37.2%. Incomplete gross surgical resection and microscopic infiltration of margins were the most important independent predictors of a poor prognosis. Conclusions The present study confirmed the importance of an aggressive surgical management for retroperitoneal sarcomas to offer these patients the best chance for long-term survival.