Laparoscopic liver resections for hepatocellular carcinoma. Is it a feasible option for patients with liver cirrhosis?

BACKGROUND: Laparoscopic surgery has gained growing acceptance, but this does not hold for laparoscopic surgery of the liver, above all for patients with hepatocellular carcinoma (HCC) and cirrhosis. This approach mainly includes diagnostic procedures and interstitial therapies. However, we believe there is room for laparoscopic liver resections in well-selected cases. The aim of this study is to assess: (a) the risk of intraoperative bleeding and postoperative complications, (b) the safety and the respect of oncological criteria, and (c) the potential benefit of laparoscopic ultrasound in guiding liver resection. METHODS: A prospective study of laparoscopic liver resections for hepatocellular carcinoma was undertaken in patients with compensated cirrhosis. Hepatic involvement had to be limited and located in the left or peripheral right segments (segments 2-6), and the tumor had to be 5 cm or smaller. Tumor location and its transection margins were defined by laparoscopic ultrasound. RESULTS: From January 1997, 22 out of 250 patients with HCC (9%) underwent laparoscopic liver resections. The mean patient age was 61.4 years (range, 50-79 years). In three patients, conversion to laparotomy was necessary. The laparoscopic resections included five bisegmentectoies (2 and 3), nine segmentectomies, two subsegmentectomies and three nonanatomical resections for extrahepatic growing lesions. The mean operative time, including laparoscopic ultrasonography, was 199 +/- 69 min (median, 220; range, 80-300). Perioperative blood loss was 183 +/- 72 ml (median, 160; range, 80-400 ml). There was no mortality. Postoperative complications occurred in two out of 19 patients: an abdominal wall hematoma occurred in one patient and a bleeding from a trocar access in the other patient requiring a laparoscopic re-exploration. Mean hospital stay of the whole series was 6.5 +/- 4.3 days (median, 5; range, 4-25), while the mean hospital stay of the 19 laparoscopic patients was 5.4 +/- 1 (median, 5; range, 4-8). CONCLUSION: Laparoscopic treatment should be considered in selected patients with HCC and liver cirrhosis in the left lobe or segments 5 and 6 of the liver. It is clear that certain types of laparoscopic resection are feasible and safe when carried out by adequately skilled surgeons with appropriate instruments.

A risk score for predicting perioperative blood transfusion in liver surgery.

BACKGROUND: It would be desirable to predict which patients are most likely to benefit from preoperative autologous blood donation. This aim of this study was to develop a point scoring system for predicting the need for blood transfusion in liver surgery. METHODS: The medical records of 480 consecutive patients who underwent hepatic resection were analysed. The data set was split randomly into a derivation set of two-thirds and a validation set of one-third. Univariable analysis was carried out to determine the association between clinicopathological factors and blood transfusion. Significant variables were entered into a multiple logistic regression model, and a transfusion risk score (TRS) was developed. The accuracy of the system was validated by calculating the area under the receiver-operator characteristic (ROC) curve. RESULTS: Factors associated with blood transfusion in multivariable analysis included preoperative haemoglobin concentration below 12.5 g/dl, largest tumour more than 4 cm, need for exposure of the vena cava, need for an associated procedure, and cirrhosis. Each variable was assigned one point, and the total score was compared with the transfusion status of each patient in the validation set. The TRS accurately predicted the likelihood of blood transfusion. In the validation set the area under the ROC curve was 0.89. CONCLUSION: Use of the TRS could lead to substantial saving by improving the cost-effectiveness of the autologous blood donation programme.

Trastuzumab in metastatic breast cancer.

Metastatic breast cancer is an incurable disease in a very high percentage of patients. Despite new progress in endocrine and other systemic therapies, this evidence remains challenging for patients and clinicians. HER2 protein is a member of the epidermal growth factor family of transmembrane receptors. HER2 is overexpressed in approximately 20% to 30% of breast cancers. Overexpression of HER2 has been shown to be associated with increased tumor proliferation and relative resistance to some types of chemotherapy and hormonal therapies. Trastuzumab, a humanized monoclonal antibody directed against HER2 protein, has been shown to be an efficacious and well tolerated treatment for HER2-overexpressing metastatic breast cancer, both as a single agent and when it is used in combination with chemotherapy.

Bilateral renal mass suggestive of cancer.

We present the case of a 44-year old man, presenting with acute left flank pain and gross haematuria, affected by bilateral renal mass and massive para-aortic and mediastinic lymphadenopathy, highly suspicious for metastatic renal cancer.

Neural contractions in colonic strips from patients with diverticular disease: role of endocannabinoids and substance P.

BACKGROUND AND AIMS: Diverticulosis is a common disease of not completely defined pathogenesis. Motor abnormalities of the intestinal wall have been frequently described but very little is known about their mechanisms. We investigated in vitro the neural response of colonic longitudinal muscle strips from patients undergoing surgery for complicated diverticular disease (diverticulitis). METHODS: The neural contractile response to electrical field stimulation of longitudinal muscle strips from the colon of patients undergoing surgery for colonic cancer or diverticulitis was challenged by different receptor agonists and antagonists. RESULTS: Contractions of colonic strips from healthy controls and diverticulitis specimens were abolished by atropine. The beta adrenergic agonist (-) isoprenaline and the tachykinin NK1 receptor antagonist SR140333 had similar potency in reducing the electrical twitch response in controls and diseased tissues, while the cannabinoid receptor agonist (+)WIN 55,212-2 was 100 times more potent in inhibiting contractions in controls (IC50 42 nmol/l) than in diverticulitis strips. SR141716, a selective antagonist of the cannabinoid CB1 receptor, had no intrinsic activity in control preparations but potentiated the neural twitch in diseased tissues by up to 196% in a concentration dependent manner. SR141716 inhibited (+)WIN 55,212-2 induced relaxation in control strips but had no efficacy on (+)WIN 55,212-2 responses in strips from diverticular disease patients. Colonic levels of the endogenous ligand of cannabinoid and vanilloid TRPV1 receptors anandamide were more than twice those of control tissues (54 v 27 pmol/g tissue). The axonal conduction blocker tetrodotoxin had opposite effects in the two preparations, completely inhibiting the contractions of control strips but potentiating those in diverticular preparations, an effect selectively inhibited by SR140333. CONCLUSIONS: Neural control of colon motility is profoundly altered in patients with diverticulitis. Their raised levels of anandamide, apparent desensitisation of the presynaptic neural cannabinoid CB1 receptor, and the SR141716 induced intrinsic response, suggest that endocannabinoids may be involved in the pathophysiology of complications of colonic diverticular disease.

Ultrasound measurement of visceral and subcutaneous fat in morbidly obese patients before and after laparoscopic adjustable gastric banding: comparison with computerized tomography and with anthropometric measurements.

BACKGROUND: There are now a variety of methods to assess body fat distribution, anthropometric (waist circumference and waist/hip W/H ratio), computed tomography (CT), and ultrasound (US) measurements, with CT considered as the reference method. Bariatric surgery leads to a significant and usually durable weight loss in morbidly obese patients; when assessing its results, it is of interest to measure changes of total fat tissue and of body fat distribution. METHODS: In this study, we compared anthropometric, US, and CT measurements of body fat distribution under basal conditions and 1 year after laparoscopic adjustable gastric banding (LAGB); 120 morbidly obese patients were considered at baseline, and 40 patients were re-evaluated 1 year after LAGB. RESULTS: Thickness of visceral and subcutaneous fat measured through CT and US methods was superimposable both under basal conditions and 1 year after LAGB, and the highest correlation was found between CT and US data on visceral fat, followed by CT and US data on subcutaneous fat; a fair correlation was also found between CT and US data on visceral fat and waist circumference. CONCLUSION: We suggest that evaluation of body fat distribution is accomplished by US instead of CT measurement, because of its lower cost and low exposure risk. Waist circumference stands as a reasonable surrogate of both methods, while W/H ratio is poorly correlated with other measures of body fat distribution.

Functional assessment of neuronal cannabinoid receptors in the muscular layers of human ileum and colon.

BACKGROUND & AIMS: The notion that specific receptors account for the ability of natural and synthetic cannabinoids to alter physiological functions, prompted this study aimed at assessing their functional presence in the human gut. METHODS: The effects have been studied of cannabinoids and selective antagonists of their receptors on chemically or electrically evoked contractions in preparations of human intestinal smooth muscle in vitro. RESULTS: Atropine prevented the contractions of longitudinal and circular muscle strips of ileum and colon induced by carbachol or electrical field stimulation; tetrodotoxin abolished only the latter which suggests they do involve activation of cholinergic neurons. The synthetic cannabinoid (+)WIN 55,212-2 had no effect on carbachol contractions, but in a concentration-dependent fashion prevented those elicited by electrical field stimulation - which were insensitive to the putative endogenous cannabinoid anandamide - more potently in longitudinal than in circular strips. The selective CB1 receptor antagonist SR141716, which had no effect in the absence of (+)WIN 55,212-2, competitively antagonised its inhibition of electrical field stimulation contractions, unlike the selective CB2 antagonist SR144528. CONCLUSIONS: Cannabinoid CB1 receptors are functionally present in the human ileum and colon; their pharmacological activation apparently results in inhibition of excitatory cholinergic pathways subserving smooth muscle contraction.

Extrahepatic biliary stenoses after hepatic arterial infusion (HAI) of floxuridine (FUdR) for liver metastases from colorectal cancer.

Hepatic arterial infusion of floxuridine is an effective treatment for unresectable hepatic metastases from colorectal cancer. Despite its pharmacological advantage of higher tumor drug concentration with minimal systemic toxicity, hepatic arterial infusion of floxuridine is characterized by regional toxicity, including hepatobiliary damage resembling idiopathic sclerosing cholangitis (5-29% of treated cases). Unlike previous reports describing biliary damage of both intrahepatic and extrahepatic ducts, a case series of extrahepatic biliary stenosis after hepatic arterial infusion with floxuridine is herein described. Between September 1993 and February 1999, 54 patients received intraarterial hepatic chemotherapy based on continuous infusion of floxuridine (dose escalation 0.15-0.30 mg/kg/day for 14 days every 28 days) plus dexamethasone 28 mg. Twenty-seven patients underwent laparotomy to implant the catheter into the hepatic artery, the other 27 patients receiving a percutaneous catheter into the hepatic artery through a transaxillary access. Five patients (9.2%) developed biliary toxicity with jaundice and cholangitis (3 cases), alterations of liver function tests and radiological features of biliary tract abnormalities. They received from 9 to 19 cycles (mean 14.5 +/- 6.3 cycles) of floxuridine infusion with a total drug delivered dose ranging from 20.3 to 41.02 mg/kg (mean: 31.4 +/- 13.5 mg/kg). Extrahepatic biliary sclerosis was discovered by computed tomography scan and ultrasound, followed by endoscopic retrograde cholangiopancreatography and/or percutaneous cholangiography in 3 cases. Radiological findings included common hepatic duct complete obstruction in 1 case, common hepatic duct stenosis in 2 cases, common bile duct obstruction in 1 case, and intrahepatic bile ducts dilation without a well-recognized obstruction in 1 case. Two patients were treated by sequentially percutaneous biliary drainage and balloon dilation while 1 patient had an endoscopic transpapillary biliary prosthesis placed. Percutaneous or endoscopic procedures obtained the improvement of hepatic function and cholestatic indexes without subsequent jaundice or cholangitis. In two patients suppression of floxuridine infusion allowed the improvement of hepatic function. The present series suggests that in some patients receiving hepatic arterial infusion of floxuridine extrahepatic biliary stenosis may represent the primary event leading to a secondary intrahepatic biliary damage that does not correlate with specific floxuridine toxicity but results from bile stasis and infection, recurrent cholangitis and eventually biliary sclerosis. Aggressive research for extrahepatic biliary sclerosis is advised, since an early nonsurgical treatment of extrahepatic biliary stenosis may prevent an irreversible intrahepatic biliary sclerosis worsening the prognosis of metastatic liver disease.

Role of hepatic resection in the treatment of hepatolithiasis.

BACKGROUND: The aim of the present study was to evaluate the safety and the efficacy of hepatic resection in the treatment of hepatolithiasis with intrahepatic biliary strictures. EXPERIMENTAL DESIGN: retrospective study. SETTING: University hospital, Italy. PATIENTS: 6 consecutive patients with single lobe hepatolithiasis operated on during the 4-year period 1994-98 inclusive. INTERVENTIONS: major hepatic resections (3 left hepatectomies, 2 left lobectomies, 1 right hepatectomy). MAIN OUTCOME MEASURES: type and duration of the surgical procedure, intra/postoperative blood losses, intra/postoperative course and complications, pathology, and hepatolithiasis recurrence. RESULTS: Mean operative time was 3.34+/-0.02 hrs (range 3.0-4.3 hrs). Mean blood loss was 233+/-150 ml (range 100-500 ml). No patient required intra/postoperative blood transfusions. No intraoperative complication was recorded. Mean postoperative hospitalization was 17+/-7 days (range 6-28 days). Postoperative course was uneventful in 4 (66%) cases. No postoperative mortality was recorded. One pancreatitis and 1 biliary fistula occurred, for an overall postoperative morbidity of 33%. Pathology showed cholangiocarcinoma in 2 cases (33%). During the follow-up period (range 3-48 months, mean 19.1+/-16.4 months), 1 patient had recurrent cholangitis due to right lobe lithiasis and 1 patient died for cholangiocarcinoma. CONCLUSIONS: Hepatic resection is the treatment of choice in patients with single lobe hepatolithiasis and unreversible biliary strictures or possible presence of cholangiocarcinoma. An early indication for surgery may reduce the mortality/morbidity rates of hepatic resection for hepatolithiasis.

[Advanced age as risk factor in liver resection surgery]. / L'età avanzata come fattore di rischio nella chirurgia resettiva epatica.

To evaluate the influence of age on the outcome of liver resections, 105 consecutive patients undergoing hepatic resection were divided into two groups: age > or = 65 years [Old Group (O-Group)] and age < 65 years [Young Group (Y-Group)]. O-Group and Y-Group patients were analyzed comparatively in terms of primary diagnosis, concomitant diseases, previous surgery, type of operation (major or minor resection), associated procedures, presence and length of portal clamping, intraoperative blood losses and transfusions, and length of operation. The end points of the study were postoperative mortality, morbidity, transfusions, and length of post-operative hospitalization. The Y-Group included 61 resections in 60 patients, with a mean age of 52 +/- 10 years (mean +/- SD), range 23-64 years, and the O-Group 44 resections in 43 patients, with a mean age of 71 +/- 4 years, range 65-82 years. The O-Group included more cases of hepatoma (45.4% vs 18%, p = 0.002) and cirrhosis (40.9% vs 18.7%, p = 0.017). Median length of operation was slightly higher in the Y-Group (330 vs 270 minutes, p = 0.003). The O- and Y-Groups were comparable (p = n.s.) when evaluated for all other variables listed. As regards the end points of the study, length of post-operative hospitalization was identical in both groups (median 9 days, range 5-60 days) and neither PRBC transfusions (O-Group vs Y-Group: 16% vs 25%) nor FFP transfusions (O-Group vs Y-Group: 13.6% vs 6.5%) showed any statistically significant difference. Postoperative mortality consisted in 1 death among the younger patients while no deaths were recorded among the older patients. Postoperative morbidity was higher in the Y-Group than in the O-Group (31.1% vs 20.5%, p = 0.59). Advanced age does not negatively affect the outcome of liver resections.

Right hepatic artery indwelling catheter for adjuvant chemotherapy after right hepatectomy.

Intraarterial hepatic adjuvant chemotherapy after radical hepatic resection for liver metastases from colorectal carcinoma lowers the rate of liver disease relapse. The technique for catheter implantation in the right hepatic artery for subsequent intraarterial hepatic adjuvant chemotherapy after right hepatectomy is herein described and recommended as an effective alternative approach to the standard catheter implantation in the gastroduodenal artery in cases of hepatectomies for liver metastases from colorectal cancer.

Functional assessment of beta adrenoceptor subtypes in human colonic circular and longitudinal (taenia coli) smooth muscle.

BACKGROUND AND AIMS: The subtype and species related heterogeneity of beta adrenoceptors prompted a functional reappraisal of these molecular targets of motility inhibition in the human colon. METHODS: Relaxation of muscle strips was measured in vitro. RESULTS: The following agonists had decreasing relaxing potency (effective concentration range 10(-8)-10(-4) mol/l): (-)isoprenaline (non-selective), terbutaline (beta(2) selective), CGP 12177 (beta(3) selective, also beta(1), beta(2) antagonist), and SR 58611A (beta(3) selective). Isoprenaline and terbutaline were more potent on circular than taenia strips; CGP 12177 and SR 58611A weakly and partially relaxed taenia but had little effect on circular strips. The potency of isoprenaline on circular strips was greatly reduced by the beta(1) selective antagonist CGP 20712 (10(-7) mol/l), and less so by ICI 118551 (10(-7) mol/l, beta(2) selective). CGP 20712 and ICI 118551 together (both 3 x 10(-6) mol/l) had no effect on taenia relaxation by SR 58611A and rendered isoprenaline and terbutaline virtually inactive on circular strips, although not on taenia, which was relaxed at higher than control concentrations and maximally by isoprenaline. Propranolol, a beta(1), beta(2) non-selective antagonist, at high concentrations (10(-5) mol/l) prevented taenia relaxation by CGP 12177 and SR 58611A; its quantitative antagonism of isoprenaline (in common with that of CGP 12177 used as an antagonist) was competitive in circular strips but not on taenia. CONCLUSIONS: beta(1), beta(2), and beta(3) adrenoceptors are functionally detectable in the human colon; agonist stimulation of any one type relaxed taenia but only isoprenaline was fully effective at the beta(3) subtype.

Thirty months experience with laparoscopic adjustable gastric banding.

INTRODUCTION: Since June 1996 we performed laparoscopic adjustable silicone gastric banding (LASGB), because of low invasivity, absence of malabsorption, reversibility, and postoperative regulation. MATERIALS AND METHODS: Criteria included body mass index (BMI) >40 or >35 with serious obesity-related conditions. 154 patients underwent LASGB. BMI ranged from 35 to 65.7 (mean 43.7+/-6.2). RESULTS: The laparoscopic procedure was successfully completed in 150 patients (97.4%). One patient was converted to the laparotomic procedure because of hepatomegaly; 4 patients had to be converted for gastric laceration during the laparoscopic approach. In one of these patients, the band was removed 7 days later for sepsis, followed by an uneventful postoperative course. The mean length of postoperative hospitalization was 2.3+/-0.9 days. Per cent of excess weight loss was 42.5+/-22.4 after 1 year. CONCLUSIONS: LASGB was feasible and effective.

Complications of blind placement technique in 980 subcutaneous infusion ports.

PURPOSE: Subcutaneous Infusion Ports (SIPs) for prolonged venous access are useful tools for drug administration in a wide range of chronic diseases. An extensive use of these devices has to be balanced against the potential complications worsening the length and the quality of life of frequently compromised patients. The aim of the present study is the prospective evaluation of early and late complications of the technique for the blind placement of totally implantable devices for prolonged venous access. METHODS: Between April l, 1991 and September 30, 1999, 980 SIPs were implanted in 967 patients. Thirteen patients received 2 SIPs. The surgical procedure, the catheter through peel-away technique after infraclavicular approach to the right or left subclavian vein, was performed without intraoperative fluoroscopy (blind placement technique) in the operating room under local anaesthesia. A postoperative chest radiography to rule out any procedure- related complications and to check the position of the catheter tip was obtained in all cases. For the purpose of the study, intraoperative complications as well as all SIP-related complications were recorded during the follow-up period and classified as major and minor complications. RESULTS: The study population consisted of 524 males/443 females, with a mean age of 56.3 +/- 11.4 years (range 19-85 years). Primary diagnosis was malignancy in 916 patients (94.7%), acquired immunodeficiency syndrome (AIDS) in 44 patients (4.5%), and short gut syndrome secondary to subtotal small bowel resection in 2 cases (0.2%), others in 5 cases (0.5%). Perioperative complications were recorded in 12.9% of the 980 insertion pro-cedures, including 77 cases of arterial puncture (7.8%) of the subclavian artery, 1 case of hemoptysis (without clinical and radiological evidence of pneumothorax) (0.1%), 23 cases of pneumothorax (2.3%), 20 of which (86.9%) required chest drainage, 10 cases of unsuccessful progression of the J-wire after the venepuncture (1%), 16 cases of catheter malposition (1.6%). As for the follow-up, 919 patients (95.0%) who had received 942 SIPs turned out to be suitable for long-term analysis, while 48 patients (5.0%) were excluded due to missing data. Seventy-seven SIPs (8.2%) were removed during the follow-up period, 13 of which received a second SIP. Long-term complications were recorded in 9.5% of the 942 SIPs, including mechanical complications (2.9%), infections (4.4%) and venous thrombosis (1.2%). Minor and major complication rates were 7.3% and 2.2% respectively. The overall incidence of SIP-related complications was 22.1%, including 44 major complications (4.5%) and 173 minor complications (17.6%). CONCLUSIONS: Given the low rate of major complications, SIPs should be considered safe and effective devices, representing the first choice approach for prolonged venous access. Blind placement technique performed by full-trained operators yields adequate success rate to be suggested as a routine procedure.

Arterial devices for regional hepatic chemotherapy: transaxillary versus laparotomic access.

Introduction. Intra-Arterial Hepatic Chemotherapy (IAHC) based on floxuridine (FUdR) infusion is an effective treatment for hepatic metastases from colorectal cancer. A percutaneously implanted intra-arterial device may overcome the surgical stress of the laparotomic placement allowing an increase in the number of patients treated by IAHC. The aim of the present study is the comparative analysis of surgical and percutaneous transaxillary approaches to implant the catheter into the hepatic artery (HA) for IAHC. Materials and Methods. Between September 1993 and February 1999, 56 patients received an implantable infu-sion system [SynchroMed(R) (Medtronic, USA) or Port-a-cath(R) (Deltec, USA) connected to an external infusion pump (CADD(R) , Deltec, USA)] for IAHC. Twenty-eight patients (LPT group) underwent laparotomy to implant the catheter into the HA, the other 28 patients (PCT group) received a percutaneous catheter into the HA through a transaxillary percutaneous access. Indications for the laparotomic placement were: 1) synchronous metastases not suitable [technically unresectable or large (>40% of liver parenchyma) or multiple (> 3) metas-tases] for hepatic resection during colorectal surgery; 2) metachronous metastases treated by radical hepatic resection and subsequent adjuvant IAHC. Indications for percutaneous placement were: 1) metachronous metastases not suitable [see above] for hepatic resection; 2) metachronous metastases suitable for hepatic resection after neoadjuvant IAHC for tumor downstaging. All patients received IAHC based on continuous infusion of FU-dR (dose escalation 0.15-0.30 mg/kg/day for 14 days every 28 days) plus dexamethasone 28 mg. For the purpose of the study, the LPT group and the PCT group were comparatively analyzed in terms of age, gender, primary diagnosis, vascular anatomy of HA, ligation/embolization of aberrant HA, previous intestinal or hepatic surgery, contextual systemic chemotherapy, concomitant diseases. Safety and efficacy of surgical and percutaneous transaxillary approaches were then comparatively analyzed in terms of number of IAHC cycles adminis-tered, device-related complications causing temporary or definitive suppression of IAHC, biological costs of the procedures (procedure-related complications, postoperative pain and hospitalization). LPT cases without concomitant surgical procedure other than catheter placement (Cath-LPT group - 10 cases) were also compared with the PCT group for the same end points of the study. Results. LPT group and PCT group were comparable (p=n.s.) when evaluated for all the above listed variables. As for the end points of the study, mean postoperative hospitalization was 8.2+/-2.2 days in the LPT group and 1.8+/-0.7 days in the PCT group (p<0.0001), while mean analgesic requirements were 9.7+/-3.2 doses in the LPT group and 2+/-0.9 doses in the PCT group (p<0.0001). Mean number of IAHC cycles administered was 6.5+/-4.2 in the LPT group and 4.3+/-3.4 in the PCT group (p=0.038). Device-related complications causing temporary or de-finitive suppression of IAHC included catheter displacement in 10 cases (35.7%), HA thrombosis in 1 case (3.5%) and catheter occlusion in 1 case (3.5%) in the PCT group, while in the LPT group 1 case (3.5%) of catheter occlusion and 1 case (3.5%) of HA thrombosis occurred. The overall incidence of device-related complications causing temporary or definitive suppression of IAHC was 42.7% in the PCT group and 7.1% in the LPT group (p=0.005). Comparison of Cath-LPT group and the PCT group showed mean postoperative hospitalization of 5.5+/-0.7 days in the Cath-LPT group and 1.8+/-0.7 days in the PCT group (p<0.0001), and mean anal-gesic requirements of 8+/-3.1 doses in the Cath-LPT group and 2+/-0.9 in the PCT group (p<0.0001). Conclusions. Surgically implanted indwelling catheters for IAHC present lower incidence of device-related complications than percutaneous transaxillary implanted catheters. In spite of its irreversibility and significant biological costs, surgical implant is still advised when laparotomy has to be performed for other contextual procedures, such as colorectal or hepatic resection, while percutaneous transaxillary catheter placement is indicated for palliative or neoadjuvant IAHC.

In vitro functional evidence of different neurotensin-receptors modulating the motor response of human colonic muscle strips.

1. The newly developed non-peptide neurotensin (NT)-receptor antagonists SR 48692 and SR 142948 were used to challenge NT responses of human colonic circular smooth muscle strips in vitro. The presence of NT1 and NT2 receptor transcripts in this tissue was tested by reverse transcriptase polymerase chain reaction (RT - PCR) analysis. 2. NT potently and dose-dependently contracted muscle strips, with significant regional differences in potency and efficacy between the transverse and distal colon: EC50, 3.6 and 7.5 nM; the maximal effect was 70 and 55% of 0.1 mM carbachol. Colonic responses to NT in both segments were virtually the same in the presence of atropine (1 microm), levocabastine (10 microM) or tetrodotoxin (1 microM). 3. SR 142948 (10 nM - 1 microM) competitively antagonized NT responses in the transverse and distal colon with similar affinities: pA2 values 8.71 and 8.45, slopes 0.98 and 0.99. SR 48692 (10 nM - 10 microM) antagonized the NT response competitively in the distal colon (pA2 6.55, slope 0.79) and non-competitively in the transverse colon (pA2 8.0, slope 0.51). Neither compound had any agonist effect. 4. The fact that the specific antagonists prevented NT-evoked atropine- and tetrodotoxin-insensitive mechanical responses of colonic muscle strips is highly consistent with the presence in these tissues of non-neuronal NT receptors, whose heterogeneity in the transverse segment is supported by the non-competitive antagonism of SR 48692. The finding of NT1 receptor transcript in both transverse and distal colon suggests its identity with the lower affinity site disclosed functionally by SR 48692 in these segments.