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.

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.

[D2 gastrectomy in the surgical treatment of gastric cancer]. / Gastrectomia D2 nel trattamento chirurgico del cancro gastrico.

The study is conducted on a series of 57 patients treated with D2 gastrectomy with curative intent for gastric cancer between January 2000 and December 2004, at Policlinico Multimedica (Milan). Postoperative mortality was 2%. Recurrence rate was 10%. The overall survival of the series is 36% at 4 years follow-up. Negative prognostic factors were: high grade tumor, locally advanced primary disease, presence of lymph node metastases, advanced stage of disease and recurrent disease at follow-up. The data of the study are comparable to those in the literature.

[Intraperitoneal hyperthermic chemotherapy. Preliminary experience with 22 consecutive patients]. / Chemioterapia ipertermica intraperitoneale. Esperienza preliminare in 22 pazienti consecutivi.

The study analyses the results of surgical treatment and intraperitoneal hyperthermic chemotherapy on a group of 22 patients, affected by peritoneal carcinomatosis of different origins, and treated at Policlinico Multimedica (Milan) between June 2001 and December 2004. Surgical major complications were present in the 23% of the patients, and post-operative mortality rate was 13%. None of the patients presented chemotherapy related toxicity. Six patients died within 2 and 40 months after surgery, while 13 are alive within 4 and 40 months after operation.

[Principles of oncologic radicality in the surgical treatment of gastric carcinoma]. / Principi di radicalità oncologica nel trattamento chirurgico del carcinoma gastrico.

To date the basic guidelines in surgical oncology of the stomach may be summarized in the correct definition of "R0" exeresis (curative operation), but there is still much debate on which should practically be the extension of the gastric resection and which the kind of lymphatic dissection in order to fulfill all the criteria for a correct definition of "curative surgery". As regards the T factor, almost all Authors agree on the fact the a correct R0 gastric resection must include a tumor-free distal margin at least 6 cm from the superior edge of the neoplasm; a safe distal margin should be at least at 1 cm. below the pylorus. Provided that these principles are thoroughly observed, there is no oncologic advantage in performing a total gastrectomy instead of a sub-total gastric resection. Differently, as regards the N factor, there is no agreement on which kind of lymph nodal dissection shoul be routinely adopted: published reports on this subject are somewhat controversial and also whereas a systematic extended lymphadenectomy showed a possible statistical benefit in long term-survival, unacceptable morbidity rates discourage a diffuse application of extended lymphatic dissection out of dedicated; institutions. Anyhow, at the moment it is almost universally accepted that a minimum of 25 removed nodes are necessary for a correct and comparable staging of gastric cancer. At last, literature data do not support the routine use of splenectomy, with the only exception of those cases with documented lymph nodal enlargement at the splenic hilum.

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.

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.

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.

Differential device performances for hepatic arterial chemotherapy: a technical report on totally implantable pumps and ports for both continuous and bolus infusion.

Performances of totally implantable infusion systems were analyzed in patients with colorectal liver metastases undergoing intra-arterial treatment. It consisted of 14-day continuous infusion of 5-fluor-2'deoxyuridine with pumps (pump14, 44 patients) or ports fed by external pumps (port14, 34 patients), or bolus infusion of cisplatin (port21, 57 patients) or epirubicin (port7, 22 patients) every 3rd week and weekly, respectively. Toxicity and disease progression were the most common causes of treatment interruption. System failure occurred in 2 pump14, 9 port14, 6 port21 and 2 port7 cases. Pocket problems were most frequent in the pump14 group (30%), whereas catheter- and infusion-related problems were mostly observed in the port14 group (109%). The devices were still functional after 12 months in 92% of pump14, 24% of port14, 65% of port21 and in 78% of port7 patients. Although implantable ports allow adequate infusion periods, in most cases they appear especially suitable for bolus infusions.

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.

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.

[Liver metastasis. Clinico-pathological prognostic factors in metastasis from colorectal cancer]. / Le metastasi epatiche. Fattori prognostici clinico-patologici nelle metastasi de cancro colorettale.

Hepatic Metastases (HM) from colorectal cancer represents one of the main problems of oncologic treatment: from 80 to 90 percent of patients undergo chemotherapy and a minority hepatic resection. The natural history of patients with unresectable HM has been recently investigated by uni and multivariate analyses; the percentage of hepatic replacement, the stage and grade of primary colorectal tumours, alkaline phosphatase and the presence of extrahepatic disease proved to be the most important independent prognostic factors. Albumin and carcino-embryonic antigen (CEA) levels, age and weight loss of patients were also prognostic. The groups of patients with more favourable factors had a median survival ranging from 21 to 35 months, in contrast to a median survival of 4 to 8 months for those with adverse factors. The outcome of more than 3400 patients submitted to hepatic resection, has been investigated. At multivariate analysis twelve variables resulted independently related to prognosis: stage of primary tumour, extent of liver involvement and presence of extrahepatic metastases were considered to be the most important. The knowledge of prognostic factors is extremely important in selecting patients candidated to various treatments, to interpret the results and to plan new therapeutic strategies.

[Liver metastasis: therapeutic strategy]. / Metastasi epatiche: strategia terapeutica.

The liver is one of the most frequent sites of metastatic growth, in particular from digestive malignancies (DM). The first goal is to reduce the incidence of metastases. Adjuvant systemic chemotherapies have been demonstrated to reduce the recurrence rate and to improve survival in Dukes C colon cancer. Fluorouracil is the pivot of adjuvant treatment modulated by Leucovorin or Levamisol. A short postoperative administration of fluorouracil by intraportal route has been tested, but the results are controversial. Adjuvant treatments for different DM are under investigation. When hepatic metastases are clinically evident, therapeutic decisions depend on several factors: site and nature of primary, extent of hepatic and extrahepatic disease, patient characteristics, efficacy of treatments. A staging system should be adopted to allow a rational approach. In selected cases a locoregional treatment can achieve consistent results. Hepatic Intrarterial Chemotherapy (HIAC) for colorectal metastases achieves objective responses in more than 50% of patients. Survival seems positively affected. When feasible, Ro hepatic resection is the most effective treatment, five-year survival rate being about 30% when metastases are from colorectal cancer. Since the liver is the most frequent site of recurrence after resection, repeat resection have been successfully performed.

[Function and complications of diverse totally implantable systems for continuous intra-arterial infusion of FUdR in colorectal hepatic metastases]. / Funzionalità e complicanze di diversi sistemi totalmente impiantabili per l'infusione intraarteriosa continua di FUdR nelle metastasi epatiche colo-rettali.

Different totally implantable arterial infusion systems were compared in patients with liver metastases from colorectal cancer undergoing continuous intra-arterial infusion. Seventy-eight patients received continuous FUdR infusion using either totally implantable pumps (group a = 44 pts.) or ports fed by external portable pumps (group b = 34 pts.), and 57 patients received bolus infusion of Cisplatin (group c). Devices were cared for patency even after interruption of treatment, commonly caused by disease progression. Pocket problems most frequently occurred in group a (30%) compared to groups b (9%) and c (7%), whereas a higher incidence of catheter and infusion related problems was observed in group b (109%). System failure was recorded as a cause of interruption of treatment in two, 9, and 6 cases in groups a to c, respectively. The 12-months patency rate was 92% in group a, 24% in group b (median 9 months), and 65% in group c (median 17 months). Though implantable ports allow adequate infusion periods in most cases they seem more adequate for bolus infusions.

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.

Morbidity and mortality after hepatic resection of metastases from colorectal cancer.

A review was carried out of morbidity and mortality after hepatic resection for metastatic colorectal cancer in 208 consecutive patients who underwent this procedure between 1980 and 1992. Overall postoperative morbidity and mortality rates were 35 and 2.4 per cent respectively. The major morbidity rate was 18 per cent, the main complications being intra-abdominal sepsis, biliary fistula and haemorrhage. Of the different factors examined, morbidity was significantly related to the extent of liver resection (53 versus 21 per cent after major and minor resections respectively), amount of blood transfused (18 versus 52 per cent for no transfusion and more than 300 ml transfused respectively) and the date of the operation (53 versus 24 per cent before and after 1986 respectively). Multivariate analysis showed that only the extent of hepatic resection and the period at which surgery was performed retained their statistical significance. These data support the opinion that surgical treatment of hepatic metastases from colorectal cancer is an effective procedure with acceptable mortality and morbidity rates. An extensive experience of hepatic surgery is, however, necessary to optimize results.

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.

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.