Pancreatic ductal adenocarcinoma and paraaortic lymph nodes metastases: The accuracy of intraoperative frozen section.

BACKGROUND: Pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) with paraaortic lymph nodes metastases (PALN +) is associated with poor survival. Still, there are no current guidelines advocating systematic detection of PALN+. METHODS: All consecutive patients who underwent surgical exploration/resection with concurrent paraaortic (group 16) lymphadenectomy for PDAC between 2009 and 2016 were considered for inclusion. Resection was systematically aborted in case of intraoperative PALN + detection. Diagnostic performance of preoperative imaging upon blind review and intraoperative PALN dissection with frozen section (FS) for PALN detection were evaluated. Additionally, the prognostic significance of PALN + on overall survival (OS) was analyzed. RESULTS: Over the study period, among 129 patients undergoing surgery for PDAC, 113 had intraoperative PALN dissection with FS analysis. Median number of resected PALN was 3 (range, 1-15). Overall, PALN+ was found in 19 patients (16.8%). Upon blind review, preoperative imaging performed poorly for PALN + detection with a low agreement between imaging and final pathology (Kappa-Cohen index<0.2). In contrast, PALN FS showed high detection performances and strong agreement with final pathology (Kappa-Cohen index = 0.783, 95%CI 0.779-0.867, p < 0.001). Regarding survival outcomes, there was no difference between patients with PALN+ and patients not resected in the setting of liver metastases or locally unresectable disease found at exploration (p = 0.708). CONCLUSIONS: Before PD for PDAC, intraoperative PALN dissection and FS analysis yields accurate PALN assessment and allows appropriate patient selection. This should be routinely performed and aborting resection should be strongly considered in case of PALN+.

B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia.

B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ITP and to support B cell differentiation and antiplatelet antibody-production may participate to RTX inefficiency. Whereas it is well established that the survival of TFH depends on B cells in animal models, nothing is known in humans yet. To determine the effect of B cell depletion on human TFH, we quantified B cells and TFH in the spleen and in the blood from ITP patients treated or not with RTX. We showed that B cell depletion led to a dramatic decrease in splenic TFH and in CXCL13 and IL-21, two cytokines predominantly produced by TFH. The absolute count of circulating TFH and serum CXCL13 also decreased after RTX treatment, whatever the therapeutic response. Therefore, we showed that the maintenance of TFH required B cells and that TFH are not involved in the inefficiency of RTX in ITP.

Immunologic effects of rituximab on the human spleen in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell-related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell depletion in the blood and a significant reduction in splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved in ITP pathogenesis, RTX-induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug.

Point on the Aortic Bicuspid Valve.

Background-Bicuspid aortic valve (BAV) disease is the most prevalent congenital heart disease in the world. Knowledge about its subtypes origin, development, and evolution is poor despite the frequency and the potential gravity of this condition. Its prognosis mostly depends on the risk of aortic aneurysm development with an increased risk of aortic dissection. Aims-This review aims to describe this complex pathology in way to improve the bicuspid patients' management. Study design-We reviewed the literature with MEDLINE and EMBASE databases using MeSH terms such as "bicuspid aortic valve", "ascending aorta", and "bicuspid classification". Results-There are various classifications. They depend on the criteria chosen by the authors to differentiate subtypes. Those criteria can be the number and position of the raphes, the cusps, the commissures, or their arrangements regarding coronary ostia. Sievers' classification is the reference. The phenotypic description of embryology revealed that all subtypes of BAV are the results of different embryological pathogenesis, and therefore, should be considered as distinct conditions. Their common development towards aortic dilatation is explained by the aortic media's pathological histology with cystic medial necrosis. At the opposite, BAV seems to display a profound genetic heterogeneity with both sporadic and familial forms. BAV can be even isolated or combined with other congenital malformations. Conclusions-All those characteristics make this pathology a highly complex condition that needs further genetic, embryological, and hemodynamic explorations to complete its well described anatomy.

Feasibility and Effectiveness of an Enhanced Recovery Program after Early Cholecystectomy for Acute Calculous Cholecystitis: A 2-Step Study.

BACKGROUND: Enhanced recovery programs (ERPs) are associated with a lower morbidity rate and a shorter length of stay. The present study's objective was to determine whether an ERP is feasible and effective for patients undergoing early cholecystectomy for grade I or II acute calculous cholecystitis. STUDY DESIGN: A 2-step multicenter study was performed. In the first step (the feasibility study), patients were consecutively included in a dedicated, prospective database from March 2019 until January 2020. The primary endpoint was the ERP's feasibility, evaluated in terms of the number and nature of the ERP components applied. During the second step, the ERP's effectiveness in acute calculous cholecystitis was evaluated in a case-control study. The ERP+ group comprised consecutive patients who were prospectively included from March 2019 to November 2020 and compared with a control (ERP-) group of patients extracted from the ABCAL randomized controlled trial treated between May 2010 and August 2012 and who had not participated in a dedicated ERP. RESULTS: During the feasibility study, 101 consecutive patients entered the ERP with 17 of the 20 ERP components applied. During the effectiveness study, 209 patients (ERP+ group) were compared with 414 patients (ERP- group). The median length of stay was significantly shorter in the ERP+ group (3.1 vs 5 days; p < 0.001). There were no intergroup differences in the severe morbidity rate, mortality rate, readmission rate, and reoperation rate. CONCLUSIONS: Implementation of an ERP after early cholecystectomy for acute calculous cholecystitis appeared to be feasible, effective, and safe for patients. The ERP significantly decreased the length of stay and did not increase the morbidity rate.

Abdominal and pelvic injuries caused by road traffic accidents: characteristics and outcomes in a French cohort of 2,009 casualties.

BACKGROUND: The frequency, characteristics, and effect on outcome of abdominal and pelvic injuries (API) caused by road traffic accidents are not well known. We studied them in a well-defined geographical area in France. METHODS: The medical data of all hospitalized victims of road traffic accidents that occurred over a 3-year period were recorded. Injuries were coded according to the Abbreviated Injury Scale (AIS). The Injury Severity Score (ISS) was calculated. Continuous and qualitative variables were described by means and standard deviations or medians and percentages, respectively. Proportions and means were compared using the χ2 and Student tests, respectively. RESULTS: Of 6,977 victims of road traffic accidents, 2,009 were hospitalized (mean ISS=7.9). API were present in 9.3% (n=186) of all hospitalized victims and in 32.2% (n=82) of the most severely injured (ISS≥16, n=255) hospitalized victims. The most frequently seriously injured abdominopelvic organs (AIS≥3) were the spleen, the retroperitoneal organs, and the liver. The mean ISS and the mortality rate were significantly higher for victims with API than those without API (17.5 vs. 6.9, P<0.001; 9.7% vs. 1.9%, P<0.001). In multivariate analysis, the presence of severe API increased the mortality rate by a factor of 2.5. CONCLUSIONS: In this study, API were present in one third of the most severely injured victims of road traffic accidents and were a significant factor of gravity and mortality. This study, conducted in France where there is no National Trauma Registry, underlined the need for establishing such registry.

CT-scan imaging of iron marked chorda tympani nerve: anatomical study and educational perspectives.

The chorda tympani nerve (CTN) is the last collateral branch of the facial nerve in its third intraosseous portion just over the stylomastoid foramen. After a curved course against the medial aspect of the tympanum where it is likely to be injured in middle ear surgery, CTN reaches the lingual nerve in the infratemporal fossa. Knowledge of CTN topographic anatomy is not easily achieved by the students because of the deep location of this thin structure. The aim of this study was to assess the spatial relationships of the CTN in the infratemporal fossa. Therefore, ten nerves were dissected in five fresh cadavers. All the nerves were catheterized with a 3/0 wire. After a meticulous repositioning of surrounding structures, standard X-ray and CT scan examinations were performed with multiplanar acquisitions and three-dimensional surface rendering reconstructions. Ventral projection of the CTN corresponded to the middle of the maxillary sinus. Lateral landmark was the mandibular condyle. The CTN was present and unique in all the dissections. The average length of the nerve, as measured on CT scans, was 31.8 mm (29-34, standard deviation of 1.62); the anastomosis of the CTN to the lingual nerve was located at a mean 24.9 mm below the skull base (24-27, standard deviation of 0.99), approximately in the same horizontal plane as the lower part of the mandibular notch. The acute angle opened dorsally and cranially between CTN and LN measured mean 63.2° (60-65, standard deviation of 1.67). Three-dimensional volumetric reconstructions using surface rendering technique provided realistic educational support at the students' disposal.

Lessons for the clinical nephrologist: a rare case of unfused renal ectopia.

Right crossed inferior unfused renal ectopia is a rare developmental anomaly in which both kidneys are located on the left side of the body. It's the result of a halt in migration of kidneys to their normal location during the embryonic period and in ureteral bud faulty that migrates to the opposite side and induces the metanephric blastema on the wrong side. In this article, we aim to review embryology and complete description of renal ectopia anatomy and describe a rare case of right crossed unfused inferior renal ectopia with a left lower kidney artery originated directly from an abdominal aortic aneurism (AAA). The treatment consisted in AAA's exclusion with a custom-made endograft device shaped on purpose with a dedicated branch allowing perfusion of the ectopic lower left kidney.

C-reactive protein is an early predictor of septic complications after elective colorectal surgery.

BACKGROUND: Nowadays, most patients who undergo colorectal surgery are discharged early. An early predictor of septic complications could avoid readmissions and decrease morbidity. CRP could be a good predictor allowing a safe discharge. METHODS: A prospective, observational study was conducted from November 2007 to October 2008. All patients who underwent elective colorectal surgery were included. Clinical (temperature, pulse, abdominal tenderness, bowel movements) and laboratory data (C-reactive protein, leukocyte count) were recorded and evaluated as early predictors of septic complications (namely, anastomotic leaks). All detected leaks were considered fistulas, independently of their clinical significance. Clinical and inflammatory parameters were analyzed with univariate and multivariate techniques; logistic regression was performed and areas under the receiver operating characteristic curve were compared. RESULTS: A total of 133 patients were included. The overall incidence of anastomotic leaks was 15.5% and mortality was 4.5%. C-reactive protein at postoperative days 2 and 4 was a good predictor of anastomotic leak (areas under the curve were 0.715 and 0.845, respectively) and other postoperative septic complications (areas under the curve were 0.804 and 0.787), showing the highest accuracy among clinical and laboratory data. A cutoff of 125 mg/l in the level of C-reactive protein at postoperative day 4 yielded a sensitivity of 81.8% and a negative predictive value of 95.8% for the detection of anastomotic leakage. CONCLUSIONS: C-reactive protein is a simple way to ensure a safe discharge from hospital after elective colorectal surgery. Patients with CRP values >125 mg/l on the fourth postoperative day should not be discharged.

A simple method to locate mandibular foramen: preliminary radiological study.

INTRODUCTION: The position of mandibular foramen is variable at the medial aspect of mandibular ramus. Nevertheless its location is useful for the oral and maxillofacial surgeon in orthognatic surgery, especially in vertical ramus osteotomy (VRO) procedure. The aim of our study is to analyse the position of mandibular foramen in order to provide simple and reliable surgical landmarks. MATERIALS AND METHODS: A radio-anatomical study was undertaken on normal mandibular panoramic X-ray examinations. Precise reproductions were outlined on tracing paper. Original orthonormal landmark was designed using posterior border of the ramus, mandibular incisure and anterior border of the ramus. All these elements are visible in the patient in VRO. Measurements of the position of mandibular foramen in horizontal and vertical dimensions were then performed with a ruler by two independent observers: l (width of mandibular branch), x (distance between posterior border of the ramus and mandibular foramen), h (height of mandibular branch) and y (distance between sigmoid notch and mandibular ramus). x/l and y/h ratios were calculated in order to minimise magnifications and image distortions due to the imaging process. RESULTS: Forty-six panoramic X-rays were analysed, including 24 male and 22 female specimens (sex-ratio 1.1/1) with the mean-age 21 years. In vertical dimension, y/h ratio was distributed on a gaussian mode with a peak around 0.30-0.35, mandibular foramen was located around the midpoint of the inferior two-thirds and the superior third of the ramus, preferentially under this point. In horizontal dimension, x/l ratio observed the same model with a peak around 0.35; mandibular foramen was located around the midpoint of the anterior two-thirds and the posterior third of the ramus, preferentially in front of this point. Mandibular foramen was situated in the ventral and inferior two-thirds of the ramus without difference according to the side, sex or age. DISCUSSION: Posterior and superior thirds of the ramus constitute a "safety zone" where mandibular foramen is unlikely to be found. This area can be used by the oral and maxillofacial surgeon in vertical ramus osteotomy of the mandible with low inferior alveolar nerve morbidity probability.

Arterial embolotherapy for endoscopically unmanageable acute gastroduodenal hemorrhage: predictors of early rebleeding.

BACKGROUND & AIMS: Severe bleeding from gastrointestinal ulcers is a life-threatening event that is difficult to manage when endoscopic treatment fails. Transcatheter embolization has been proposed but factors that influence the angiographic outcome are not well documented. We aimed to identify predictors of recurrent bleeding within 30 days after transcatheter embolization for refractory hemorrhage from gastroduodenal ulcers. METHODS: This retrospective single-center study of 60 consecutive emergency embolization procedures included hemodynamically unstable patients (41 men, 19 women; mean age, 69.4 +/- 15 y), referred from 1999 to 2008 for selective angiography after failed endoscopic treatment. Predictors of early rebleeding were tested with univariate analysis and a multivariate logistic regression model. RESULTS: The procedural success rate was 95%, the primary clinical success rate was 71.9% (41 of 57), and secondary clinical success was achieved in 3 patients (77.2%) after repeat embolization. No major catheterization-related complications occurred. Periprocedural mortality was 26.7% (16 of 60). Early bleeding recurrence was associated with coagulation disorders (P = .007), longer time to angiography (P = .0005), greater preprocedural blood transfusion volume (P = .0009), 2 or more comorbidities (P = .005), and use of only coils (P = .003). Two factors were independent predictors of embolization failure: coagulation disorders (odds ratio, 6.18; P = .027) and the use of coils as the only embolic agent (odds ratio, 6.24; P = .022). The median follow-up time was 7 months (range, 1 day to 103 months). CONCLUSIONS: Angiographic embolization should be performed early in the course of bleeding, and not with coils alone, in critically ill patients. It is important to correct coagulation disorders throughout the embolization procedure.

Incidence, patterns of failure, and prognosis of perforated colorectal cancers in a well-defined population.

INTRODUCTION: Few population-based studies investigate perforated colorectal cancers. This study was designed to compare the epidemiologic characteristics of perforated CRC with those of uncomplicated CRC and to determine patterns of failure and prognosis in a well-defined French population. METHODS: Between 1976 and 2000, 89 patients who received an emergency operation caused by perforation and 5,462 who underwent elective surgery were registered in the digestive cancer registry of Burgundy (France). RESULTS: Perforated colorectal cancers represented 1.6 percent of registered colorectal cancers. The five-year cumulative local recurrence rate was higher for perforated (15.7 percent) than for uncomplicated cancers (7.8 percent; P = 0.021), as well as for the peritoneal carcinomatosis rate (respectively 13.8 and 6.3 percent; P = 0.036). In multivariate analysis, perforation was an independent risk factor for local recurrence or peritoneal carcinomatosis (odds ratio, 2.17; P = 0.004). Operative mortality was higher among perforated cancers (20.2 percent) than after elective surgery (6.6 percent, P < 0.001). The five-year relative survival rates were 37 percent after emergency surgery and 49.2 percent after elective surgery (P = 0.036). After adjustment for sex, stage, and age, perforation remained significantly associated with a poor prognosis. After exclusion of operative mortality, perforation was no more significant. CONCLUSIONS: Perforation is a rare complication of colorectal cancer. The prognosis is poor because of high operative mortality and high risk of local recurrence and peritoneal carcinomatosis.

Short- and long-term results of transcatheter embolization for massive arterial hemorrhage from gastroduodenal ulcers not controlled by endoscopic hemostasis.

BACKGROUND AND AIM: Severe bleeding from gastrointestinal ulcers is a life-threatening event that is difficult to manage when endoscopic treatment fails. Transcatheter embolization has been suggested as an alternative treatment in this situation. The present study reports on the efficacy and long-term outcomes of transcatheter embolization after failed endoscopic treatments were assessed in high operative- risk patients. METHODS: A retrospective review of 60 consecutive emergency embolization procedures in hemodynamically unstable patients (41 men, 19 women; mean [+/-SD] age 69.4+/-15 years) was conducted. Patients were referred for selective angiography between 1999 and 2008 after failed endoscopic treatment of massive bleeding from gastrointestinal ulcers. Mean follow-up was 22 months. RESULTS: Embolization was feasible and successful in 57 patients. Sandwich coiling of the gastroduodenal artery was used in 34 patients, and superselective occlusion of the terminal feeding artery (with glue, coils or gelatin particles) was used in 23 patients. Early rebleeding occurred in 16 patients and was managed with endoscopy (n=8), reembolization (n=3) or surgery (n=5). No major embolization-related complications occurred. Sixteen patients died within 30 days after embolization (including three who died from rebleeding) and 11 died thereafter. No late bleeding recurrences were reported. CONCLUSIONS: Selective angiographic embolization is safe and effective for controlling life-threatening bleeding from gastroduodenal ulcers. The procedure usually obviates the need for emergency surgery in these high-risk patients. Survival depends chiefly on underlying conditions.

Comparison of the biomechanical behavior of the liver during frontal and lateral deceleration.

BACKGROUND: The trunk of a car occupant can be injured by a frontal or lateral impact. Lesions can be either intrusion injuries or due to the effects of deceleration alone. The aim of this study conducted with human cadavers was to explore the effects of deceleration on the liver during frontal or lateral deceleration. METHODS: Trunks previously instrumented with accelerometers in three sites, the left and right lobes of the liver and the retrohepatic inferior vena cava, were subjected to substantial deceleration in three orientations: frontal, left, and right lateral. The anatomic consequences and deceleration data were measured. A deceleration ratio was defined as a peak deceleration measured in the liver divided by peak deceleration imposed on the trunk. RESULTS: Peak deceleration imposed on the trunks was up to 60 g, which caused peak deceleration up to 26 g in the liver. No anatomic injury was observed. For each orientation, deceleration ratios were not significantly different among the three sites (p = 0.64) or between left and right lateral decelerations (p = 0.12). Deceleration ratios were significantly different (p = 0.001) between frontal (3 sites combined) and lateral (3 sites of left and right lateral orientations combined) decelerations: 39.4% (+/-6) versus 48.4% (+/-11). CONCLUSIONS: In conclusion, at tested decelerations, under the hepatic injury threshold, cadaveric liver seemed to be subjected to higher deceleration when the trunk was decelerated in lateral than in frontal direction, without terminal impact.

Spatial relationships between lingual nerve and mandibular ramus: original study method, clinical and educational applications.

Lingual nerve damage complicating oral surgery would sometimes require electrographic exploration. Nevertheless, direct recording of conduction in lingual nerve requires its puncture at the foramen ovale. This method is too dangerous to be practiced routinely in these diagnostic indications. The aim of our study was to assess spatial relationships between lingual nerve and mandibular ramus in the infratemporal fossa using an original technique. Therefore, ten lingual nerves were dissected on five fresh cadavers. All the nerves were catheterized with a 3/0 wire. After meticulous repositioning of the nerve and medial pterygoid muscle reinsertion, CT-scan examinations were performed with planar acquisitions and three-dimensional reconstructions. Localization of lingual nerve in the infratemporal fossa was assessed successively at the level of the sigmoid notch of the mandible, lingula and third molar. At the level of the lingula, lingual nerve was far from the maxillary vessels; mean distance between the nerve and the anterior border of the ramus was 19.6 mm. The posteriorly opened angle between the medial side of the ramus and the line joining the lingual nerve and the anterior border of the ramus measured 17 degrees . According to these findings, we suggest that the lingual nerve might be reached through the intra-oral puncture at the intermaxillary commissure; therefore, we modify the inferior alveolar nerve block technique to propose a safe and reproducible protocol likely to be performed routinely as electrographic exploration of the lingual nerve. What is more, this original study protocol provided interesting educational materials and could be developed for the conception of realistic 3D virtual anatomy supports.

Closed hyperthermic intraperitoneal chemotherapy with open abdomen: a novel technique to reduce exposure of the surgical team to chemotherapy drugs.

BACKGROUND: Exposure of the surgical team to toxic drugs during hyperthermic intraperitoneal chemotherapy (HIPEC) remains a matter of great concern. During closed-abdomen HIPEC, operating room staff are not exposed to drugs, but the distribution of the heated liquid within the abdomen is not optimal. With open-abdomen HIPEC, the opposite is true. Although the open-abdomen method is potentially more effective, it has not become a standard procedure because of the risk of exposure of members of the team to drugs. METHODS: We present a new technique (closed HIPEC with open abdomen) which ensures protection against potentially contaminating exposure to liquids, vapours and aerosols, and allows permanent access to the whole abdominal cavity. Its principle is to extend the abdominal surgical wound upwards with a sort of "glove-box". The cutaneous edges of the laparotomy are stapled to a latex "wall expander". The expander is draped over a special L-section metal frame placed above the abdomen. A transparent cover containing a "hand-access" port, like those used in laparoscopic surgery, is fixed inside the frame. RESULTS: In 10 patients, this device proved to be hermetic for both liquids and vapours. Intra-abdominal temperature was maintained between 42 and 43 degrees C during most of the procedure. The whole abdominal cavity was accessible to the surgeon, allowing optimal exposure of all peritoneal surfaces. CONCLUSION: This technique allows optimal HIPEC, while limiting the potential toxic effects for the surgical, medical and paramedical teams.

Transcatheter arterial embolization of splenic artery aneurysms and pseudoaneurysms: short- and long-term results.

We evaluated outcomes of endovascular treatment of splenic artery aneurysms and pseudoaneurysms. From April 2002 to May 2007, 17 patients (mean age 55.2 years, range 17-82) with splenic artery aneurysms (n = 7) or pseudoaneurysms (n = 10) underwent endovascular treatment. Six patients were asymptomatic, three had symptomatic nonruptured aneurysms, and eight had ruptured aneurysms. Lesions were in the proximal splenic artery (n = 5), intermediate splenic artery (n = 3), splenic hilum (n = 6), or parenchyma (n = 3). Embolization was with microcoils by sac packing (n = 8), sandwich occlusion of the main splenic artery (n = 4), or cyanoacrylate glue into the feeding artery (n = 4). Computed angiotomography was done within the first month and magnetic resonance angiography after 6 and 12 months, then yearly. Mean follow-up was 29 months (range 1-62). Exclusion of the aneurysm was achieved in 16 (94.1%) patients. One patient with an intraparenchymal pseudoaneurysm underwent splenectomy after failed distal catheterization. No major complications occurred. Postembolization syndrome developed in four patients, who had radiographic evidence of splenic microinfarcts. Transcatheter embolization of splenic artery aneurysms/pseudoaneurysms is safe and effective and may induce less morbidity than open surgery, in particular by preserving the spleen. Coil artifacts may make magnetic resonance angiography preferable over computed tomography for follow-up.

Attempts to improve locoregional chemotherapy for the prevention of colonic cancer liver metastasis in the rat.

AIM OF THE STUDY: To improve prophylactic local treatment of hepatic metastasis from colonic cancer cells in the rat. METHODS: The in vitro anticancer activity of 30 mn exposure to different drugs was first evaluated by dimethyl-thiazol-diphenyl-tetrazolium-bromide assay on confluent DHD/K12/PROb rat and HT29 human colonic cancer cells. Hepatic metastasis was induced by portal vein infusion of 12 x 106 PROb colonic cancer cells in syngenic BDIX rats. Hepatic and general tolerance to epirubicin was studied. Rats were treated with epirubicin delivered by either intravenous (IV), intraperitoneal (IP) or intraportal (Ipo) administration to compare their antitumoral effects. Hepatic distribution of epirubicin was assessed by fluorescence microscopy after IV, IP, Ipo, and combined administration. High pressure liquid chromatography was used to measure hepatic concentrations of epirubicin. RESULTS: Only pirarubicin was fully cytotoxic in vitro against the two types of tumor cells. No general or hepatic toxicity was observed. The preventive effect on hepatic metastasis was similar for IV, IP, and Ipo pirarubicin treatments. Hepatic pirarubicin concentrations obtained by Ipo administration were 4.1-fold higher than those obtained after IV administration (P=0.013). Three hours after IP and Ipo administration, hepatic remnants of pirarubicin were similar and significantly higher that those obtained after IV administration (P=0.074). Clamping the hepatic vein doubled hepatic pirarubicin concentrations after Ipo administration (P=0.048). Combined hepatic and intraportal administration was necessary to achieve diffuse, intense and homogeneous fluorescence throughout the entire liver. CONCLUSION: Homogeneous hepatic diffusion of pirarubicin was successfully achieved with combined hepatic vein and intraportal administration but systemic, intraperitoneal or intraportal administration had no preventive effect on hepatic metastasis. Other drugs could be tested using this approach to evaluate their efficacy and toxicity.