Jean-Bernard Otte

Endoscopic stapling technique of esophagodiverticulostomy for Zenker's diverticulum☆

We present an endoscopic technique of division of the common wall between the esophagus and the hypopharyngeal (Zenkers) diverticulum. The novelty of the technique, as compared with endoscopic sutureless coagulating methods, consists of stapling the esophageal to the diverticular wall using the Endo-GIA 30 stapler (US Surgical Corp, Norwalk, CT), which protects the neck from any contamination from the digestive lumen and ensures optimal hemostasis of the wound edges. The stapler has been designed such that perforation of the bottom of the diverticulum is not likely. The technique has been applied to 6 patients.

Size reduction of the donor liver is a safe way to alleviate the shortage of size-matched organs in pediatric liver transplantation.

The development of pediatric liver transplantation is considerably hampered by the dire shortage of small donor organs. This is a very sad situation because in most experienced centers, liver replacement can offer a long-term hope of survival of more than 70% in a growing variety of pediatric liver disorders. The reported experience with 54 reduced-size grafts on a total of 141 transplants performed in 117 children between 1984 and 1988 demonstrates that the technique of reduced-size liver transplantation not only allows long-term survival but, in fact, offers the same survival hope with the same quality of liver function, regardless of the childs age and clinical condition. The prominent feature of our experience with the reduced liver concerns its deliberate use for elective cases. Seventy-seven per cent of the 30 children who electively received a reduced liver were alive 1 year after transplantation, as were 85% of the 62 children who received a full-size graft. There is no difference in the long-term survival rate of patients who received elective grafts, which is in the range of 75% with both techniques.

Hepatocellular carcinoma in children: results of the first prospective study of the International Society of Pediatric Oncology group.

PURPOSE To improve survival and reduce operative morbidity and mortality in children with primary epithelial liver tumors by using preoperative chemotherapy, as well as to collect information on the epidemiology, natural history, and prognostic factors. PATIENTS AND METHODS Forty children with hepatocellular carcinoma (HCC) were registered onto the Group for Epithelial Liver Tumors International Society of Pediatric Oncologys first study from January 1990 to February 1994. The outcome could be analyzed in 39 of those patients. Disease was often advanced at the time of diagnosis; metastases were identified in 31% of the children and extrahepatic tumor extension, vascular invasion, or both in 39%. Multifocal tumors were common (56%). Thirty-three percent of tumors were associated with hepatic cirrhosis. All but two patients received preoperative chemotherapy (cisplatin and doxorubicin). RESULTS Partial response was observed in 18 (49%) of 37 patients; there was no response or progression in the remainder. Complete tumor resection was achieved in 14 patients (36%). Twenty patients (51%) never became operable. Overall survival at 5 years was 28%, and event-free survival was 17%. Most deaths resulted from tumor progression (26 of 28). Presence of metastases and pretreatment extent of disease system grouping at diagnosis had an adverse influence on overall survival in multivariate analysis. CONCLUSION Survival for pediatric HCC patients is significantly inferior to that for children with hepatoblastoma. Complete tumor excision remains the only realistic chance of cure, although it is often prevented by advanced disease. The presence of metastases is the most potent predictor of poor prognosis. A prospective worldwide cooperation in the field of pediatric HCC should be encouraged to look for novel therapeutic concepts.

Ratio between Epstein-Barr viral load and anti-Epstein-Barr virus specific T-cell response as a predictive marker of posttransplant lymphoproliferative disease.

Background. Posttransplant lymphoproliferative disease (PTLD) is closely linked to primary Epstein-Barr virus (EBV) infection and a defect of EBV specific cellular immunity is supposed to be the basis of PTLD. However, EBV load is so far the only marker proposed to evaluate PTLD risk, and no study has investigated the role of specific anti-EBV T lymphocytes (EBV-TL). Methods. We therefore prospectively measured the EBV-TL by enzyme-linked immunospot (elispot) assay, in correlation to EBV load by real-time quantitative PCR and lymphoproliferation occurrence in 45 liver transplanted children. Results. EBV load at the time of primary infection was high in all patients irrespective to subsequent emergence of PTLD. Seven patients developed PTLD, all of them following primary EBV infection. All seven had low EBV-TL (<2/mm3) associated with high viral load (>25,000 copies/&mgr;g DNA). Both parameters can be combined in a 100% positive predictive index. Healing from lymphoma was characterized by rapid EBV-TL increase concomitant to decreasing viral load. EBV-TL follow-up helped to adapt immunomodulation. No patient had PTLD whenever EBV-TL were above 2/mm3. Conclusions. We conclude that high viral load is systematic in patients who underwent primary EBV infection and is indicative of the PTLD risk only if there is low concomitant cellular immune response. Healing from PTLD requires modulation of immunosuppression, and appearance of EBV-TL.

Early signs and risk factors for the increased incidence of Epstein-Barr virus-related posttransplant lymphoproliferative diseases in pediatric liver transplant recipients treated with tacrolimus.

BACKGROUND Posttransplant lymphoproliferative disease (PTLD) is a life-threatening condition the incidence of which in pediatric solid organ transplantation may be related to the immunosuppressive load. It has been suggested that tacrolimus, a new and potent immunosuppressor, causes an increased incidence of this syndrome. METHODS The incidence, early signs, and risk factors for lymphoproliferative disease were reviewed in a cohort of 89 pediatric liver transplant recipients treated with tacrolimus. RESULTS Eighteen patients (20%) developed a PTLD-16 concomitant to a primary Epstein-Barr virus (EBV) infection and 2 with previous immunity against EBV. Three additional patients had preliminary signs of PTLD concomitant to primary EBV infection, but did not develop individualized lymphoid masses. Six patients died (6.7% of all tacrolimus-treated patients). Mean tacrolimus blood level during the 3 months preceding EBV infection reached 11.8+/-1.8 ng/ml in PTLD patients versus 9.4+/-3.4 ng/ml in non-PTLD patients (0.05<P<0.1). Previous OKT3 or antithymocyte globulin treatment was also significantly associated to PTLD. There was no association with age, rejection episodes, steroid-resistant rejection, prior cytomegalovirus infection, HLA mismatch, living donor or cadaveric organ transplantation, United Network for Organ Sharing status at the time of orthotopic liver transplant, and primary or rescue tacrolimus treatment. A significant increase of total gamma-globulin level occurred in PTLD patients, and mono/oligoclonal production was significantly associated to PTLD. CONCLUSION In EBV-infected pediatric liver transplant recipients, use of OKT3 or antithymocyte globulin and high tacrolimus blood levels are risk factors for a significant increase in the incidence of PTLD. An increase in total gamma-globulin level and appearance of mono/oligoclonal immunoglobulin production are the major preliminary signs of the syndrome.

Successful Treatment of Childhood High-Risk Hepatoblastoma With Dose-Intensive Multiagent Chemotherapy and Surgery: Final Results of the SIOPEL-3HR Study

PURPOSE The primary objective was to determine the efficacy of a newly designed preoperative chemotherapy regimen in an attempt to improve the cure rate of children with high-risk hepatoblastoma. PATIENTS AND METHODS High risk was defined as follows: tumor in all liver sections (ie, Pretreatment Extension IV [PRETEXT-IV]), or vascular invasion (portal vein [P+], three hepatic veins [V+]), or intra-abdominal extrahepatic extension (E+), or metastatic disease, or alpha-fetoprotein less than 100 ng/mL at diagnosis. Patients were treated with alternating cycles of cisplatin and carboplatin plus doxorubicin (preoperatively, n = 7; postoperatively, n = 3) and delayed tumor resection. RESULTS Of the 151 patients (150 evaluable for response) 118 (78.7%) achieved a partial response to chemotherapy. Complete resection of the liver tumor could be achieved in 115 patients (76.2%) either by partial hepatectomy (55.6%) or by liver transplantation (20.6%). In 106 children (70.2%), complete resection of all tumor lesions (including metastases) was achieved. Among the patients with initial lung metastases, 52.2% achieved complete remission of the lung lesions with chemotherapy alone. In half of the patients with initial PRETEXT-IV tumor as the only high-risk feature, the tumor could be completely resected with partial hepatectomy. Event-free (EFS) and overall survival (OS) estimates at 3 years were 65% (95% CI, 57% to 73%) and 69% (95% CI, 62% to 77%) for the whole group. EFS and OS for all patients with PRETEXT-IV tumor were 68% and 69%, respectively, and they were 56% and 62%, respectively, for patients with metastasis. CONCLUSION The applied treatment rendered a great proportion of tumors resectable, and, in comparison with previously published results, led to an improved survival in patients with high-risk hepatoblastoma.

Predictive Value of the Pretreatment Extent of Disease System in Hepatoblastoma: Results From the International Society of Pediatric Oncology Liver Tumor Study Group SIOPEL-1 Study

PURPOSE Preoperative staging (pretreatment extent of disease [PRETEXT]) was developed for the first prospective liver tumor study by the International Society of Pediatric Oncology (SIOPEL-1 study; preoperative chemotherapy and delayed surgery). Study aims were to analyze the accuracy and interobserver agreement of PRETEXT and to compare the predictive impact of three currently used staging systems. PATIENTS AND METHODS Hepatoblastoma (HB) patients younger than 16 years who underwent surgical resection (128 of 154 patients) were analyzed. The centrally reviewed preoperative staging was compared with postoperative pathology (accuracy) in 91 patients (81%), and the local center staging was compared with the central review (interobserver agreement) in 97 patients (86%), using the agreement beyond change method (weighted kappa). The predictive values of the three staging systems were compared in 110 patients (97%) using survival curves and Cox proportional hazard ratio estimates. RESULTS Preoperative PRETEXT staging compared with pathology was correct in 51%, overstaged in 37%, and understaged in 12% of patients (weighted kappa = 0.44; 95% CI, 0.26 to 0.62). The weighted kappa value of the interobserver agreement was 0.76 (95% CI, 0.64 to 0.88). The Childrens Cancer Study Group/Pediatric Oncology Group-based staging system showed no predictive value for survival (P = .516), but the tumor-node-metastasis-based system and PRETEXT system showed good predictive values (P = .0021 and P = .0006, respectively). PRETEXT seemed to be superior in the statistical fit. CONCLUSION PRETEXT has moderate accuracy with a tendency to overstage patients, shows good interobserver agreement (reproducibility), shows superior predictive value for survival, offers the opportunity to monitor the effect of preoperative therapy, and can also be applied in patients who have not had operations. For comparability reasons, we recommend that all HB patients included in trials also be staged according to PRETEXT.

Pediatric liver transplantation with cadaveric or living related donors: comparative results in 90 elective recipients of primary grafts.

STUDY DESIGN Between July 1993 and March 1997, 110 children were listed for primary elective liver transplantation with cadaveric (Cad: n = 68) or living-related (LR: n = 42) donors. Pregraft mortality, post-transplant survival, and surgical and immunologic complications were retrospectively compared in both groups. RESULTS The pregraft mortality rate was 10 (15%) of 68 versus 1 (2%) of 42 in the Cad and LR groups, respectively (P =.049). Postliver transplantation 1-year patient and graft survival rates were 87% and 75% in the Cad group (n = 49) versus 92% and 90% in the LR group (n = 41), respectively (NS). The incidence of post-transplant complications was as follows: hepatic artery thrombosis (Cad: 16%; LR: 0%, P =.020), portal vein thrombosis (Cad: 8%; LR: 2%, NS), and biliary complications (Cad: 14%; LR: 34%, P =.044). The overall incidence of acute rejection was similar in both groups; however, a lower incidence of acute rejection occurred in LR graft recipients treated with tacrolimus. CONCLUSIONS The introduction of an LR donor liver transplantation program allowed a significant decrease in the pretransplant mortality rate, with a consequent overall improvement in patient survival compared with the Cad series. The incidence of biliary complications was higher in the LR series, whereas better human leukocyte antigen matching in this subgroup did not result in a lower rejection incidence.

Impact of innovative techniques on the waiting list and results in pediatric liver transplantation.

The wide application of liver transplantation in children is hampered by the shortage of size-matched pediatric donors; this results in high mortality rate on the waiting list, a long waiting time, worsening of the clinical condition of the waiting patient, deterioration of the overall results, and an increase in the cost. Reduced-size liver transplants have been shown to be a safe way to alleviate the shortage of size-matched organs. We have retrospectively analyzed the impact of the reduced-size liver transplants on the waiting list and the results in a consecutive series of 314 transplants performed in 261 children over an 8-year period (1984-1991). Among these 314 grafts, 160 (51%) were innovative techniques including 86 reduced livers (stricto senso), 66 partial livers (with preservation of the recipient vena cava), and 8 split livers. Such an extensive use of these technical variants allowed a sharp decrease in the waiting list mortality: from 14.9% between 1984 and 1989 to 6.6% in 1990 and 5% in 1991; the corresponding figures for infants registered under the age of 1 year were 25%, 13.3%, and 8.3%, respectively. Results obtained with a full-size graft or a technical variant were similar regarding surgical complications (with a significantly lower incidence of arterial thrombosis for the reduced transplants), graft loss, and patient survival. The 5-year survival of the whole group was 78.1% without any significant difference regarding type of transplant, indications (with the best results: 89.4% 5-year survival obtained in 41 children grafted for metabolic diseases), or age (the 5-year survival was 82.2% for the 41 infants transplanted under the age of 1 year, 78.9% for the 124 children transplanted between 1 and 3 years, and 81.3% for the 96 children transplanted between 6 and 15 years). This series of reduced-size liver transplants, which is the largest worldwide single institutional experience, confirms that the extensive use of reduced transplants in children is safe; this study also shows that innovative techniques, including the split liver, allow a drastic decrease of the waiting list mortality of candidates in the pediatric age range without alterations of the results.

En-bloc and Standard Esophagectomies by Thoracoscopy

Subtotal esophagectomy was attempted by right thoracoscopy on 13 patients, 10 having cancer and 3 long caustic stenosis. Thoracoscopy was converted into thoracotomy in 2 patients, owing to loss of selectivity in one-lung ventilation in 1 and injury to a right intercostal artery flush to the aorta in the other. One patient with cancer underwent an esophageal bypass operation only, owing to tumor invasion into the lung at exploratory thoracoscopy. The ten esophagectomies that could be performed in totality by thoracoscopy consisted of seven en bloc resections of the esophagus with extensive lymph node clearance in the posterior mediastinum, and three standard resections without any lymph node dissection. Postoperative complications included one death due to hepatic failure, two cases of acute pneumonitis, and one persistent chest wall discomfort at the trocar sites. Up to 51 lymph nodes were found in the resected specimens of the cancer patients. Six of the 7 cancer patients who were discharged from the hospital after esophagectomy completed by thoracoscopy were alive at 2 to 20 months of follow-up. Five of them were disease free. The study shows that esophageal resections as extensive as those carried out by thoracotomy can be performed by thoracoscopy. It suggests that prompt management of untoward injury to any mediastinal structure adjacent to the esophagus is less easy by thoracoscopy than by thoracotomy, and that classic complications of open thoracic surgery may occur after thoracoscopy as well.