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Objective: To investigate the state of activation of the ATP-ubiquitin-dependent proteolytic system in the skeletal muscle of gastric cancer patients., Summary Background Data: Muscle wasting in experimental cancer cachexia is frequently associated with hyperactivation of the ATP-dependent ubiquitin-proteasome proteolytic system. Increased muscle ubiquitin mRNA levels have been previously shown in gastric cancer patients, suggesting that this proteolytic system might be modulated also in human cancer., Methods: Biopsies of the rectus abdominis muscle were obtained intraoperatively from 23 gastric cancer patients and 14 subjects undergoing surgery for benign abdominal diseases, and muscle ubiquitin mRNA expression and proteasome proteolytic activities were assessed., Results: Muscle ubiquitin mRNA was hyperexpressed in gastric cancer patients compared to controls. In parallel, three proteasome proteolytic activities (CTL, chymotrypsin-like; TL, trypsin-like; PGP, peptidyl-glutamyl-peptidase) significantly increased in gastric cancer patients with respect to controls. Advanced tumor stage, poor nutritional status, and age more than 50 years were associated with significantly higher CTL activity but had no influence on TL and PGP activity., Conclusions: These results confirm the involvement of the ubiquitin-proteasome proteolytic system in the pathogenesis of muscle protein hypercatabolism in cancer cachexia. The observation that perturbations of this pathway in gastric cancer patients occur even before clinical evidence of body wasting supports the thinking that specific pharmacologic and metabolic approaches aimed at counteracting the upregulation of this pathway should be undertaken as early as cancer is diagnosed.

Purpose: Sacral neuromodulation is a novel treatment for selected urinary and bowel dysfunctions. A new method is described for electrode implantation, the "minimally invasive sacral neuromodulation implant technique.", Methods: After the percutaneous nerve evaluation test, a small longitudinal incision (3 cm) is made, and a catheter cannula segment is inserted through the sacral foramen beside an insulated needle. The electrode is introduced into the catheter cannula, which is then removed and fixed to the sacrum by means of small anchors. The proximal part of the lead is tunneled into the subcutaneous tissue, reaching the pocket made to accommodate the neurostimulator., Results: This procedure was performed in ten patients (5 male; mean age, 50.4 years). In four patients a single electrode was implanted, and in six patients two electrodes were implanted. The minimally invasive technique was significantly faster, saving a mean time of 20 minutes for each electrode. The incision made directly on the sacral foramen was significantly reduced (3 vs. 12 cm), avoiding the wide, blunt dissection of subcutaneous fat tissue. Application of the catheter cannula allowed the electrode to be introduced easily and correctly. The electrode anchors never failed: no cases of lead displacement or suboptimal position of the electrode occurred. A unilateral, sterile subcutaneous seroma occurred in one of the ten patients., Conclusions: The minimally invasive sacral neuromodulation implant technique seems to be a safe procedure-making sacral neuromodulation implant easier, faster, and safer, in as much as complications could be potentially reduced.

Purpose: Patients with unresectable, locally advanced rectal cancer are reported to have a dismal prognosis. The aim of this study was to analyze the effect of combined-modality therapy on clinical outcome., Methods: From March 1990 to December 1997, 43 patients (28 males; median age, 62 years; median follow-up, 74 months) with locally advanced (T4 and/or N3) nonmetastatic rectal cancer received external-beam radiation (23.6 plus 23.6 Gy (split course), 8 patients; 45 Gy, 35 patients) plus 5-fluorouracil (96-hour continuous infusion, Days 1-4, at 1,000 mg/m(2)/day) and mitomycin C (10 mg/m, intravenous bolus, Day 1). Concomitant chemotherapy was repeated at the beginning of the second course (split-course group) or in the last week of radiotherapy (continuous-course group). After 6 to 8 weeks, patients were evaluated for surgical resection and intraoperative radiation therapy (10 to 15 Gy). Thereafter, adjuvant chemotherapy (5-fluorouracil plus leucovorin, 6-9 courses) was prescribed., Results: During chemoradiation, 5 patients (11.6 percent) developed Grade 3 to 4 hematologic toxicity. After chemoradiation, 29 patients (67.4 percent) had an objective clinical response (complete response, 2.3 percent; partial response, 65.1 percent). Thirty-eight patients underwent radical surgery (anterior resection, 24 patients; abdominoperineal resection, 14 patients; intraoperative radiation therapy boost on the tumor bed, 19 patients), and 2 patients had partial tumor resection. No perioperative deaths occurred in the patient group. Five-year survival and local control rates were 59.9 and 69.1 percent, respectively. Distant metastasis occurred in 44.2 percent of patients. Statistically significant relationships between intraoperative radiation therapy and local control (P = 0.0104), radical surgery and survival (P = 0.0120), and adjuvant chemotherapy and disease-free survival (P = 0.0112) were observed., Conclusions: Our data suggest that combined-modality therapy was relatively well tolerated and resulted in good local control and survival. With regard to the impact of surgical resection on survival, additional studies aimed at improving the local response rate are necessary, whereas the positive impact of intraoperative radiotherapy on local control appears to justify the inclusion of this therapeutic modality in prospective multi-institutional trials.

Objective: To examine the characteristics of thymoma when associated with MG and to evaluate those conditions that can complicate management and affect survival., Methods: The study includes 207 myasthenic patients who were operated on for thymoma, with at least 1-year follow-up from surgery. MG severity and response to treatment, the occurrence of paraneoplastic diseases and extrathymic malignancies, thymoma histologic types and stages, adjuvant therapy, tumor recurrences, and causes of death were recorded., Results: MG-associated thymoma was predominantly of B type and was invasive in the majority of patients. MG was generally severe, and most patients remained dependent on immunosuppressive therapy. Other paraneoplastic disorders and extrathymic malignancies were found in 9.66 and 11.11% of patients. Thymoma recurrences occurred in 18 of 115 patients with invasive tumors (15.65%) and were often associated with the onset/aggravation of autoimmune diseases. On completion of the study, MG and thymoma accounted for a similar mortality rate., Conclusions: Thymoma should be considered as a potentially malignant tumor requiring prolonged follow-up. The presence of myasthenic weakness can still complicate its management. Thymoma-related deaths are bound to outnumber those due to MG in the future.

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.

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.

Purpose: To evaluate the impact of tumor response; tumor and nodal downstaging; and cTNM, yTNM (clinical stage after chemoradiation, based on preoperative imaging), and pTNM classifications on long-term outcome in patients with rectal cancer treated with preoperative 5-fluorouracil (5-FU)-based concurrent chemoradiation., Methods and Materials: Between January 1990 and March 1998, 165 consecutive patients with locally advanced extraperitoneal cancer of the rectum were treated with preoperative chemoradiation. Four patients had a cT2 lesion (2.5%), 120 had a cT3 lesion (74.5%), and 41 had a cT4 lesion (23%). The nodal involvement at combined imaging was cN0 in 21%, cN1 in 41%, cN2 in 34%, and cN3 in 4%. Preoperative chemoradiation was delivered according to 1 of 3 schedules: (1) FUMIR-T3 (from 1990 to 1995) for patients with cT3N0-2 or cT2N1-2 rectal carcinoma (82 patients): 37.8 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4, continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Day 1; (2) FUMIR-T4 (from 1990 to 1999) for patients with cT4N0-3 or cT3-4N3 rectal carcinoma (40 patients): 45 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4 and 29-32, continuous infusion, and mitomycin-C, 10 mg/m(2)/d on Days 1 and 29; and (3) PLAFUR-4 (from 1995 to 1998) for patients with cT3N0-2 or cT2N1-2 rectal carcinoma (42 patients): 50.4 Gy (1.8 Gy/fraction) plus 5-FU, 1 g/m(2)/d on Days 1-4 and 29-32, continuous infusion, and cisplatin, 60 mg/m(2)/d on Days 1 and 29. Four to five weeks after chemoradiation, patients were reevaluated for clinical response by imaging studies (CT scan, transrectal ultrasonography, barium enema, liver ultrasonography, chest X-rays) and restaged (yTNM). Surgery was performed 6-8 weeks after chemoradiation. Adjuvant chemotherapy (5-FU + l-folinic acid) was delivered to 26 patients in the FUMIR-T4 protocol group. Local control (LC), freedom from distant metastases (FDM), disease-free survival, and overall survival (OS) were evaluated according to the clinical response and cTNM, yTNM, and pTNM classification. The median follow-up was 67 months., Results: The 5-year survival rate was 100% for cT2, 77% for cT3, and 62% for cT4 (p = 0.0497); after chemoradiation, it ranged between 81% and 91% for pT0-pT2 and dropped to 66% for pT3 and 47% for pT4 (p = 0.014). The 5-year local control rate was, at the first staging, 84% for cT3 and 72% for cT4; after chemoradiation, the pT stage correlated significantly with LC (p = 0.0012): 100% for pT0, 83% for pT1, 88% for pT2, 79% for pT3, and 46% for pT4. N stage was statistically significant in predicting FDM and OS at any staging step. A significant impact of tumor response, tumor downstaging, and nodal downstaging on LC, FDM, disease-free survival, and OS was also recorded. If the residual tumor, before surgery, had a tumor index <30 (i.e., width less than one-quarter of rectal circumference and length in its caudocranial axis < or =30 mm), the 5-year LC, FDM, disease-free survival, and OS rates were significantly higher at both the univariate and the multivariate analyses. The surgical procedure was tailored according to tumor downstaging, and thus the choice of sphincter-preserving surgery was based on the distance between the lower pole of the tumor and the anorectal ring "after" chemoradiation. In 36 patients with the lower pole of the lesion in the range of 0-30 mm from the anorectal ring, 16 patients (44%) underwent a sphincter-saving procedure. All clinical outcomes were similar compared with 20 patients with tumor located at the same rectum level who received an abdominoperineal resection., Conclusion: After preoperative chemoradiation, clinical response and tumor/nodal pathologic downstaging showed a close correlation with improved outcomes. The better 5-year survival and local control in pT0-2 patients regardless of their initial stage seems to confirm a heterogeneity in rectal cancer patients. The responder population showed a behavior similar to rectal cancer diagnosed at Stage cT1-2 and treated with conservative surgery alone. Additional studies aimed at improving local tumor response seem justified. Trials of sphincter-saving surgery after a major response are warranted.

Purpose: Mesorectal involvement is a common feature in rectal tumors. Neoplastic foci can be identified at pathologic examination of the mesorectum, but their incidence and prognostic significance remain to be defined., Methods: A series of 77 patients with extraperitoneal rectal cancer, resected with total mesorectal excision, entered the study. After fixation, the excised specimens were submitted to serial transverse sections and staining. Direct tumor infiltration, lymph node involvement, and neoplastic microfoci in the mesorectum were investigated. Patients with mesorectal foci were compared with those without deposits with regard to clinical and pathologic parameters; different patterns of foci (endovasal, endolymphatic, perineural, isolated) were also considered. Univariate and multivariate analyses were used to evaluate the impact on survival rate., Results: Neoplastic mesorectal involvement was found in 64 patients (83.1 percent). Direct tumor infiltration was detected in 66.2 percent, node involvement in 28.6 percent, microscopic foci in 44.2 percent of cases (endovasal in 11.7 percent, endolymphatic in 15.7 percent, perineural in 26 percent, isolated in 14.3 percent). In 7 cases (10.9 percent) microfoci alone (without any kind of other mesorectal involvement) were detected. Deposits were found in 18.8 percent of TNM Stage I tumors, in 46.9 percent of Stage II and in 59.3 percent of Stage III cancers. Similar incidence was found in patients treated with integrated therapies and surgery alone (43.3 vs. 44.7 percent, P = not significant). Poorer median (44.5 vs. 57 months, P = 0.04) five-year overall survival rate (43.4 vs. 63.3 percent, P = 0.016) and disease-free survival rate (43.3 vs. 57.7 percent, P = 0.048) were observed in patients with microscopic foci compared with those without deposits. Tumor configuration was found to be a independent prognostic factor for both overall and disease-free survival rates; furthermore, endolymphatic, perineural, and isolated foci significantly affected overall survival rate, while TNM staging affected disease-free survival rate., Conclusions: The incidence of neoplastic foci in the mesorectum is high, even in early staged tumors and despite aggressive preoperative treatment. They seem to affect prognosis. Such features should, therefore, be considered when local excision of the tumor is planned. Presence of mesorectal foci should modify conventional staging of the rectal tumor.

The use of raltitrexed ('Tomudex') as concomitant chemotherapy during preoperative radiotherapy in chemonaïve patients with stage II/III rectal cancer has been examined in this study and its recommended dose in conjunction with radiotherapy investigated. Forty-five Gray (Gy) of radiotherapy (1.8 Gy daily, 5 days per week) was delivered to the posterior pelvis, followed by a 5.4 Gy boost. Single doses of raltitrexed (2.0, 2.5 and 3.0 mg/m(2)) were administered on days 1, 19 and 38. Only 1 of the 15 patients entered experienced a dose limiting toxicity (DLT) (grade 3 leucopenia) at the 3.0 mg/m(2) dose level. The overall response rate was 80% (five complete responses, seven partial responses). These preliminary data suggest that raltitrexed is a well tolerated and effective treatment when combined with preoperative radiotherapy in patients with stage II/III rectal cancer. The recommended dose of raltitrexed for future phase II studies will be 3.0 mg/m(2).

Background: Local recurrence remains one of the most complex problem in the management of rectal carcinoma. Often, surgery alone is not able to prevent local recurrence development, particularly in locally advanced cancer. A better local control is obtained using the association with radiotherapy and chemotherapy. Intraoperative Radiation Therapy (IORT) represents an innovative therapeutic modality., Patients and Methods: 141 patients, 97 with "high risk" cancer (T2N1-2 or T3N0-2) and 44 with "locally advanced" tumor (T3N3, T4N0-3 or local recurrence). 64 patients with extraperitoneal "high risk" rectal cancer have been treated with preoperative radiotherapy (38 Gy), surgical excision and IORT (10 Gy). In other 33 "high risk" cases, preoperative radio- (50.4 Gy) chemotherapy (Tomudex 2-3 mg), surgery and IORT (10 Gy) have been given. Fourty four patients with "locally advanced" rectal tumor have had external radiotherapy (48 Gy) + chemotherapy (5FU + Mitomicin C) preoperatively, surgery, IORT (10-15 Gy) and chemotherapy (5FU + Levamisolo) postoperatively., Results: Among "high risk" patients, 52-83% of cases have had a sphincter-saving surgical procedure, 5-year local control is 93%, 5-year overall survival 80%, and 5-year disease free survival 77%. In 50-60% of "high risk" tumors treated with preoperative chemo-radiotherapy the pathologic staging have found a T0-1 tumor. Among "locally advanced" primary tumors, 5-year local control is 90.9%, 5-year disease free survival 47.1%, 5-year overall survival 60.7%. Among patients treated for local recurrence, in 60% a complete tumor resection has been performed; 5-year local control is 79.5%, 5-year disease free survival 19.4%, 5-year overall survival 41.4%., Conclusions: Integrated treatment with radiotherapy, chemotherapy, surgery and IORT has allowed a good local control and seems prolong survival also.

Purpose: There are several options in the treatment of fecal incontinence; it is often difficult to choose the most appropriate, adequate treatment. The consolidated experience gained in the urologic field suggests that sacral nerve stimulation may be a further option in the choice of treatment. The aim of our study was to evaluate the preliminary results of the peripheral nerve evaluation test obtained in a multicenter collaborative study on patients with defecatory and urinary disturbances., Methods: Forty patients (9 males; mean age, 50.2; range, 26-79 years) underwent the peripheral nerve evaluation test, 28 (70 percent) for fecal incontinence and 12 (30 percent) for chronic constipation. Fourteen (35 percent) patients also had urinary incontinence; six had urge incontinence, two had stress incontinence, and six had retention incontinence. Associated diseases were scleroderma (2 patients), spinal injuries (4 patients), and syringomyelia (1 patient). All the patients underwent preliminary investigations with anorectal manometry, pudendal nerve terminal motor latency testing, anal ultrasound, defecography, and if required, urodynamic tests. The electrode for sacral nerve stimulation was positioned percutaneously under local anesthesia in the S2 (4), S3 (34), or S4 (1) foramen unilaterally (1 patient not accounted for because of no response to acute test), based on the best motor and subjective responses of paresthesia of the pelvic floor. Stimulation parameters were average amplitude, 2.8 (range, 1-6) V and average frequency, 15 to 25 Hz., Results: The mean duration of the tests was 9.9 (range, 7-30) days; tests lasting fewer than seven days were not evaluated. There were four early displacements of the electrode. In 22 of the 25 evaluable patients with fecal incontinence, there was an improvement of symptoms (88 percent), and 11 (44 percent) were completely continent to liquid or solid stools, whereas in 7 symptoms were unchanged. Mean number of episodes of liquid or solid stool incontinence per week was 8.1 (range, 4-18) in the prestimulation period and 1.7 (range, 0-12) during the peripheral nerve evaluation test. (P = 0.001; Wilcoxon's signed-rank test). The most important manometric findings were: increase of maximum rest pressure (39.4 +/- 7.3 vs. 54.3 +/- 8.5 mmHg; P = 0.014, Wilcoxon's test) and maximum squeeze pressure (84.7 +/- 8.8 vs. 99.5 +/- 1.1 mmHg; P = 0.047), reduction of initial threshold (63.6 +/- 5.2 vs. 42.4 +/- 4.7 ml; P = 0.041) and urge sensation (123.8 +/- 0.6 vs. 78.3 +/- 8.9 ml; P = 0.05). An improvement was also found in patients with constipation, with reduction in difficulty emptying the rectum, with prestimulation at 7 (range, 2-21) episodes per week and end of peripheral nerve evaluation test at 2.1 (range, 0-6) episodes per week, P < 0.01) and in the number of unsuccessful visits to the toilet, which dropped from 29.2 (7-24) to 6.7 (0-28) per week (P = 0.01). The most important manometric findings in constipated patients were an increase in amplitude of maximum squeeze pressure during sacral nerve stimulation (prestimulation, 63 +/- 0 mm Hg; end of peripheral nerve evaluation test, 78 +/- 1 mm Hg; P = 0.009) and a reduction in rectal volume for urge threshold (prestimulation, 189 +/- 52 ml; end of peripheral nerve evaluation test, 139 +/- 45 ml; P = 0.004)., Conclusions: In functional bowel disorders short-term sacral nerve stimulation seems to be a useful diagnostic tool to assess patients for a minor invasive therapy alternative to conventional surgical procedure.

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.

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.

Purpose: Sacral nerve modulation appears to offer a valid treatment option for some patients with fecal incontinence and functional defects of the internal anal sphincter or of the striated muscle., Methods: Sixteen patients with fecal incontinence (4 males; mean age, 51.4 (range, 27-79) years) with intact or surgically repaired (n = 1) anal sphincter underwent permanent sacral nerve stimulation implant. Cause was traumatic in two patients, and associated disorders included scleroderma (2 patients) and spastic paraparesis (1 patient); eight (50 percent) of the patients also had urinary incontinence, and two (12.5 percent) had nonobstructive urinary retention. All patients were selected on the basis of positive findings from at least one peripheral nerve evaluation. The stimulating electrode was positioned in the S2 (1 patient), S3 (14 patients), or S4 (1 patient) sacral foramen., Results: Mean follow-up was 15.5 (range, 3-45) months. Mean preimplant Williams score decreased from 4.1 +/- 0.9 (range, 2-5) to 1.25 +/- 0.5 (range, 1-2) (P = 0.01, Wilcoxon test), and the number of incontinence accidents for liquid or solid stool in 14 days decreased from 11.5 +/- 4.8 (range, 2-20) before implant to 0.6 +/- 0.9 (range, 0-2) at the last follow-up. Important manometric data were an increase in mean maximal pressure at rest of 37.7 +/- 14.9 mmHg (implantable pulse generator 49.1 +/- 18.7, P = 0.04) and in mean maximal pressure during squeeze (prestimulation 67.3 +/- 21.1 mmHg, implantable pulse generator 82.6 +/- 21.0, P = 0.09)., Conclusions: Neuromodulation can be considered an option for fecal incontinence. However, an accurate clinical and instrumental evaluation and careful patient selection are required to optimize outcome.

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.

Background: The number of hepatic resections for benign and malignant lesions has constantly increased over the past 20 years, as a consequence, surgical experience acquired over the past few years has decreased post-operative morbidity and mortality rates., Aims: Analysing the relation between potential preoperative risk factors and the occurrence of severe post-operative complications, an attempt is made to identify the variables determining surgical risk in elective hepatic surgery both in normal and cirrhotic liver., Patients and Methods: The hospital records of 254 patients who underwent elective liver surgical procedures for hepatic lesions in our department, between 1984 and 1999, were reviewed. The following variables were entered into univariate and multivariate analysis: age, sex, nature of liver lesion (benign or malignant), presence of cirrhosis or cholestasis, synchronous resection of other organs, disorders of blood coagulation, intraoperative blood requirement, the extent of surgical procedures and Pringle's manoeuvre., Results and Conclusions: The multivariate analysis of the 254 surgical operations on the liver indicates that the most powerful independent predictors favouring a serious adverse effect includes intra-operative blood transfusions, advanced age and cirrhosis. Scrupulous preoperative clinical evaluation and expert surgical skills minimize intra-operative bleeding and proved to be the most significant factors influencing morbidity and mortality rates.

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.

Controversy still surrounds the value of extensive regional lymphnode dissection in the treatment of gastric cancer. The aim of the present paper is to give this topic a contribution through the review of the literature and the analysis of personal results.

Background: Tumour necrosis factor-alpha (TNF) has been regarded as a potential mediator of cancer cachexia. Assessment of TNF circulating levels in cancer patients and their correlation with weight loss has led to controversial results., Materials and Methods: We measured TNF circulating levels in 28 patients with gastrointestinal cancer and 29 controls with benign gastrointestinal diseases at different times (08.00 h, 14.00 h, 20.00 h) before operation., Results: TNF activity was not detected in any of controls at any times. In cancer patients, TNF circulating levels were detectable in 18 cases (64.3%) and appeared to be discontinuous. TNF levels above the limit of detection were present in 15 patients (53.6%) at 08.00 h, in 14 (50%) at 014.00 h and in nine (32.1%) at 20.00 h. Mean TNF levels were 14.3 +/- 4 pg mL(-1) at 08.00 h, 16.7 +/- 4.6 pg mL(-1) at 14.00 h (P = 0.05) and 18.5 +/- 10.2 pg mL(-1) at 20.00 h (P < 0.05 vs. 08.00 h and 14.00 h). According to Spearman's analysis, the sum of TNF concentrations at the three times significantly correlated with the severity of weight loss (Spearman's correlation coefficient = - 0.420; P = 0.026). TNF concentrations were consistently and significantly higher in patients with severe weight loss than in those with moderate or light weight loss at 08.00 h (26.3 +/- 8.3, 8.9 +/- 4.2, 3.8 +/- 2.1, respectively; P = 0.04 at one-way ANOVA). TNF levels were higher in anorectic than in nonanorectic patients at any hour, but the differences were not statistically significant., Conclusions: The present study demonstrates that TNF is intermittently or discontinuously detectable in patients with gastrointestinal cancer and that its levels correlate with the severity of weight loss.

The hospital records of 639 patients affected by primary gastric cancer who were consecutively admitted to our unit during the period 1981-1995 were reviewed. Overall 220 underwent total gastrectomy (38 palliative), 12 had resection of the gastric stump, 195 had distal subtotal gastrectomy (55 palliative), 78 had bypass procedures, 72 had explorative laparotomy, and 62 had no operation. Univariate and multivariate analyses were used to evaluate 5-year survival with respect to the main clinical, pathologic, and treatment variables after both curative and palliative treatments. Overall the 5-year survival after curative treatment (320 patients-operative mortality excluded) was 55.5%: 91.1% for stage IA, 71.5% IB, 62.4% II, 37.5% IIIA, 31.5% IIIB. Among patients who underwent palliative treatment 5-year survival was 13.1% after gastric resection (total or distal subtotal), 4.9% after the bypass procedures, 0 after explorative laparotomy, and 0 after no operation. Univariate and multivariate survival analyses showed that variables independently associated with poor survival were advanced stage, upper location and D1 lymphadenectomy after curative treatment, tumor spread to distant sites, and nonresectional surgery after palliative treatment. Multivariate analysis showed that even though survival with gastric cancer depends on predetermined factors, the type of surgery can have a significant effect on prognosis after both curative and palliative treatment.

Background/aims: This study was designed to evaluate the effectiveness of a diagnostic and therapeutic approach adopted in 118 consecutive patients affected by primary malignancy of the extrahepatic bile duct., Methodology: After diagnostic procedures were performed (ultrasound examination, endoscopic retrograde cholangiopancreatography and computed tomography scan) 25 patients underwent surgical resection. For the remaining 93 patients considered unresectable for cure, stenting by endoscopic means was almost always the only palliative treatment performed., Results: The morbidity and mortality rates were 28% and 8% for patients treated with surgical resection and the curative and overall 3-year survival rate was 30% and 22% respectively. The procedure related morbidity and mortality rates were 13% and 4% for patients endoscopically treated and the median survival rate was 7.3 months. The quality of life evaluated in 68 patients out of 93 was good in 57% of cases, fair in 19% and poor in the remaining 22%., Conclusions: The results of the present study demonstrate the safety and efficacy of endoscopic stenting in the palliative treatment of extrahepatic bile duct cancer while potential cure can only be achieved by radical surgical resection.

Background: Pancreas-preserving total gastrectomy for gastric cancer has been proposed to remove lymph nodes along the upper border of the pancreas without performing a distal pancreatic resection. However, the original technique includes the ligation of the splenic artery at its origin and thus carries the risk of pancreatic necrosis., Hypothesis: A technique of pancreas-preserving total gastrectomy that includes ligation of the splenic artery approximately 5 cm distally from the root may reduce the risk of postoperative pancreatic necrosis., Design: Case series., Setting: Both primary and referral hospital care., Patients: Hospital records of 228 consecutive patients who, according to a personal technique, underwent D3 pancreas-preserving total gastrectomy for gastric cancer from 1981 to 1997 were reviewed., Main Outcome Measures: Surgical complications, postoperative deaths, and survival., Results: Hospital morbidity and mortality were 33.3% and 3.9%, respectively. No patients experienced pancreatic necrosis. The 5-year survival rate after curative resection was 53.6%: 96.9% for stage IA, 76.3% for stage IB, 63.0% for stage II, 35.6% for stage IIIA, 27.0% for stage IIIB, and 20.3% for stage IV (N3-positive patients) disease., Conclusion: Results of the present study show the efficacy of this method of radical resection for gastric cancer as demonstrated by the low incidence of postoperative complications and high survival rates.

A retrospective study was undertaken to evaluate the results of surgical treatment in a series of patients with primary retroperitoneal sarcomas consecutively treated by the same surgical team. The hospital records of 42 patients with primary retroperitoneal sarcomas who underwent surgical exploration at our unit from 1984 to 1995 were reviewed. A univariate analysis was used to identify the main clinical, pathologic, and treatment-related factors affecting long-term survival. Twenty-five patients (59.6%) underwent radical surgery. The 5-year survival and 5-year disease-free survival after radical resection were 48.1% and 38.8%, respectively. According to the univariate analysis of survival tumor classification (T), stage and gross surgical margins significantly affected prognosis. The study indicates that even though there are predetermined and unmodifiable tumor-related factors, such as tumor classification (T) and stage, that influence survival in patients with retroperitoneal sarcomas, wide surgical excision offers a concrete chance for long-term survival.

Background: After trauma or surgery, researchers have suggested that medium-chain triglycerides have metabolic advantages, although they are toxic in large doses. To try to reduce this potential toxicity, structured lipids, which provide a higher oxidation rate, faster clearance from blood, improved nitrogen balance, and less accumulation in the reticuloendothelial system, could be used. Therefore, we evaluated, through a blind randomized study, the safety, tolerance, and efficacy of structured triglycerides, compared with long-chain triglycerides (LCT), in patients undergoing colorectal surgery., Methods: Nineteen patients were randomized to receive long-chain or structured triglycerides as a lipid source. They received the same amount of calories (27.2/kg/d), glucose (4 g/kg/d), protein (0.2 g/kg/d), and lipids (11.2 kcal/kg/d). Patients were evaluated during and after the treatment for clinical and laboratory variables, daily and cumulative nitrogen balance, urinary excretion of 3-methyl-histidine, and urinary 3-methylhistidine/creatinine ratio., Results: No adverse effect that required the interruption of the treatment was observed. Triglyceride levels and clinical and laboratory variables were similar in the two groups. A predominantly positive nitrogen balance was observed from day 2 until day 5 in the LCT group and from day 1 until day 4 in the structured triglycerides group. The cumulative nitrogen balance (in grams) for days 1 to 3 was 9.7+/-5.2 in the experimental group and 4.4+/-11.8 in the control group (p = .2). For days 1 to 5 it was 10.7+/-10.5 and 6.5+/-17.9 (p = .05), respectively. The excretion of 3-methylhistidine was higher in the control group but decreased in the following days and was similar to the experimental group on day 5., Conclusions: This study represents the first report in which structured triglycerides are administered in postoperative patients to evaluate safety, tolerance, and efficacy. It suggests that Fe73403 is safe, well tolerated, and efficacious in terms of nitrogen balance when compared with LCT emulsion.

Few reports of the Western countries have investigated the value of palliative surgery for stomach cancer. The aim of this study was to evaluate the results of palliative surgery in a large series of patients affected by gastric carcinoma, consecutively treated by the same surgical team. The hospital records of 305 patients affected by gastric cancer who did not undergo surgical treatment or who underwent a palliative surgical procedure at our unit between 1981 and 1995 were reviewed. Univariate and multivariate analyses were used to calculate the 5-year survival probabilities with respect to the following variables: demographic data, tumor location and gross appearance, spread of the disease, histological type according to P. Lauren, and type of treatment. Multivariate logistic regression analysis showed that resectional surgery and tumor spread limited to local sites were independently associated with better survival. The study indicates that even though there are host-related factors that govern survival in far-advanced stomach cancer, the type of surgery can have a significant effect on prognosis; resectional surgery should be undertaken whenever possible in such patients.

Background/aims: Few reports from the Western hemisphere have investigated the impact of pathological features and surgical modalities on the prognosis of patients affected by early gastric cancer (EGC). In particular, the extent of lymphadenectomy (limited vs. extended) and the type of gastric resection (subtotal vs. total) remain controversial issues in the management of EGC. The aim of this study was to identify factors influencing prognosis in patients affected by EGC., Methodology: Hospital records and pathological specimens of 72 patients with EGC undergoing resective surgery during the period 1981-1995 were retrospectively reviewed. Patient status was determined by follow-up examination or by telephone contact. Univariate and multivariate analysis was used to calculate the 5-year survival probabilities with respect to the following variables: age (< or = 65, > 65), sex, depth of invasion (mucosal, submucosal) tumor location (upper, middle and lower third), gross appearance (type I, type II and type III), size (< or = 1.5 cm, > 1.5 cm), presence or absence of lymph node metastasis, histological type (intestinal, diffuse), extent of lymphadenectomy (limited or extended), and type of gastrectomy (total or distal subtotal). Survival was the outcome variable studied., Results: Multivariate logistic regression analysis showed that age, nodal involvement and depth of invasion were independently associated with poor survival., Conclusions: Results showed a significant dominance of host- and tumor-related factors over the type of surgical procedure on prognosis of EGC patients.

Purpose: Lymph-node involvement is the most important prognostic factor in colorectal cancers. Many staging systems adopted node status as a parameter of tumor classification. However, the number of identified and positive glands varies across articles, depending on specimen examination. There is a consistent risk of substaging tumors and undertreating patients. Aim of this study was to investigate the prognostic significance of different pathologic methods., Methods: Eight hundred one patients who underwent curative resection of colorectal cancer entered the study and were divided into two groups. In Group 1 the specimen was "en bloc" fixed, and nodes were identified by sight and palpation. In Group 2 the mesentery of the excised specimen was dissected away from the bowel, stretched, and pinned to cork board. The mesenteric segment surrounding the origin of principal vessels was divided from the segment surrounding the colic vessels. All specimen segments were fixed, node identification being performed by sight and palpation. Examined and positive nodes were recorded, and metastatic rate and incidence was calculated in the two groups. Patients were classified with use of different staging systems. Survival rates were calculated, related to tumor stage, and compared statistically. Pathologic procedures were included in a multivariate analysis., Results: A significantly higher number of detected and positive nodes and metastatic rate (37.5 vs. 30.2 percent; P < 0.05) were observed in Group 2; 45.2 percent of Group 2 and 25.3 percent of Group 1 cases had more than three positive nodes (P < 0.05). In Group 2 several patients shifted from earlier to more advanced stages compared with Group 1 cases. Five-year and ten-year survival rates were significantly higher (P = 0.04) in Group 2 (81.5 and 77.2 percent) than in Group 1 (76.7 and 61.5 percent), mostly in patients with TNM Stage N0. Survival analysis related to Astler and Coller's and Tang's classifications confirmed such features. Higher rates of local recurrences and distant metastases were found in Group 1, particularly if related to node status (P < 0.05). Multivariate analysis demonstrated the pathologic method is an independent prognostic factor., Conclusions: This study demonstrates the prognostic impact of specimen examination. Inaccurate methods could down-stage the tumor and exclude the patient from adjuvant therapies, with detrimental effects on the outcome of the case.

Aims and Background: The prognosis of pancreatic cancer remains poor. Surgery, when feasible, is rarely curative. Radiation therapy (RT) and concomitant 5-fluorouracil (5-FU) have been shown to improve survival in locally advanced pancreatic cancer. In an attempt to improve resectability and disease control, we used preoperative chemoradiation in a combined modality therapy protocol. The purpose of this study was to evaluate our initial results in terms of acute toxicity and response., Methods: From October 1995 to May 1998, 20 patients (11 males, 9 females; mean age, 60.1 years; median follow-up, 28 months) with unresectable (12 patients) or resectable (8 patients) non-metastatic pancreatic tumors, received external beam radiation (39.6 Gy) plus 5-FU (96 hours continuous infusion, days 1-4 at 1000 mg/m2/day). After 4 weeks, patients were evaluated for surgical resection. In resected patients, electron-beam intraoperative radiation therapy (10 Gy) was given before reconstruction. Thereafter, in resected patients, adjuvant chemotherapy was prescribed (6 courses: 5-FU, mitomycin C, adriamicine)., Results: During chemoradiation, no patients developed grade 3-4 acute toxicity. Three out of twelve (25%) patients with unresectable tumors had tumor downstaging. No patients showed partial or complete responses. Four out of twenty patients (20%) had minimal tumor response. Three patients showed disease progression after chemoradiation (liver or peritoneal metastases). Nine patients underwent surgical resection and IORT, with 1 postoperative death. The median survival time for the 20 patients was 9.4 (18.5 and 8.3 months in resected and unresected patients, respectively)., Conclusion: Our preliminary results suggest that preoperative 5-FU chemoradiation was well tolerated and may result in tumor downstaging but the response-rate is still low. Based on the impact of surgical resection on survival, an improvement in local response rate is necessary.

Background: Immunosuppression associated with homologous blood transfusion was first observed in renal allograft transplantation. Clinical effects of transfusion-induced immunosuppression in surgical patients have been debated in the literature for more than a decade with contradictory results., Objective: To investigate whether homologous blood transfusions significantly affect postoperative septic morbidity and mortality in patients undergoing elective surgery for gastric cancer., Design: Case series., Setting: Hospitalized care., Patients: The hospital records of 209 patients who underwent elective surgery for gastric cancer at the Department of Surgery of the Hospital del Mar, Autonomous University of Barcelona in Spain, and at the Department of Surgery of the Catholic University of Rome in Italy from April 1984 to December 1990 were reviewed, and 179 patients were included in the study., Main Outcome Measures: The following variables were entered into univariate and multivariate analyses to identify factors potentially affecting postoperative septic morbidity: demographic data, weight loss, preoperative serum albumin level and lymphocyte count, type and duration of operative procedure, amount and timing of blood transfusion, and stage of disease., Results: Univariate analysis showed that a large quantity of blood transfused (> 1500 mL) and transfusion in the postoperative period (group C) were associated with a worse clinical outcome. Postoperative transfusion was an independent predictor of septic morbidity in multivariate analysis., Conclusions: Despite transfusion-induced immunomodulation, homologous blood transfusion should not be considered a risk factor for postoperative septic morbidity in patients undergoing elective major abdominal surgery. The timing-response relationship between transfusions and septic morbidity in multivariate analysis may be the effect of uncontrolled confounders such as variation of volemia induced by stress response in patients who were developing or had just developed infectious complications.

Purpose: Identification of prognostic factors is a primary basis for planning the treatment and predicting the outcome of patients with colorectal cancer. Reviewing studies from the literature performed using univariate and multivariate analyses and their own study, the authors critically discuss the prognostic value of the clinicopathologic parameters of the tumor., Methods: Among 853 patients with colorectal tumors seen at the Department of Clinical Surgery of the Catholic University of Rome, Italy, 690 cases that were curatively resected the study. Overall survival rate, related to the clinicopathologic variables, was calculated, and univariate and multivariate analyses were performed., Results: Five-year and ten-year overall survival rates were 70 and 55 percent, respectively. Univariate and multivariate analyses showed that node involvement, distant metastases, bowel obstruction, and patient gender are factors independently related to outcome., Conclusions: Data from the literature and the present study suggest that only a few clinical parameters, particularly bowel obstruction, and some pathologic factors (tumor stage, vessels invasion, and tumor ploidy) are related to patient survival rate and are the most reliable prognostic criteria. In prospective clinical studies, any other new pathologic or molecular factors should be matched with these parameters to confirm their value in outcome prediction.

Local recurrence affects approximately 50% of patients undergoing surgery for pancreatic adenocarcinoma. To lower the incidence of locoregional recurrence, the combination with surgery of adjuvant radiotherapy has been proposed. The latter is based on external radiotherapy (ERT), intraoperative radiotherapy (IORT) or their combination. To evaluate the impact on local control and survival, results achieved in a a group of patients undergoing surgical resection and combined adjuvant radiotherapy, are analyzed. 17 patients with adenocarcinoma of the exocrine pancreas were treated with a therapeutic protocol based on pancreatectomy and intraoperative radiotherapy (IORT) to the tumor bed (10 Gy) followed by postoperative radiotherapy (50 Gy); 9 patients underwent also preoperative radiotherapy (5 Gy) to the pancreas and liver. With a median follow-up of 45 months, in 3 patients (17.6%) local recurrence was observed while 12 patients (70.6%) showed liver metastases or peritoneal spread. Median survival was 17.5 months and actuarial survival at 2 and 5 years was 41.2% and 11.2%, respectively. As compared to a moderate local control, the prognosis of patients undergoing surgical resection remained disappointing. Thus, the effort of improving results with new therapeutic modalities as preoperative radiochemotherapy and adjuvant chemotherapy, seems justified.

A series of 101 consecutive patients undergoing pancreatic resection for cancer was retrospectively analyzed to define factors that may affect the immediate postoperative outcome. Overall morbidity and mortality were 28.7% and 10.9%, respectively, although these figures were greatly reduced during the last years; the complication rate dropped from 55.6% (1981-1987) to 20.0% (1993-1995) and the mortality from 16.7% to 6.7%. At univariate statistical analysis the patient characteristics (sex, age, American Society of Anesthesiologists [ASA] class, nutritional status, jaundice), tumor characteristics (site, size, TNM stage, and grading), and type of surgery were found not to affect postoperative morbidity and mortality. In contrast, a significantly lower rate of complications was observed in patients not undergoing gastric resection, in those who received 3 units or less of blood intraoperatively, and in subjects operated more recently (after 1990). At multivariate analysis the period when the operation was performed was the only independent variable that affected the immediate postoperative outcome. Among the examined factors, only the experience acquired over time regarding the intra- and perioperative treatment of these patients seems able to lower the rate of postoperative complications.

Thirty-six patients with pancreatic head carcinoma entered a protocol, but only 20 were suitable for resection and evaluation of long-term survival. They were nine males and 11 females, with a mean age of 64.3 years. Following surgical resection, 10 Gy was delivered to the tumor bed intraoperatively. Postoperative radiotherapy was performed 4-6 weeks after surgery: patients were treated with 50.4 Gy (1.8 Gy/day, 5 days/week) to the tumor and nodal bed. Since 1991, 10 patients have also received preoperative short-course radiotherapy (5 Gy) of the liver and pancreas. Postoperative morbidity was 25%; two postoperative deaths were observed in patients with locally advanced neoplasms, in whom a vascular resection was also performed. Only 14 patients started postoperative radiotherapy, which was interrupted in two cases. At present, 14 patients are dead and four are alive and disease free. The local recurrence rate was 11.1% and distant metastases were observed in 66.7% of cases. The median actuarial survival was 11.9 months, but it was 18.5 months in patients with disease-free resection margins. A significantly better survival was also observed in patients submitted to short-course preoperative radiotherapy. These preliminary results show that intraoperative and perioperative radiotherapy is feasible and may improve local control of disease. Unfortunately, these results are not matched by a significant improvement in survival due to the high incidence of intraabdominal metastases. Thus, new therapeutic modalities, including preoperative radiotherapy (with or without chemotherapy), should be tested.

In 1983, Shepherd and Lee described the solitary necrotic nodule of the liver, an uncommon non-malignant lesion with a characteristic histological appearance. This nodule can often be misinterpreted as a necrotic secondary tumour. Limited liver resection can make differential diagnosis and cure the lesion.

Background/aims: This study was designed to evaluate the effectiveness of radical surgery for liver hydatid disease., Materials and Methods: Hospital charts of 104 consecutive patients with liver hydatidosis observed in our unit during the period 1982-1994 were reviewed. A total of 121 cysts in 89 patients were treated surgically: with cystopericystectomy in 66 and liver resection in 23., Results: The overall incidence of postoperative complications was 19%: 19.7% and 17.1% after cystoperi-cystectomy and liver resection respectively (p = 0.32). Overall postoperative mortality was 1%. Among the 72 patients available for follow-up, only one (1%) had a local recurrence of the disease., Conclusions: Results suggest the safety and efficacy of radical procedures in the surgical management of liver hydatid disease. Total cystopericystectomy is the treatment of choice but liver resection is justified in selected cases.

The review of the literature shows the improvement of outcome of patients with gastric cancer after resection and extended lymphadenectomy. Lymphadenectomy D2/D3 was performed in 206 out of 639 patients with gastric cancer: 5-year survival was 66.3% versus 41.5% of the 121 patients that underwent D1 resection (p < 0.0001). Univariate and multivariate analyses show that proximal location of the cancer, advanced stage and lymphadenectomy limited to perigastric stations are negative prognostic factors. Although there are still different opinions regarding D2 or D3 lymphadenectomies for the operative risks, pancreatic resection (preferring pancreas sparing techniques) and splenectomy is subtotal gastrectomy for antral carcinoma, extended lymphadenectomy remains an important point to improve survival.

Purpose: Risk of local recurrence of rectal cancer remains high despite extensive therapeutic strategies, many of which have been tried to achieve better local control (i.e., external beam radiation therapy (EBRT)). Recently, intraoperative radiation therapy (IORT) has been introduced in clinical protocols to boost the areas at risk of local recurrence., Methods: Between April 1990 and December 1995, 44 patients with "high risk" (T3,N0-2 primary tumors) extraperitoneal rectal tumors and 24 patients with "locally advanced" (2 T3,N3 and 11 T4,N0-3 primary tumors; 11 local recurrences) tumors entered a protocol that included preoperative EBRT (38 Gy), surgery plus IORT (10 Gy) in the high-risk group, and preoperative EBRT (45-48 Gy) and concomitant computerized tomography (5-fluorouracil plus mitomycin C), surgery plus IORT (10-15 Gy), and postoperative adjuvant computerized tomography (5-fluorouracil plus folinic acid) in the locally advanced group., Results: In the high-risk group, acute Grade 3 (Radiation Therapy Oncology Group scale) skin toxicity, attributable to preoperative treatment, involved one patient (2.2 percent); among locally advanced cases, Grade 3 hematologic toxicity was observed in one patient (4.1 percent). Treatment was discontinued in no patients. On average, IORT prolonged surgery by 48 minutes. There was no mortality. Four anastomotic leakages, one pelvic infection, and five wound infections were observed. No chronic IORT-related toxicity occurred. After mean follow-up periods of 28.3 and 25.9 months, 41 and 15 patients in the high-risk and locally advanced groups, respectively, are alive and disease-free. In one high-risk patient, an anastomotic recurrence occurred. In four patients with locally advanced tumors (1 T4 primary, 3 local recurrences) an unresectable tumor relapse developed locally. Distant metastases occurred in two high-risk patients and in eight patients with a locally advanced tumor. Three-year actuarial survival was 100 percent in both high-risk and locally advanced primary tumors and 68.2 percent in local recurrences., Conclusions: Results of this study suggest that multimodal treatment (including IORT) in rectal cancer is safe, has no significant increase of mortality and morbidity, and also shows a trend for local improvement. A longer term follow-up and larger numbers of patients could demonstrate the therapeutic efficacy of IORT in rectal cancer.

Purpose: Best chances of a cure from colorectal cancer are obtained before metastatic spread. Lack of specific tests allowing early diagnosis of the tumor accounts for investigation of gene alterations involved in carcinogenesis by a noninvasive method. In the present study, K-ras codons 12 and 13 mutations were studied in neoplastic cells shed from the bowel into the stool and those contained in the tumor and normal mucosa. Moreover, healthy patients and a few others with precancerous conditions were examined., Methods: Stool, tumor, and mucosa samples were taken from 25 patients with colorectal adenocarcinoma. Stool and mucosa samples were obtained from 11 healthy patients, and stool, pathologic bowel tissue, and normal mucosa samples were obtained from 3 patients with adenoma (1) or ulcerative colitis (2). Polymerase chain reaction amplification and restriction enzyme analysis were performed., Results: K-ras codon 12 mutations were detected in both tumor and stool samples of 10 cancer patients, and no gene alterations were observed in 14 patients. In one patient with a tumor, a mutation was shown in only the tumor tissue. The agreement rate in tumor and stool analysis was 96 percent. A normal pattern of K-ras codons 12 and 13 was observed in the bowel mucosa. All stool and mucosa samples from healthy patients were not altered in K-ras. Agreement was registered between samples taken from patients with preneoplastic lesions., Conclusions: These preliminary findings show a high rate of accuracy in the investigation of K-ras alterations in the colorectal cells shed into the feces, suggesting that such an approach could be used to study other gene alterations and, prospectively, to identify early colorectal cancers.

Objectives: To identify factors that influence mortality in patients who are affected by intra-abdominal infections (IAIs) and to make a comparison among three different scoring systems: the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the sepsis score of Elebute and Stoner, and the Mannheim peritonitis index., Design: Case series., Setting: Both primary and referral hospital care., Patients: The hospital records of 604 patients who consecutively underwent emergency operations for unequivocal IAIs, both spontaneous and postoperative, from 1981 to 1993, were retrospectively reviewed. Patients with IAIs that were related to peritoneal dialysis or infected ascites, those patients who were affected by primary peritonitis from a distant site, and those patients who underwent operations for acute appendicitis or acute cholecystitis without peritoneal contamination were excluded from the study. Univariate and multivariate analyses were used to calculate the prognostic significance of the following variables: age (< or = 70 vs > 70 years); sex; type (spontaneous vs postoperative) and extent (localized vs diffuse) of infection; preoperative serum levels of albumin, cholesterol, and hemoglobin; preoperative total lymphocyte count; amount of intraoperative blood loss; presence of preoperative organ impairment; the APACHE II score; the sepsis score of Elebute and Stoner; and the Mannheim peritonitis index., Main Outcome Measure: Death was the outcome variable that was studied., Results: Multivariate logistic regression analysis showed that the APACHE II score, the Mannheim peritonitis index, hypoalbuminemia, hypocholesterolemia, and preoperative organ impairment were independent predictors of death., Conclusions: Results showed a significant dominance of host-related factors over the type and source of infection on the prognosis of patients with IAIs. Both the APACHE II score and the Mannheim peritonitis index correctly graded IAI severity and were strongly and independently associated with the outcome; however, the latter score has the advantage of being easier to calculate.

Objective: A prospective multicenter randomized trial was designed to evaluate the clinical efficacy of postoperative protein-sparing therapy., Summary Background Data: The metabolic effect of postoperative protein-sparing therapy has been shown by several studies, but the clinical utility of this treatment has not been investigated by large prospective trials., Methods: Six hundred seventy-eight patients undergoing major elective abdominal surgery were randomly assigned to receive either protein-sparing therapy after surgery (protein-sparing therapy group) or conventional therapy (control group). The patients were monitored for postoperative complications and mortality., Results: The rate of major postoperative complications was similar in both groups (protein-sparing therapy group, 19.5%; control group, 20.9%; p=0.66) as were the overall postoperative mortality rates (4.7% and 3.5%, respectively; p=0.43)., Conclusions: The present study indicates that routine protein-sparing therapy for patients normonourished or mildly malnourished undergoing major abdominal surgery is not clinically justified.

Colorectal cancer (CRC) is a neoplasm with a steadily growing incidence in Western countries. Moreover the age of 50 and over is a critical risk factor. The relationship between dietary, environmental factors and CRC has been evaluated. At present, a number of genetic risk factors such as the genetic susceptibility, tumor suppressor genes and oncogenes are thought to play a major role. The correlation of CRC with adenomatous polyps and chronic inflammatory disease, ulcerative colitis in particular, has been evaluated. Prevention of CRC is mainly based on a rational diet and in the adoption of mass screening programmes.

The authors report a case of hormonally silent duodenal somatostatinoma. The main clinical features, the natural history and the currently available therapies of these rare neoplasms are described on the basis of this case and of the scientific literature. Although the antiblastic therapies are still debated, the patient showed a surprising outcome following chemotherapy.

Objective: To compare the results of closed treatment (CT) with the results of open treatment (OT) that uses laparostomy and marsupialization of the lesser sac in patients affected by secondary pancreatic infections., Design: Retrospective cohort study., Setting: Both primary and referral hospital care., Patients: Forty-two patients undergoing emergency operations for unequivocal secondary pancreatic infections (infected pancreatic necrosis [n = 26] and pancreatic abscess [n = 14]) were retrospectively divided into two treatment groups on the basis of the operative treatment: conventional CT (n = 24) (1981 through 1986) and OT by laparostomy and marsupialization of the lesser sac (n = 18) (1987 through 1991). The OT and CT groups were homogeneous regarding demographic characteristics, mean APACHE (Acute Physiology and Chronic Health Evaluation) II score (17.1 +/- 6.0 vs 17.9 +/- 7.2, respectively; P value was not significant), and distribution of patients according to the type of pancreatic infection (infected pancreatic necrosis [13 vs 15, respectively] and pancreatic abscess [five vs nine, respectively]). The use of medical supportive care, including total parenteral nutrition and heavy doses of broad-spectrum antibiotics, was similar in both groups., Main Outcome Measures: Surgical complications; recurrent or persistent sepsis; postoperative death., Results: The incidence of major surgical complications was 55.5% and 8.3% in OT and CT groups, respectively (P = .001). In OT and CT groups, signs of recurrent or persistent sepsis were observed in 5.6% vs 41.7% of the patients, respectively (P = .008): 7.7% vs 46.7% in patients with infected pancreatic necrosis (P = .02) and 0% vs 33.3% in patients with pancreatic abscess (P value was not significant). Overall mortality rates were 22.2% and 28.5% in the OT and CT groups, respectively (P value was not significant). The mortality rates due to recurrent or persistent sepsis in the OT and CT groups were 5.5% and 29.1%, respectively (P = .03)., Conclusions: Although the frequency of major surgical complications after OT is significantly higher than that observed after CT, open drainage by means of laparostomy and marsupialization of the lesser sac controls pancreatic infection better, thus reducing mortality rate due to persistent or recurrent sepsis.