Traumatic avulsion of the intrapancreatic common bile duct: case report.

Injuries of the extra hepatic biliary tree following blunt trauma to the abdomen are rare. We present a case of avulsion of the intrapancreatic common bile duct. Very often the lesion is not identifiable until the signs of jaundice and biliary ascites occur. Intraoperative cholangiography is mandatory for the diagnosis, but the noninvasive magnetic resonance cholangiopancreatography could readily depict the injury of the extrahepatic bile duct preoperatively. When the diagnosis is late the corner stone of treatment is biliary diversion and definitive repair after complete resolution of sepsis with a choledochojejunostomy.

EGFR in colorectal cancer: more than a simple receptor.

BACKGROUND: Advances in the understanding of tumor biology have led to the development of targeted therapies allowing progress in colorectal cancer treatment. One of the most promising targets is the epidermal growth factor receptor (EGFR). METHOD: The presence and distribution of high- and low-affinity EGFR was investigated retrospectively in a group of 82 colorectal cancer samples (43 normal colon-colon cancer paired samples) using a specific ligand binding assay (Scatchard Analysis). FINDINGS: A large majority of tumor samples exhibited one class of high-affinity binding sites (78%). Eighteen cases (22%) exhibited both high- and low-affinity binding sites. A wide interpatient variability was observed for the site number, with physiologically-relevant high-affinity sites ranging from 7 to 310 fmol/mg protein in tumors and from 6 to 313 fmol/mg protein in normal mucosa. A significant positive correlation was demonstrated between tumor and normal mucosa for the high-affinity Kd values and for the number of high-affinity sites, suggesting a common regulation for both tumor and normal tissue. INTERPRETATION: These observations (i) could explain recently-reported clinically-active EGFR targeting in colorectal tumors apparently negative for EGFR, and (ii) may offer a plausible explanation for the link observed between toxicity in normal tissue (cutaneous rash) and clinical outcome of patients treated with anti-EGFR drugs. Present data extends our understanding of EGFR identity in colorectal cancer which could be useful in reconsidering the predictive tools for the identification of tumors putatively responsive to EGFR targeted therapy.

Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications.

BACKGROUND: Epidermal growth factor receptor (EGFR) plays an important role in the pathogenesis of colorectal cancer (CRC). There are several potential strategies to target EGFR. However, monoclonal antibodies and low molecular weight tyrosine kinase inhibitors are the most advanced in clinical development. The majority of studies so far have merely required EGFRs to be expressed by CRC cells. The detection of EGFR expression is usually performed by immunohistochemistry (IHC) in the primary tumor. There are few data regarding the EGFR status in the corresponding distant metastases. PATIENTS AND METHODS: EGFR status was analyzed by IHC in 80 patients (31 male, 49 female) with CRC (70 colon, 10 rectum) and at least one distant metastatic lesion. Metastatic sites analyzed (n=80) were liver (79 patients) and lung (one patient). RESULTS: EGFR reactivity was similar in the primary tumor and the related metastases. Among the 80 paired primary/metastatic tumors, only five (6.3%) showed discordance in EGFR status: two cases with EGFR expression in the primary tumor but not in the metastasis, and three samples with EGFR expression in the metastasis but not in the primary tumor. CONCLUSIONS: Between the paired primary tumors and distant metastatic lesions, 94% of samples had concordant EGFR status when analyzed by IHC.

[Rupture of a pancreaticoduodenal artery aneurysm with median arcuate ligament syndrome: report of a case]. / Rupture d'un anévrisme des arcades duodénopancréatiques associé à une sténose du tronc coeliaque: à propos d'un cas.

Aneurysms of pancreaticoduodenal arteries represent only 2% of all aneurysms of digestive arteries. Occurrence of these aneurysms are favoured by stenosis or occlusion of the celiac axis. Aneurysm rupture is frequent and carries a mortality rate of 20%. Computed tomography with intravenous contrast and selective coeliomesenteric arteriography can make the diagnosis of this disease which can be treated by either surgery or embolotherapy. We report the case of a patient with a ruptured aneurysm of the pancreaticoduodenal arcades mimicking a perforated duodenal ulcer, and successfully treated by surgical ligation.

Anatomy of the presacral venous plexus: implications for rectal surgery.

The presacral venous plexus results from anastomoses between the lateral and median sacral veins, and courses into the pelvic fascia covering the anterior aspect of the body of the sacrum. The presacral venous plexus is not directly visible during rectal surgery, and injuries to this plexus may be life-threatening. Dissection of the retrorectal plane or anchoring of the rectum to the sacral promontory as in rectal prolapse surgery exposes the patient to the risk of injury to the presacral venous plexus. The aim of this study was to identify some avascular areas in the anterior aspect of the sacrum in order to lower the occurrence of such injuries during rectal surgery. The pelvis of 10 fresh cadavers was dissected after injection of a colored resin into the inferior vena cava, and the presacral venous plexus was studied. Four avascular tetragonal areas were common to all the specimens. The corners of a square with a side of 3 cm, centered on the anterior aspect of the body of sacrum, were always contained in the avascular areas. The upper side of this square was parallel to a line passing through the sacral promontory, at a 3 cm distance from it. Staples or sutures should be placed in the avascular areas to avoid injuries to the presacral venous plexus.

[Colostomy vs self-expanding metallic stents: comparison of the two techniques in acute tumoral left colonic obstruction]. / Colostomie de décharge vs endoprothèse colique autoexpansive: comparaison des deux techniques dans l'occlusion colique gauche aiguë par obstacle tumoral.

UNLABELLED: Self-expanding metallic stents is an alternative treatment to colostomy that is the treatment of choice in acute tumoral left colonic obstruction. AIM OF THE STUDY: To compare morbidity, mortality, length of hospital stay and treatment performed after desobstruction using the two methods. PATIENTS AND METHODS: Thirty-three patients admitted for acute obstruction of the left colon were retrospectively separated in two groups depending on the type of intervention performed to treat the obstruction ("colostomy" group: 17 patients and "self-expanding stent group": 16 patients). We studied complications after desobstruction, hospital courses and surgical strategy performed after the acute phase. RESULTS: Time between desobstruction and colectomy was shorter in the "self-expanding stent group" than in the "colostomy group" (18.5 days versus 73 days). Age superior than 75 years and colostomy were the two main factors predicting the risk of definitive colostomy (P < 0.05). Global mean hospital stay was longer in the colostomy group (32.7 days versus 19.3 days, P = 0.02). Two perforations and one local recurrence occurred in the "self-expanding stent group". CONCLUSIONS: Self-expanding metallic stent can decrease the permanent colostomy rate and the number of interventions. The recurrence rate seems to be theoretically increased with the stenting method. Then, colostomy must be done for patients in curative situation. The self-expanding metallic stent should be used as a palliative care.

Anatomical study of the blood supply of the coxal bone: radiological and clinical application.

The aim of this work was to study the arterial blood supply of the coxal bone in order to optimize radiological embolization and to minimize the risk of postoperative osteonecrosis. Ten fresh cadavers were dissected after intra-arterial injection of colored resin. All the collateral vessels running to this bone were described and counted. On 25 dry bones, the vascular foramina were measured with the aid of a millimetric gauge and a vascular map was created. The posterior part of the ilium appears to be twice as well vascularized as the anterior part. Fractures of the posterior arch of the pelvis are theoretically more hemorrhagic. The presence of the iliolumbar artery in contact with the sacroiliac joint increases the risk with open book or shearing fractures. The artery of the ischium, a collateral of the pudendal artery, supplies the posterior and lateral parts of the acetabulum and the artery of the roof of the acetabulum, its superior and lateral parts. The branches of the anterior and posterior divisions of the obturator artery supply the superior part of the surroundings of the obturator foramen and the antero-inferior and postero-inferior parts of the acetabulum. The Kocher approach may injure the artery of the ischium. Letournel's extended lateral approach and Mears' triradiate approach may injure the artery of the ischium and the artery of the roof of the acetabulum. The risk of osteonecrosis appears to be theoretically increased if one adds an endopelvic approach. The anterior approach to the acetabulum appears to be that which theoretically leads to the least devascularization. The French version of this article is available in the form of electronic supplementary material and can be obtained by using the Springer Link server located at http://dx.doi.org/10.1007/s00276-002-0029-2.

[Treatement of colorectal obstruction with self-expanding metallic stents under fluoroscopic guidance]. / Traitement de l'occlusion colique tissulaire par prothèse métallique auto-expansible sous contrôle fluoroscopique.

PURPOSE: To prospectively evaluate fluoroscopic-assisted insertion of self-expanding metallic stents before surgery or for palliative treatment of soft tissue colorectal obstruction. Materials and methods. From January 1999 to October 2000, 18 consecutive patients with colorectal obstruction were included in the study. Treatment with self-expanding metallic stent was either the first line of treatment before surgery (n=8) (group I) or purely palliative (n=10) (group II). Colic stenosis was located proximal to the sigmoid in seven cases. RESULTS: Technical success was achieved in 83.3% of cases and colic decompression was observed after 48 hours in all patients with a stent. Thirty days mortality and stent related complications were respectively 0% and 37.5% for group I, and 20% and 50% for group II. All complications were minor except for one colic perforation by a guidewire. CONCLUSION: Stent insertion was effective and provided relief of colic obstruction in the majority of cases. Randomized studies would be necessary to demonstrate a definitive reduction in mortality and morbidity with this technique as compared to the classical surgical approach.

Subcutaneous or intrahepatic injection of suicide gene modified tumour cells induces a systemic antitumour response in a metastatic model of colon carcinoma in rats.

BACKGROUND: Suicide gene therapy consists of the transfer into tumour cells of a "suicide" gene that can convert a non-toxic compound into a lethal drug. Expression of the cytosine deaminase gene leads to the conversion of the non-toxic compound 5-fluorocytosine to 5-fluorouracil. We have recently shown that "suicide cell based vaccination" consisting of intrahepatic injection of cytosine deaminase expressing colon cancer cells followed by 5-fluorocytosine treatment induces regression of a distant wild-type liver tumour in rats. AIMS: This study was conducted to test if (i) a distant bystander effect on a liver tumour can be induced after subcutaneous suicide cell based vaccination and (ii) suicide cell based vaccination is efficient in limiting tumour dissemination to extrahepatic compartments. METHODS: An aggressive variant of rat colon carcinoma cells was selected after successive passages in vitro. Rats carrying an experimental liver "metastasis" generated by injection of these cells were vaccinated by subcapsular or subcutaneous injection of cytosine deaminase expressing cells followed by 5-fluorocytosine treatment. RESULTS: Subcutaneous and subcapsular vaccination induced 70% regression in the median volume of the pre-established liver tumour (p=0.001) and abolished tumour dissemination compared with control animals. CONCLUSIONS: This study has compared for the first time the efficiency of subcutaneous and intrahepatic suicide cell based vaccination in a metastatic colorectal carcinoma model in rats. The results indicate that both modes of vaccination are equally efficient in inducing a systemic antitumour response, suggesting that this strategy is a powerful approach against the development and dissemination of metastatic colon carcinoma.

Determination of microsatellite instability, p53 and K-RAS mutations in hepatic metastases from patients with colorectal cancer: relationship with response to 5-fluorouracil and survival.

In vitro and clinical studies have suggested that high-frequency microsatellite instability (MSI-H) phenotype, p53 and K-ras mutations might influence the response to chemotherapy in a variety of tumors, including primary colorectal cancers (CRC). Unresectable hepatic metastases from CRC are commonly treated with 5-fluorouracil (5FU) and folinic acid. Since several new active drugs are now used for treating CRC, molecular determinants predictive to response to 5FU would thus be crucial for optimizing indications of chemotherapy to those patients. MSI-H phenotype, p53 and K-ras status were characterized in a prospective study of 56 patients with CRC metastatic to the liver and treated with 5FU-based chemotherapy. The objective response rate after a 3-month treatment was 32.1%. The prevalence of p53 mutations, K-ras mutations and MSI-H phenotype was 62.5%, 30.3% and 1.8%, respectively. No significant association was found between response to chemotherapy and p53 mutations (78% mutated tumors in responders vs. 55% in nonresponders; p = 0.10) and K-ras mutations (39% mutated tumors in responders vs. 26% in nonresponders; p = 0.34). Survival was longer for patients with p53-mutated metastases than for patients with unresected wild-type p53 metastases (median survival 15 months vs. 17 months; p = 0.06). The determination of the MSI-H phenotype, p53 and K-ras status in hepatic metastases from CRC does not discriminate a group of patients that should preferentially benefit from 5FU-based chemotherapy. The prognosis of patients with treated liver metastases is better when p53 is mutated.

[Vaccination by suicide gene therapy against a model of hepatic metastasis from colon cancer in the rat]. / Vaccination par thérapie génique suicide contre un modèle de métastases hépatiques de cancer colique chez le rat.

UNLABELLED: Suicide gene therapy consists of transferring into tumor cells a viral or bacterial gene encoding for an enzyme which converts a non-toxic product into a lethal drug. STUDY AIM: To analyze the therapeutic potential of vaccination with tumor cells expressing the bacterial cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) treatment in a rat liver metastasis model. MATERIAL AND METHOD: We used a rat colon carcinoma cell line which, after subcapsular or intraportal injection in syngenic animals, generates single or multiple experimental liver metastases, respectively. We have shown that introduction of a vector expressing the CD gene in this colon carcinoma cell line results in 5-FC sensitivity (PRObCD). RESULTS: Intrahepatic subcapsular injection of PRObCD tumor cells, followed by 5-FC treatment, induces total regression of a wild-type tumor pre-established in the contralateral liver lobe in 45% of animals with a 96% decrease in mean volume (p < 0.0001), demonstrating the existence of a distant bystander effect. This vaccination significantly increased the survival of rats with single (log-rank p < 0.0001) or multiple (log-rank p = 0.01) liver metastasis CONCLUSIONS: These results suggest that suicide gene-modified tumor cells can act as potent therapeutic vaccines against liver metastasis from colon carcinoma.

Characterization of centromere alterations in liposarcomas.

Supernumerary ring and large marker chromosomes are a characteristic of atypical lipomas and well-differentiated liposarcomas (ALP-WDLPS) and are composed of amplified 12q14-15 sequences in association with variable segments from other chromosomes. Although stably transmitted, these chromosomes contain centromeric alterations, showing no detectable alpha-satellite sequences. We performed C-banding, fluorescence in situ hybridization, and immunostaining with anti-centromere antibodies in 8 cases of liposarcomas with supernumerary rings and large markers, including 5 ALP-WDLPS and 3 dedifferentiated-LPS and high-grade LPS. Our results with alpha-satellite probes and anti-CENPB antibodies confirm the lack of detectable alpha-satellite sequences in the five ALP-WDLPS supernumerary chromosomes, whereas centromeric activity was proved by the detection of kinetochores by using anti-CENPC antibodies. In contrast, the high grade and dedifferentiated liposarcomas showed a different pattern. In 2 cases, amplified chromosome 12 sequences, including amplification of alpha-satellite 12 sequences in 1 case, were present on chromosomes with typical centromeres. In another case, the rings were similar to WDLPS-ALP rings, but a large marker contained a chromosome 5 centromere and amplified alpha-satellite sequences from chromosome 8. ALP-WDLPS is the first example of a tumor class for which the presence of stable analphoid chromosomes is a constant and specific abnormality. Formation of newly derived centromeres, so-called neocentromeres, could be an original and effective way to maintain a selective advantage in neoplastic cells by conferring stability to the supernumerary chromosomes of ALP-WDLPS. The activation of normally non-centromeric sequences might be obtained by an epigenetic mechanism due to the peculiar chromatin conformation of these highly complex chromosomes.

Lumbar artery compression by the diaphragmatic crus: a new etiology for spinal cord ischemia.

We describe a new cause of spinal cord ischemia illustrated by two cases--compression by the diaphragmatic crus of a lumbar artery giving rise to a spinal artery. The diagnosis has been established by dynamic spinal angiography, showing complete occlusion of the lumbar artery. Surgical section of the diaphragmatic crus prevents irreversible infarction.

Regression of experimental liver tumor after distant intra-hepatic injection of cytosine deaminase-expressing tumor cells and 5-fluorocytosine treatment.

Cytosine deaminase (CD) gene of E. coli converts the non-toxic compound 5-fluorocytosine (5-FC) into 5-fluorouracil. We have introduced a vector expressing the CD gene in a rat colon carcinoma cell line. Expression of the CD gene confers 5-FC sensitivity to these cells in vitro and in vivo. In a bifocal model consisting in a simultaneous engrafment of a CD+ tumor on one lobe of the liver and a wild-type parental tumor on the opposite lobe, treatment with 5-FC results in regression of both type of tumors, indicating the existence of a distant bystander effect.

Endoscopic management of sump syndrome after choledochoduodenostomy: retrospective analysis of 30 cases.

BACKGROUND: Side-to-side choledochoduodenostomy is a frequently performed operation. Postoperative biliary "sump syndrome" is infrequent, a complication for which endoscopic sphincterotomy is regarded as the treatment of choice. METHODS: We retrospectively analyzed 30 cases of sump syndrome and describe the symptoms, the delay before the appearance of symptoms, laboratory abnormalities, the nature of the biliary obstruction, and the outcome of endoscopic sphincterotomy including its efficiency and complications. RESULTS: The median clinical latency was 5 years (range 1 month to 28 years), the median delay between surgery and diagnosis was 6 years (range 1 month to 28 years). Fourteen patients had abdominal pain with fever, 5 had isolated abdominal pain, 4 had post-prandial pain, 4 had hepatic abscesses, and 3 had acute pancreatitis. Liver function tests were abnormal in 79%. During endoscopic retrograde cholangiopancreatography, food debris was identified in 18 patients in the biliary sump, biliary calculi in 10 patients, and a mixture of food and calculi in 2 patients. All patients underwent endoscopic sphincterotomy without complication. Recurrence during a median follow-up of 36 months (range 3 months to 11 years) was not observed. CONCLUSIONS: Sump syndrome most often becomes symptomatic only after a long delay. Abdominal pain with fever was the most frequent symptom. Liver function tests were abnormal in the majority of patients. Food debris was the most frequent cause. Endoscopic sphincterotomy appeared to be a safe, reliable treatment.

Ursodeoxycholic acid modulates cyclosporin A oral absorption in liver transplant recipients.

The aim was to study the ursodeoxycholic acid (UDC) effect on the cyclosporin A (CsA) pharmacokinetics after oral administration of the microemulsion formulation Neoral (CsA-ME) in liver transplant recipients, and test the potential protective effect of this bile acid on liver and renal CsA-ME-induced toxicity. At entry into the study, 12 patients who underwent orthotopic liver transplantation received CsA-ME, for at least 6 months. They then received a cotreatment CsA-ME plus UDC (13.8 mg x kg(-1) x day(-1)) for three months. Blood concentrations of CsA were measured using a monoclonal antibody specific for the parent compound. The kinetic data were analysed by a mathematical model incorporating a time dependent rate coefficient for CsA intestinal absorption, before and after UDC treatment. Changes in serum markers of hepatic and renal injury were assessed. Individual serum bile acids were determined by chromatography. Serum levels of UDC increased from 3 to about 45% of total serum bile acids after UDC treatment. The estimated model parameters indicate that UDC administration modulates CsA intestinal absorption. In the nine non-cholestatic patients, UDC reduced the absorption rate and the bioavailability of CsA without modifying the elimination rate constant of CsA and the CsA pre-drug levels. In contrast, in the three cholestatic patients, the bioavailability tended to be higher and the absorption rate faster when CsA was combined with UDC. UDC significantly decreased elevated gamma-glutamyl transferase and creatinine serum levels and induced some clinical improvements such as disappearance of headaches in four patients. In conclusion, a 3-month UDC treatment modifies CsA intestinal absorption without affecting CsA elimination rate constant. On the other hand, UDC supplementation appears to improve CsA tolerability.

[Endometriosis of the rectus abdominis muscles]. / Endométriose des muscles grands droits de l'abdomen.

The authors report three cases of endometriosis of the rectus abdominis muscle, presenting as a mass of the abdominal wall associated with pain during menstruation in women with a history of cesarean section. Treatment consisted in wide surgical resection followed by prosthetic abdominal wall repair in one recurrent case. Abdominal wall endometriosis is a rare disease that can be explained by grafting of endometrial cells to the abdominal wall during laparotomy for pelvic surgery, particularly cesarean section. Isolation of the abdominal wall during cesarean section and irrigation of the abdominal wall at the end of the operation are two theoretical measures designed to prevent endometrial cell engraftment. When abdominal wall endometriosis occurs, only radical surgical resection can prevent recurrence.