Ernest F. Rosato

Prognostic nutritional index in gastrointestinal surgery

Based on assessment of 161 nonemergency general surgical patients, a multiparameter index of nutritional status was defined relating the risk of postoperative complications to baseline nutritional status. When applied prospectively to 100 gastrointestinal surgical patients, this index provided an accurate, quantitative estimate of operative risk, permitting rational selection of patients to receive preoperative nutritional support.

Enteral nutrition during multimodality therapy in upper gastrointestinal cancer patients.

ObjectiveThe objective of this study was to evaluate long-term enteral nutrition support in postoperative cancer patients. BackgroundMultimodality therapy of surgical patients with upper gastrointestinal malignancies may improve survival, but often results in substantial malnutrition, immunosuppression, and morbidity. The benefits of combined inpatient and outpatient enteral feeding with standard diets or diets supplemented with arginine, RNA + ω-3 fatty acids are unclear. MethodsSixty adult patients with esophageal (22), gastric (16), and pancreatic (22) lesions were stratified by disease site and percent usual weight and randomized to receive supplemental or standard diet via jejunostomy beginning on the first postoperative day (goal = 25 kcal/kg/day) until hospital discharge. Patients also were randomized to receive (n = 37) or not receive (n = 23) enteral jejunostomy feedings (1000 kcal/day overnight) for the 12− to 16-week recovery and radiation/chemotherapy periods. Plasma and peripheral white blood cells were obtained for fatty acid levels and PGE2 production measurements. ResultsMean plasma and cellular ω3/ω6 fatty acid levels (percent composition) increased significantly (p < 0.05) in the arginine + ω-3 fatty acid group by postoperative day 7 (0.30 vs. 0.13) and (0.29 vs. 0.14) and continued to increase over time. Mean PGE2 production decreased significantly (p < 0.05) from 2760 to 1600 ng/106 cells/mL at day 7 in the arginine + ω-3 fatty acid group, whereas no significant change over time was noted in the standard group. Infectious/wound complications occurred in 10% of the supplemented group compared with 43% of the standard group (p < 0.05); mean length of hospital stay was 16 vs. 22 (p < 0.05) days, respectively. Of the patients who received postoperative chemoradation therapy, only 1 (6%) of the 18 patients randomized to receive tube feeding did not continue, whereas 8 (61%) of the 13 patients not randomized to tube feedings required crossover to jejunostomy nutritional support. ConclusionsSupplemental enteral feeding significantly increased plasma and peripheral white blood cell ω3/ω6 ratios and significantly decreased PGE2 production and postoperative infectious/wound

EUS compared with CT, magnetic resonance imaging, and angiography and the influence of biliary stenting on staging accuracy of ampullary neoplasms

BACKGROUND Computerized tomography (CT), magnetic resonance imaging (MRI), and transabdominal ultrasound frequently fail to detect ampullary lesions. Endoscopic ultrasound (EUS) is a sensitive modality for detecting and staging ampullary tumors. Accurate staging may be affected by biliary stenting, which is frequently performed in these patients with obstructive jaundice. The present study assessed the accuracy of ampullary tumor staging with multiple imaging modalities in patients with and those without endobiliary stents. METHODS Fifty consecutive patients with ampullary neoplasms from two endosonography centers were preoperatively staged by EUS plus CT (37 patients), MRI (13 patients), or angiography (10 patients) over a 3(1/2) year period. Twenty-five of the 50 patients had a transpapillary endobiliary stent present at the time of endosonographic examination. Accuracy of EUS, CT, MRI, and angiography was assessed with the TNM classification system and compared with surgical-pathologic staging. The influence of an endobiliary stent present at the time of EUS on staging accuracy of EUS was also evaluated. RESULTS EUS was more accurate than CT and MRI in the overall assessment of the T stage of ampullary neoplasms (EUS 78%, CT 24%, MRI 46%). No significant difference in N stage accuracy was noted between the three imaging modalities (EUS 68%, CT 59%, MRI 77%). EUS T stage accuracy was reduced from 84% to 72% in the presence of a transpapillary endobiliary stent. This was most prominent in the understaging of T2/T3 carcinomas. CONCLUSIONS EUS is superior to CT and MRI in assessing T stage but not N stage of ampullary lesions. The presence of an endobiliary stent at EUS may result in underestimating the need for a Whipple resection because of tumor understaging.

Adjuvant therapy of resected adenocarcinoma of the pancreas.

Seventy-two patients underwent resections of pancreatic carcinomas between 1981 and 1989 at the Hospital of the University of Pennsylvania and were evaluable for follow-up. There were three treatment groups as treatment policies evolved. Initially, patients were observed after surgery without adjuvant treatment (Group 1-33 patients). Beginning in 1984, patients were offered adjuvant radiation therapy postoperatively (Group 2-19 patients) and eight of these patients also received 5-FU as an IV bolus on the first 3 days of the first and fifth weeks of treatment. Twenty patients were treated with chemosensitized radiation therapy following surgery using 96-hour 5-FU infusions during the first and fifth weeks of treatment. There were four postoperative deaths, which are excluded from the analysis, and sites of failure could not be determined for five other patients. Among evaluable patients, local recurrences occurred in 85% of the patients in group 1, 55% of the patients in group 2, and 25% of the patients in group 3. The 2-year survival was 35% in group 1, 30% in group 2, and 43% in group 3. Patients with involved surgical margins had a poor survival; only 2 of these 16 patients survived longer than 18 months. Among patients with negative margins, the 2-year survival is 41% in group 1, 33% in group 2, and 59% in group 3. Although the number of patients is smaller, the 3-year survival is 22% in group 1, 11% in group 2, and 47% in group 3. Chemosensitized irradiation is well tolerated in these patients. The major challenge in this group of patients is nutritional maintenance. There was no other significant toxicity. The trend in these observations suggests that survival following pancreatic resection is substantially improved with the addition of adjuvant chemosensitized radiation therapy.

Pneumatic Dilatation or Esophagomyotomy Treatment for Idiopathic Achalasia: Clinical Outcomes and Cost Analysis

The choice between pneumatic dilatation and surgical esophagomyotomy as the initial treatment for achalasia is controversial. The aims of this study were to determine the long term clinical outcome and costs of treating achalasia initially with pneumatic dilatation as compared to esophagomyotomy. Of 123 patients undergoing an initial pneumatic dilatation for achalasia at our institution from 1976 to 1986, 71 (58%) received no further treatment for achalasia during a mean follow up of 4.7±2.8 years. Only 15 of these 123 patients (12%) eventually underwent surgical esophagomyotomy, (two for perforation during pneumatic dilatation, 13 for persistent or recurrent symptoms). The degree of dysphagia at follow up was improved to a similar degree in patients treated with an initial pneumatic dilatation as compared to patients treated with an initial esophagomyotomy. Patients with age≥45, years at time of initial pneumatic dilatation had fewer subsequent treatments for persistent or recurrent symptoms and had less dysphagia on follow up as compared to patients <45 years. Subsequent pneumatic dilatations to treat persistent or recurrent symptoms were less beneficial than an initial pneumatic dilation. The cost of esophagomyotomy was 5 times greater than the cost of pneumatic dilatation. When costs were analyzed to include subsequent treatments of symptomatic patients, the total expectant costs of treating with an initial esophagomyotomy remained 2.4 times greater than treating with an initial pneumatic dilatation. This study suggests that an initial pneumatic dilatation will be the only treatment needed for the majority of patients with achalasia. A treatment regimen starting with penumatic dilatation has less overall costs than starting with esophagomyotomy. For each subsequent pneumatic dilatation, however, the clinical benefit leans toward, surgery.

Host‐tumor interaction and nutrient supply

Adequate parenteral nutritional support improves nutritional status in cancer patients, but its effect on tumor growth remains controversial. Using a transplantable mammary adenocarcinoma in a rat‐TPN model, the relative effect of different exogenous intravenous nutrients on tumor growth and host maintenance was studied. Relative to chow controls, starvation increased host depletion without reducing tumor growth. Adequate carbohydrate calories alone neither improved host maintenance nor stimulated tumor growth, yet adequate amino acids alone did improve host maintenance but also stimulated tumor growth. Adequate amino acids and carbohydrates given simultaneously maximized both host maintenance and tumor growth. In contrast, an isocaloric, isonitrogenous, intravenous diet providing non‐nitrogenous calories as fat promoted host maintenance equivalent to carbohydrate‐based TPN with no tumor stimulation. This apparent differential utilization of fat calories by normal and malignant cells may permit manipulation of the relative benefit of parenteral nutrition to host or to tumor, permitting host repletion without tumor stimulation or alternatively tumor stimulation at appropriate times to increase sensitivity to phase‐specific antineoplastic therapy.

The efficacy of nutritional assessment and support in cancer surgery.

Malnutrition is common in cancer patients and may be an important determinant of operative morbidity and mortality. To determine whether preoperative nutritional assessment can be used to identify a group of high‐risk patients, and whether preoperative TPN decreases morbidity and mortality in this group, retrospective, nonrandomized review of 159 patients who were subjected to major cancer surgery was performed. All patients underwent preoperative multiparameter assessment. A previously developed and validated nutritional assessment model (Prognostic Nutritional Index) was used to evaluate the probability of operative complications. Based on predicted outcome (PNI), patients were assigned to either a high‐risk or low‐risk group for statistical comparison with actual outcome. The effect of preoperative TPN was then analyzed in both risk groups for determination of efficacy of preoperative nutritional support. Substantial malnutrition was found to exist among patients undergoing major cancer surgery and was closely correlated with subsequent morbidity and mortality. This predictive nutritional assessment model accurately identifies a subset of cancer surgery patients at increased risk of operative morbidity and mortality. In this high risk group (PNI ≥ 40%), preoperative nutritional support significantly reduces operative morbidity (P <0.001) and mortality (P <0.025).

Long term survival after pancreatic resection for pancreatic adenocarcinoma

OBJECTIVE:The aim of this study was to determine the long term survival of patients with pancreatic adenocarcinoma who underwent surgical resection and to assess the association of clinical, pathological, and treatment features with survival.METHODS:Between January, 1990, and December, 1998, 125 patients underwent a pancreaticoduodenal or partial pancreatic resection for pancreatic ductal adenocarcinoma at our institution. The records of these patients were reviewed for demographics, tumor characteristics including size, histological grade, margin status, lymph node status, surgical TNM staging, and postoperative adjuvant therapy. The primary outcome variable analyzed was survival.RESULTS:A total of 116 patients had complete follow-up and were included in the final analysis. The median survival after surgery was 16 months. The 1-, 3-, 5-, and 7-yr survival rates for all 116 patients were 60%, 23%, 19%, and 11%, respectively. The 1-, 3-, 5-, and 7-yr survival rates for patients who received adjuvant therapy were 69%, 28%, 23%, and 18% compared with 20% and 0% in patients who did not receive adjuvant therapy (p < 0.0001). The 1-, 3-, 5-, and 7-yr survival rates for patients with negative lymph nodes were 73%, 38%, 26%, and 22% compared with survival rates of 52%, 14%, 14%, and 9% in patients with positive lymph nodes (p = 0.01). In multivariate analyses, adjuvant therapy was the only feature found to be strongly associated with survival (hazards ratio = 0.26, 95% CI = 0.15–0.44).CONCLUSIONS:The overall 5- and 7-yr survival rates of 19% and 11% in our study further validate that surgical resection in patients with pancreatic adenocarcinoma can result in long term survival, particularly when performed in association with adjuvant chemoradiation.

Application of backpropagation neural networks to diagnosis of breast and ovarian cancer

Neural network programs have been developed in an attempt to improve the diagnosis of breast and ovarian cancer using a group of laboratory tests and the age of the patient. The laboratory tests employed in this study include albumin, cholesterol, HDL-cholesterol, triglyceride, apolipoproteins A1 and B, NMR linewidth (the Fossel Index) and a tumor marker (i.e., CA 15-3 or CA 125). The breast cancer study involved 104 patients (45 malignant and 59 benign subjects). The ovarian cancer study involved 98 individuals (35 malignant, 36 benign and 27 control subjects). Methods are outlined for identification of the most influential input parameters and optimization of network structure and training. Network characteristics were contrasted with the test results of the appropriate serum tumor marker assay. For the breast cancer study, the best neural network program, using six input parameters, had a sensitivity of only 55.6% and a specificity of 72.9%. The tumor marker CA 15-3 alone gave results of 61.3% and 64.4%, respectively. For the ovarian cancer study, the best neural network program, using six input parameters, had a sensitivity of 80.6% and a specificity of 85.5%. The tumor marker CA 125 alone gave results of 77.8% and 82.3%, respectively. These methods provide an objective approach to neural network optimization and parameter selection applicable to other data bases of clinical and laboratory data.

Ten years experience with intravenous hyperalimentation and inflammatory bowel disease.

A retrospective analysis was conducted on 74 patients with inflammatory bowel disease who were treated with intravenous hyperalimentation at the Hospital of the University of Pennsylvania between the years 1967–1976. Intravenous hyperalimentation can ameliorate the inevitable protein-calorie malnutrition present in patients with inflammatory bowel disease. Combined with complete bowel rest, intravenous hyperalimentation can effectively function as the primary treatment or as an adjunct to the surgical management of the complications of inflammatory bowel disease. Intravenous hyperalimentation can be safely administered to these severely ill patients, almost certainly improving survival rates in the patients treated.