Jacques Baulieux

Influence of the Interval Between Preoperative Radiation Therapy and Surgery on Downstaging and on the Rate of Sphincter-Sparing Surgery for Rectal Cancer: The Lyon R90-01 Randomized Trial

PURPOSE The optimal timing of surgery after preoperative radiotherapy in rectal cancer is unknown. The aim of this trial was to evaluate the role of the interval between preoperative radiotherapy and surgery. PATIENTS AND METHODS Patients with rectal carcinoma accessible to rectal digital examination, staged T2 to T3, NX, M0, were randomized before radiotherapy (39 Gy in 13 fractions) into two groups: in the short interval (SI) group, surgery had to be performed within 2 weeks after completion of radiation therapy, compared with 6 to 8 weeks in the long interval (LI) group. Between 1991 and 1995, 201 patients were enrolled onto the study. RESULTS A long interval between preoperative radiotherapy and surgery was associated with a significantly better clinical tumor response (53. 1% in the SI group v 71.7% in the LI group, P =.007) and pathologic downstaging (10.3% in the SI group v 26% in the LI group, P =.005). At a median follow-up of 33 months, there were no differences in morbidity, local relapse, and short-term survival between the two groups. Sphincter-preserving surgery was performed in 76% of cases in the LI group versus 68% in the SI group (P = 0.27). CONCLUSION A long interval between preoperative irradiation and surgery provides increased tumor downstaging with no detrimental effect on toxicity and early clinical results. When sphincter preservation is questionable, a long interval may increase the chance of a successful sphincter-saving surgery.

Improved Sphincter Preservation in Low Rectal Cancer With High-Dose Preoperative Radiotherapy: The Lyon R96-02 Randomized Trial

PURPOSE The potential advantage of high-dose preoperative radiotherapy to increase tumor response and improve the chance of sphincter preservation for low rectal cancer remains controversial. The aim of this trial was to evaluate the role of escalating the dose of preoperative radiation to increase sphincter-saving procedures. PATIENTS AND METHODS Patients with rectal carcinoma located in the lower rectum, staged T2 or T3, Nx, or M0 with endorectal sonography, and not involving more than two-thirds circumference, were randomly assigned to one of two groups: preoperative external-beam radiotherapy (EBRT; 39 Gy in 13 fractions over 17 days) versus the same EBRT with boost (85 Gy in three fractions) using endocavitary contact x-ray. RESULTS Between 1996 and 2001, 88 patients were enrolled onto the study. A significant improvement was seen in favor of the contact x-ray boost for complete clinical response (24% v 2%) and for a complete or near-complete sterilization of the operative specimen (57% v 34%). A significant increase in sphincter preservation was observed in the boost group (76% v 44%; P =.004). At a median follow-up of 35 months, there was no difference in morbidity, local relapse, and 2-year overall survival. CONCLUSION A dose escalation with endocavitary irradiation provides increased tumor response and sphincter preservation with no detrimental effect on treatment toxicity and early clinical outcome.

Long term histological improvement and clearance of intrahepatic hepatitis C virus RNA following sustained response to interferon-ribavirin combination therapy in liver transplanted patients with hepatitis C virus recurrence.

Background and objective: A proportion of liver transplanted patients with recurrent chronic hepatitis have a sustained virological response to combination therapy with interferon plus ribavirin. However, the long term benefit of antiviral therapy with regard to hepatitis C virus (HCV) RNA clearance remains unknown in patients with HCV recurrence. This study examined the long term biochemical, virological, and histological outcome in transplanted patients with recurrent chronic hepatitis who had a sustained virological response to antiviral therapy. Patients and methods: Fifty four patients with recurrent hepatitis C were treated with antiviral therapy involving induction by combination therapy (interferon (IFN) plus ribavirin) for six months and maintenance ribavirin therapy for 12 months. Fourteen patients who had recurrent chronic hepatitis and sustained virological response to antiviral therapy were followed for three years after the end of antiviral therapy. Serum alanine aminotransferases were assessed every three months during the observation period. Serum hepatitis C RNA detected by polymerase chain reaction was evaluated every six months during follow up, and protocol biopsy procedures were performed routinely every year. Semiquantitative histopathological assessment of allograft hepatitis was performed using the Knodell score and HCV was also detected by polymerase chain reaction on frozen graft tissue samples. Results: At the end of antiviral therapy, the sustained response rate was 26%. A complete response (normal serum alanine aminotransferase level and undetectable serum HCV RNA) was achieved in 13/14 (93%) patients three years after the end of treatment. A comparison of liver histology findings before and after a mean of three years after antiviral therapy showed a clear improvement in 12/14 (86%) patients. In 5/14 (36%) patients, the last biopsy showed normal or near normal histological findings. After three years of follow up, the total Knodell score was 3.2 (range 1–8) versus 8.3 (range 5–12) before treatment (p=0.001). Graft HCV RNA was detectable before treatment in all 14 patients and was undetectable at the end of follow up in 13/14 (93%) patients tested. Conclusion: In patients with biochemical and virological responses induced by ribavirin and interferon, a complete response was sustained in 93% for at least three years after cessation of therapy. This long term response was associated with absence of detectable intrahepatic hepatitis C RNA and marked histological improvement.

Predictors of Long-Term Survival After Liver Transplantation for Metastatic Endocrine Tumors: An 85-Case French Multicentric Report

Liver transplantation (LTx) for metastatic endocrine tumors (MET) remains controversial due to the lack of clear selection criteria. From 1989 to 2005, 85 patients underwent LTx for MET. The primary tumor was located in the pancreas or duodenum in 40 cases, digestive tract in 26 and bronchial tree in five. In the remaining 14 cases, primary location was undetermined at the time of LTx. Hepatomegaly (explanted liver ≥120% of estimated standard liver volume) was observed in 53 patients (62%). Extrahepatic resection was performed concomitantly with LTx in 34 patients (40%), including upper abdominal exenteration (UAE) in seven.

Benefit of sustained virological response to combination therapy on graft survival of liver transplanted patients with recurrent chronic hepatitis C.

Recurrent hepatitis C infection is an important cause of progressive fibrosis, cirrhosis and graft loss after liver transplantation. Treatment for post‐transplant recurrence results in sustained virological response (SVR) in up to 30% of cases. The aim of this study was to evaluate the impact of SVR on patients and graft survival. Thirty‐four patients with an SVR to IFN‐ribavirin were included. Forty‐six nonresponders to the combination formed the control group. Follow‐up data were recorded every 6 months and included HCV RNA, and the occurrence of clinical problems (cirrhosis, decompensation, hepatocellular carcinoma, death). A graft biopsy was performed every year. The mean follow‐up duration was 52 months in responders and 57 months in nonresponders. Two patients died in each group of patients. Two patients with SVR developed late virological relapse. Fibrosis decreased in 38% of patients with SVR, remained stable in 44% and worsened in 18%. In contrast, fibrosis increased in the majority of nonresponder patients (74%, p < 0.001). At the end of follow‐up, no patient without cirrhosis at inclusion developed cirrhosis of the graft versus 9 among nonresponder patients (p = 0.009). No difference in patient survival was observed in the two groups. In conclusion, this study shows that HCV eradication has a positive impact on graft survival.

Role of Radiotherapy With Surgery for T3 and Resectable T4 Rectal Cancer: Evidence From Randomized Trials

PurposeThe main treatment for resectable rectal cancer T2–T4 N0–N2 M0 is surgery. The benefit of preoperative or postoperative radiation therapy can be analyzed in terms of improvement of local control, sphincter preservation, and survival weighted against increased toxicity.MethodsOnly randomized trials can provide strong evidence of a positive cost-benefit ratio of such combined approach. The most recent trials were reviewed.ResultsThree randomized trials, including the latest German CAO-ARO trial, have demonstrated the superiority of preoperative radiotherapy with or without chemotherapy (vs. postoperative) in terms of local control and toxicity. The Ducth TME trial showed that even with modern standard surgery, preoperative radiotherapy improved local control. Preoperative irradiation using a high dose in a small volume and a long interval before surgery may improve sphincter preservation (Lyon trials). Concurrent chemoradiation (FFCD 9203, EORTC 22921, did not significantly improve sphincter preservation or survival but significantly reduced the local recurrence rate.ConclusionsIn 2005 examination of randomized trials provides evidence for the benefit of preoperative chemoradiation in improving local control and probably sphincter preservation in rectal cancer. Randomized trials should be designed to further demonstrate improved sphincter preservation and to increase survival using adjuvant medical treatments.

Anatomical variations of the hepatic artery: study of 932 cases in liver transplantation

The aim of this study was to identify and to classify anatomical hepatic artery (HA) variations concerning 932 HA dissections in liver transplantation (LT). Normal HA distribution was found in 68.1%. Variations of HA were detected in 31.9% and were divided into three groups describing 48 common hepatic artery (CHA) anomalies, 236 left or right hepatic artery (RHA) anomalies and 13 rare variations including one case of RHA stemmed from the inferior mesenteric artery and one case of normal CHA passed behind the portal vein. The authors propose a modified classification for HA anomalies which are based on the origin of the hepatic arterial supply (either by the CHA as the only source of the arterial vascularization or by additional or replaced right and left arteries) in order to improve management of liver disease thus as in LT.

Hepatic outflow study after piggyback liver transplantation

BACKGROUND Hepatic vein outflow is discussed in liver transplantation after preservation of recipient retrohepatic vena cava. The aim of this study was to compare two methods of suparahepatic caval anastomosis. METHODS From January 1993 to January 1995, 81 patients received 88 liver transplants because of liver cirrhosis (n = 70), acute liver failure (n = 7), elective retransplantation after hepatic artery thrombosis (n = 2), giant hemangioma (n = 1), and combined liver-small bowel transplantation (n = 1). Seven patients underwent urgent retransplantation, 12 had preoperative transjugular intrahepatic portocaval stent, and 11 had portal vein thrombosis. Five patients required extracorporeal venous shunt. A total of 82 liver transplantations had preservation of RHVC, and 70 patients received temporary end-to-side portacaval shunt. Suprahepatic caval anastomosis was carried out in 52 patients (group 1) between the graft suprahepatic vena cava and the ostia of recipient left and median hepatic veins. Thirty patients (group 2) had associated 3 cm vertical cavotomy with partial clamping of RHVC. In the fourth postoperative month 20 patients from each group had pressure and gradient measurement made among the hepatic veins, right atria, and the RHVC. RESULTS Mean pressure gradient between hepatic veins and right atria was 0.75 +/- 0.49 mm Hg in group 1 and 2.06 +/- 0.85 mm Hg in group 2. Between the RHVC and the right atria it was 0.63 +/- 0.5 mm Hg in group 1 and 2.22 +/- 1.29 mm Hg in group 2. A pressure gradient higher than 3 mm Hg was considered hemodynamically significant. This pressure gradient was found between the hepatic veins and right atria in 10% of patients in group 1 and 40% of patients in group 2 (p = 0.03) and between the RHVC and right atria in 15% of patients in group 1 and 30% of patients in group 2 (p = 0.3). CONCLUSIONS Preservation of the recipient RHVC with recipient caval anastomosis at the ostia of the median and left hepatic veins is a reliable technique without any hepatic venous outflow alteration. Associated cavotomy is not necessary.

Primary squamous-cell carcinoma of the rectum: report of six cases and review of the literature.

AbstractPURPOSE: The majority of colorectal carcinomas diagnosed are adenocarcinomas. Squamous-cell carcinoma is a rare pathologic curiosity. Since 1943, only 18 cases have been described in the medical literature. The aim of this study was to report retrospectively six new cases and to review the medical literature. PATIENTS: Of the 6 cases, 4 were females, and age ranged from 43 to 93 years. Tumors were located 7 to 12 (mean, 8.5) cm from the anal verge. Five patients underwent surgical resection. Intraoperative radiotherapy was performed in one case. One patient was treated only by external beam radiotherapy. In two cases neoadjuvant combination of external beam radiotherapy and chemotherapy and in one case neoadjuvant contact x-ray treatment were performed. This treatment was followed by external beam radiotherapy in two cases and by chemotherapy in two cases, in patients with lymph node involvement. RESULTS: The clinical tumor response to radiotherapy was almost complete for the patient who did not undergo surgery. One tumor was sterilized by preoperative radiation. Three patients were alive without recurrence at 6 months, 2 years, and 16 years. CONCLUSION: The etiopathogenicity of squamous-cell carcinoma of the rectum is discussed. The prognosis of these tumors seems to be worse than that for adenocarcinoma because of a delayed diagnosis. Surgical resection seems to be the most important treatment. Chemotherapy and especially radiotherapy may have some indications.

Diagnostic value and tolerance of Lipiodol-computed tomography for the detection of small hepatocellular carcinoma : correlation with pathologic examination of explanted livers

BACKGROUND/AIMS This study aimed to assess the tolerance and the real sensitivity of Lipiodol-computed tomography in the detection of small hepatocellular carcinoma by comparison with pathological examination of the explanted livers. METHODS Seventy-two patients with cirrhosis (Child A=8, B=36, C=28) awaiting orthotopic liver transplantation underwent Lipiodol-computed tomography to determine the presence, number and location of possible hepatocellular carcinoma nodules. Before liver transplantation six patients had a presumed single hepatocellular carcinoma diagnosed by biopsy. Liver transplantation was performed a mean of 6 months after Lipiodol-computed tomography. Explanted livers were sectioned at 0.8- to 1-cm intervals. Lipiodol-computed tomography staging and pathologic findings were compared. RESULTS Pathologic studies showed 24 hepatocellular carcinoma nodules (diameter, 2-42 mm) not diagnosed before liver transplantation in 14 of the 72 livers. Lipiodol-computed tomography detected 6 of these 24 nodules, but none of the daughter lesions (n=9) in the six patients with a presumed single hepatocellular carcinoma. Lesion-by-lesion analysis revealed a sensitivity of 37%. Lipiodol-computed tomography falsely detected three additional nodules not confirmed by pathologic examination (1 haemangioma, 2 nondysplastic regenerating nodules). One Child C patient developed variceal bleeding within 2 days after injection of Lipiodol. CONCLUSIONS Tolerance of this procedure was satisfactory, even in Child C patients. Lipiodol-computed tomography has a low sensitivity in the detection of small hapatocellular carcinoma. These results must be considered when liver resection or liver transplantation is proposed for the treatment of hepatocellular carcinoma.