Presence of villin, a tissue-specific cytoskeletal protein, in sera of patients and an initial clinical evaluation of its value for the diagnosis and follow-up of colorectal cancers.

Villin is an actin-binding protein found in a few normal adult epithelia, namely epithelial cells in the digestive and urogenital tracts. Moreover, villin production is maintained in malignant cells. We assumed that cell lysis and necrosis of solid tumors producing villin might result in villin release into blood. We analyzed the villin content of sera from 788 patients and controls using an enzyme-linked immunosorbent assay. Patients and controls were classified into healthy donors, patients with benign diseases of the gastrointestinal tract, patients with colorectal cancers, and patients with malignant nondigestive diseases. In the panel of sera analyzed, the sensitivity of the assay for colorectal cancers was 50.5%, and its overall specificity for malignant digestive tumors was 94.5%. Results were statistically analyzed comparing each group of sera with each other. We conclude that the presence of villin is indicative of a pathological state in the gastrointestinal tract (P less than 0.001). Finally, we followed villin levels after tumor resections (60 patients). We found that the villin level in sera remains low in remissions but is raised in recurrences. We suggest that the villin assay may have clinical utility as a diagnostic adjunct for adenocarcinoma of the gastrointestinal tract. It may also have some value in monitoring patients with advancing colorectal carcinomas after resection of these tumors.

Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors.

Genetic alterations, such as loss of heterozygosity (LOH) at the 17p13 and 11p15 loci and overexpression of the insulin-like growth factor (IGF)-II gene, are associated with the malignant phenotype in sporadic adrenocortical tumors. A high risk of recurrence after surgery for adrenocortical tumors is predicted in cases with regional invasion or distant metastases. However, patients with localized tumors also have a high risk of recurrence. Reliable prognostic markers are required to identify subjects at high risk of recurrence. The aim of this study was to assess the prognostic value of three molecular markers (17p13 LOH, 11p15 LOH, and overexpression of the IGF-II gene) by assessing disease-free survival in a large series of adult patients with sporadic adrenocortical tumors. Adult patients (114) were prospectively followed up from diagnosis of the disease to June 1999 or to death. Malignancy was initially diagnosed in 18 patients (McFarlane stage III: n = 1 and stage IV: n = 17). The remaining 96 patients with localized adrenal disease at diagnosis (stage I: n = 60 and stage II: n = 36) were at risk of recurrence. Histological grade was assessed according to Weiss criteria, and tumors were classified into two groups (Weiss score or=4). Tumor samples were analyzed for LOH at the 17p13 and 11p15 loci and for IGF-II gene mRNA content. 17p13 LOH was a strong predictor of shorter disease-free survival in univariate analysis (P = 0.001; relative risk, 27), as were histological grade (Weiss score >or=4; P = 0.00001; relative risk, 15), 11p15 LOH (P = 0.004; relative risk, 9), tumor size (size >5 cm; P = 0.006; relative risk, 18), and overexpression of the IGF-II gene (P = 0.01; relative risk, 5). In a Cox proportional hazards regression model, histological grade (P = 0.04; relative risk, 4.2) and 17p13 LOH (P = 0.009; relative risk, 21.5) were independently associated with recurrence. Molecular markers, particularly 17p13 LOH, are predictive of long-term outcome in patients with sporadic adrenocortical tumors. In patients who have undergone curative surgery, routine assessment of these tumor markers is a useful complement to histological scoring for predicting recurrence and guiding decisions for subsequent follow-up and management.

Orthotopic liver transplantation for Byler disease.

Byler disease is a rare form of familial intrahepatic cholestasis that is fatal before puberty. This retrospective study reviewed the results of orthotopic liver transplantation in 14 children with Byler disease using 12 whole-liver grafts and 2 reduced-size grafts. One post-operative death occurred after retransplantation for arterial thrombosis. In the other patients, infectious problems and rejection episodes were the most frequent complications during the postoperative period. In the 13 patients alive, graft function, growth, and quality of life were good after an average follow-up of 17 months without any sign of disease recurrence.

Orthotopic liver transplantation in children with chronic liver disease and severe hypoxemia.

Liver transplantation has been considered until recently as an absolute contraindication in hypoxemic patients. We report our experience in nine patients who had orthotopic liver transplantation between June 1986 and June 1992. These patients had cirrhosis-related hypoxemia with intrapulmonary shunting (IPS). The arterial oxygen pressure (PaO2) on room air ranged from 47 to 78 mmHg. OLT resulted in resolution of hypoxemia and closure of IPS in five patients whose hypoxemia was higher than 60 mmHg, and in death for the remaining four patients who had severe hypoxemia (PaO2 < 60 mmHg). We conclude that hypoxemia is no longer a contraindication to liver transplantation. Patients having PaO2 levels higher than 60 mmHg should have OLT as soon as possible before reaching lower levels of PaO2, and combined lung-liver transplantation or heart-lung-liver transplantation should be discussed in patients with severe hypoxemia (PaO2 < 60 mmHg).

Adrenocortical carcinoma in surgically treated patients: a retrospective study on 156 cases by the French Association of Endocrine Surgery.

BACKGROUND: Because of the rarity of adrenocortical carcinoma, survival rates and prognosis for patients who have undergone operation are not well known. The purpose of the French Association of Endocrine Surgery was to evaluate these factors in all patients treated during a 12-year period by its members. METHODS: One hundred fifty-six patients (95 women, 61 men) with a mean age of 47 years were included. Functional symptoms were found in 52% of patients, and hormonal studies revealed secreting tumors in 62% of cases. Ninety-four percent of the patients underwent resection of the adrenal tumor, and 20% of them had extensive resection because of invasive cancers. Complete resection was achieved in 127 patients (81%) and incomplete resection in 29 patients. Mean tumor weight was 714 gm (range, 12 to 4750 gm), and the mean diameter was 12 cm (range, 3 to 30 cm). The results of the tumor staging were stage I, eight patients (5%); stage II (local disease), 75 patients (48%); stage III (locoregional disease), 39 patients (25%); and stage IV (metastases), 34 patients (22%). RESULTS: The 5-year actuarial survival rates were 34% overall, 42% in curative group, 53% in local cancer group, 24% in regional disease group, and 27% in the reoperated group. One-year actuarial survival rate of the palliative group was 9% (median survival, 6 months). Multivariate analysis showed that better prognosis occurred in patients younger than 35 years of age (p = 0.01) and in patients with androgen-secreting tumors, precursor-secreting tumors, or nonsecreting tumors (p = 0.003). Mitotane improved the survival rate only in patients with metastases who received it after operation (vs non-mitotane-treated patients [p < 0.05]). CONCLUSIONS: In this study age, extent of disease, aspect of the surgical resection, and type of hormonal secretion influenced survival.

Orthotopic liver transplantation with a reduced-size graft: an ideal compromise in pediatrics?

This study retrospectively reviewed the results of 81 orthotopic liver transplantations in 72 pediatric patients with either a full-size graft (n = 41) or a reduced-size graft (n = 40) during a 4-year period. Two types of liver reduction were used to obtain a left lobe graft (n = 30) or a left lateral segment graft (n = 10). The choice of the reduction technique was based on two criteria: the donor/recipient body weight ratio and the transverse size of the recipient's abdomen. The patients who underwent transplantation with a reduced-size graft were younger and smaller than those who received a full-size graft. The mortality rate of the candidates on the pediatric transplantation waiting list was 2.7% during the same period. The 3-year survival rate after elective transplantation was 85% and 75% in the full-size graft group and the reduced-size graft group, respectively (difference not significant). The use of reduced-size grafts was associated with higher amounts of red cell and fresh-frozen plasma transfusions after graft revascularization. The incidence of postoperative bleeding and bile leakage from the transected surface was low, whereas hepatic artery and biliary complications were less frequent in the reduced-size graft group than in the full-size graft group. At the time of follow-up, liver biochemical test results and quality of life were not different between the two groups. Despite the constraining technique and the increase in intraoperative blood loss, orthotopic liver transplantation with a reduced-size graft allows us to overcome the shortage of pediatric donors and improve the overall survival rate of children with end-stage liver disease.

Unilateral neck exploration under local anesthesia: the approach of choice for asymptomatic primary hyperparathyroidism.

BACKGROUND: Conventional parathyroidectomy involves a bilateral neck exploration with the patient under general anesthesia with a thorough search for all parathyroid tissue. The purpose of this study was to assess the efficacy and safety of unilateral neck exploration under local anesthesia in patients with asymptomatic primary hyperparathyroidism (first-degree hyperparathyroidism). METHODS: Of 679 patients who underwent parathyroidectomy for first-degree hyperparathyroidism from July 1989 to June 1997, 230 asymptomatic patients underwent unilateral neck exploration under local anesthesia. Selection criteria for this approach included the successful identification of a solitary parathyroid adenoma on preoperative imaging, no thyroid disease, and no family history of multiple endocrine neoplasia. Intact parathyroid hormone levels were monitored during the operation. RESULTS: Total serum calcium levels were normal in 220 patients (96%) 3 to 6 months after surgery. Ten patients (4%) experienced persistent hypercalcemia, 8 of whom had multiple gland disease and 2 of whom had false-positive imaging. Two of these patients underwent bilateral neck exploration under general anesthesia and were cured, although 8 patients remained asymptomatic and were followed up non-operatively. The mean operating time was 30 minutes (range, 12-65 minutes). There were two complications (0.87%) including one wound hematoma and one transient recurrent laryngeal nerve palsy. CONCLUSIONS: Unilateral neck exploration under local anesthesia is an efficacious and safe approach to the treatment of first-degree hyperparathyroidism and should be considered in all patients with asymptomatic disease.

Partial hepatic resection for ischemic graft damage after liver transplantation: a graft-saving option?

BACKGROUND: Intrahepatic biliary strictures or parenchymal infarcts may occur after liver transplantation as a complication of ischemic damage to the graft. In some selected cases the lesions appear to be confined to a part of the liver. We report our experience with partial graft resection in this setting. METHODS: From January 1984 to December 1991, 286 liver transplantations were performed in 257 recipients. Seven patients, three children and four adults, underwent partial hepatectomy 3 to 218 weeks after liver transplantation of a full-size graft. The clinical presentation included septic parenchymal infarcts (n = 4) and nonanastomotic biliary strictures (n = 3) complicating (n = 5) artery thrombosis or not (n = 2). There were four left hepatectomies, two left lobectomies, and one right hepatectomy. In four instances partial hepatectomy was performed after failed attempt at biliary reconstruction (n = 2) or arterial revascularization (n = 2). Partial graft resection was performed extrafascially without Pringle's maneuver and mobilization of the remnant liver to preserve its vascularization. RESULTS: No surgical complications occurred, and none of the patients experienced acute hepatic failure during the postoperative period. All patients were discharged home 10 to 96 days (median, 23 days) after liver resection. Two patients had recurrent ischemic cholangitis. One patient underwent successful regrafting for recurrent Budd-Chiari syndrome; one patient died of tumor recurrence. Six patients were alive with a follow-up ranging from 12 to 45 months. CONCLUSIONS: These results suggest that partial graft resection is a safe and graft-saving option after liver transplantation in selected patients with localized ischemic damage of the graft.

Portal and hepatic arterial blood flow measurements of human transplanted liver by implanted Doppler probes: interest for early complications and nutrition.

Hepatic artery thrombosis and early acute rejection are severe complications of orthotopic liver transplantation (OLT). Their rapid detection is most desirable. The purpose of this study was to assess the usefulness of monitoring hepatic artery (HABF) and portal vein (PVBF) blood flows during the first week after OLT. At the end of operation, microprobes were sutured to the vessels, and their connecting tubes were externalized and connected to a pulsed Doppler flowmeter operating at 8 MHz. In 10 patients (ages ranged from 2 to 54 years) of 106, measurements of HABF and PVBF were done during alternative clamping of both vessels and before and after abdominal closure, every 12 hours during 7 days, and at day 7, before and after a 150 gm carbohydrate meal. At day 7 the probes were pulled out by gentle traction without complication, and all patients were allowed to go home. Reciprocal increase of flow during selective clamping was only observed for HABF (+45.8% +/- 47.6%; p less than 0.01). Abdominal closure decreased both HABF and PVBF by 13.8%, p less than 0.01, and 26%, p less than 0.05, respectively. In seven cases no significant variation of HABF and PVBF was observed during 7 days. In two patients with histologically confirmed early acute rejection, a marked decrease of diastolic HABF, without modification in PVBF, was the first manifestation and was rapidly corrected by boluses of steroids. In one patient disappearance of systolic and diastolic HABF led us to diagnose an arterial obliteration caused by a plicature, which was successfully surgically treated in the emergency department. In all patients, after oral ingestion of the carbohydrate meal, and only after this type of diet, a significant and deep decrease (-87%, p less than 0.001) of HABF was observed between 7 and 120 minutes without any change in PVBF. Such an effect was not observed in control patients. We conclude that this Doppler flowmetric technique with implantable microprobes is useful for rapid diagnosis of and strategy in treating early complications and is a new tool for pathophysiologic study of OLT consequences.

Endoscopic ultrasonography for the preoperative localization of insulinomas.

Preoperative radiological localization of insulinomas often fails because of the small size of the tumors. We studied retrospectively the value of different procedures in preoperative localization of insulinomas in 18 patients. Radiological assessment included transabdominal ultrasonography, computed tomography, angiography, magnetic resonance imaging, transhepatic venous sampling, and endoscopic ultrasonography (EUS) for the last 11 patients. During surgery, the association of palpation and intraoperative ultrasonography localized 16 solitary tumors and two multiple tumors (mean size, 1.8 +/- 1.1 cm). There insulinomas were found to be malignant. Conventional preoperative methods correctly localized the tumor in seven of 18 cases (38%), whereas the sensitivity of EUS was 10 of 11 cases (90%). Surgical procedures involved eight enucleations, nine distal pancreatectomies, and one total pancreatectomy. Because of its high sensitivity and safety, EUS was found to be the best method for preoperative localization of insulinomas, and we recommend that EUS replace conventional methods for the majority of cases.

Extrafascial hyper-reduction of the hepatic graft.

The technique and limits of graft reduction in orthotopic liver transplantation (OLT) are not well-defined, especially for small recipients. To reduce the hepatic graft to the left lateral segment (segments II and III), the authors have used an extrafascial hepatectomy without any dissection of the hepatic hilum. Among 165 pediatric OLT, 22 procedures using such hyper-reduced hepatic grafts were performed upon 21 children of median age 2.6 years between 1988 and 1992. These 22 hyper-reduced hepatic grafts were transplanted orthotopically with conservation of the inferior vena cava of the recipient. The three-year patient survival rate was 66 percent (80 and 50 percent for those patients undergoing elective and emergent procedures, respectively). The main postoperative complications were: primary graft nonfunction (n = 1), arterial complications (n = 2), portal vein thrombosis (n = 1), intra-abdominal bleeding (n = 2) and biliary complications (n = 2). This technique is useful in instances of a large size discrepancy between the donor and recipient. However, it does not increase per se the absolute number of hepatic grafts available for transplantation.

Technetium-99m sestamibi scintigraphy, magnetic resonance imaging and venous blood sampling in persistent and recurrent hyperparathyroidism.

Surgical treatment for primary hyperparathyroidism (HPT) is effective in 90% of cases. Recurrent or persistent HPT occurs in 10% of cases. Parathyroid imaging is indicated to confirm and locate an abnormal gland before reoperation. The aim of this study was to evaluate whether the combination of 99Tcm sestamibi scintigraphy, MRI and venous blood sampling (VBS) improved the overall sensitivity for abnormal parathyroid gland detection. 18 patients with recurrent or persistent HPT underwent sestamibi scintigraphy (n = 18), MRI (T1 weighted and STIR sequences) (n = 18) and venous blood sampling (n = 12) at different sites (internal jugular veins, innominate veins, and superior vena cava). All patients underwent surgical exploration. MRI yielded positive results in 15 cases (sensitivity 88%), sestamibi scintigraphy in 14 cases (83%) and VBS in 10 cases out of 12 (83%). Combined results of MRI, sestamibi and VBS yielded positive results in 16 cases (94%). The combination of MRI, sestamibi scintigraphy and VBS improved accuracy in detecting abnormal parathyroid glands before reoperation.

[Papillary adenocarcinoma of Wirsung's duct]. / Adénocarcinome papillaire du canal de Wirsung.

We describe a new case of ductal papillary adenocarcinoma of the pancreas, resected in 1976 (cephalic pancreatoduodenectomy). The patient is still alive. This particular histological type of pancreatic cancer seems to be very rare (9 cases published). The difficulty of preoperative diagnosis and the possibility of long-term postoperative survival clearly differentiate ductal papillary adenocarcinoma from other glandular adenocarcinomas of the pancreas.

Liver transplantation in patients with a surgical portasystemic shunt.

Of 220 patients undergoing liver transplantation between March 1982 and April 1991, eighteen (8.1 percent) already had a surgical portasystemic shunt. Four patients had a distal splenorenal shunt, six a side-to-side portacaval shunt, three an end-to-side portacaval shunt, and five, a mesocaval shunt. The splanchnic venous system was assessed by Doppler ultrasound examination and angiography before liver transplantation. Perioperative mortality rate was higher but not significantly different from that observed in the population of patients without previous portasystemic shunt (33.3 percent versus 21.7 percent). Liver transplantation was particularly difficult in the six patients with a previous side-to-side portacaval shunt, in which the perioperative mortality rate was high (66.6 percent). Liver transplantation is feasible in patients with a previous portasystemic shunt but carries a higher risk. It is easier when no previous dissection of the hepatic pedicle has been done. Suppression of the shunt after revascularization of the graft must be performed in order to provide optimal venous flow to the hepatic graft.

[Ectasing cholangitis and secondary biliary cirrhosis following intra-arterial hepatic chemotherapy. Treatment by liver transplantation]. / Cholangite ectasiante et cirrhose biliaire secondaire après chimiothérapie intra-artérielle hépatique. Traitement par transplantation hépatique.

A case of ectasing cholangitis, following intra-arterial chemotherapy with discontinuous infusion of fluorouracile, is described. The severe destruction of the intra-hepatic biliary ducts led to the constitution of large cavities in continuity with the biliary tree. These cavities were responsible for images which were mistakenly thought to be metastases. Consequently, secondary biliary cirrhosis developed, requiring orthotopic liver transplantation.

[Budd-Chiari's syndrome with caval membranous web treated by liver transplantation]. / Syndrome de Budd-Chiari par membrane cave traité par transplantation hépatique.

In this paper, the case of a 30 year-old Asiatic man with a Budd-Chiari syndrome secondary to a caval membranous web, associated with cirrhosis is presented. After unsuccessful percutaneous dilatation, liver transplantation associated with membranotomy treated the venous obstacle and ensured satisfactory recovery. Orthotopic liver transplantation is the most effective treatment in this setting.

[Single-stage resection of at least 6 liver segments in cases of liver tumors]. / Résection d'au moins six segments anatomiques en un temps pour tumeur du foie.

Seven partial liver resections of at least six hepatic segments (five extended left hepatectomies, also called left trisegmentectomies, and two subtotal hepatectomies) were performed for tumor (of malignant nature in 6 cases). Six of seven patients were admitted for liver transplantation and one for liver resection. These procedures were performed under total vascular exclusion of the liver in six cases (with a veno-venous bypass in two cases) and with the Pringle maneuver in one case. Postoperative liver function was satisfactory in six cases whereas one patient died of hepatic failure on the tenth postoperative day. There was one bile duct stricture at eight months, after extended left hepatectomy. Four patients survived more than one year, three with hepatic tumor recurrence and one with distant metastases. Two patients were still alive, one after fourteen months with tumor recurrence in the liver, the other after seventeen months. In selected cases, partial hepatic resection of more than six segments can be performed for very large tumors. In cases of malignant tumors, a short period of survival with good quality of life can be offered to these patients.

[Peroperative echography in 14 cases of pancreatic insulinoma and gastrinoma]. / Echographie per-opératoire au cours de 14 cas d'insulinomes et de gastrinomes pancréatiques.

Fourteen cases of endocrine tumors (10 insulinomas and 4 gastrinomas) were to studied by intraoperative ultrasonography (IOU). Localization was established by preoperative ultrasonography in 1/14, by CT scan in 1/11, by arteriography in 6/12 and by pancreatic venous sampling in 7/8. Tumor size ranged from 0.5 cm to 2.5 cm. Manual palpation was positive in 10/14. The tumor was accurately and completely localized by IOU in 9/10 insulinomas: the one false negative was probably due to micro-adenoma. The intrapancreatic tumor was localized only in 1/14 gastrinomas. Intraoperative sonography localized lymph nodes in all cases. One distal pancreatectomy was improperly performed because of an accessory spleen. After reviewing 59 other cases in the literature, we propose: a) to abandon venous sampling in insulinomas because of adequate performance of IOU; b) to use IOU as a complementary investigative method along with other preoperative methods of localization in gastrinoma.

[Pregnancy and motherhood after liver transplantation in terminal autoimmune active hepatitis with primary amenorrhea]. / Grossesse et maternité après transplantation hépatique pour hépatite active auto-immune terminale avec aménorrhée primaire.

We report the case of a young patient with end-stage auto-immune chronic active hepatitis and primary amenorrhea who became pregnant 18 months after orthotopic liver transplantation. She continued an uncomplicated pregnancy on treatment with ciclosporin A and spontaneously gave birth to a full term and healthy child.

[Parathyroid adenoma encapsulated in a thyroid adenoma: an anatomical curiosity]. / Adénome thyroïdien renfermant un adénome parathyroïdien: une curiosité anatomique.

We describe a primitive hyperparathyroid in a old woman due to a parathyroid adenoma localized by Technetium 99m, Thallium 201 scintigraphy within the thyroid gland. During surgery, this adenoma was found inside a thyroid adenoma. It is the second case reported on the literature in a such localization. We underline the interest of the scintigraphy Technetium 99m, Thallium 201, for the detection of ectopic parathyroid adenoma.