[Combined multimodal treatment for liver and lung metastasis from colorectal cancer: a new therapeutic option?]. / Il trattamento multimodale combinato delle metastasi epatiche e polmonari da cancro colorettale: una nuova opzione terapeutica?

The authors analyse which therapeutic strategy to adopt on the basis of prognostic factors and staging of hepatic and pulmonary metastases from colorectal cancer. They underline the effectiveness of combined multimodal therapy in the treatment of very advanced metastatic stages. 218 patients with metastases from colorectal cancer (12 pulmonary and 206 hepatic metastases) were treated from January 1980 to October 2000. Among these patients, 159 underwent surgery (4 pulmonary and 155 hepatic resections), 16 were reoperated on for metastatic relapse, 14 with multiple metastases underwent locoregional therapy and 29, deemed unresectable initially, were treated with neoadjuvant chemo- and radiotherapy. In the operated patient group the 5-year actuarial survival rate was 22% with an operative mortality of 3.8% and a morbidity of 17.5%. The 16 patients reoperated on for metastatic relapse had a 5-year actuarial survival of 21% with an operative mortality of 6.2% and a morbidity of 15.8%. The 14 patients treated with locoregional therapy had a median survival of 6 months whereas the 29 patients treated in two different periods with combined multimodal treatment had a response rate of 59.2%. Five patients had a complete response and 4 are currently disease-free. Surgical resection is at present the best known treatment for metastatic disease. In very advanced, as yet undisseminated stages, in which there is no surgical indication for metastases a neoadjuvant treatment is proposed if the primary tumour has already been completely resected. The aim of this therapeutic strategy, called combined multimodal therapy, is to obtain the disease regression with the aid of systemic chemo- and radiotherapy and to offer a chance of re-staging the disease.

Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer: a multicentric phase II study.

We have recently reported high clinical activity against advanced colorectal cancer of a regimen-alternating bolus FUra, modulated by methotrexate (MTX), and continuous infusion FUra, modulated by 6-s-leucovorin (6-s-LV). Considering the low toxicity of the bolus part of this regimen and our recent in vitro finding of a strong synergism between bolus FUra and natural-beta-IFN (n-beta-IFN), this cytokine was incorporated in the bolus part of our treatment programme. Fifty-six patients with untreated, advanced, measurable colorectal cancer were treated with two biweekly cycles of FUra bolus (600 mg m(-2)), modulated by MTX (24 h earlier, 200 mg m(-2)), and n-beta-IFN (3 x 10(6) IU i.m. every 12 h, starting at the time of FUra administration for four doses), alternating with a 3-week continuous infusion of FUra (200 mg m(-2) daily), modulated by 6-s-LV (20 mg m(-2) weekly bolus). After a 1-week rest, the whole cycle (8 weeks) was repeated if indicated. A total of 5 complete and 17 partial responses were obtained (response rate, 41%; 95% confidence limits, 28-55%) in 54 assessable patients. After a median follow-up time of 36 months, five patients are still alive. Overall, the median time to treatment failure was 6.4 months. The median duration of survival was 15.0 months. There was one treatment-related death after a course of MTX --> bolus FUra/n-beta-IFN and grade III-IV toxicity occurred in 18% of the patients. As the addition of n-beta-IFN results in high toxicity, whereas the efficacy seems to be similar to that of the same regimen without the cytokine, our groups are currently randomizing the original regimen, without IFN, against standard modulated bolus FUra.

Reducing the occupational risk of infections for the surgeon: multicentric national survey on more than 15,000 surgical procedures.

The objective of this study was to find the incidence of accidental exposures to blood and body fluids among surgeons during operations and to describe their dynamics. A probabilistic model was also used to predict the cumulative 30-year risk to the surgeon of contracting hepatitis B and C viruses (HBV, HCV) or human immunodeficiency virus (HIV) infection and estimate the effect of preventive strategies in reducing this risk. A multicentric prospective survey, based on self-administered questionnaires, was conducted during a period of 6 months in 39 Italian hospitals. As accidental exposure to blood or body fluids occurred in 9.2% of 15,375 operations. In about 2% of procedures a parenteral-type injury, such as actual skin puncture or eye contamination, was suffered by the operating surgeon. A needle-stick injury was the commonest accident, and its occurrence was found to vary with the phase of the procedure and its length. The current lifetime risk of acquiring HBV, HCV, and HIV infection in our regions was estimated to be as high as 42.7%, 34.8%, and 0.54%, respectively. The adoption of preventive strategies is expected to reduce this risk to 21% for HBV, 16.6% for HCV, and 0.23% for HIV infection. Active immunization of surgeons against HBV is strongly recommended. The case is also made for the use of a face-shield combined with a permanent change in our surgical practice capable of reducing the current high rate of parenteral injuries.

Repeated hepatic resections for recurrent metastasis of colorectal cancer.

BACKGROUND/AIM: Few cases of repeated hepatic resection for recurrent metastasis have been in literature. This paper focuses on metastatic recurrences and their surgical treatment, comparing the outcome of resective therapy with the natural history of metastases. Results of alternative methods (alcoholization and trans-arterial chemo-embolization), are evaluated through the analysis of indications, complications and real benefit. MATERIALS AND METHODS: Between January 1980 and Jan 1995, 163 patients with hepatic metastases were operated on in our Department. In 132 cases, metastases originated from colorectal cancer: 105 were submitted to hepatic resection, 3 were treated by selective ischemia, 5 by chemotherapy through an infusaid catheter, 5 by alcoholization under ultrasonographic control, 14 by a new phase II trial of schedule oriented biochemical modulation of FUra bolus by MTX and B interferon and FUra continuous infusion by leucovorin. RESULTS: Out of 76 metachronous metastases operated on, 10 were metastatic hepatic recurrences surgically treated by second resection. The average time-interval intercurring between the two hepatic resections was 15 months. The average follow-up and survival period after repeated resection was 27 months (range 2-129). CONCLUSIONS: Through the analysis of these ten cases, we sorted out the segmentary localization of hepatic metastases, the type of operation performed, the disease free interval, serum CEA patterns, morbidity and survival.

Multiparametric evaluation of functional outcome after pylorus-preserving duodenopancreatectomy.

The aim of the present study was to evaluate the clinical, morphological and functional results obtained in a group of patients previously submitted to Traverso-Longmire pylorus-preserving duodeno-pancreatectomy (PPDP). The study was performed as a clinical, endoscopic, radioisotopic and electro-manometric evaluation. An analysis of the results allowed us to conclude that: 1) most patients show good clinical features, and this becomes more evident as post-operative time progresses; 2) bile reflux gastritis is an infrequent event; 3) gastric emptying times in patients overlap those seen in control subjects, and progressive normalization occurs postoperatively. The best clinical results coexist with normal gastric emptying times; 4) gastrojejunal interdigestive motor activity shows a reduction in phase 3 and a relative increase in phase 2. We argue that the motor activity of the upper gastrointestinal tract can restore, from a functional point of view, the new anatomical situation. On the basis of the good clinical and functional results, pyloric preservation seems to be the most physiological procedure for the restoration of alimentary continuity following duodenopancreatic resection.

Klatskin tumour: radical and palliative treatment.

Primitive neoplasms of proximal extrahepatic bile ducts keep their peculiar morphological and spreading patterns, as firstly described by J. Klatskin. Diagnostic and therapeutic approach were modified in the last year, on the basis of technological progress in imaging and more aggressive surgical attitude. Authors reviewed their clinical experience from 1970 to 1995 concerning proximal extrahepatic bile ducts tumors management, mainly evaluating the evolution of diagnostic work-up and the role of resection. Preoperative work-up is now trimed to non invasive techniques, in order to evaluate the intra and extra biliary diffusion; PTC-PTBD performed preoperatively give a clear biliary map, and could be the first step of a palliative definitive treatment in case of non operable patients. Radical resection remains the gold standard of therapy, with the best long-term results. Palliation must be obtained by the easiest comfortable method for the patient (i.e. self-blocking percutaneously inserted endoprosthesis).

Intrahepatic lithiasis above a bilio-digestive anastomosis.

The authors review their experience of twenty-five cases of intrahepatic lithiasis proximal to a bilio-digestive anastomotic stricture. Patients were operated on between 1970 and 1990, with a later follow-up in 1993. The pathogenesis of stone formation, in these cases, was relatable to multiple factors: biliary infection, presence of lithogenic nuclei (e.g. foreign bodies such as suture stitches), biliary stasis due to the stenosis. Management of this peculiar disease must take into account both surgical options and percutaneous as well as endoscopic methods. Our approach is the reconstruction of the stenotic anastomosis at its highest point, associated with intraoperative lithotomy followed by post-operative lithotomy and lithotripsy (if necessary) using PTCS (percutaneous transhepatic cholangioscopy). The best results are achieved with cooperation between surgeon, radiologist and endoscopist, aimed at preventing post-operative complications and severe consequences for the patient.

Neoplasm of the hepatic hilum: the role of resection.

A series of one hundred cases of primitive tumors of the biliary confluence (Klatskin tumor) observed between 1970 and 1990 are reviewed with respect to the variations occurring in the diagnostic backup and treatment policy. The need for peroperative staging is noted: On the basis of their clinical experience, the authors restricted the preoperative study to those investigations providing more information about endo- and exobiliary diffusion of tumoral mass (ultrasound, direct cholangiography). The review demonstrates the possibilities of a surgical approach to a palliative or resectional treatment in all patients in whom no local or general contraindications are present. Other cases are treated with percutaneous or endoscopic biliary stenting. The authors conclude that tumor resection with bilio-digestive anastomosis is the treatment of choice in selected patients, and results in a better quality of life with an improved "comfort index".

Primitive hepatic hilum neoplasm.

One hundred ten cases of primitive hepatic hilum neoplasms (Klatskin tumor) observed from January 1970 to June 1992 are reviewed and the variations occurring in the diagnostic back-up and treatment policy are considered. The importance of careful preoperative staging is stressed. Preoperative tests should be limited to investigations supplying most informations about endo- and esobiliary diffusion of the tumoral mass (ultrasound, direct cholangiography, portography). This paper demonstrates that a surgical approach with both palliative or resective aims is suitable for all patients with no local or general contraindications. Other cases are treated with percutaneous or endoscopic biliary stenting. The authors conclude by pointing out that tumoral resection with biliodigestive anastomosis is in any case the treatment of choice in these patients as it gives a better quality of life (improved "comfort index").

Percutaneous fibercholangioscopies.

This is a report on our experience in 309 percutaneous fiberendoscopies of the biliary tract done in 106 patients of the 115 scheduled for the procedure. We describe the relevant approaches, techniques, complications and results. In particular, percutaneous transhepatic cholangioscopies (PTCS) were accomplished on transhepatic percutaneous drainages located radiologically in 35 patients: in 13 for differential diagnosis to distinguish between malignant and benign stenoses (diagnostic accuracy in 92% of the biopsies), in 22 cases with therapeutic intent, including 14 lithotomies for extrahepatic biliary tract calculosis, combined in 4 cases with a simple dilatation of the papilla and a percutaneous "descending" papillotomy; in 7 patients a dilatation of the biliary tract (BT) or of the stenosis of a biliodigestive anastomosis was accomplished (malignant in 4 patients, benign in 3 patients). In 38 patients postoperative percutaneous transhepatic cholangioscopies were performed along surgically located transparietohepatic drains, both to assess the biliodigestive anastomosis healing process carried out by two different techniques (30 patients), and to complete the biliary tract drainage as part of the primary and secondary endoscopic surgical treatment of massive intrahepatic lithiasis. In two further patients affected by such pathology, PTCS was done in combination with fibercholangioscopy performed via a transjejunal approach using a Völker drain on a Y-shaped loop. Nine of these patients were treated successfully and one patient later underwent a left hepatectomy, since attempts to drain that area had remained unsuccessful. The transjejunal approach was carried out in 3 patients as a diagnostic measure: in two cases to check the lithotomy, and in one case to check a cholangiojejunal anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)