Biomedical subjects

J P Campion

Publications and source records attributed to J P Campion.

At least 19 recordsLinked to original sources

PubMed2005

Laparoscopic rectopexy for full-thickness rectal prolapse: a single-institution retrospective study evaluating surgical outcome.

BACKGROUND: The laparoscopic approach promises to become the gold standard for the transabdominal management of full-thickness rectal prolapse. The aim of this study was to review our experience and to highlight the functional results achieved with this new technique. METHODS: Forty-eight patients with full-thickness external prolapse underwent laparoscopic repair between February 1997 and February 2003. All patients underwent preoperative evaluation of their rectal function. Patients with isolated rectal ulcer without prolapse or with internal prolapse and patients deemed by the anesthesiologist to be unfit for general anesthesia were excluded from the study. The laparoscopic technique was either a mesh rectopexy without resection (n = 35) or a suture rectopexy with sigmoid resection (n = 13). Patients with intractable constipation preceding the development of the rectal prolapse were advised to have a resection-rectopexy. In the postoperative follow-up, attention was paid to mortality, morbidity, recurrent prolapse, incontinence, and constipation. Follow-up was done by clinical review and postal questionnaire. RESULTS: There were no deaths and no septic or anastomotic complications. The postoperative morbidity rate was 5%. Oral intake was started on postoperative day 1. Discharge from the hospital was on postoperative day 4 in patients without sigmoid resection and on postoperative day 7 in patients with sigmoid resection. Two patients (4%) developed recurrent total prolapse during a median follow-up period of 36 +/- 15 months (range, 7-77). The functional results were good or excellent in 72% of the cases, without digitations or dyschesia. Continence was improved in 31% of the patients and remains unchanged in 64% of them. In 11 patients (23%), constipation was worsened by the procedure. CONCLUSION: Laparoscopic rectopexy with or without resection is both safe and effective. Advantages include low-morbidity, improved cosmesis, the rapid return of intestinal function, early discharge from hospital, and a low recurrence rate. The fecal continence score is improved; however, constipation is frequently worsened.

Adolescent↗

PubMed2005

[Laparoscopic rectal excision for cancer using total mesorectaol excision (TME). Long term outcome of a series of 179 patients].

BACKGROUND: The purpose of this study was to evaluate the outcomes and the five-year survival of 179 consecutive patients with rectal carcinoma operated with a laparoscopic procedure between April 1992 and April 2003. METHODS: Patients with obstructing, bulky cancers were excluded from this study. Tumor stage was defined according to the TNM classification. Preoperative radiation therapy was offered to T(3) N(0) or N(+) patients (45 Gy). The laparoscopic-assisted technique included total mesorectal excision (TME), primary high vascular ligation, centrifugal dissection of the mesentery, and "no touch" technique. All the N+ patients received adjuvant chemotherapy. The outcomes were defined as five-years recurrence (local recurrence and distant metastasis) and the diseases-free survival. The survival rates were calculated with the Kaplan-Meier test. RESULTS: There were 108 males and 71 females, median age was 67 (range 39-88). There were 61 upper rectum localizations (34%), 68 middle rectum (38%) and 50 low rectum (28%). Twenty-nine patients required open conversion (16%). Surgical operative morbidity was 24% and medical morbidity was 4%. There were 60 stage I (40%), 25 stage II (16%), 49 stage III (32%), and 16 stage IV (10%). Ninety patients (71%) are alive and disease free, ten (5%) are alive with disease recurrence, and 37 patients (20%) are deceased. Only one case of trocar site implantation occurred after curative resection during an average follow up of 76 months. Five-year observed survival rate were 85% for stage I, 70% for stage II, and 63% for stage III. CONCLUSION: In our experience laparoscopic rectal resection could be done safely. The oncologic outcome was similar to that of open surgery. Further randomized trials will be necessary to confirm the value of this technique.

Adult↗

PubMed2001

Effects of hypothermic machine perfusion on rat liver function depending on the route of perfusion.

BACKGROUND AND METHODS: The aim of this study was to evaluate the efficacy of hypothermic machine perfusion (HMP) to preserve rat livers according to the route of perfusion, i.e., via portal vein, hepatic veins (retrograde), or hepatic artery. Livers were preserved for 24 or 48 hr by simple cold storage (SCS) or by HMP. Preservation solution was supplemented with (HMP) or without (SCS) hydroxyethyl starch. After preservation, grafts were reperfused for 2 hr with an oxygenated Krebs-Henseleit bicarbonate buffer. RESULTS: After 24 hr of preservation, total glutathione concentrations in HMP livers were similar (1287+/-37, 1418+/-118, and 1471+/-62 nmol/g in hepatic artery, portal vein, and hepatic vein HMP livers, respectively) and higher than in the SCS (833+/-118 nmol/g, P<0.05) group. These higher total glutathione values were due to higher reduced glutathione concentrations. ATP concentrations in the liver tissue were similar in HMP groups (0.75+/-0.4, 0.64+/-0.1, and 0.77+/-0.1 micromol/g in hepatic artery, portal vein, and hepatic vein HMP livers, respectively) and higher than in SCS (0.32+/-0.06 micromol/g, P<0.05). After 2 hr of normothermic reperfusion, bile production in the HMP portal and HMP retrograde groups were similar (391+/-29 ml and 372+/-25 ml) and higher than in the HMP artery or SCS groups (275+/-25 ml and 277+/-32 ml, respectively; P<0.05). Aspartate transaminase, alanine transaminase, lactate dehydrogenase, and purine nucleoside phosphorylase release into the perfusate of HMP portal and HMP retrograde perfused livers was similar and significantly lower compared to the HMP artery and SCS groups. At the end of reperfusion, no statistical differences were found for glutathione concentration and energetic reserves in the livers of each group. After 48 hr of preservation, livers from the HMP portal and HMP retrograde groups did significantly better than livers from the HMP artery or SCS groups. CONCLUSIONS: This study confirms the superiority of HMP over SCS to preserve the liver graft. It shows that retrograde perfusion is similar to PV perfusion and that perfusion by HA is less beneficial.

Animals↗

PubMed2001

Tumor progression is associated with a significant decrease in the expression of the endostatin precursor collagen XVIII in human hepatocellular carcinomas.

Endostatin inhibits angiogenesis and tumor growth in mice. The role of its endogenous precursor collagen XVIII in human cancer is unknown. In normal tissues, two variants of collagen XVIII, namely, the short and long forms regulate tissue specificity, the long form being almost exclusively expressed by hepatocytes in the liver. We analyzed RNA arrays from 57 hepatocellular carcinomas (HCCs) with common and variant-specific probes and investigated the relationships between collagen XVIII expression and angiogenesis by measuring the CD34-positive microvessel density. Low collagen XVIII expression by tumor hepatocytes was associated with large tumor size (r, -0.63; P < 0.001) and replacement of trabeculae with pseudoglandular-solid architecture (chi2, 28; P < 0.001), which indicate tumor progression. Tumors expressing the highest collagen XVIII levels were smaller and had lower microvessel density (P = 0.01) than those expressing moderate levels; and HCCs with the lowest collagen XVIII levels approached a plateau of microvessel density, which indicated that a decrease in collagen XVIII expression is associated with angiogenesis in primary liver cancer. HCCs recurring within 2 years of resection showed 2.2-fold lower collagen XVIII mRNA than nonrecurring ones (P = 0.02). The findings relied on the hepatocyte-specific long form. Thus, the endogenous expression of the endostatin precursor decreases along with tumor progression in HCCs.

Alternative Splicing↗

PubMed2001

Tumor hepatocytes and basement membrane-Producing cells specifically express two different forms of the endostatin precursor, collagen XVIII, in human liver cancers.

Endostatin is an endogenous inhibitor of angiogenesis and tumor growth in mice, which may be generated by proteolytic cleavage of collagen XVIII. In normal tissues, 2 variants of the endostatin precursor, namely the SHORT and LONG forms, regulate tissue specificity. We analyzed 53 human liver biopsies (18 hepatocellular carcinomas, 16 metastases of colorectal cancer, 3 cholangiocarcinomas, and 16 controls) by RNA dot blots, double-labeling immunohistochemistry, and in situ hybridization, using common and variant-specific probes. Tumor hepatocytes expressed the LONG form, whereas cholangiocarcinoma cells expressed the SHORT form, which was deposited in tumor basement membranes. Metastatic colorectal carcinoma cells did not express collagen XVIII. In the stromal compartment of primary and metastatic cancers, myofibroblasts and vascular endothelial cells expressed the SHORT form. Both basement membrane components, collagen IV and the SHORT collagen XVIII form, were codistributed and their mRNA levels strongly correlated (R =.75, P <.001). In addition, freshly isolated human hepatocytes expressed the LONG form and culture-activated stellate cells the SHORT form. Moreover, the full-length LONG form is a plasma protein. Thus, the LONG form is a hepatocyte-specific variant, and the SHORT form is a major component of the tumor extracellular matrix in primary and metastatic liver cancers. In the clinical context, the global expression of the endogenous endostatin precursor, collagen XVIII, in liver cancer results from the combined expression profiles of tumor cells, stromal cells, and nontumor hepatocytes at the advancing edge of the tumor, particular to each type of cancer.

Basement Membrane↗

PubMed2001

Increased extracellular matrix remodeling is associated with tumor progression in human hepatocellular carcinomas.

Matrix metalloproteinase-2 (MMP2) is a key enzyme in the process of extracellular matrix remodeling involved in tumor invasion and metastasis. The activation of MMP2 involves interplay with the membrane type-matrix metalloproteinase-1 (MT1-MMP) and the tissue inhibitor of metalloproteinase-2 (TIMP2). In vitro, activated hepatic stellate cells are a main source of MMP2 and collagen I induces MMP2 activation. The steady-state mRNA levels of MMP2, MT1-MMP, TIMP2, collagen I, collagen IV, and laminin gamma1 were compared with MMP2 activity in 55 hepatocellular carcinomas, 47 matching nontumor biopsies and 19 histologically normal livers. In hepatocellular carcinomas, increased collagen I mRNA levels were strongly associated with those of MMP2 (Spearman R =.74, P <.001), MT1-MMP (R =.65, P <.001) and TIMP2 (R = 0.61, P <.001). MMP2 activity was correlated with the mRNA expression of collagen I (R =.45 P <.01), collagen IV (R =.40, P <.01) and laminin gamma1 (R =.33, P <.05). Unlike collagen IV and laminin gamma1 mRNAs, MMP2, MT1-MMP, TIMP2, collagen I mRNA levels were increased in nonencapsulated compared with encapsulated tumors (P <.05). In addition, MMP2 activity was fourfold higher (P <.01) in tumors arising in cirrhotic livers than in those arising in noncirrhotic livers. Moreover, tumor recurrence was associated with 4.6- and 2.8-fold (P <.05) higher collagen I and MMP2 mRNA levels, respectively, in hepatocellular carcinomas arising in cirrhotic livers. Thus, a high extracellular matrix remodeling favors tumor progression in hepatocellular carcinomas.

Aged↗

PubMed2001

A new mutation of E-cadherin gene in familial gastric linitis plastica cancer with extra-digestive dissemination.

Over a 12-month period, we diagnosed poorly differentiated infiltrative independent-cell gastric adenocarcinoma in two brothers and one sister aged 41 to 47 years. Their father had died from antral cancer at the age of 34 years. These cancers had two characteristic clinical features: rapid course and distant malignant dissemination. In all three patients, polymerase chain reaction-sequencing of the E-cadherin (CDH1) gene of white blood cells identified a heterozygous nonsense mutation of exon 3, producing a stop codon at position 95 (Q95X), resulting in a truncated protein. The alteration of this protein, which plays a crucial role in epithelial cell adhesion, probably explains the clinical expression in this type of familial diffuse gastric cancer.

Adult↗

PubMed2000

Characterization and inhibition by a wide range of xenobiotics of organic anion excretion by primary human hepatocytes.

Organic anion secretion by human hepatocytes was characterized using primary liver parenchymal cell cultures and the anionic fluorescent dye carboxy-2',7'-dichlorofluorescein (CF). Probenecid, a well-known common blocker of the membrane transport process for anions, was shown to increase CF accumulation in primary human hepatocytes by inhibiting cellular CF efflux in a dose-dependent manner, thereby establishing the presence of an efflux system for organic anions in cultured hepatocytes. Outwardly directed transport of CF from hepatocytes was found to be temperature-dependent; it was not altered by changes in the ionic composition of the incubation medium used in efflux experiments. In addition to probenecid, various structurally and functionally unrelated xenobiotics such as glibenclamide, rifampicin, vinblastine, MK-571, indomethacin, and cyclosporin A were shown to inhibit secretion of CF by primary human hepatocytes, thus suggesting that organic anion excretion by human liver may be impaired by various drugs. Northern blot and Western blot analyses of the expression of multidrug resistance proteins (MRP), such as MRP1 and MRP2, which are known to mediate cellular outwardly directed transport of organic anions indicated that MRP2 was present at substantial levels in cultured human hepatocytes as well as in their in vivo counterparts, whereas MRP1 expression was only barely detectable. These results therefore suggest that MRP2, unlike MRP1, may contribute to the organic anion efflux system displayed by primary human hepatocytes and inhibited by a wide range of xenobiotics.

Anion Transport Proteins↗

PubMed1999

Detoxifying activity in pig livers and hepatocytes intended for xenotherapy.

BACKGROUND: Both livers and hepatocytes from pigs have been proposed for the treatment of end-stage liver diseases, as an alternative to allogeneic liver transplants. However, little is known of the capability of porcine hepatocytes to fulfill the biotransformation pathways of toxic compounds, including those released from livers in acute failure. We have studied the activity and expression of detoxifying enzymes in porcine livers and in cultured hepatocytes and their induction by phenobarbital. METHODS: Cytochromes P450 (CYP) 1A, 2B, and 3A and GST-like activities were tested with the following specific substrates: 7-ethoxyresorufin, 7-pentoxyresorufin, nifedipine, testosterone, 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, and ethacrinic acid. CYP 1A1/2-, 2B1/2-, 2E1- and 3A4-related and GSTalpha proteins were analyzed by Western blotting and CYP 1A1/2, 2B1/2, 2C6, 2E1, and 3A4, aldehyde dehydrogenase, epoxide hydrolase, and GSTalpha-like RNA by Northern blotting. RESULTS: Enzymatic activities reflecting the expression of CYP 1A-, CYP 2B-, CYP 2E1-, and CYP 3A-like genes, that is, ethoxyresorufin-O-deethylase, pentoxyresorufin-O-deethylase, nifedipine oxidase and testosterone 6beta-hydroxylase, and chlorzoxazone 6-hydroxylase, were identified in pig livers. CYP 1A and CYP 2E1, GSTalpha-like proteins, CYP 1A, 2C, and 2E, epoxide hydrolase, aldehyde dehydrogenase, and GST like RNA were expressed in vivo and in vitro. CYP 2B and CYP 3A RNA and proteins, and their associated activities were induced by phenobarbital. CONCLUSIONS: Porcine hepatocytes express the most important biotransformation enzymes and their corresponding activities and RNA. Thus, livers and hepatocytes from pigs can detoxify a large spectrum of exogenous and endogenous compounds, which makes them a convenient substitute for allogeneic transplants for patients with liver failure.

Aldehyde Dehydrogenase↗

PubMed1999

A refined approach to the repair of postcholecystectomy bile duct strictures.

OBJECTIVE: To assess the results of a refined approach to repair of postcholecystectomy bile duct strictures. DESIGN: An 11-year retrospective review of patients who had surgical repair of bile duct strictures developing late after cholecystectomy. SETTING: A major university teaching hospital in France. PATIENTS AND INTERVENTIONS: During an 11-year period from 1987 to 1997, 22 patients (mean [+/-SD] age, 55+/-15 years) were operated on for bile duct strictures after cholecystectomy (11 after laparoscopic surgery and 11 after open surgery). Thirteen (59%) of the 22 patients had previous repair. Most patients had episodic cholangitis (14 patients [64%]) and biochemical evidence of cholestasis (20 patients [91%]). There were 5 Bismuth type 1 strictures; 4, type 2; 7, type 3; 5, type 4; and 1, type 5. The average (+/-SD) time from initial surgery to repair was 6.3+/-9.6 years. Intraoperative cholangiography was used to plan the repair in 18 patients (82%). Fifteen patients (68%) were repaired with high Hepp-Couinaud hepaticojejunostomies. The last 4 patients had the hilum exteriorized by the posterior approach to improve access. RESULTS: There was 1 intraoperative complication (bleeding) and 4 postoperative complications (biloma, fistula, and 2 cholangitis). There were no deaths; mean (+/-SD) length of stay was 12.8+/-5.8 days; and mean (+/-SD) follow-up was 4.8+/-3.3 years (range, 1-10.7 years). Three patients were reoperated on, 1 with an obstructed Roux-en-Y limb and the 2 others for incisional hernias. Eighteen patients remain well, 3 had sporadic recurrent cholangitis after surgery that resolved spontaneously, and 1 patient remains unwell requiring antibiotics to control cholangitis. CONCLUSIONS: Hepp-Couinaud hepaticojejunostomy without stenting remains a reliable repair of postcholecystectomy strictures. Intraoperative cholangiography and exteriorizing the hilum by the posterior approach are useful adjuncts to this technique.

Biliary Tract Surgical Procedures↗

PubMed1999

Who benefits from portal vein resection during pancreaticoduodenectomy for pancreatic cancer?

Portal vein resection during pancreaticoduodenectomy has recently experienced renewed interest. We describe our results with this procedure over a 20-year period. Among 88 consecutive pancreatectomies for cancer of head of the pancreas, 14 included en bloc removal of the portal vein. There was no hospital mortality. Only 21% were found to have histologically confirmed cancer invasion, and the remainder had inflammatory adherence. Two-year survival was 15% compared to 34% for patients who did not have portal vein resection. There were no 5-year survivors. We discuss our results in light of other recent reports.

Adenocarcinoma↗

PubMed1999

Proximal bile duct cancer: high resectability rate and 5-year survival.

OBJECTIVE: To review and update the authors' experience with resectional surgery for proximal bile duct carcinoma (Klatskin tumor) and assess the role of liver resection over the past 25 years. BACKGROUND: Until recently, resection of proximal bile duct carcinoma was uncommon, with most patients undergoing palliative procedures. The authors adopted a radical surgical approach aimed at definitive cure in 1974. Recent reports suggest that resection improves outcome. METHODS: The records of 40 of 94 patients (23 men, 17 women, age range 34-81 years) diagnosed with proximal bile duct carcinoma who underwent resection between 1968 and 1993 were reviewed. According to the Bismuth classification, there were five type I, four type II, 25 type III, and six type IV lesions; 11 patients underwent tumor resection alone, and 25 patients had combined tumor and liver resection (seven of these also underwent an associated regional vascular resection). In 3 patients, venous allografts were harvested from cadaveric donors and used to reconstruct the portal vein. Four patients underwent liver transplantation; in two, organ cluster-type resections including the liver with porta hepatitis and pancreas were performed. RESULTS: The resectability rate in the more recent period of the study was 49.4%. Most type I, three (of four) type II, T in situ, T1a, T1b, and all stage 0 tumors were resected without hepatectomy. In the other subgroups of tumors, the main surgical procedure was hepatectomy. Thirty-day mortality was 12.5%. After tumor resection alone, survival at 1, 3, and 5 years was 81.8%, 45.5%, and 27.3%, respectively. After tumor resection and hepatectomy without vascular resection, 1-, 3-, and 5-year survival was 66.7%, 16.7%, and 6%, respectively. With vascular resection, survival rates were similar: 64%, 20%, and 4%, respectively. CONCLUSION: The type of surgery required to achieve cure is closely related to tumor location, TNM classification, and staging. Increasing resectability through the use of hepatectomy improves survival and offers a chance of cure in patients with more advanced disease.

Adult↗

PubMed1998

Neoadjuvant chemotherapy and hyperfractionated radiotherapy with concurrent low-dose chemotherapy for squamous cell esophageal carcinoma.

PURPOSE: We conducted a prospective study of neoadjuvant treatment for squamous cell carcinoma of the esophagus, modifying the chemotherapy protocol by adding l-folinic acid and giving bifractionated radiotherapy with a cis-diaminedichloroplatinum (CDDP) injection before each fraction. METHODS AND MATERIALS: Thirty-two patients, 30 men, 2 women, mean age 56.2+/-8.9 years, with resectable squamous cell carcinoma of the esophagus (TNM stage I=4, IIA=4, IIB=13, III=11) were included. Chemotherapy, CDDP (80 mg/m2 D2), 5-fluorouracil (5-FU; 600 mg/m2, D1-4), and l-folinic acid (200 mg/m2, D1-4), was given in two sessions with a 3-week interval during which the patients received radiotherapy (45 Gy), two fractions per day (150 cGy/fraction). A 3-mg injection of CDDP was given prior to each fraction. Patients underwent surgery 4 to 7 weeks after neoadjuvant therapy. RESULTS: No severe side effects were observed in 12 patients. Grade 3 effects (WBC, platelets, mucositis) occurred in 16 patients and grade 4 effects (platelets, mucositis) in four including 1 death due to septicemia with an infected catheter. Surgery was performed in 29 patients; 26 had resectable tumors (81%). Operative mortality was 10%. The 26 surgical specimens showed complete response (n=18), persistent microscopic residues (n=4), or not significant modification (n=4). Survival at 1, 2, and 3 years was 81, 61, and 51.6% and disease-free survival was 75, 59, and 54% respectively. CONCLUSIONS: This new therapeutic combination is aggressive and associated with a high postoperative mortality but has a remarkable histological effect since complete response was achieved in 56% (95% CI: 39-73%) of the patients and 3-year survival reached 52%, a very high rate in our experience.

Antidotes↗

PubMed1998

Collagen XVIII is localized in sinusoids and basement membrane zones and expressed by hepatocytes and activated stellate cells in fibrotic human liver.

Type XVIII collagen is a recently discovered nonfibrillar collagen associated with basement membranes in mice and expressed at high levels in human liver. We studied the origin, distribution, and RNA levels of type XVIII collagen in normal and fibrotic human livers by in situ hybridization, immunohistochemistry, and Northern and dot blots and compared procollagen alpha1(XVIII) RNA levels with those of procollagen alpha1(IV) and laminin gamma1, the two major components of liver basement membranes. In normal liver, type XVIII collagen was heavily deposited in perisinusoidal spaces and basement membrane zones. The major source of type XVIII collagen was hepatocytes and, to a lesser extent, endothelial, biliary epithelial, and vascular smooth muscle cells and peripheral nerves. In cirrhosis, type XVIII collagen formed a thick deposit along capillarized sinusoids. Grain counts after in situ hybridization showed myofibroblasts to increase their expression 13-fold in active and twofold in quiescent fibrosis, whereas hepatocytes increased their expression only twofold in both active and quiescent fibrosis. Activated stellate cells in vitro expressed type XVIII collagen at high levels. These data indicate that type XVIII collagen is a component of the perisinusoidal space and is associated with basement membrane remodeling. Hepatocytes and activated stellate cells are important sources of type XVIII collagen in normal and fibrotic liver respectively, which suggests tissue-specific regulation of its expression.

Basement Membrane↗

PubMed1998

Differential expression and origin of membrane-type 1 and 2 matrix metalloproteinases (MT-MMPs) in association with MMP2 activation in injured human livers.

Matrix metalloproteinase-2 (MMP2) activation is associated with basement membrane remodeling that occurs in injured tissues and during tumor invasion. The newly described membrane-type MMPs (MT-MMPs) form a family of potential MMP2 activators. We investigated the localization and steady-state levels of MT1-MMP and MT2-MMP mRNA, compared with those of MMP2 and tissue inhibitor of MMP-2 in 22 hepatocellular carcinomas, 12 liver metastases from colonic adenocarcinomas, 13 nontumoral samples from livers with metastases, 10 benign tumors, and 6 normal livers. MMP2 activation was analyzed by zymography in the same series. The expression of MT1-MMP mRNA and the activation of MMP-2 were increased in hepatocellular carcinomas, metastases, and cholestatic nontumoral samples. MT2-MMP mRNA was rather stable in the different groups. MT1-MMP mRNA levels, but not MT2-MMP mRNA, correlated with MMP-2 and tissue inhibitor of MMP-2 mRNA levels and with MMP2 activation. In situ hybridization showed that MT1-MMP mRNA was expressed in stromal cells, and MT2-MMP mRNA was principally located in both hepatocytes and biliary epithelial cells. Consistently, freshly isolated hepatocytes expressed only MT2-MMP mRNA, and culture-activated hepatic stellate cells showed high levels of MT1-MMP mRNA. These results indicate that in injured livers, MMP2 activation is related to a coordinated high expression of MMP2, tissue inhibitor of MMP-2, and MT1-MMP. Furthermore, the finding of a preferential expression of MT2-MMP in hepatocytes, together with our previous demonstration that the activation of stellate cell-derived MMP2 in co-culture requires interactions with hepatocytes (Am J Pathol 1997, 150:51-58), suggests that parenchymal cells might play a pivotal role in the MMP2 activation process.

Adenocarcinoma↗

PubMed1998

Laminin isoforms in non-tumoral and tumoral human livers. Expression of alpha1, alpha2, beta1, beta2 and gamma1 chain mRNA and an alpha chain homologous to the alpha2 chain.

BACKGROUND/AIMS: Laminins, the major non-collagenous basement membrane components, are involved in various biological processes. Laminin isoforms have never been characterized in human livers. The expression of five laminin mRNA was investigated in livers with or without cancer and in hepatoma cells and, by comparison, in both rat hepatoma and hepatic stellate cells. METHODS: Laminin alpha1, alpha2, beta1, beta2 and gamma1 mRNA was detected by northern blot and/or RT-PCR in livers without chronic disease (n=5), in both tumoral and non-tumoral areas of livers with hepatocellular carcinomas (n=13) or metastases (n=18), in human HBGC2 and rat Faza-567 hepatoma cell lines, and in 6-day-old rat hepatic stellate cell cultures. RESULTS: Laminin alpha1, alpha2 and beta1 mRNA were found in 25-33% and gamma1 mRNA in 58% of the livers, the signal for laminin beta2 mRNA being faint in all the samples. Laminin alpha2, beta1, beta2 and gamma1 mRNA were expressed in hepatoma and stellate cells. The laminin alpha2 cDNA probe recognized a 3.5 kb mRNA different from the expected 9 kb mRNA. Using degenerated oligonucleotides, RT-PCR products from both rat hepatoma and stellate cells revealed 90% identity with the alpha2 chain sequence. Antibodies against peptide deduced from the conserved C-terminal domain of both alpha1 and alpha2 chains recognized polypeptides corresponding to the degradation products of alpha2 chain in liver extracts and both media and cell layers from hepatoma and stellate cells. In addition, a Mr=130000 polypeptide was revealed by these antibodies in liver extracts and cell layers, which was consistent with the expected size deduced from the 3.5 kb mRNA. CONCLUSIONS: This first report on laminin isoforms in human livers indicates that laminin 1 (alpha1-beta1-gamma1), 2 (alpha2-beta1-gamma1), 3 (alpha1-beta2-gamma1) and 4 (alpha2-beta2-gamma1) mRNA and a polypeptide homologous to the alpha2 isoform, which could correspond to a truncated form of this chain, are usually expressed in non-tumoral and/or tumoral livers.

Animals↗

PubMed1998

Gastric bypass for malignant esophagotracheal fistula: a series of 21 cases.

OBJECTIVE: Patients with cancer of the esophagus who develop an esophagotracheal fistula die within 1 month in dramatic conditions of malnutrition and asphyxia. We assessed the beneficial palliative effect of the Kirschner operation in the treatment of esophagotracheal fistula. METHODS: Between January 1980 and August 1995, 21 patients among a continuous series of 847 with cancer of the esophagus developed an esophagotracheal fistula. Prior to surgery, 2 patients had an esophageal prosthesis followed by radio- and/or radiochemotherapy and 6 had radio- and/or chemotherapy at curative doses. The Kirschner operation was carried out in all patients with exclusion of the lower end of the esophagus using a Roux-en Y-loop (n = 19) or ligature (n = 2). RESULTS: Within 1 month of surgery, 8 patients (38%) died. Median length of stay in the intensive care unit and hospitalization was 6 days (1-30) and 17 days (3-57), respectively. Among the 13 survivors, pulmonary infections (n = 2) and cervical fistulae (n = 5) complicated the postoperative period. Among the cervical fistula, 3 of them resolved favorably. Radio- and/or chemotherapy was given postoperatively in 7 patients without any improvement in survival. Among the 13 patients surviving beyond the postoperative period, median survival was 109 days; 7 were able to resume oral nutrition and quality of life was assessed as excellent in 6 of them. CONCLUSION: The Kirschner operation can provide a beneficial palliative effect in patients with an esophagotracheal fistula despite the high risk of operative mortality. Ideally, the Kirschner should be carried out in young patients who are still in good general health, before the development of respiratory complications compromises surgery.

Adenocarcinoma↗

PubMed1998

[Hepatocytes in cell therapy].

Cell-based therapy could represent an alternative treatment to orthotopic liver transplantation in acute liver failures and for the correction of genetic defects of various enzymatic functions. Several recent studies indicate that hepatocytes injected either in the spleen or in portal vein can restore liver-specific function(s) in animal model systems. Alternatively, an extracorporal hybrid bioartificial liver might provide liver-specific functions, maintain the patient alive and allow spontaneous recovery of the patient's own liver, or act as a bridge toward liver transplantation in acute liver failures. Various drawbacks of devices such as flat culture substrates, hollow-fiber bioreactors or microcarriers led us to develop a reliable extracorporeal bioartificial liver based on alginate-entrapped hepatocytes. This system was used successfully for the correction of the Gunn rat genetic defect which results in the lack of bilirubin conjugation. The development of this system for clinical purposes requires large yields of functional hepatocytes. We isolated porcine hepatocytes by collagenase perfusion of the liver and cells were immobilized within alginate beads which were subsequently inoculated in a bioreactor. Porcine hepatocytes expressed liver-functions at high levels, particularly those involved in detoxification and biotransformation processes; they were immunoisolated from immunoglobins and could be cryopreserved. This system represents a promising tool for the design of an extracorporeal bioartificial liver in human beings.

Animals↗