Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms.

The diagnostic value of elevated human chorionic gonadotropin (hCG) and its free alpha (hCG alpha) and beta (hCG beta) subunit serum levels as specific tumor markers for nongonadal malignancies is controversial. In the present report, different monoclonal based immunoradiometric assays specific for hCG and its free hCG alpha and hCG beta subunits have been used to reevaluate the presence of these molecules in the serum of patients with a wide variety of tumors. Serum samples from patients with newly diagnosed, persistent, or recurrent malignancies of either known (n = 717) or unknown (n = 32) primary site, healthy blood donors (n = 309), and nonmalignant disease controls (n = 86) were studied using four highly specific and sensitive monoclonal based immunoradiometric assays to hCG and its free subunits. Low level hCG elevations (less than 1000 pg/ml) were found to be common in cancer patients, normal subjects, and disease controls. However, serum levels greater than 1000 pg/ml were highly diagnostic of gonadal tumors and specifically identified nonseminomatous testicular tumors. Significant serum elevations of free hCG alpha subunit (as high as 3000 pg/ml) were found in approximately 96% of cancer patients, normal individuals, and disease controls. In contrast, free hCG beta subunit levels (greater than or equal to 100 pg/ml) were detected in 70 and 50% of patients with nonseminomatous and seminomatous testicular cancers, respectively, and in 47% of bladder, 32% of pancreatic, and 30% of cervical carcinomas. All normal subjects and disease controls had free hCG beta levels less than 100 pg/ml. Thus, the detection of the free hCG beta subunit in serum of nonpregnant subjects was highly diagnostic of malignancy in general and specifically defines a subgroup of aggressive nongonadal malignancies.

Phase I-II study of two consecutive courses of high-dose epipodophyllotoxin, ifosfamide, and carboplatin with autologous bone marrow transplantation for treatment of adult patients with solid tumors.

We describe a phase I-II study of two consecutive 5-day courses of a three-drug regimen of ifosfamide (IFM), carboplatin (CBDCA), and either etoposide (VP-16) (regimen 1) or teniposide (VM-26) (regimen 2) in high doses together with autologous bone marrow transplantation (ABMT), for previously treated patients with ovarian carcinoma (OC), germ cell tumors (GCT), gestational trophoblastic disease (GTD), or oat cell carcinoma (OCC). Forty-four patients entered the study. Two patients with OC received regimen 1, and 22 were given regimen 2. Sixteen patients with GCT, two with GTD, and two with OCC were treated with regimen 1. Six patients (13%) died of toxicity. Nephropathy and esophagitis were the dose-limiting toxic effects. The maximum-tolerated doses (MTDs) were 1,500 and 200 mg/m2/d for 5 days for IFM and CBDCA, respectively, in combination with VP-16 250 mg/m2/d for 5 days (regimen 1), and 150, 1,500, and 200 mg/m2/d for 5 days for VM-26, IFM, and CBDCA, respectively (regimen 2). The response rate of patients with OC was 78% (complete response [CR], 14%). For patients previously resistant to chemotherapy, the response rate was 70%. There were no long-term disease-free survivors among patients with OC. The response rate of patients with GCT was 60% (CR, 33%). All responders with GCT were resistant to previous chemotherapy. Unmaintained CRs lasted 2, 6, 8+, 27+, and 37+ months. Of the two patients with GTD, one with previous resistance to chemotherapy attained a CR of 18+ months. One patient with OCC attained a CR lasting 6 months. The regimen possesses great antitumor activity. It produced CRs of long duration in a number of patients with GCT and GTD who were previously resistant to chemotherapy.

Primary sclerosing cholangitis: liver transplantation or biliary surgery.

BACKGROUND: Little information is available on the indications for, and the efficacy and timing of, liver transplantation in patients with primary sclerosing cholangitis (PSC). This issue is particularly relevant because prolonged survival has been reported in patients who do not undergo transplantation. METHODS: Long-term results of therapeutic interventions including liver transplantation was assessed in a representative series of 51 patients. Patient survival was compared with that expected from prognostic models. RESULTS: Actuarial symptom-free survival rate in patients treated by nontransplantation biliary surgery (n = 23) was 35% at 10 years. Actuarial survival rate from onset of PSC (56% at 10 years) was identical to that expected from the prognostic model. Actuarial patient (n = 28) survival rate 5 years after transplantation was greater than that expected from prognostic models (89% versus 31%; p < 0.001). Previous abdominal surgery was associated with an increased in-hospital mortality rate (p < 0.05). Cumulative actuarial incidence of cancer 5 and 10 years after the onset of PSC was 13% and 31%, respectively. CONCLUSIONS: Liver transplantation improves the prognosis of patients with PSC. Failure to identify patients who will benefit from nontransplantation therapeutic interventions or in whom a cancer will develop, and the risk associated with previous abdominal surgery, suggest that liver transplantation should be indicated early after onset of symptoms.

Major liver resection for carcinoma in jaundiced patients without preoperative biliary drainage.

BACKGROUND: The role of preoperative biliary drainage (PBD) before liver resection in the presence of obstructive jaundice remains controversial. Our patients with proximal duct carcinoma undergo noninvasive assessment followed by rapid laparotomy without PBD if the lesion is deemed resectable. HYPOTHESIS: Our aim was to report operative outcome of these patients and to analyze their specific features by comparison with patients without biliary obstruction who underwent major liver resection. DESIGN: A case-comparison study. SETTING: A tertiary care university hospital in a metropolitan area. PATIENTS: Twenty consecutive jaundiced patients underwent major liver resection without PBD. The jaundiced patients were matched with 27 nonjaundiced patients with normal underlying liver selected from a computer bank of 261 patients undergoing liver resections and identical for age, tumor size, type of liver resection, and vascular occlusion. MAIN OUTCOME MEASURE: Postoperative course including mortality, morbidity, transfusion rates, and results of liver function tests. RESULTS: Seventeen jaundiced patients (85%) and 13 nonjaundiced patients (48%) received blood transfusions (P = .03). Morbidity was 50% in jaundiced and 15% in nonjaundiced patients (P = .006), mainly resulting from subphrenic collections and bile leaks occurring only in jaundiced patients. In contrast, there were no significant differences for mortality (5% vs 0%) and liver failure (5% vs 0%). Postoperative changes in liver function test results were comparable between groups. CONCLUSIONS: Major liver resections without PBD are safe in most patients with obstructive jaundice. Recovery of hepatic synthetic function is identical to that of nonjaundiced patients. Transfusion requirements and incidence of postoperative complications, especially bile leaks and subphrenic collections, are higher in jaundiced patients. Whether PBD could improve these results remains to be determined.

Prognostic value of thoracic recurrent nerve nodal involvement in esophageal squamous cell carcinoma.

BACKGROUND: The determination of a simple and reliable prognostic factor that allows identification of patients at high risk of early cancer recurrence and subsequent death after resection of esophageal carcinoma should contribute to more accurate management of patients suffering from this disease. STUDY DESIGN: The aim of this study was to assess the prognostic value of thoracic recurrent nerve nodal involvement after curative resection of esophageal squamous cell carcinoma. The prognostic importance of gender, age, tumor penetration, and extent of lymph node involvement was evaluated in 55 patients after curative resection of esophageal squamous cell carcinoma. RESULTS: Thirty-four of 55 patients (62%) had nodal metastases and 10 of 55 (18%) had thoracic recurrent nerve nodes involved. The median overall survival was 28 months. By univariate analysis, survival was higher in association with the absence of adventitial invasion (p = 0.04), of nodal involvement (p = 0.03), and of thoracic recurrent nerve nodal involvement (p = 0.0001). In a Cox proportional hazards regression model, thoracic recurrent nerve nodal involvement appeared the strongest predictive factor (adjusted hazard ratio 8.4 (3.0-23.7)). CONCLUSIONS: Assessment of thoracic recurrent nerve nodes is appropriate to identify patients who are at high risk of disease-related death after surgical resection.

Safety of selective vascular clamping for major hepatectomies.

BACKGROUND: Although hepatic vascular clampings are widely used during major hepatic resections, they may not always be necessary. Selective vascular clamping, which only controls the afferent blood flow of the resected liver, could be a valuable alternative, provided that blood loss is not increased because the opposite liver remains perfused. STUDY DESIGN: The aim of the study was to assess the safety of selective vascular clamping in 43 patients who underwent 36 right hepatectomies and 7 left hepatectomies for lesions located peripherally within the liver. Blood transfusions, hepatic tests, morbidity, mortality, and hospital stay were evaluated. RESULTS: Selective vascular clamping was efficient in 34 of the 43 attempts (79%), but bleeding from the contralateral liver required conversion to portal triad damping in 9 patients (21%). Median blood transfusions were 0 units (range 0 to 4 U), and 28 patients (65%) did not require transfusions. Postoperative laboratory tests showed that larger changes occurred at day 1 and tended to return to preoperative values at the end of the first postoperative week. Median time of hospitalization was 10 days (range 7 to 28 days). Postoperative course was uneventful in 35 patients (81%). Nonlethal complications occurred in 7 patients (16.3%). One patient (2%) with massive hepatic steatosis died of liver failure after right hepatectomy. CONCLUSIONS: Selective vascular clamping is a safe alternative to total inflow occlusion for major hepatectomies applicable in 80% of selected patients with peripheral liver tumors.

Fully automatic anatomical, pathological, and functional segmentation from CT scans for hepatic surgery.

OBJECTIVE: To improve the planning of hepatic surgery, we have developed a fully automatic anatomical, pathological, and functional segmentation of the liver derived from a spiral CT scan. MATERIALS AND METHODS: From a 2 mm-thick enhanced spiral CT scan, the first stage automatically delineates skin, bones, lungs, kidneys, and spleen by combining the use of thresholding, mathematical morphology, and distance maps. Next, a reference 3D model is immersed in the image and automatically deformed to the liver contours. Then an automatic Gaussian fitting on the imaging histogram estimates the intensities of parenchyma, vessels, and lesions. This first result is next improved through an original topological and geometrical analysis, providing an automatic delineation of lesions and veins. Finally, a topological and geometrical analysis based on medical knowledge provides hepatic functional information that is invisible in medical imaging: portal vein labeling and hepatic anatomical segmentation according to the Couinaud classification. RESULTS: Clinical validation performed on more than 30 patients shows that delineation of anatomical structures by this method is often more sensitive and more specific than manual delineation by a radiologist. CONCLUSION: This study describes the methodology used to create the automatic segmentation of the liver with delineation of important anatomical, pathological, and functional structures from a routine CT scan. Using the methods proposed in this study, we have confirmed the accuracy and utility of the creation of a 3D liver model compared with the conventional reading of the CT scan by a radiologist. This work may allow improved preoperative planning of hepatic surgery by more precisely delineating liver pathology and its relationship to normal hepatic structures. In the future, this data may be integrated with computer-assisted surgery and thus represents a first step towards the development of an augmented-reality surgical system.

[Rupture of a jejunal artery pseudo-aneurysm after a cephalic duodenopancreatectomy]. / Rupture d'un pseudo-anévrisme d'une artère jéjunale après duodénopancréatectomie céphalique.

Arterial pseudo-aneurysms complicating pancreaticoduodenectomy are rare but have a poor prognosis. They usually result from arterial erosion due to pancreatic fistula. The authors report a pseudo-aneurysm with an uncommon localization (first jejunal artery), diagnosed after a negative first arteriography, and successfully treated by radiological embolization. Special features of pseudo-aneurysms complicating pancreaticoduodenectomy are reviewed.

[A new model of isolated perfused heart. Study of hypodermin A in hyperacute xenograft rejection]. / Mise au point d'un modèle de coeur isolé perfusé. Application à l'étude de l'hypodermine A dans la prévention du rejet suraigu xénogénique.

AIMS OF THE STUDY: Isolated perfused heart (IPH) system and heart transplantation in the guinea-pig/rat combination represent a good model for the study of hyperacute xenograft rejection (HAR) in which the component plays a central role. Hypodermin A (HA), a protease cleaving the component, could be used to delay the HAR. METHODS: Creation of an original IPH working with rat serum (30 mL) and ex vivo study of HAR and I'HA. RESULTS: Study of HAR is possible with this IPH system. The mean guinea-pig heart survival after perfusion by normal rat serum was 38 +/- 7 min and was lower than survival observed after perfusion by guinea-pig serum (210 +/- 34 min) (p < 0.001), by decomplemented rat serum (177 +/- 45 min) (p < 0.001), and by rat serum with 20 micrograms/mL of HA (154 +/- 71 min) (p < 0.001). CONCLUSION: We developed an original system of isolated perfused heart allowing ex vivo study of HAR. HA delayed the occurrence of the HAR and confirmed the central role of the component in the HAR.

[Applications of transgenesis in xenotransplantation. Experimental results and clinical prospects]. / Applications de la transgénèse à la xénotransplantation. Résultats expérimentaux et perspectives cliniques.

Transgenesis is now a genetic procedure commonly performed. The first clinical application of transgenesis could be xenografting between distant species such as swine and human. Transgenic expression of human complement regulatory proteins including CD55 and CD59 in pig has already been reported. An alternative strategy aims at reducing the expression of the xenoantigens on the cell surface by knocking out relevant genes through homologous recombination. Preliminary results of xenotransplantation of transgenic organs to macacus have suggested that xenogeneic hyperacute rejection could be overcome. After these recent advances, new attempts of xenotransplantation in human could be performed in a short term, at least as a bridge in the expectation of an allogeneic graft.

[Xenotransplantation: physiopathology of hyperacute and differentiated rejection, and therapeutic perspectives]. / La x¿enotransplantation, physiopathologie du rejet suraigu et diff¿er¿e, et perspectives th¿erapeutiques.

The mechanisms of xenograft rejection involved in closely related species of donors and recipients are not the same as in disparate combinations. When the donor and the recipient are phylogenetically close, such as the monkey and the human being, the rejection of xenografts is essentially mediated by a cellular immune response, and is clinically similar to a strong allograft rejection. When the donor and the recipient belong to widely disparate species, such as in the pig-to-human combination, the graft is destroyed by a hyperacute rejection before a cellular rejection has started. Hyperacute rejection is triggered by the fixation of the recipient's preformed antibodies on the graft endothelium, and subsequent activation of the recipient's complement. The activation of endothelial cells that ensues leads to the formation of an extensive thrombosis within the graft and to its necrosis within minutes or hours after grafting. When hyperacute rejection is overcome by means of complement inhibitors, a delayed vascular rejection occurs within 36 to 48 hours, mainly involving antibody-dependent cellular cytotoxicity and contributing to the extension of the thrombosis. Both hyperacute and delayed vascular rejections can be prevented by depletion of preformed antibodies, inhibition of complement activation, or by masking the dominant xeno-epitope Gal alpha 1,3 Gal. Transgenic pigs expressing molecules that inhibit xenogeneic rejection are being produced. However, prior to any clinical use, the infectious risks, and particularly the viral risk must be evaluated.

Relationship of apical lymph node involvement to survival in resected colon carcinoma.

In a prospective study of 197 patients with resected colon carcinoma treated between 1974 and 1985, we explored the relationships between pathologic parameters, and the effect of the latter on survival, to identify the parameter whose systematic measurement would improve the predictive capacity of pathologic staging. Prognostic characteristics were studied by univariate analysis. The results showed significant relationships between the location and number of lymph nodes involved, blood vessel invasion, depth of tumor penetration, and metastases. The five-year survival rates were 45 percent and 17 percent (P < 0.001) for patients without and with apical lymph node involvement, respectively, and 44 percent and 6 percent (P < 0.05) for those with four or less nodes involved and more than four involved, respectively. Among the patients treated by incomplete resection, the respective survival rates of those resected for metastases and of those resected for apical lymph node involvement did not differ significantly. We conclude that the involvement of apical lymph nodes has a significant effect on prognosis and suggest systematic pathologic examination of these nodes to allow simpler and more reproducible selection of patients for treatment by incomplete resection who are at high risk of disease-related death.

Teleeducation in surgery: European Institute for Telesurgery experience.

The information age is revolutionizing the practice and education of surgery. The use of video-conference systems through Integrated Service Digital Network (ISDN) teletransmission connects surgeons around the world without the limits of distance. Teleeducation, teleteaching, teletraining, telementoring, and teleaccreditation have been clearly demonstrated and are now common practice. Pre- and perioperative surgical advice may be obtained from expert networks. Patient data can be reconstructed as virtual tridimensional images analyzed by computers, and the surgical procedure can be simulated to obtain an optimal surgical decision. Finally, the use of the Internet will provide access to this information, whenever and wherever necessary, through dedicated websites. It remains to be adequately demonstrated that these means will allow improvement in patient care.

Telerobotic laparoscopic cholecystectomy: initial clinical experience with 25 patients.

OBJECTIVE: To determine the safety and feasibility of performing telerobotic laparoscopic cholecystectomies. This will serve as a preliminary step toward the integration of computer-rendered three-dimensional preoperative imaging studies of anatomy and pathology onto the patient's own anatomy during surgery. SUMMARY BACKGROUND DATA: Computer-assisted surgery (CAS) increases the surgeon's dexterity and precision during minimally invasive surgery, especially when using microinstruments. Clinical trials have shown the improved microsurgical precision afforded by CAS in the minimally invasive setting in cardiac and gynecologic surgery. Future applications would allow integration of preoperative data and augmented-reality simulation onto the actual procedure. METHODS: Beginning in September 1999, CAS was used to perform cholecystectomies on 25 patients at a single medical center in this nonrandomized, prospective study. The operations were performed by one of two surgeons who had previous laboratory experience using the computer interface. The entire dissection was performed by the surgeon, who remained at a distance from the patient but in the same operating room. The operation was evaluated according to time of dissection, time of assembly/disassembly of robot, complications, immediate postoperative course, and short-term follow-up. RESULTS: Twenty of the 25 patients had symptomatic cholelithiasis, 1 had a gallbladder polyp, and 4 had acute cholecystitis. Twenty-four of the 25 laparoscopic cholecystectomies were successfully completed by CAS. There was one conversion to conventional laparoscopic cholecystectomy. Set-up and takedown of the robotic arms took a median of 18 minutes. The median operative time for dissection and the overall operative time were 25 and 108 minutes, respectively. There were no intraoperative complications. There was one postoperative complication of a suspected pulmonary embolus, which was treated with anticoagulation. All patients were tolerating diet at discharge. CONCLUSIONS: Laparoscopic cholecystectomy performed by CAS is safe and feasible, with operative times and patient recovery similar to those of conventional laparoscopy. At present, CAS cholecystectomy offers no obvious advantages to patients, but the potential advantages of CAS lie in its ability to convert the surgical act into digitized data. This digitized format can then interface with other forms of digitized data, such as pre- or intraoperative imaging studies, or be transmitted over a distance. This has the potential to revolutionize the way surgery is performed.

Extrahepatic portal hypertension following liver transplantation: a rare but challenging problem.

This study reports our experience of 8 cases of extrahepatic portal hypertension after 273 orthotopic liver transplantations in 244 adult patients over a 10-year period. The main clinical feature was ascites, and the life-threatening complication was variceal bleeding. Extrahepatic portal hypertension was caused by portal vein stenosis in 6 patients, and left-sided portal hypertension in 2 patients after inadventent ligation of portal venous tributaries or portasystemic shunts. All patients with portal vein stenosis had complete relief of portal hypertension after percutaneous transhepatic venoplasty (n = 4) or surgical reconstruction (n = 2), after a median follow-up of 33 (range: 6-62) months. Of the 2 patients with left-sided portal hypertension, one died after splenectomy and one rebled 6 months after left colectomy. This study suggests that extrahepatic portal hypertension is a series complication after liver transplantation that could be prevented by meticulous portal anastomosis and closure of portal tributaries or portasystemic shunts to improve the portal venous flow. However, any ligation has to be performed under ultrasound guidance to avoid inadventent venous ligations.

Risk of major liver resection in patients with underlying chronic liver disease: a reappraisal.

OBJECTIVE: To explore the relation of patient age, status of liver parenchyma, presence of markers of active hepatitis, and blood loss to subsequent death and complications in patients undergoing a similar major hepatectomy for the same disease using a standardized technique. SUMMARY BACKGROUND DATA: Major liver resection carries a high risk of postoperative liver failure in patients with chronic liver disease. However, this underlying liver disease may comprise a wide range of pathologic changes that have, in the past, not been well defined. METHODS: The nontumorous liver of 55 patients undergoing a right hepatectomy for hepatocellular carcinoma was classified according to a semiquantitative grading of fibrosis. The authors analyzed the influence of this pathologic feature and of other preoperative variables on the risk of postoperative death and complications. RESULTS: Serum bilirubin and prothrombin time increased on postoperative day 1, and their speed of recovery was influenced by the severity of fibrosis. Incidence of death from liver failure was 32% in patients with grade 4 fibrosis (cirrhosis) and 0% in patients with grade 0 to 3 fibrosis. The preoperative serum aspartate transaminase (ASAT) level ranged from 68 to 207 IU/l in patients with cirrhosis who died, compared with 20 to 62 in patients with cirrhosis who survived. CONCLUSION: A major liver resection such as a right hepatectomy may be safely performed in patients with underlying liver disease, provided no additional risk factors are present. Patients with a preoperative increase in ASAT should undergo a liver biopsy to rule out the presence of grade 4 fibrosis, which should contraindicate this resection.

Assessing the effectiveness of mesorectal excision in rectal cancer: prognostic value of the number of lymph nodes found in resected specimens.

PURPOSE: The aim of this study was to determine whether the number of involved or uninvolved lymph nodes in resected specimens can be used to predict the effectiveness of surgical resection for rectal cancer. METHODS: Local recurrence and survival rates for 118 patients undergoing curative resection for rectal carcinoma, without adjuvant therapy, were retrospectively studied. RESULTS: Mean follow-up was 62+/-37 months. Mean number of involved or uninvolved lymph nodes per resected specimen was 12+/-7. Overall local recurrence rate was 15.2 percent. In patients without involved lymph nodes (N0 patients) and with T1 or T2 tumors, the local recurrence rate ranged from 0 to 8 percent (not significant), depending on the number of lymph nodes on the specimen. In patients without involved lymph nodes and those with T3 tumors, the actuarial survival rate at ten years was significantly lower (P < 0.05), and the local recurrence rate was higher (P < 0.02) in patients with fewer than ten lymph nodes than in those with more than ten nodes. In patients with involved lymph nodes, the mean number of nodes on the resected specimen correlated closely with the mean number involved by the tumor. CONCLUSION: The assessment of the effectiveness of rectal excision for cancer is in part helped by the number of involved or uninvolved lymph nodes found on the resected specimen. This is of particular interest in patients without involved lymph nodes and those having infiltrating T3 tumors, for whom the long-term survival and local recurrence rates were significantly better when more than ten lymph nodes were present. On the other hand, when fewer than ten nodes were found, whatever the cause, adjuvant radiotherapy had to be considered, because of the high risk of local failure rate.