Surgical treatment of iatrogenic lesions of the proximal common bile duct.

Between January 1979 and September 1999 a series of 96 patients were operated on at our institution for iatrogenic biliary injuries, and among them 62 involved the proximal biliary tract. Injuries, according to the Strasberg classification, were type E2 in 18 patients, type E3 in 29 patients, and type E4 in 15 patients. The most frequent primary surgical procedures were laparoscopic cholecystectomy in 27 of the 62 patients (43.6%) and open cholecystectomy in 30 patients (48.3%). Previous repair had been attempted in 25 patients (40.3%). A total of 58 cholangiojejunostomies were performed. Repair had been performed directly, and a T-tube had been left in the main bile duct in four patients with E2 Strasberg lesions. Postoperative death occurred in four patients (6.4%). Outcome was graded as excellent, good, or poor depending on clinical symptoms, liver function tests, and the need for reintervention due to anastomotic stricture. The final outcome was evaluated in 54 patients. The mean follow-up was 5.9 +/- 0.3 years, with the longest follow-up 10.2 years. Following our first repair 49 of the 54 patients (90.7%) had excellent results, 1 (1.9%) had good results, and 4 (7.4%) had poor results. None of the patients who underwent immediate or early repair had complications. Diagnostic and therapeutic courses are given on the basis of the type of lesion and the timing of repair. We emphasize the importance of timing (i.e., carrying out surgical repair as soon as possible) and of cholangiojejunostomy reconstruction in respect to defined technical principles. Moreover, we believe that repair treatment at a hepatobiliary center with multidisciplinary competence greatly influences the final long-term outcome.

[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.

D1 versus D2 pancreatoduodenectomy in surgical therapy of pancreatic head cancer.

BACKGROUND/AIMS: The aim of this study was to evaluate the influence of standard pancreatoduodenectomy versus pancreatoduodenectomy with extended lymphadenectomy and the role of adjuvant therapy on survival in patients with ductal adenocarcinoma of the pancreatic head. In addition the problems related to resection are discussed. METHODOLOGY: A total number of 124 pts operated on between 1985 and 1999 were divided into three groups according to our different strategies. Standard resection (D1) was performed on 48 patients (group A), extended resection (D2) on 45 patients (group B) and combined treatment (extended resection plus adjuvant therapy) on 31 patients. The outcome of these three groups was compared with regard to postoperative morbidity and survival. RESULTS: There was no significant difference in terms of survival between group A and B, while adjuvant therapy (group C), achieved statistical significance as factor influencing survival, together with tumor stage. CONCLUSIONS: Our data suggest that no further improvement can be obtained on long-term survival by extended retroperitoneal dissection while chemoradiotherapy showed a doubling of median survival.

Role of p53 mutations on survival after pancreatoduodenectomy for ductal adenocarcinoma of the pancreatic head.

BACKGROUND/AIMS: To determine the role of p53 mutations on survival after pancreatoduodenectomy for adenocarcinoma of the pancreatic head. METHODOLOGY: Resected specimens were assessed for expression of wild-type or mutated p53. Survival of p53-negative and- positive patients was investigated, and differences noted at 0.05 level. RESULTS: Expression of wild-type p53 is associated with a significant improvement in overall survival, especially for patients without nodal metastases. CONCLUSIONS: Preoperative p53 determination could enable further patient selection for aggressive surgery.

Surgery for hilar cholangiocarcinoma: an Italian experience.

From January 1980 to June 1997 we treated 159 patients with carcinoma of the hepatic duct confluence. Seventy-five patients underwent surgical resection (overall resectability rate: 47.2%), and radical resection was attempted in 46 patients (radical resectability rate: 28.9%) classified in the first three stages of our staging system. Perioperative mortality was 10% (16 patients). The 5-year survival rate for 46 patients with curative resection was 17.5% with a median survival of 19 months. The 5-year survival rate for those patients who underwent combined caudate lobectomy (n = 17) was 25%, whereas the survival rate for those who did not was zero. The difference between these two groups' results was statistically significant. The importance of careful preoperative staging is stressed. Preoperative tests should be limited to investigations (ultrasound with Doppler scan, spiral computed tomography, percutaneous transhepatic cholangiography) supplying most information about intra- and extrabiliary diffusion of the tumoral mass. We conclude by highlighting the importance of resection as the only treatment potentially improving long-term survival. On the basis of these results, caudate lobectomy is always recommended in association with resectional treatment of the neoplasm.

Upper abdominal surgery: does a lung function test exist to predict early severe postoperative respiratory complications?

We evaluated the capacity to predict severe respiratory complications (SRCs) following upper abdominal surgery (UAS) by using the results of a respiratory questionnaire and preoperative pulmonary function tests. Lung volumes, flows and transfer factor of the lung for carbon monoxide (TL,CO,sb) were assessed in 361 consecutive adult patients (248 males and 113 females). SRCs were diagnosed 24 h after UAS by clinical examination and chest radiography. Univariate and stepwise multiple logistic regression analyses were performed to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of each single input variable, and to determine which indices best predicted outcome. These patients had a 1% mortality rate and 14% incidence of SRCs, with a male:female ratio of 0.86. The best predictors for SRCs by multiple analysis were: preoperative current hypersecretion of mucus (OR=133; p<0.0001); an increase in residual volume (RV) (OR=3.11; p=0.01); and, to a lesser extent, low percentage of predicted values both of forced expiratory volume in one second (FEV1 % pred) and TL,CO,sb. The algorithm thus obtained (logit theta) was extremely sensitive (84%), specific (99%), and accurate (95%) for preoperative prediction of SRCs. We have found that preoperative current hypersecretion of mucus and pulmonary hyperinflation, and to a lesser extent percentage predicted values both of forced expiratory volume in one second and transfer factor of the lung for carbon monoxide, have a significant predictive capacity for severe respiratory complications following upper abdominal surgery.

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.

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).

[Surgical resection of exocrine neoplasms of the pancreatic head: indications and requirements]. / La chirurgia resettiva nelle neoplasie esocrine della testa del pancreas: indicazioni e presupposti.

Surgical resection is the only curative procedure for the treatment of the cancer of the pancreatic head: this paper describes the precise indications for surgery. These are: tumour size (diameter less than 4 cm), no metastases in the extra regional lymph nodes, no arterial invasion or involvement of the portal vein of more than 1.2 cm in length or its bilateral narrowing. The authors point out that only the complete removal of the retropancreatic tissue allows control of local recurrence and metastasis. They examine different resective procedures, concluding, on the basis of the literature and their own experience, that R2 subtotal pancreatoduodenectomy leads to a curative resection because of the removal of the foci of micrometastasis, a better control of local recurrence and, perhaps, a longer survival. They discuss the problem of the use of pyloro preserving pancreatic duodenectomy (PPDP) for exocrine tumours of the pancreas and conclude that it is correct to perform such an operation even for the treatment of these tumours if the local extension of the neoplasm allows it. Finally, the authors underline the need to use other adjuvant therapies to improve results: these however, are very often, quite limited.

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.

Enoxaparin in the prevention of deep venous thrombosis after major surgery: multicentric study. The Italian Study Group.

DVT is a very frequent complication of general surgery. Heparin and, more recently, LMWHs can successfully prevent post surgical thromboembolism. One thousand one hundred and twenty-two patients (533 males and 589 females; mean age 62.2 +/- 11.4 yrs) were enrolled in a multicentre controlled study, to evaluate the efficacy and safety of enoxaparin in comparison to calcium heparin in the prevention of deep venous thrombosis (DVT) following general surgery. Patients assigned to the enoxaparin and the calcium heparin groups received 1 daily dose of 20 mg (2000 I.U.) and 2 daily doses of 0.2 ml (5000 I.U.), respectively starting 2 hours before the operation. Both drugs were given by subcutaneous route. A Doppler or Duplex Scan diagnosis of DVT was made in 3 (0.5%) patients in the enoxaparin group (2 cases during treatment and 1 patient at the end of treatment) and in 6 (1.1%) patients in the calcium heparin group (5 cases during treatment and 1, bilateral, after the end of treatment). Pulmonary embolism (PE) was ascertained by angiography in 1 patient (0.18%) in the enoxaparin group and in 2 patients (0.36%) in the calcium heparin one. Hemorrhagic complications occurred in 29 patients (5.2%) in the enoxaparin group and in 34 (6.1%) in the calcium heparin group. Haematomas located in the injection site were reported in 16.1% and 25.3% in the enoxaparin and calcium heparin groups respectively (p = 0.0001). Local pain in the injection site at the 5th day of treatment was reported in 8.4% and 16.6% in the enoxaparin and calcium heparin groups respectively (p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

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").

Formation of the N-nitroso derivatives of six beta-adrenergic-blocking agents and their genotoxic effects in rat and human hepatocytes.

Six beta-adrenergic-blocking drugs, atenolol, metoprolol, nadolol, oxprenolol, propranolol and sotalol, were found to react with sodium nitrite in HCl solution, yielding the corresponding N-nitrosamines. The genotoxic activity of the six nitrosamines was evaluated in primary cultures of both rat and human hepatocytes; DNA fragmentation was measured by the alkaline elution technique, and DNA repair synthesis by quantitative autoradiography. Positive dose-related responses were produced in cells of both species after 20 h of exposure to the following subtoxic concentrations: NO-propranolol, 0.01-0.1 mM; NO-oxprenolol, 0.03-1 mM; NO-atenolol and NO-metoprolol, 0.1-1 mM; and NO-nadolol and NO-sotalol, 0.3-3 mM. Modest but statistically significant differences between the DNA-damaging potencies for the two species were observed with NO-atenolol and NO-oxprenolol, which were both more active against rat hepatocytes, and with NO-propranolol, which was more active against human hepatocytes. At equal or higher concentrations, the six N-nitrosamines did not produce DNA fragmentation in Chinese hamster lung V79 cells; this indicates that they behave as indirectly acting compounds, which need to be transformed into reactive metabolites in order to exert a genotoxic effect.

Percutaneous transhepatic biliary drainage--twelve years' experience.

Our experience with percutaneous transhepatic biliary drainage in a total of 362 patients carried out between January 1977 and December 1988 is described. Three hundred and fifty drains were correctly placed, and results were good in 285 (81.5%), fair in 53 (15.1%) and poor in 12 (3.4%). In 12 of the total number of cases (3.4%) it was not possible to position the drain effectively. The mortality rate of the method was 0.8% (3 cases). Complications were as follows: obstruction 7 (1.9%), dislodgement 15 (4.1%), hemobilia 15 (4.1%), hemoperitoneum 1 (0.2%), cholangitis 6 (1.6%), and choleperitoneum 10 (2.7%). In view of the good results and low incidence of complications the conclusion is that in skilled hands, percutaneous transhepatic biliary drainage is a very useful method that should be available in any center specializing in hepatobiliary surgery.

Percutaneous transhepatic biliary drainage twelve years' experience.

Experience with a total of 362 percutaneous transhepatic biliary drainage (PTBD) carried out between January 1977 and December 1988, is described. Of these, 350 drains were correctly placed and 285 (81.5%) showed a good result, 53 (15.1%) a fair result and 12 (3.4%) a poor outcome. In 12 of the total number of cases (3.4%) it was not possible to position the drain effectively. The mortality rate of the method was 0.8% (3 cases). Complications were as follows: obstruction 7 (1.9%), dislodgement 15 (4.1%), hemobilia 15 (4.1%), hemoperitoneum 1 (0.2%), cholangitis 6 (1.6%), choleperitoneum 10 (2.7%). In view of the good results and low incidence of complications it is concluded that in skilled hands PTBD is a very useful method that should be available at any center specializing in hepatobiliary surgery.

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)

Comparative study of DNA damage and repair induced by ten N-nitroso compounds in primary cultures of human and rat hepatocytes.

Ten carcinogenic N-nitroso compounds were assayed for DNA-damaging activity in primary cultures of human and rat hepatocytes. DNA fragmentation was measured by the alkaline elution technique, and unscheduled DNA synthesis by quantitative autoradiography. Positive dose-related responses in the range of subtoxic concentrations indicated were obtained in cells of both species with N-nitrosodiethylamine (10-32 mM), N-nitrosodi-n-propylamine (1.8-10 mM), N-nitrosomorpholine (1-3.2 mM), N-nitrosopiperidine (1-3.2 mM), N-nitrosopyrrolidine (3.2-18 mM), N-nitroso-N-methylurea (0.32-1.8 mM), N-nitroso-N-ethylurea (0.32-1.8 mM), and N-nitroso-N-butylurea (0.1-0.32 mM). N-nitrosodi-n-butylamine was practically inactive at the maximal soluble concentration (1 mM). The responses of human hepatocytes were qualitatively similar to those of rat hepatocytes, but statistically significant differences between the two species in the amounts of DNA damage and/or unscheduled DNA synthesis were observed with N-nitrosodimethylamine, N-nitrosomorpholine, N-nitrosopiperidine, N-nitrosopyrrolidine, and N-nitroso-N-butylurea. On the other hand, quantitative differences in the genotoxic effects induced by 5 mM N-nitrosodimethylamine in cultures derived from 20 human donors and from 20 rats were greater than average interspecies differences displayed by this nitrosamine and by other N-nitroso compounds. These results indicate that the rat hepatocyte DNA repair assay is a valid model for predicting the genotoxic potential of N-nitroso compounds in human hepatocytes.