Femoral hernia repair. Kugel retroparietal approach versus plug alloplasty: a prospective study.

Plug insertion for primary femoral hernia repair may cause p.o. discomfort. The Kugel technique may avoid this problem. Patients' satisfaction to the Kugel and the plug techniques is compared in the present study. Demographics, surgical, outcome and analgesic consumption data of 26 patients treated for with the plug technique (P group) are compared with 24 operated with the Kugel patch (K group). Patients' p.o. discomfort to the two procedures was measured with quantitative (VAS score) and a qualitative (the short form of McGill pain questionnaire, SF-MPQ) methods, and compared. P group presented higher early p.o. pain (P<0.001), higher analgesic consumption and a significative delay in the return to physical activity (P<0.001). SF-MPQ scores at p.o. day 8, day 30 and month 6 were significantly lower for K group (P<0.001, P<0.001, P<0.005). The Kugel technique for femoral hernia treatment seems to cause less p.o. discomfort to patients than the plug technique.

Cell proliferation-related markers in colorectal liver metastases: correlation with patient prognosis.

PURPOSE: We analyzed the relation between phenotypic (DNA ploidy) and functional markers (S-phase cell fraction, p53, and bcl-2 protein expression) and defined their relevance on clinical outcome on a retrospective series of radically resected liver metastases from colorectal cancer. PATIENTS AND METHODS: Among 104 patients with resectable liver metastases from colorectal cancer, DNA ploidy was determined by flow cytometry, 3H-thymidine labeling index (TLI) by autoradiography, and expression of p53 and bcl-2 by immunohistochemistry. RESULTS: TLI was a significant indicator for relapse at 4 years from radical surgery, DNA ploidy was a suggestive indicator of clinical outcome, and p53 and bcl-2 expression provided no clinical information. By multivariate analysis, cell proliferation rate and Dukes' stage remained independent prognostic parameters. In the most representative subgroup of patients with H1 liver lesions (86 cases), TLI was always associated with relapse, and DNA ploidy and p53 expression provided discriminant information within slowly proliferating liver lesions. CONCLUSION: Tumor-cell proliferation of liver lesions should be used with stage of the primary colorectal cancer for a more accurate prognosis in patients submitted to curative hepatic resection.

Evaluation of the balance between angiogenic and antiangiogenic circulating factors in patients with breast and gastrointestinal cancers.

Angiogenesis is a critical determinant of tumor growth. Tumor cells produce or induce angiogenic molecules that act specifically on endothelial cells (ECs) but also release angiostatic molecules. Thus, tumor angiogenesis represents a net balance between positive and negative regulators of neovascularization. Sera from patients with breast or gastrointestinal cancers were evaluated for their capacity to selectively modulate the proliferation of human umbilical vein ECs; sera from 15 of 78 (19%) breast cancer patients and 8 of 53 (15%) gastrointestinal cancer patients induced human umbilical vein EC growth, whereas sera from 4 of 78 (5%) breast cancer patients and 1 of 53 (2%) gastrointestinal cancer patients inhibited EC proliferation. Growth-stimulatory sera were significantly more frequent among postmenopausal (14 of 53) than premenopausal (1 of 25) breast cancer patients; inhibitory activity was observed in 3 of 25 premenopausal patients versus 1 of 53 postmenopausal individuals. The half-life of serum-stimulating and -inhibiting factors seemed to differ, because stimulatory activity but not inhibitory activity was decreased at 5 days after surgery. The levels of vascular endothelial growth factor were elevated in about 45% of patients with growth-stimulatory sera, whereas the serum inhibition of EC growth was found to be due, at least in part, to high levels of soluble thrombospondin.

Kugel hernia repair: open "mini-invasive" technique. Personal experience on 620 patients.

A large monoinstitutional series adopting the Kugel retroparietal technique for inguinal hernia surgery is analysed. Our aim is to assess the "mini-invasiveness" of this technique. Six hundred and twenty patients (pts) affected by monolateral inguinal hernia were treated with a preperitoneal alloplasty with a posterior approach (Kugel hernia repair, KHR) between January 2002 and September 2004. The surgical incision extension was 3.5 cm on average (range 2-4.5). The mean operation time was 33 min (range 20-45). Spinal anaesthesia and ambulatory procedure were applied in 595 cases (96%). Postoperative complications affected 20 pts (3%). The postoperative pain was well controlled. No chronic neuropathic pain was registered at follow-up. Patients resumed work after an average of 9 days (range 7-12) from operation. Recurrence rate was 0.8%. Conclusions. The Kugel hernia repair satisfies the standards to be awarded as a "mini-invasive" technique.

Adjuvant CMF for node-negative and estrogen receptor-negative breast cancer patients.

From December 1980 to September 1985, a total of 90 eligible patients with stage T1-3a, node-negative, and estrogen receptor-negative (less than or equal to 10 fmol/mg of cytosol protein) tumors were entered into a randomized study to assess the effectiveness of adjuvant intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) in a subset of patients at high risk of early disease relapse. High values of [3H]thymidine labeling index were documented in two thirds of 62 assessed specimens from the patient population, and one half of the patients had histologically undifferentiated tumors. Patients were allocated to either local-regional modality alone (control group, 45 women) or to CMF (45 patients) after surgery. A full dose of CMF (600 mg/m2 each of cyclophosphamide and fluorouracil, and 40 mg/m2 of methotrexate) was administered IV on day 1, and then repeated every 3 weeks for a total of 12 treatments. After a median follow-up of 80 months, the 7-year results confirmed the superiority of adjuvant CMF compared to local-regional modality alone (relapse-free survival 85% vs 42%, P = .0001; total survival 86% vs 58%, P = .006). A benefit from adjuvant CMF was observed in all subgroups, and the rates of both local-regional and distant failure were decreased. Treatment was fairly well tolerated and devoid of life-threatening toxicity. Present results confirm our previous observation concerning the dismal prognosis of node-negative and estrogen receptor-negative breast cancer patients as well as the beneficial effect of adjuvant chemotherapy in this selected subset.

T3b-T4 breast cancer: factors affecting results in combined modality treatments.

Two hundred and seventy-seven consecutive patients with T3b-T4 breast cancer referred to the Milan Cancer Institute between 1973 and 1980 were treated with a combined modality approach. Chemotherapy (CT) consisted of AV, i.e. adriamycin (60-75 mg/m2 day 1) and vincristine (1.2 mg/m2 days 1 and 8) and was given for three to four cycles prior to local regional modality. Local-regional treatment consisted of either radiotherapy (RT) in 198 patients or surgery (S) in 79 women. Additional chemotherapy was then administered to a total of 205 patients. In the absence of distant metastases, frequency of good local control was significantly inferior in patients given CT + RT (63.9 per cent) compared to those treated with CT + RT + CT (75.4 per cent) and CT + S + CT (82.3 per cent, P = 0.033). Also freedom from progression (FFP) and overall survival (SURV) were significantly superior in the groups receiving more prolonged chemotherapy treatment compared to patients treated with CT + RT (FFP: P less than 0.0001; SURV: P = 0.002). None of the variables examined was able to affect the response rate, while axillary nodal status and tumor size played a major role in the duration of FFP and SURV. Our findings indicate that a more aggressive treatment is needed to improve current results in this stage of disease. To overcome the problem of local-regional recurrence, treatment should probably begin with cytoreductive surgery followed by postoperative radiotherapy in all patients with the exception of those having inflammatory carcinoma. Systemic treatment should then be delivered to control distant micrometastases.

Doxifluridine in colorectal cancer patients resistant to 5-fluorouracil (5-FU) containing regimens.

Doxifluridine (5-dFUR) is a fluoropyrimidine derivative, which is preferentially converted to 5-fluorouracil (5-FU) within tumour tissues. Although the activity of 5-FU in metastatic colorectal cancer is well recognised, resistance to this agent is frequently observed and remains its major limitation. The aim of this phase II study was to evaluate the activity of oral and i.v. 5-dFUR in metastatic or locally advanced colorectal cancer patients, who had been previously treated with a 5-FU containing regimen in either an adjuvant or metastatic setting. We treated 48 patients who, on the basis of tumour progression during, or within 8 weeks of the discontinuation of 5-FU therapy, were considered 5-FU resistant, 14 of the patients received 5-dFUR 3000 mg/m2 as a 1-h i.v. infusion, combined with L-leucovorin 25 mg/dose on days 1-5, every 3 weeks; the remaining 34 received oral 5-dFUR 1200 mg/m2 for 5 days followed by 5 days off. Oral L-leucovorin 25 mg/dose was administered 2 h before 5-dFUR. On the basis of WHO criteria, 4/14 (29%, 95% CI 4-51) partial responses were noted in the i.v. treated patients, and 4/34 (12%, 95% CI 1-23) in those treated orally. The radiological examinations documenting the response were a CT scan in 4 cases, ultrasound in 2 and NMR in 2. The median response duration was 6 months (range 3-11+), whereas the median time to treatment failure was 4 months (range 2-17). The responses were achieved in cases previously treated with a median of 9250 mg/m2 (range 5500-18,650) of 5-FU. No CTC-NC1 grade 4 toxicity was observed, although grade 3 diarrhoea occurred in 5 of the orally treated and in 3 of the intravenously treated patients. This is the first report documenting the efficacy of 5-dFUR in patients resistant to 5-FU therapy, and suggests that there is an absence of complete cross-resistance between these two fluoropyrimidines.

Surgical treatment of gastric cancer invading the oesophagus.

INTRODUCTION: There is controversy regarding which type of surgical treatment is most appropriate for upper gastric cancer invading the oesophagus. METHODS: A review of the pertinent literature was carried out regarding oesophageal involvement in gastric cancer. RESULTS: Invasion of the oesophagus occurred in 26-63% of Western surgical series. It was more frequent in Borrmann IV type, linitis plastica, pT3-pT4, diffuse type by Lauren, N+ or tumours exceeding 5 cm in diameter. Lymphatic tumour spread was caudad (coeliac nodes, hepatoduodenal nodes, paraortic nodes) but mediastinal nodes were also involved if tumour growth in the oesophagus exceeded 3 cm or if there was transmural oesophageal infiltration. In Western countries there was less than 30% 5-year survival and no long-term survivors when hepatoduodenal or mediastinal nodes were metastatic. Mediastinal dissection through thoracotomy did not provide any benefit. CONCLUSIONS: A rational approach involves total gastrectomy plus partial oesophagectomy. Abdominal transhiatal resection may be performed in the case of a localized, non-infiltrating tumour and oesophageal involvement <2 cm. However, infiltrating, poorly differentiated or Borrmann III-IV tumours require a right thoracotomy to achieve a longer margin of clearance. When oesophageal involvement is >3 cm, or hepatoduodenal or mediastinal nodes are positive, no surgical procedure is curative and the literature demonstrates that extended aggressive surgery has no benefits.

Comparing surgical resection of limited hepatic metastases from colorectal cancer to non-operative treatment.

The survival of two groups of patients, affected by liver metastases (Stage I and II by Gennari et al.) from a previously operated colorectal cancer and treated by surgical resection (Group 1, 39 patients) or chemotherapy with various cytotoxic drugs (Group 2, 31 patients) at the Istituto Nazionale Tumori, Milan, is reported. In comparison with Group 2, Group 1 included more patients with metachronous lesions, with high level of serum bilirubin and with primary tumour originating from the colon. A univariate analysis (log rank test) identified a statistically significant prognostic role of type of treatment (surgery vs chemotherapy) and of the level of serum bilirubin. However the multivariate analysis by the Cox's regression model showed that the only independent statistically significant prognostic factor was type of treatment, since the hazard ratio of surgery vs chemotherapy was 0.490 with a 95% confidence interval of 0.256-0.936. The survival probabilities at 24 and 36 months were respectively 60% and 47% in surgical patients, vs 30% and 23% in those receiving chemotherapy, the difference between the curves being statistically different (P = 0.001). The median survival of Group 1 patients was 30 months whereas the median survival of Group 2 patients was 19 months, a value quite similar to that published in literature for untreated patients with limited metastatic disease-thus indicating that this patients' population was not selected according to unfavourable criteria. These findings suggest a beneficial role of surgical resection in patients with colorectal metastases confined to the liver in Stages I and II.

Subcutaneous jejunostomy.

When the surgeon must obviate to an impending obstruction because of an unresectable tumor of the supramesocolic space and an intestinal bypass is not feasible, a jejunostomy is usually indicated. We describe a new method to provide enteral nutrition via a subcutaneous jejunostomy without any external device, which can be used only when the patient is at risk for developing an obstruction or dysphagia. The feeding tube is inserted into the jejunum and then connected to a Port-a-Cath lodged in a subcutaneous pocket. Subsequently, the nutrition can be delivered via a Huber needle inserted in the port, or, to minimize the need for strict aseptic surveillance, the tube can be exteriorized from the pocket and used as the usual tube jejunostomy. This procedure allows placing a precautionary jejunostomy without distortion of the body-image.

Intrahepatic doxorubicin in unresectable hepatocellular carcinoma. The unfavorable role of cirrhosis.

To investigate the relationship between the presence of cirrhosis and the antitumor effects of locoregional chemotherapy with doxorubicin, 16 patients with nonresectable hepatocellular carcinoma (HCC) and satisfactory baseline clinical conditions (Child class A or B, Karnofsky index greater than 70%) were studied. Eight patients had post-necrotic cirrhosis, five had serum HBsAg. The dose of doxorubicin was 0.3 mg/kg body weight/day, given by continuous intracoeliac infusion for 8 consecutive days. Eight patients (six with cirrhosis) died prematurely after the first course of chemotherapy. Six (2 with cirrhosis) responded to therapy; they survived 3-33 months (median: 10). In these patients, the type and severity of drug-related side effects were comparable to those reported for patients treated by intravenous chemotherapy. The implication that in many patients with cirrhosis intrahepatic chemotherapy with doxorubicin may hasten death, lessens our interest in its use for nonresectable HCC. In fact, in Italy these cancers frequently occur in association with cirrhosis.

Microbiological patterns of four new imidazole derivatives.

The authors present an in vitro experimental study concerning the microbiological properties of four imidazole derivatives, with a piperazine group between two benzene rings. Seventy strains of Gram-positive and Gram-negative bacteria, 30 of yeasts, 14 of filamentous fungi and 10 strains of Trichomonas vaginalis were tested. The new compounds revealed a good inhibitory activity against Gram-positive bacteria, yeasts and dermatophytes. These results compare well with those obtained with the other known imidazoles. Moreover any mutagenic activity is absent.

Mutagenicity studies on dihydroergocristine.

Dihydroergocristine (DHEC) is an ergot derivative used for the therapy of patients with cerebrovascular insufficiency. It was tested for mutagenicity by means of four tests. In the mutagenicity in vitro assay on Salmonella typhimurium, DHEC was checked at 10,000 micrograms/plate on TA98 and TA1538 strains and at 3000 micrograms/plate on TA1535, TA1537 and TA100 strains with and without metabolic activation. In a quantitative in vitro test for mutagenicity in V79 Chinese hamster cells, DHEC was studied at concentrations between 30 and 0.3 microgram/ml with and without metabolic activation. DHEC was tested for its ability to induce chromosomal damage in human lymphocyte cultures utilizing the concentrations of 10, 3 and 1 microgram/ml. In the in vivo mouse (Swiss strain) micronucleus assay, DHEC was orally administered at two dosages (50% and 16% of LD50) following the schedule of the test. Dihydroergocristine is a drug free of mutagenic activity on the basis of all the results obtained from the above in vitro and in vivo tests.

Morbidity and mortality after surgical resection of liver tumors. Analysis of 229 cases.

Two hundred and twenty-nine resections of hepatic tumors were performed over the past 10 years. The intraoperative death rate, 30-day operative mortality and major complication rate were 1.3%, 8.3% and 20%, respectively. Both morbidity and mortality were significantly related to the type of surgery and to the extent of the resection to contiguous organs and/or structures. Cirrhotic patients (40% in hepatocellular carcinoma) had a higher mortality rate (19%). Intraoperative blood loss was related to the extent of the resection and was significantly higher in patients with major complications and/or death. The main problem was postoperative liver failure in cirrhotic patients, which is difficult to predict and to treat.

Surgical strategies in colorectal cancer metastatic to the liver.

Surgical resection remains a milestone in the treatment of colorectal metastases to the liver. There is a distinct subset of patients who benefit from surgical resection in terms of longer survival or definitive cure. The main effort of the surgical oncological regards the safety of the procedure and the adequacy of the recommendation. Many studies, some of them including multivariate analysis, have shown the presence of prognostic determinants of long-term survival and prognostic indexes of the outcome after hepatectomy. It is now accepted that liver resection should be done when the complete excision of all demonstrable tumor with clear resection margins is feasible. Major contra-indication is represented by the presence of extra-hepatic intra-abdominal disease or of unresectable lung metastatic deposits. There is a wide literature indicating that in very selected patients liver reresection and multiorgan synchronous or metachronous resections are beneficial. The role of neoadjuvant chemotherapy and especially postoperative adjuvant local (intra-hepatic) and systemic chemotherapy is promising and supported by recent multicenter randomised clinical trials.

Prognostic effects of lymph node micrometastases in patients undergoing curative gastrectomy for cancer.

AIMS & BACKGROUND: It is not known whether the presence of micrometastases in the regional lymph nodes has an impact on the oncologic outcome of patients undergoing a curative (R0) gastrectomy for cancer. The aim of the study was to assess the effects of the presence of micrometastases on survival. METHODS: We reviewed 29 patients operated on for curative (R0) gastrectomy, with a final diagnosis of pN0, 16 or more lymph nodes in the specimen, and a follow-up of at least 4 years. The original hemotoxylin and eosin slides were reviewed, and a new section was cut from the lymph nodes and immunostained with a pool of antibodies against different types of cytokeratins. Micrometastases were detected in 5 patients (27.5% of the series) and 11 lymph nodes (1.51% of all removed lymph nodes). RESULTS: Mortality due to cancer progression occurred in 3 patients from the pN0 group (14.2%) and 1 patient from the pN1 group (12.5%). CONCLUSIONS: There was no suggestion from the data that the presence of micrometastases carries an ominous prognosis in terms of survival.

Prognostic factors for survival and disease-free survival in hepatic metastases from colorectal cancer treated by resection.

The prognostic factors of 219 patients submitted to Ro hepatic resection for colorectal metastases have been statistically analyzed. The overall 5-year actuarial survival rate was 24% and the 5-year disease-free survival rate was 18%. At univariate analysis four variables resulted significant: 1) The stage of primary colorectal cancer: if the meserentic lymph nodes were metastatic (Dukes C) or uninvolved (Dukes B) 5-year survival was respectively 16 and 38% (p < 0.001). 2) The percentage of hepatic replacement: the 5-year survival rate of patients with H1 (< 25%), H2 (25-50%) and H3 (> 50%) was 27, 16 and 8% respectively (p < 0.001). 3) The number of metastases: the 5-year survival of patients with 1, 2-3, > 3 hepatic nodules was 29, 21 and 17% respectively (p < 0.05). 4) The extent of surgical resection: 5-year survival after minor and major resection was 28 and 18% respectively (p < 0.05). At multivariate analysis only stage of primary and percentage of hepatic replacement retained statistical significance. In 60% of 154 patients with recurrent disease the liver was again involved.

Feasibility of intraportal chemotherapy with fluorouracil and folinic acid immediately after hepatic resection for colorectal metastases.

BACKGROUND: About 50% of recurrence after resection of hepatic metastases from colorectal cancer remain confined to the liver. Adjuvant locoregional treatments could reduce the failure rate, but these treatments have been scantily investigated. Experimental models have shown that both intra-arterial chemotherapy (IAC) and intraportal chemotherapy (IPC) in adjuvant setting were able to reduce metastatic growth, but IPC should be initiated in the immediate postoperative period. AIMS: To evaluate the feasibility of immediate postoperative IPC of fluorouracil (5-FU) plus folinic acid (FA) in a consecutive series of patients undergoing hepatic resection for metastatic colorectal cancer. METHODS: Forty-three consecutive patients underwent hepatic resection. The first 25 (Control Group = CG) received only surgery; the latter 18 (Treated Group = TG) were candidate to postoperative IPC of 5-FU 750 mg/m2 plus FA 20 mg/m2/day continuous infusion for 8 days. One patient was not treated owing to bleeding, thus only 17 received the treatment. RESULTS: Postoperative morbidity was 14%, equally distributed in both groups. Biochemical hepatic parameters of TG were not statistically different from those of CG. Five patients (29%) developed systemic toxicity: one hematologic grade 4; 3 mucositis grade 3 and one allergic erythema. Three of these patients had been treated by systemic chemotherapy less than one year before. DISCUSSION: IPC of 5-FU plus FA in the immediate postoperative period has not yet been tested. The schedule we have investigated neither affected the postoperative outcome, nor influenced hepatic function and regeneration. Systemic toxicity was evident and severe mainly in patients already pretreated by systemic chemotherapy. In these patients, however, toxicity did not affect further outcome. This study confirms the feasibility of immediate intraportal chemotherapy after hepatic resection.

Axillary lymph node metastases from occult carcinoma of the breast.

From the case records of the Istituto Nazionale Tumori of Milan from 1956 to 1976, 49 cases of metastases in axillary lymph nodes from an occult carcinoma of the breast were selected. Forty-four patients underwent removal of the suspicious breast. In 11 patients no tumor was found at the pathologic examination. The survival of these patients was no different from the survival of those in whom the tumor was found. The 5-year survival of the total series was 87%, confirming that this type of presentation of breast cancer has a prognosis that is better than that generally reported for stage II carcinoma of the breast.

[Comparison of the performance of a totally implantable pump and conventional access systems in regional arterial chemotherapy of liver tumors]. / Paragone di affidabilità tra pompa totalmente impiantabile e sistemi tradizionali di accesso per la chemioterapia arteriosa regionale dei tumori epatici.

Forty-nine patients with liver tumors have been submitted to regional arterial chemotherapy by means of either totally implantable Infusaid 400 pumps (29 casse) or implantable ports (20 cases). The latter were subsequently perfused with external pumps. There was one single major operative complication and no operative deaths. Most patients underwent continuous FUDR infusion. Access related complications in the Pump and Port groups respectively included 1 and 0 malfunctions, 7 and 2 seromas, 2 and 0 pocket necroses, 8 and 10 thromboses, 2 and 4 catheter dislocations, 0 and 2 portal breakages. Treatment was stopped for access related complications in 5 and 5 patients respectively. In most of those cases, however, more than 6 cycles of chemotherapy have been performed. The Infusaid 400 pumps showed a 12-month duration of 58.4% with a 13 month median versus 17% and 9 month median of the Ports. The difference was not significant. The new implantable systems give better results in comparison with traditional regional methods; the performance of the Port systems appear very similar to the totally implantable pumps, with an obvious advantage, however, for the pumps as far as quality of life is concerned.