Percutaneous cholecystostomy in the treatment of acute cholecystitis: is there still a role? A 20-year literature review.

OBJECTIVE: Percutaneous cholecystostomy (PC) is used for the treatment of acute cholecystitis in patients with high surgical risk due to the severity of cholecystitis and/or the underlying acute or chronic medical comorbidities. The evidence for this strategy is unclear. MATERIALS AND METHODS: We searched PubMed and the Cochrane databases for English-language studies published from January 1979 through December 31, 2019, for randomized clinical trials (RCTs), meta-analyses, systematic reviews, and observational studies. RESULTS: The two randomized studies that have compared PC with cholecystectomy (CCY) or conservative treatment have shown that the clinical outcomes did not differ significantly between the groups. Similar results have been found in the large majority of retrospective cohorts or single-center studies that have compared PC with CCY. CONCLUSIONS: PC does not seem to offer any benefit compared with CCY in the treatment of acute cholecystitis in patients with high surgical risk due to the severity of cholecystitis and/or the underlying acute or chronic medical comorbidities. A large, prospective, randomized study that compares percutaneous PC and CCY in patients with high surgical risk and/or moderate to severe cholecystitis is warranted.

Comparison of cholecystectomy and percutaneous cholecystostomy in acute cholecystitis: results of a retrospective study.

OBJECTIVE: To retrospectively compare the clinical outcomes of percutaneous cholecystostomy (PC) and cholecystectomy in patients with acute cholecystitis admitted to an urban University Hospital. PATIENTS AND METHODS: We studied 646 patients with acute cholecystitis. Ninety patients had placement of a PC at their index hospitalization, and 556 underwent cholecystectomy. Of the 90 patients with PC, 13 underwent subsequent elective cholecystectomy. RESULTS: Overall, in-hospital mortality and postoperative complications were significantly higher in patients who received PC than in those who underwent cholecystectomy. In the ASA score 1-2 group, patients with PC were significantly older and had a longer postoperative stay while their mortality and morbidity were similar to patients who underwent cholecystectomy. In patients with ASA score of 3, PC and cholecystectomy did not differ significantly for demographic variables and clinical outcomes such as hospital stay, in-hospital mortality, postoperative complications and distribution of complications according to the classification of Clavien-Dildo. In mild, moderate, and severe cholecystitis, patients who underwent PC were significantly older than those who received cholecystectomy. In general, in mild, moderate and severe cholecystitis, the clinical outcomes did not differ significantly between patients who received PC and cholecystectomy. Morbidity was higher in patients with mild cholecystitis who underwent PC. Of the 77 patients dismissed from the hospital with drainage, 12 (15.6%) developed biliary complications and 5 needed substitutions of the drainage itself. CONCLUSIONS: PC does not offer advantages compared to cholecystectomy in the treatment of acute cholecystitis. Its routine use is therefore questioned. There is need of an adequate, randomized study that compares PC and cholecystectomy in high-risk patients with moderate-severe cholecystitis.

Ethical evaluation of risks related to living donor transplantation programs.

The shortage of available cadaveric organs for transplantation and the growing demand has incresed live donation. To increase the number of transplantations from living donors, programs have been implemented to coordinate donations in direct or indirect form (cross-over, paired, and domino chain). Living donors with complex medical conditions are accepted by several transplantation programs. In this way, the number of transplants from living has exceeded that from cadaver donors in several European countries. No mortality has been reported in the case of lung, pancreas, or intestinal Living donations, but the perioperative complications range from 15% to 30% for pancreas and lung donors. In living kidney donors, the perioperative mortality is 3 per 10,000. Their frequency of end-stage renal disease does not exceed the United States rate for the general population. However, long-term follow-up studies of living donors for kidney transplantations have several limitations. The frequency of complications in live donor liver transplantation is 40%, of these, 48% are possibly life-threatening according to the Clavien classification. Residual disability, liver failure, or death has occurred in 1% of cases. The changes in live donor acceptance criteria raise ethical issues, in particular, the physician's role in evaluating and accepting the risks taken by the living donor. Some workers argue to set aside medical paternalism on behalf of the principle of donor autonomy. In this way the medical rule "primum non nocere" is overcome. Transplantation centers should reason beyond the shortage of organs and think in terms of the care for both donor and recipient.

Parathyroid-gland ultrasonography in clinical and therapeutic evaluation of renal secondary hyperparathyroidism.

PURPOSE: This study evaluated the relationship between ultrasonographic (US) parameters of parathyroid glands (PTGs) in haemodialysis patients (HDP) and degree of secondary hyperparathyroidism (SHPT), therapeutic responsiveness and type of PTG hyperplasia (diffuse or nodular). MATERIALS AND METHODS: In 85 HDP, we evaluated the following US parameters of all and of the largest PTGs: number, maximum longitudinal diameter (MLD), structural (hypoechoic, heterogeneous, nodular) and vascular (nonhypovascular, intermediate, hypervascular) echo-pattern scores. Sixty-nine HDP underwent medical therapy (vitamin D, 39; vitamin D/cinacalcet, 30) and 16 underwent parathyroidectomy. The 69 HDP were classified as responders [median intact parathyroid hormone (iPTH) ≤300 pg/ml during follow-up) or nonresponders (iPTH >300 pg/ml). RESULTS: Number, MLD and structural and vascular echo patterns of PTGs were significantly correlated with iPTH and calcium concentrations. In the 41 (59%) responders, number (0-1), MLD (<10 mm) and structural and vascular scores (1-2) of the largest PTG were significantly lower than in nonresponders. Receiver operating curve (ROC) curve analysis showed high sensitivity and specificity (90% and 73%, respectively) of the MLD (<10mm) of the largest PTG in the predicting therapeutic outcome. US and histological MLD are significantly correlated and predict the type of hyperplasia. CONCLUSIONS: US parameters of PTGs are correlated to the degree of SHPT and type of hyperplasia and predict responsiveness to medical therapy.

Nutritional counselling and oral nutritional supplements in head and neck cancer patients undergoing chemoradiotherapy.

BACKGROUND: The role of nutritional counselling (NC) with or without oral nutritional supplements (ONS) in patients receiving chemoradiotherapy (CRT) for head and neck cancer (HNC) still remains to be clearly defined, particularly with regard to CRT-related toxicity. METHODS: Patients undergoing CRT for HNC received NC by the dietitian within the first 4 days of radiotherapy and weekly for the course of radiotherapy (approximately 6 weeks). A weekly supply of oral nutrition supplements [1560 kJ (373 kcal) per 100 g] for up to 3 months was provided to all patients. RESULTS: Twenty-one patients completed CRT. Mucositis G3 developed in seven (33.3%) patients, whereas mucositis G4 was absent. Dysphagia was present before the start of treatment in four patients. In the remaining 17 patients, dysphagia G3 developed during/at the end of treatment in five cases. The percentage of patients interrupting anti-neoplastic treatment for was 28% for ≥6 days, 28% for 3-5 days and 44% for 0-2 days. Mucositis G3 frequency was lower in patients with a baseline body mass index (BMI, kg m(-2) ) ≥25 (two out of 12; 16.6%) than in patients with BMI <25 (five out of nine; 55.5%) (P = 0.161) and in patients with a baseline mid arm circumference >30 cm than in those with a mid arm circumference in the range 28.1-30 cm and <28 cm, and higher in patients with a greater weight loss and a greater reduction of serum albumin and mid arm circumference. CONCLUSIONS: Nutritional counselling and ONS are associated with relatively low CRT-related toxicity and with mild deterioration of nutritional parameters.

Relationship between leptin and all–cause and cardiovascular mortality in chronic hemodialysis patients

Background: We aimed to evaluate the relationship between serum leptin and the leptin/body mass index (BMI) ratio with prevalent cardiovascular disease (CVD), and their influence on all–cause and CVD–related mortality in patients on hemodialysis (HD). Methods: 118 stable HD patients (50 women, median [interquartile range] age, 65.1 [54.7–72.2] years) were studied. All patients had baseline measurement of serum leptin concentrations. Relationships between leptin and all–cause and CVD mortality were studied by means of survival analysis and Cox regression analysis. Results: The leptin/BMI ratio was similar in patients with and without CVD at baseline (0.65 [0.29–2.23] vs. 0.68 [0.29–1.49] ng·m2/ml·kg, respectively, NS). Multiple logistic regression analysis showed that there was not an independent association between leptin/BMI ratio and prevalent CVD. During the follow–up time, 52 (44.1%) patients died. CVD was the cause of death in 27 out of 52 (51.9%) deceased patients. Survival analysis and Cox proportional multivariate regression analysis showed that there were no significant relationships between leptin levels or the leptin/BMI ratio and all–cause and CVD–related mortality. Conclusion: These results do not support that, in stable HD patients, serum leptin concentrations and the leptin/BMI ratio are related with prevalent CVD. Leptin/BMI ratio seems not to be a risk factor for mortality in these patients (AU)

Introducción: El objetivo del presente estudio ha sido evaluar la relación entre la leptina sérica y el cociente leptina/índice de masa corporal (IMC) con la enfermedad cardiovascular (ECV) prevalente y su influencia en la mortalidad global y en la mortalidad por ECV en pacientes en hemodiálisis (HD). Métodos: Se estudiaron 118 pacientes estables en HD (50 mujeres, edad mediana [recorrido intercuartílico], 65,1 [54,7–72,2] años). En todos los pacientes se cuantificó la concentración basal de leptina. La relación entre leptina y la mortalidad se evaluó mediante análisis de supervivencia y análisis de regresión de Cox. Resultados: El cociente leptina/IMC fue similar en pacientes con y sin ECV prevalente (0,65 [0,29–2,23] frente a 0,68 [0,29–1,49] ng·m2/ml·kg, respectivamente, NS). El análisis de regresión logística mostró que no existía una asociación independiente entre el cociente leptina/IMC y la enfermedad cardiovascular prevalente. Durante el seguimiento 52 pacientes fallecieron (44,1%). La ECV fue causa de muerte en 27 de 52 pacientes fallecidos (51,9%). El análisis de supervivencia y el análisis multivariante de Cox mostraron que no hubo relación significativa entre los niveles de leptina o el cociente leptina/IMC y la mortalidad global o por causa de ECV. Conclusión: Estos resultados no apoyan la hipótesis de que, en pacientes estables en HD, las concentraciones de leptina y el cociente leptina/IMC estén relacionados con la ECV prevalente. Más aún, el cociente leptina/IMC no parece ser un factor de riesgo de mortalidad en estos pacientes (AU)

Transplantation and mental retardation: what is the meaning of a discrimination?

The issue of transplantation for patients affected by mental retardation (MR) has been and continues to be a matter of discussion. The recent policy of the Veneto region, a highly populated area in northern Italy, indicates that patients with MR are not eligible for any transplant of solid organs, indicating intelligence quotient (IQ) <50 as absolute and IQ <70 as a relative exclusion criteria. In the present study, we review current conceptualizations of MR, along with the current knowledge on transplantation in this population. Finally, we will review the international guidelines on this matter and discuss the social, ethical and political significance of such policy, arguing that it discriminates persons affected by MR.

[Malnutrition in patients on chronic hemodialysis: prevalence, pathogenesis, and treatment]. / La malnutrizione nel paziente in emodialisi cronica: prevalenza, patogenesi, terapia.

Malnutrition is common in patients on hemodialysis and is a strong predicor of morbidity and mortality. Much progress has been made in recent years in identifying the causes and pathogenesis of malnutrition in hemodialysis patients as well as in recognizing the link between malnutrition and morbidity and mortality. Nevertheless, there is no consensus concerning its management. Conventional interventions such as nutritional counseling, oral nutritional supplements and intradialytic parenteral nutrition and novel preventive and therapeutic strategies such as appetite stimulants, growth hormone, androgenic anabolic steroids, and antiinflammatory drugs have been tested with contradictory and inconclusive results. Malnutrition still remains an important challenge for the nephrologist in the third millennium.

Muscle myostatin signalling is enhanced in experimental cancer cachexia.

BACKGROUND/AIMS: Myostatin belongs to the transforming growth factor-beta superfamily and negatively regulates skeletal muscle mass. Its deletion induces muscle overgrowth, while, on the contrary, its overexpression or systemic administration cause muscle atrophy. The present study was aimed at investigating whether muscle depletion as occurring in an experimental model of cancer cachexia, the rat bearing the Yoshida AH-130 hepatoma, is associated with modulations of myostatin signalling and whether the cytokine tumour necrosis factor-alpha may be relevant in this regard. MATERIALS AND METHODS: Protein levels of myostatin, follistatin (myostatin endogenous inhibitor) and the activin receptor type IIB have been evaluated in the gastrocnemius of tumour-bearing rats by Western blotting. Circulating myostatin and follistatin in tumour hosts were evaluated by immunoprecipitation, while the DNA-binding activity of the SMAD transcription factors was determined by electrophoretic-mobility shift assay. RESULTS: In day 4 tumour hosts muscle myostatin levels were comparable to controls, yet follistatin was reduced, and SMAD DNA-binding activity was enhanced. At day 7, both myostatin and follistatin increased in tumour bearers, while SMAD DNA-binding activity was unchanged. To investigate whether tumour necrosis factor-alpha contributed to induce such changes, rats were administered pentoxifylline, an inhibitor of tumour necrosis factor-alpha synthesis that partially corrects muscle depletion in tumour-bearing rats. The drug reduced both myostatin expression and SMAD DNA-binding activity in day 4 tumour hosts and up-regulated follistatin at day 7. CONCLUSIONS: These observations suggest that myostatin pathway should be regarded as a potential therapeutic target in cancer cachexia.

Anorexia in hemodialysis patients: an update.

Anorexia, defined as the loss of the desire to eat, is relatively common in hemodialysis (HD) patients, occurring in one-third of cases. The pathogenesis is essentially unknown. It has been proposed that uremic toxins as middle molecules, inflammation, altered amino-acid pattern, leptin, ghrelin, and neuropeptide Y are involved. Anorexia reduces oral energy and protein intakes, thus contributing to the development of malnutrition and cachexia. Unquestionably, it contributes to poor quality of life. The clinical relevance of anorexia as an independent prognostic factor in HD patients is a matter of debated issue. The treatment of this debilitating condition is based on a therapeutic strategy which may include daily dialysis sessions and nutritional counseling. Normalization of plasma branched-chain amino acids through branched-chain amino acids supplementation may decrease anorexia and improve energy and protein intake. The role of megestrol acetate as appetite stimulant needs to be validated through adequate randomized trials. Subcutaneous ghrelin administration and melanocortin-receptor antagonists appear promising therapeutic interventions.

Skeletal muscle wasting in tumor-bearing rats is associated with MyoD down-regulation.

Cachexia is a syndrome characterized by profound skeletal muscle wasting that frequently complicates malignancies. A number of studies indicate that protein hypercatabolism, largely mediated by classical hormones and cytokines, is the major component of muscle depletion. Impaired regeneration has been suggested to contribute to the reduction of muscle size. In particular, it has been shown that the expression of MyoD, a muscle-specific transcription factor, is down-regulated by cytokines such as TNFalpha and IFNgamma in a NF-kappaB-dependent posttranscriptional manner. The present study investigated whether modulations of the transcription factor MyoD are associated with the onset of muscle wasting in a well established model of cancer cachexia. Rats bearing the Yoshida AH-130 hepatoma develop a condition of muscle protein hypercatabolism, largely dependent on TNFalpha bioactivity. In the gastrocnemius of these animals the expression of MyoD was markedly reduced, paralleling the decrease of muscle weight. This pattern is associated with increased nuclear translocation of AP-1, while DNA-binding assays did not detect any change in NF-kappaB activity. This is the first observation demonstrating that muscle depletion in tumor-bearing rats is associated with a down-regulation of MyoD levels. Although the underlying mechanisms remain to be clarified, this change is compatible with the hypothesis that a reduced expression of molecules involved in the regulation of the regenerative response may concur to muscle wasting in cancer cachexia.

Adjuvant radiotherapy in resectable pancreatic carcinoma.

AIM: Pancreatic cancer is a near fatal disease. External beam radiotherapy and intraoperative radiation therapy (IORT) has been proposed with the aim to improve clinical outcome in resectable tumors. The aim of this study is to assess the feasibility and outcome in patients with cT1-3 pancreatic cancer, treated with surgery, external beam radiotherapy and IORT. METHODS: From 1990 to 1996, 17 patients with clinical stage T1-3N0-1M0 adenocarcinoma of the head of the pancreas were treated with pancreatectomy and pre- (nine patients: 5 Gy), intra- (all patients: 10 Gy) and post-operative (all patients: 50 Gy) radiotherapy. The pathologic T stages were: 4 pT2 and 13 pT3. The pathologic N stages were: 9 pN0 and 8 pN1. Minimum follow-up in living patients was 60 months. RESULTS: No perioperative mortalities were recorded. Two patients showed postoperative morbidity (11.8%) which required a subsequent laparotomy. The disease-free survival at 1, 3 and 5 years was 41, 23 and 18%, respectively (median: 9 months). The overall survival at 1, 3 and 5 years was 70%, 41% and 18%, respectively (median: 17.5 months). Three patients developed local failure (17.6%) and 12 patients showed distant metastases (70.6%). Univariate analysis (logrank) showed: a significant correlation between both N-stage and retroperitoneal involvement (RPI) with local control (N-stage: P=0.0155; RPI:P =0.0295), a significant correlation between maximum tumor size and metastases-free survival (P=0.0167) and overall survival (P=0.0241); the female gender was another predictor of prolonged survival (P= 0.0465). Multivariate analysis (Cox) showed a significant impact of N-stage and retroperitoneal involvement on local control and also a significant correlation between perineural involvement and tumor diameter with metastases-free survival. CONCLUSIONS: These results are similar to those of other published series and suggest that this approach is feasible with acceptable local control and survival, especially in patients with small tumors (<2.5 cm: 5 year survival=33.3%) and in female patients (5 year survival=30%). Due to the impact of gender, tumor diameter and N stage on prognosis, in the design of future trials a stratification of patients based on these categories should be considered. The search of effective chemotherapeutic agents is required, to reduce the high incidence of distant metastases, especially in larger tumors.

Anticytokine treatment prevents the increase in the activity of ATP-ubiquitin- and Ca(2+)-dependent proteolytic systems in the muscle of tumour-bearing rats.

The ascites hepatoma Yoshida AH-130 induces loss of body weight and tissue waste. Tumour necrosis factor alpha (TNF-alpha) plays a pivotal role in the pathogenesis of muscle wasting in this model system, but other cytokines, such as interleukin-6, may be involved. In order to verify whether a combined anticytokine treatment may synergistically counteract muscle protein degradation, tumour bearing rats were treated with pentoxyfilline (PTX, an inhibitor of TNF-alpha synthesis), or with suramin (SUR, an antiprotozoal drug blocking the peripheral action of several cytokines including IL-6 and TNF-alpha), or both the drugs, and the effects on muscle proteolytic systems were assessed. Muscle protein loss in the AH-130-bearing rats was associated with increased activity of both the ATP-ubiquitin- and the calpain- dependent proteolytic pathways (246% and 230% of controls, respectively). Both PTX and SUR, either alone or in combination, prevented the depletion of muscle mass and significantly reduced the activity of muscle proteolytic systems. In particular, treatment with SUR, either alone or with PTX, induced a decrease in enzymatic activities to values similar to those of controls. The results obtained in the present paper demonstrate that: (i) muscle depletion in this model is indeed associated with increased proteasome- and calpain-dependent proteolysis, as previously suggested by increased mRNA expression of molecules pertaining to both pathways; (ii) anticytokine treatments effectively reduce muscle protein loss by down-regulating the activity of at least two major proteolitic systems; (iii) SUR is more effective than PTX in reducing the activity of proteolytic systems, possibly because of its multiple anticytokine action.

Validity of thyroglobulin mRNA assay in peripheral blood of postoperative thyroid carcinoma patients in predicting tumor recurrences varies according to the histologic type: results of a prospective study.

BACKGROUND: The objective of the current study was to evaluate the ability of serum thyroglobulin mRNA assay in detecting local and distant recurrences in patients who underwent surgery for thyroid carcinoma. METHODS: Sixty-six consecutive patients were studied. One year after surgery, all patients underwent clinical examination and radioiodine scan, and a blood sample was taken for serum thyroglobulin (Tg) immunoassay and for Tg mRNA assay by reverse transcription-polymerase chain reaction (RT-PCR). RNA was extracted from cells pellet and analyzed by RT-PCR using specific primers for Tg. RESULTS: Thyroglobulin mRNA was detected in 14 (21.2%) patients. Seven of 16 patients with elevated serum thyroglobulin had detectable Tg mRNA. Six of 30 (20%) patients with absent or minimal thyroid bed radioiodine uptake and 7 of 36 (19.4%) patients with significant thyroid bed uptake had detectable Tg mRNA. Among 5 patients with metastases, only 1 (20%) showed circulating Tg mRNA. Overall, the sensitivity, specificity, and accuracy of Tg mRNA assay in predicting the results of the (131)I whole-body scans was 25%, 80%, 25%, respectively. Fourteen of 53 (26.4%) patients with papillary thyroid carcinoma had detectable thyroglobulin mRNA whereas none of the patients with other histologic types did. The sensitivity, specificity, and accuracy of Tg mRNA assay in predicting the results of the (131)I whole-body scans in patients with papillary thyroid carcinoma was 100%, 75%, and 100%, respectively. Of note, the percentage of cases with detectable Tg mRNA was similar among patients who did not receive postoperative (131)I and those who had postoperative radioiodine treatment. CONCLUSIONS: The current study suggests that the validity of the Tg mRNA assay varies according to the histologic type of thyroid carcinoma and that this assay may play a role in the identification of metastatic disease in the subgroup of patients affected by papillary thyroid carcinoma but does not appear to be sensitive or active enough to direct clinical management.

Is the identification of the external branch of the superior laryngeal nerve mandatory in thyroid operation? Results of a prospective randomized study.

BACKGROUND: The aim of this study was to investigate the incidence of injury to the external branch of the superior laryngeal nerve (EBSLN) with 2 different surgical approaches. METHODS: From 1998 to 2000, 289 consecutive patients undergoing thyroidectomy were randomly divided into 2 groups. In group A (137 patients [215 upper pole ligations]), the superior thyroid artery was ligated after identification of the EBSLN. In group B (152 patients [244 upper pole ligations]), the superior thyroid artery's branches were ligated separately close to the gland. In all patients, a phoniatric evaluation with videostrobolaryngoscopy and spectrographic examination was performed. RESULTS: The 2 groups were well matched regarding age, sex, thyroid pathological findings, and type of operation. In group A, the EBSLN was not clearly identified in 11.6% of cases. Alterations of EBSLN function were absent in both groups of patients, either postoperatively or 1 and 6 months after operation. Group B showed statistically significant shorter operative time compared with that for group A. CONCLUSIONS: Even if the EBSLN often crosses the superior thyroid pedicle, especially in large goiters, this study demonstrated that accurate distal ligation of the branches of the superior thyroid artery is a safe technique to prevent EBSLN injury.

Enteral vs parenteral nutrition after major abdominal surgery: an even match.

HYPOTHESIS: Immediate enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition. DESIGN: A prospective multicenter randomized trial. SETTING: A university hospital department of digestive surgery. PATIENTS AND INTERVENTIONS: Two hundred forty-one malnourished patients undergoing major elective abdominal surgery were randomly assigned to receive, after surgery, either enteral (enteral nutrition group: 119 patients) or parenteral nutrition (total parenteral nutrition group: 122 patients). The patients were monitored for postoperative complications and mortality. RESULTS: The rate of major postoperative complications was similar in the enteral and parenteral groups (enteral nutrition group: 37.8%; total parenteral nutrition group: 39.3%; P was not significant), as were the overall postoperative mortality rates (5.9% and 2.5%, respectively; P was not significant). CONCLUSION: The present study failed to demonstrate that enteral feeding following major abdominal surgery reduces postoperative complications and mortality when compared with parenteral nutrition.

Proximal compared with distal gastric cancer: multivariate analysis of prognostic factors.

The major determinants of the poor prognosis of the patients with proximal-third gastric cancer (proximal gastric cancer or PGC) when compared with that of patients with more distally located gastric tumors (distal gastric cancer or DGC) rely both on the more advanced age and tumor stage at the moment of clinical presentation and on the higher postoperative mortality for PGC patients. We reviewed hospital records of 707 patients with gastric cancer (187 with PGC and 520 with DGC) observed during the period 1981 through 1996 at the same surgical unit. Demographic and pathological data, type of treatment, and hospital morbidity and mortality rates were recorded. Univariate and multivariate survival analysis was used to calculate the 5-year survival probabilities with respect to the following clinical and pathological variables: age, sex, gross appearance according to Borrmann classification, histological type according to Lauren, stage of the disease, tumor location, and type of treatment. PGC was associated with more advanced tumor stage (P < 0.0001), older age (P = 0.039), and higher necessity of extended surgery (P < 0.0001) when compared with DGC. Hospital mortality was 9.6 and 5 per cent in PGC and DGC patients respectively (P = 0.033). Overall 5-year survival was 17.7 and 36.4 per cent in PGC and DGC patients (P < 0.0001): 35.9 versus 57.6% (P = 0.0001) and 3.7 versus 7.6 per cent (P = 0.03) after radical and palliative surgery respectively. At multivariate survival analysis proximal location was found to be independently associated (P = 0.0007) with poor survival. The multivariate model shows the proximal location as an independent predictor of lesser favorable outcome in gastric cancer. The major determinants of the poor prognosis of PGC with respect to DGC rely both on the more advanced age and tumor stage at the moment of clinical presentation and on the higher postoperative morbidity for PGC patients.

Increased muscle ubiquitin mRNA levels in gastric cancer patients.

The intramuscular ATP-dependent ubiquitin (Ub)-proteasome proteolytic system is hyperactivated in experimental cancer cachexia. The present study aimed at verifying whether the expression of the muscle Ub mRNA is altered in patients with cancer. Total muscle RNA was extracted using the guanidinium isothiocyanate/phenol/chloroform method from rectus abdominis biopsies obtained intraoperatively from 20 gastric cancer (GC) patients and 10 subjects with benign abdominal diseases (CON) undergoing surgery. Ub mRNA levels were measured by northern blot analysis. Serum soluble tumor necrosis factor receptor (sTNFR) was measured by ELISA. Ub mRNA levels (arbitrary units, means +/- SD) were 2,345 +/- 195 in GC and 1,162 +/- 132 in CON (P = 0.0005). Ub mRNA levels directly correlated with disease stage (r = 0.608, P = 0.005), being 1,945 +/- 786 in stages I and II, 2,480 +/- 650 in stage III, and 3,799 +/- 66 in stage IV. Ub mRNA and sTNFR did not correlate with age and nutritional parameters. This study confirms experimental data indicating an overexpression of muscle Ub mRNA in cancer cachexia. Lack of correlation with nutritional status suggests that Ub activation in human cancer is an early feature that precedes any clinical sign of cachexia.

Improved survival and local control after intraoperative radiation therapy and postoperative radiotherapy: a multivariate analysis of 46 patients undergoing surgery for pancreatic head cancer.

HYPOTHESIS: Despite aggressive approaches, locoregional tumor control and survival rates for patients with cancer of the pancreatic head remain disappointing. In the present study, we address whether intraoperative and adjuvant radiotherapy may improve the prognosis for these patients. DESIGN: A retrospective study. SETTING: University hospital. PATIENTS: From February 1985 to December 1995, 46 patients with an adenocarcinoma of the pancreatic head underwent pancreatic resection. The last 26 patients also received intraoperative radiotherapy (except 5 patients) and adjuvant external beam radiation therapy. MAIN OUTCOME MEASURES: Demographic data, tumor characteristics, surgical procedures, 5-year survival, and local control of disease were analyzed retrospectively. RESULTS: The morbidity rate was not increased by adjuvant radiation therapy; it was 43% in patients treated with surgery alone and 57% in patients treated with surgery and radiotherapy (P =.1); operative mortality was 8% (n = 2) and 9% (n = 2), respectively (P =.8). Overall 5-year survival and local control were 13% and 48.6%, respectively. The mean +/- SD 5-year survival was 5.5% +/- 5.3% (median, 10.8 months) in the surgery-alone group and 15.7% +/- 8.6% (median, 14.3 months) in the surgery plus radiotherapy group (P =.06); local control at 5 years was 29.8% +/- 16.9% and 58.4% +/- 19.9%, respectively (P<.01). Median metastasis-free survival was 8 and 9 months, respectively (P =.52). Multivariate analysis showed that adjuvant radiotherapy was an independent prognostic factor for survival (P<.01) and local control of the disease (P =.03). CONCLUSION: The present study supports the role of radiotherapy combined with pancreatoduodenectomy for treatment of cancer of the pancreatic head because even if the improvement in overall survival is moderate, it is effective in improving the local control of the tumor.