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Objective: To assess the complications of level I and II axillary lymph node dissection in the treatment of stage I and II breast cancer, with breast-conservation surgery and mastectomy., Summary Background Data: The role of axillary dissection for staging, and as an effective means of controlling regional nodal disease, has long been recognized. As small and low-grade lesions have been detected more frequently, and as its therapeutic impact has been questioned, axillary dissection has increasingly been perceived as associated with significant complications., Methods: Two hundred patients, 112 of whom had breast-conservation surgery with axillary dissection and 88 of whom had total mastectomy with axillary dissection, were evaluated 1 year or more after surgery for arm swelling as well as nonedema complications. All patients had arm circumference measurements at the same four sites on both the operated and nonoperated sides., Results: No patient had an axillary recurrence. The mean difference in circumference on the nonoperated versus operated side was 0.425 cm +/- 1.39 at the midbiceps (p < 0.001), 0.315 cm +/- 1.27 at the antecubital fossa (p < 0.001), 0.355 cm +/- 1.53 at the midforearm (p < 0.005), and 0.055 cm +/- 0.75 at the wrist (n.s.). Seven patients (3.5%) had mild swelling of the hand. Heavy and obese body habitus were the only significant predictors of edema on multivariate analysis. One hundred fifty-three (76.5%) patients had numbness or paresthesias of the medial arm and/or axilla after surgery; in 125 (82%) of these, the problem had lessened or had resolved on follow-up assessment., Conclusions: The characterization of a level I and II axillary dissection as a procedure with significant complications does not appear justified based on this experience.

Background: Increased intestinal permeability may lead to sepsis in resected upper gastrointestinal (GI) cancer patients. This study sought to determine whether these patients demonstrated increased intestinal permeability and if early postoperative enteral nutrition would alter this result., Methods: Nineteen patients undergoing complete resection of upper GI malignancy were randomized into two groups: the nonfed group received IV crystalloid, and the fed group started enteral nutrition by jejunostomy on postoperative day (POD) 1. Six nonoperative volunteers were controls. The lactulose/mannitol test was performed on PODs 1 and 5. Ten grams of lactulose and 5 g of mannitol were given, and urine was collected for 6 hours., Results: All patients (nonfed, 1.895+/-0.34; fed, 0.893+/-0.24) had elevated lactulose/mannitol ratios on POD 1 vs controls (0.262+/-0.1; p < .008 and p = .05). These elevated levels returned toward control levels in both groups by day 5 (nonfed, 0.533+/-0.1, p = .06; fed, 0.606+/-0.12, p = .08)., Conclusions: Major upper GI surgery for malignancy resulted in a significant increase in intestinal permeability on POD 1. With or without enteral nutrition, this measure of intestinal permeability returned to normal on POD 5 in well-nourished patients.

Background: Castleman's disease (CD), or angiofollicular lymph node hyperplasia, creates both diagnostic and therapeutic dilemmas for most physicians. For patients with this rare and poorly understood disease, the optimal therapy is unknown. The authors report their experience during the years 1986-1997 with this uncommon clinicopathologic entity., Methods: Sixteen patients with a histologic diagnosis of CD were identified in the pathology database. Unicentric disease was defined as a solitary mass. Multicentric disease compromised patients with widespread lymphadenectomy. Clinical, radiologic, and laboratory data were analyzed to evaluate treatment response., Results: The study group consisted of 16 patients classified into 3 clinicopathologic groups: hyaline-vascular, plasma cell, and "mixed." Of those patients who underwent complete surgical excision of a unicentric hyaline-vascular CD mass (n = 8), all remain symptom free without clinical or radiographic recurrence. Two patients remain asymptomatic following partial resection or radiation therapy for an unresectable unicentric hyaline-vascular CD mass. Two patients with multicentric hyaline-vascular CD are currently in complete remission following adjuvant therapy. Multicentric plasma cell CD was present in a single patient. This patient (who underwent surgical and systemic therapy) died of disease within 4 months of presentation. Three patients with unicentric hyaline-vascular/plasma cell-CD remain symptom free following either complete resection or observation., Conclusions: The authors recommend surgical resection for patients with the unicentric variant of CD. Surgical removal of a unicentric mass of hyaline-vascular or hyaline-vascular/plasma cell type is curative. Partial resection, radiotherapy, or observation alone may avoid the need for excessively aggressive therapy. Patients with multicentric disease, either hyaline-vascular or plasma cell type, do not benefit from surgical management and should be candidates for multimodality therapy, the nature of which has yet to be defined.

Mice bearing the experimental murine renal cancer Renca can be successfully treated with some forms of immunotherapy. In the present study, we have investigated the molecular pathways used by NK and T cells to lyse Renca cells. Renca cells normally express low levels of Fas that can be substantially enhanced by either IFN-gamma or TNF-alpha, and the combination of IFN-gamma + TNF-alpha synergistically enhances cell-surface Fas expression. In addition, cells pretreated with IFN-gamma and TNF-alpha are sensitive to lysis mediated by Fas ligand (FasL)-expressing hybridomas (dllS), cross-linking of anti-Fas Abs or soluble Fas (FasL). Lysis via Fas occurs by apoptosis, since Renca shows all the typical characteristics of apoptosis. No changes in levels of bcl-2 were observed after cytokine treatments. We also examined cell-mediated cytotoxic effects using activated NK cells and T cells from gld FasL-deficient mice, and perforin-deficient mice, as well as wild-type C57BL/6 and BALB/c mice. Interestingly, the granule-mediated pathway predominated in killing of Renca by activated NK cells, while the Fas/FasL pathway contributed significantly to cell-mediated killing of Renca by activated T cells. These results suggest that killing of Renca tumor cells by immune effector cells can occur by both granule and Fas-mediated cytotoxicity. However, for the Fas-mediated pathway to function, cell surface levels of Fas need to be increased beyond a critical threshold level by proinflammatory cytokines such as IFN-gamma and TNF-alpha.

The ras oncogene plays an important role in the multistep progression to cancer by activation of signal transduction pathways that contribute to aberrant growth regulation. Although many of these effects are cell autonomous, the ras oncogene also regulates the expression of genes that alter host/tumor interactions. We now extend the mechanisms through which ras promotes tumor survival by demonstrating that oncogenic Ras inhibits expression of the fas gene and renders Ras-transformed cells resistant to Fas-induced apoptosis. A panel of Ras-transformed clones exhibited a marked inhibition in fas mRNA and Fas cell surface expression as compared with untransformed parental cell lines. Fas expression was induced by culture in the presence of IFN-gamma + tumor necrosis factor alpha; however, the maximal level attained in Ras transformants was approximately 10-fold below the level of untransformed cells. Whereas untransformed cells were sensitive to apoptotic death induced by cross-linking surface Fas (especially after cytokine treatment), Ras-transformed cells were very resistant to Fas-induced death even under the most stringent assay conditions. To demonstrate that this resistance was mediated by oncogenic Ras and not secondary genetic events, pools of Ras-transformed cells were generated using a highly efficient retroviral transduction technique. Transformed pools were assayed 6 days after infection and demonstrated a marked decrease in fas gene expression and Fas-mediated apoptosis. Oncogenic Ras did not promote general resistance to apoptosis, because ectopic expression of a fas cDNA in Ras-transformed cells restored sensitivity to Fas-induced apoptosis. These data indicate that oncogenic Ras inhibits basal levels of expression of the fas gene, and although cytokine signal transduction pathways are functional in these cells, the level of surface Fas expression remains below the threshold required for induction of apoptosis. These data identify a mechanism by which Ras-transformed cells may escape from host-mediated immune destruction.

Closed suction drains after pancreaticoduodenectomy are theoretically used to drain potential collections and anastomotic leaks. It is unknown whether such drains are effective, harmful, or affect the outcome after this operation. Eighty-nine consecutive patients underwent pancreaticoduodenectomy for presumed periampullary malignancy and were retrospectively reviewed. Thirty-eight had no intra-abdominal drains and 51 had drains placed at the conclusion of the operation. We analyzed patient, nutritional, laboratory, and operating room factors with end points being complications and length of hospital stay. Intra-abdominal complications were defined as intra-abdominal abscess and pancreatic or biliary fistula. Postoperative interventions were defined as CT-guided drainage and reoperation. Analysis was by Student's t test and chi-square test. Two of eight surgeons contributed 92% of the patients without drains. The groups were equivalent with respect to demographic, nutritional, and operative factors. Time under anesthesia was significantly shorter in the group without drains (P = 0.0001). There was no statistical difference in the rate of fistula, abscess, CT drainage, or length of hospital stay. Intra-abdominal drainage did not significantly alter the risk of fistula, abscess, or reoperation or the necessity for CT-guided intervention after pancreaticoduodenectomy. Routine use of drains after pancreaticoduodenectomy may not be necessary and should be subjected to a randomized trial.

Background: A preoperative biliary stent is commonly used after the initial evaluation of the patient with a periampullary mass., Objective: To evaluate the effect of a preoperative biliary stent on operative difficulty, postoperative complications, and length of hospital stay after a pancreatoduodenectomy., Design: A retrospective review of a prospectively collected consecutive series., Setting: The Memorial Sloan-Kettering Cancer Center's Surgical Service, New York, NY., Patients and Methods: Seventy-four patients underwent pancreatoduodenectomy between March 1, 1994, and February 15, 1996. Thirty-five did not receive a biliary stent, and 39 received a biliary stent prior to medical evaluation. We analyzed patient, nutritional, laboratory, and operating room factors. Univariate analysis was by Student t test, chi2 test, and Fisher exact test; multivariate analysis was by logistic regression. Significance was defined at P<.05., Main Outcome Measures: Operative time, amount of blood loss, complications, and length of hospital stay. Wound complications were defined as cellulitis, superficial infections, and deep infections. Intra-abdominal complications were defined as intra-abdominal abscesses and pancreatic or biliary fistula., Results: Groups were equivalent for tumor size, risk of comorbidity, time spent in the operating room, and amount of blood loss. There was 1 perioperative death. Patients with a stent had significantly lower bilirubin (P<.03) and aspartate aminotransferase (P<.04) levels and a significantly increased risk of nodal positivity (P<.05). The patients with a biliary stent had an increased risk of wound or abdominal complications on univariate (P<.003) and multivariate (P<.02) analysis and tended toward a prolonged hospital stay (P<.04, Wilcoxon signed rank test)., Conclusions: A preoperative biliary stent was associated with an increased risk of wound or intra-abdominal complications; a stent may prolong the length of hospital stay. However, length of time under anesthesia, amount of blood loss, and transfusion requirements were not altered. A biliary stent should be used with a high degree of selectivity in the management of patients with resectable periampullary masses.

Background: Experience with soft tissue sarcoma has suggested that superficial tumors have a favorable prognosis. We evaluated the prognostic features of this subset of sarcoma., Methods: Prospective data on 215 patients presenting to Memorial Sloan-Kettering Cancer Center with primary extremity superficial soft tissue sarcomas between July 1, 1982 and July 1, 1996 were analyzed. Superficial sarcomas were defined as subcutaneous tumors not invading the investing fascia of the muscle. Analysis was by univariate and multivariate tests for local recurrence, metastasis, and tumor mortality., Results: Ninety (42%) patients were over 50 years of age, 115 (53%) had high-grade tumors, 53 (25%) had tumors > or = 5 cm, and 18 (8%) had positive margins following definitive resection. Median follow-up was 45 months (range 2 days to 151 months), 31 (14%) patients had local recurrences, 20 (9%) had distant metastases, and 15 (7%) died of disease. Five- and 10-year actuarial disease-specific survivals were 91% and 85%, respectively. On multivariate analysis, age > 50 years predicted local recurrence (RR 5.7; 95% CI, 2.4-13.3; p < 0.0001). High grade (RR 4.2; 95% CI, 1.4-12.7; p < 0.006), and size > or = 5 cm (RR 4.4; 95% CI, 1.8-11; p < 0.002) predicted distant metastases. High grade (RR 7; 95% CI, 1.5-31.4; p < 0.003), size > or = 5 cm (RR 6.9; 95% CI, 2.3-20.8; p < 0.0006), and positive margins (RR 3.8; 95% CI, 1.2-12.4; p < 0.006) predicted tumor mortality., Conclusion: Primary superficial extremity soft tissue sarcomas have a favorable prognosis. Size and grade of superficial tumors are the strongest factors in predicting survival.

Objective: The purpose of the study was to determine whether early postoperative enteral feeding with an immune-enhancing formula (IEF) decreases morbidity, mortality, and length of hospital stay in patients with upper gastrointestinal (GI) cancer., Summary Background Data: Early enteral feeding with an IEF has been associated with improved outcome in trauma and critical care patients. Evaluable data documenting reduced complications after major upper GI surgery for malignancy with early enteral feeding are limited., Methods: Between March 1994 and August 1996, 195 patients with a preoperative diagnosis of esophageal (n = 23), gastric (n = 75), peripancreatic (n = 86), or bile duct (n = 11) cancer underwent resection and were randomized to IEF via jejunostomy tube or control (CNTL). Tube feedings were supplemented with arginine, RNA, and omega-3 fatty acids, begun on postoperative 1, and advanced to a goal of 25 kcal/kg per day. The CNTL involved intravenous crystalloid solutions. Statistical analysis was by t test, chi square, or logistic regression., Results: Patient demographics, nutritional status, and operative factors were similar between the groups. Caloric intake was 61% and 22% of goal for the IEF and CNTL groups, respectively. The IEF group received significantly more protein, carbohydrate, lipids and immune-enhancing nutrients than did the CNTL group. There were no significant differences in the number of minor, major, or infectious wound complications between the groups. There was one bowel necrosis associated with IEF requiring reoperation. Hospital mortality was 2.5% and median length of hospital stay was 11 days, which was not different between the groups., Conclusion: Early enteral feeding with an IEF was not beneficial and should not be used in a routine fashion after surgery for upper GI malignancies.

The ability of Erwinia chrysanthemi to cause soft-rot diseases involving tissue maceration in many plants has been linked to the production of endo-pectate lyase E. chrysanthemi EC16 mutant UM1005, however, contains deletions in the pel genes that encode the known endopectate lyases, yet still macerates plant tissues. In an attempt to identify the remaining macerating factor(s), a gene library of UM1005 was constructed in Escherichia coli and screened for pectolytic activity. A clone (pPNL5) was identified in this library that contained the structural gene for an exopolygalacturonate lyase (ExoPL). The gene for ExoPL was localized on a 3.3-kb EcoRV fragment which contained an open reading frame for a 79,500-Da polypeptide. ExoPL was purified to apparent homogeneity from Escherichia coli DH5 alpha (pPNL5) and found to have an apparent molecular weight of 76,000 with an isoelectric point of 8.6. Purified ExoPL had optimal activity between pH 7.5 and 8.0 and could utilize pectate, citrus pectin, and highly methyl-esterified Link pectin as substrates. A PL- ExoPL- mutant of EC16 was constructed that exhibited reduced growth on pectate, but retained pathogenicity on chrysanthemum equivalent to that of UM1005. The results indicate that ExoPL does not contribute to the residual macerating activity of UM1005.