Guillain-Barre Syndrome (GBS) is believed to be caused by autoimmune mechanisms that are predomin... more Guillain-Barre Syndrome (GBS) is believed to be caused by autoimmune mechanisms that are predominantly T-cell mediated. We report GBS in organ transplant patients and bone marrow transplant patients, both of whom have iatrogenically suppressed T-cell function. We reviewed the Duke University Medical Center database from 1989-1999 for all patients who met the criteria for GBS. There were a total of 212 patients. Of these patients, two had undergone organ transplantation and two had undergone autologous bone marrow transplantation. Our report supports the notion that the humoral immune system is involved in the pathogenesis of GBS. Contrary to previous reports, however, functional recovery can occur without return of T-cell function. This suggests that in organ transplant patients, GBS may be humorally mediated and, even more importantly, responds well to treatment.
Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric monoclonal antibody used fo... more Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric monoclonal antibody used for immunoprophylaxis in organ transplantation. It was assessed in a randomized, double-blind, placebo-controlled efficacy trial in de novo liver allograft recipients who received 40 mg of basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppression with cyclosporine (INN, ciclosporin) microemulsion and corticosteroids. Serial blood samples (8.3 +/- 1.4 per patient) were collected during 12 weeks after transplantation from 184 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. Demographic-clinical covariates were explored with regression methods. Basiliximab clearance was 55 +/- 26 mL/h, the distribution volume was 9.7 +/- 4.2 L, and the half-life was 8.7 +/- 6.7 days. Patient weight, age, sex, ethnicity, history of alcoholism, hepatitis C seropositivity, and notable postoperative bleeding had no clinicall...
Dysfunction in the physiological pathways of programmed cell death may promote proliferation of m... more Dysfunction in the physiological pathways of programmed cell death may promote proliferation of malignant cells, and correction of such defects may selectively induce apoptosis in cancer cells. We measured the levels of ceramide, a candidate lipid mediator of apoptosis, in human metastatic colorectal cancer and tested in vitro and in vivo effects of various ceramide analogues in inducing apoptosis in metastatic colon cancer. Human colon cancer showed a > 50% decrease in the cellular content of ceramide when compared with normal colon mucosa. Application of ceramide analogues and ceramidase inhibitors induced rapid cell death through activation of various proapoptotic molecules, such as caspases and release of cytochrome c. Ceramidase inhibition increases the ceramide content of tumor cells, resulting in maximum activation of the apoptotic cascade. Normal liver cells were completely resistant to inhibitors of ceramidases. Treatment of nude mice with B13, the most potent ceramidase...
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2001
Biliary complications after orthotopic liver transplantation (OLT) lead to considerable morbidity... more Biliary complications after orthotopic liver transplantation (OLT) lead to considerable morbidity and occasional mortality after surgery. Bile duct strictures secondary to localized lymphoproliferative disorder of the porta hepatis is rare, with only 12 cases reported in the English literature. Posttransplant lymphoproliferative disorder develops in up to 9% of liver allograft recipients. We describe 2 adult patients who developed Epstein-Barr virus-associated localized B-cell lymphoma of donor-tissue origin confined to the porta hepatis 3 and 5 months after OLT. Both patients were administered cyclosporine (CyA) and prednisone as primary immunosuppression. One patient was administered basiliximab as induction therapy. Neither patient had CyA trough levels greater than 250 ng/mL. Both patients were treated with a hepatojejunostomy, 75% reduction in immunosuppression therapy, and acyclovir. One patient had complete involution of the tumor, and the second patient had an 80% reduction ...
We describe the unusual case of a patient who developed recurrent right upper quadrant pain 25 yr... more We describe the unusual case of a patient who developed recurrent right upper quadrant pain 25 yr after cholecystectomy. A cystic lesion containing a calculus was identified on transabdominal ultrasound, initially suggesting the possibility of gallbladder duplication. Endoscopic retrograde cholangiography identified this lesion as a massively dilated cystic duct stump. Surgical resection led to complete resolution of symptoms. Recurrent cholelithiasis involving the cystic duct stump may lead to massive dilatation, and must be considered in the differential diagnosis of postcholecystectomy syndrome.
Canadian journal of surgery. Journal canadien de chirurgie, 1993
To determine the efficacy of laparoscopic cholecystectomy (LC) in the treatment of gallstone dise... more To determine the efficacy of laparoscopic cholecystectomy (LC) in the treatment of gallstone disease, all patients who underwent elective surgery for cholelithiasis during three consecutive periods (1989, 1990 and 1991) were studied. There were 121 patients in each period. All patients in the first period underwent open cholecystectomy (OC), whereas 70 (58%) patients underwent laparoscopic procedures in the second period (OC-LC). LC was the treatment of choice in the third period. Multiple factors, including sex, age, clinical and biochemical presentation of the disease and modified Apache II score were comparable among the three groups. The authors found significant differences in length of hospitalization (6.4 +/- 4.2 days in the OC group, 3.6 +/- 2.4 days in the OC-LC group and 2.4 +/- 1.7 days in the LC group, p < 0.01 when compared with the OC group) and return to work after surgery (5.8 +/- 2.8 weeks, 2.8 +/- 1.2 weeks and 1.3 +/- 1.8 weeks respectively, p < 0.01 when co...
Lack of uniform reporting of negative outcomes makes interpretation of surgical literature diffic... more Lack of uniform reporting of negative outcomes makes interpretation of surgical literature difficult. We attempt to define and classify negative outcomes by differentiating complications, sequelae, and failures. Complications and sequelae result from procedures, adding new problems to the underlying disease. However, complications are unexpected events not intrinsic to the procedure, whereas sequelae are inherent to the procedure. Failures are events in which the purpose of the procedure is not fulfilled. We propose a classification of complications based on four grades: Grade I complications are alterations from the ideal postoperative course, non-life-threatening, and with no lasting disability. Complications of this grade necessitate only bedside procedures and do not significantly extend hospital stay. Grade II complications are potentially life-threatening but without residual disability. Within grade II complications a subdivision is made according to the requirement for invas...
Gallstone ileus as a complication of endoscopic sphincterotomy (ES) is exceptional, and this is o... more Gallstone ileus as a complication of endoscopic sphincterotomy (ES) is exceptional, and this is only the second reported case. The present case is unique in that there was no previous instrumentation to the papilla, the bowel was obstructed and perforated, and the patient survived. This case again points out the danger of performing ES for large common bile duct stones. When a large stone is not extracted after ES, close monitoring is mandatory until unequivocal stone passage through the intestine is proven. In both cases reported so far, the lack of adequate monitoring after failure of stone extraction by ES was critical to the severity of gallstone ileus.
Revista de gastroenterología del Perú : órgano oficial de la Sociedad de Gastroenterología del Perú
HELLP syndrome is a rare condition related to pregnancy; however, it can cause complications such... more HELLP syndrome is a rare condition related to pregnancy; however, it can cause complications such as a ruptured subcapsular hepatic hematoma. In most cases, this is managed surgically, but the mortality rate is high, up to 50% of all patients. We present a case with conservative management by percutaneous embolization of the right hepatic artery with a successful outcome and we propose a modern treatment algorithm.
Very few areas in medicine have seen as many controversies as the evaluation and treatment of pat... more Very few areas in medicine have seen as many controversies as the evaluation and treatment of patients with liver diseases. Many novel therapies, often marketed before conclusive demonstration of their efficacy, have been developed to enable selective destruction of liver tumors to minimize the risk of liver failure associated with major surgery. Whether these techniques are effective and result in
Of 1192 patients treated for breast cancer, four had extrahepatic gastro-intestinal metastases as... more Of 1192 patients treated for breast cancer, four had extrahepatic gastro-intestinal metastases as first clinical manifestation of the tumour dissemination. One woman presented with gastric metastases mimicking a linitis plastica. Another had metastases localized to the rectum also mimicking a linitis plastica. Two women had peritoneal and retroperitoneal metastases that caused, in one case, a right hydronephrosis. Histology of the four primary tumours showed invasive lobular carcinoma (ILC) mixed with invasive ductal carcinoma in two. However, ILC exclusively was found at the site of the gastro-intestinal metastases involving the serosal layer (two cases) and extending to the submucosa (one case) or to the mucosal stroma (one case). Thus, when a women with previous history of invasive lobular breast cancer experiences gastro-intestinal symptoms, particular attention should be paid to the large and deep biopsy of lesions to ascertain the histological type and whether oestrogen or progesterone receptors differ from those of the primary breast lesion. Since survival is extremely variable (one woman is alive 7 years after the discovery of gastro-intestinal metastases), treatment including surgery, hormonal manipulation and chemotherapy with the expectation of a cure is often justifiable, particularly if no other extensive metastases are present.
... Correspondence: Pierre-Alain Clavien, MD, PhD, Professor of Surgery, Zurich University Hospit... more ... Correspondence: Pierre-Alain Clavien, MD, PhD, Professor of Surgery, Zurich University Hospital, Zurich 8091, Switzerland ... bleeding from submucosal gastric collaterals secondary to occlusion of the proximal segment of the splenic artery, possibly from a blunt abdominal trauma ...
The purpose of this study was to compare the use of phased array MR imaging of the liver at 1.5 T... more The purpose of this study was to compare the use of phased array MR imaging of the liver at 1.5 T with and without ferumoxides with dual-phase helical CT for the detection of hepatic lesions in candidates for hepatic surgery. Patients with known or suspected hepatic lesions who were eligible for surgery underwent dual-phase helical CT at 20 and 70 sec after the start of contrast material injection and phased array MR imaging using fast spin-echo T2-weighted imaging and gradient-echo T1-weighted imaging before and after ferumoxides infusion of 0.56 mg of iron per kilogram of body weight. Three observers who were unaware of the surgical findings separately reviewed the CT scans and unenhanced and enhanced MR images of 24 patients who completed the protocol. The observers&amp;amp;#39; findings were compared with results obtained at surgery using intraoperative sonography and having histopathologic confirmation. Statistical analysis was performed using a segment-by-segment analysis. Eighty-two lesions were found at surgery. The sensitivity of CT, unenhanced MR imaging, and enhanced MR imaging for blinded observers was 60.4%, 62.0%, and 68.2%, respectively. The specificity was 89.2%, 81.9%, and 81.6%, respectively. Five lesions in three patients were not detected preoperatively using any of the techniques. MR imaging found additional lesions not detected on CT in four patients; CT detected one additional lesion not seen on MR imaging. Ferumoxides-enhanced MR imaging of the liver shows a trend toward increased sensitivity compared with dual-phase helical CT. Specificity of helical CT was superior to that of enhanced MR imaging for most observers.
We aimed to determine the rate of hepatitis E virus (HEV) infection, a recently increasingly reco... more We aimed to determine the rate of hepatitis E virus (HEV) infection, a recently increasingly recognized disease in the Western world, in liver transplant patients by direct molecular testing of liver tissue. A RT-PCR assay was designed for detecting the HEV open reading frame (ORF) 2/3 gene region in formalin-fixed, paraffin-embedded tissues, and applied to all liver biopsies (n=683) taken 4 weeks or later from all patients (n=282) after liver transplantation of two large academic centers. HEV-RNA was detected in ten biopsies from four different patients (rate: 1%). Histology in early HEV infection was variable including cases with only few hepatocellular apoptoses, no or only minute inflammation. Hepatitis lasted for at least 6 months in 3/4 patients. Serologic testing for HEV-RNA in a subcohort (159 patients) was positive in five patients (rate: 3%), resulting in an overall HEV detection rate of 3% (8/282). In case both liver tissue and sera of a patient were available from the same time period, all cases tested positive in one material were also tested positive in the other material, respectively. All patients had de novo autochthonous infection with HEV genotype 3. Our data confirm that HEV infection is a relevant cause of liver injury after liver transplantation. Molecular testing for HEV in routinely processed transplant liver biopsies is powerful for evaluating patients with elevated transaminases of unknown origin. Histology of HEV infection under immunosuppression in the early phase is distinct from HEV infection in immunocompetent individuals.
Guillain-Barre Syndrome (GBS) is believed to be caused by autoimmune mechanisms that are predomin... more Guillain-Barre Syndrome (GBS) is believed to be caused by autoimmune mechanisms that are predominantly T-cell mediated. We report GBS in organ transplant patients and bone marrow transplant patients, both of whom have iatrogenically suppressed T-cell function. We reviewed the Duke University Medical Center database from 1989-1999 for all patients who met the criteria for GBS. There were a total of 212 patients. Of these patients, two had undergone organ transplantation and two had undergone autologous bone marrow transplantation. Our report supports the notion that the humoral immune system is involved in the pathogenesis of GBS. Contrary to previous reports, however, functional recovery can occur without return of T-cell function. This suggests that in organ transplant patients, GBS may be humorally mediated and, even more importantly, responds well to treatment.
Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric monoclonal antibody used fo... more Basiliximab is a high-affinity interleukin-2 receptor (CD25) chimeric monoclonal antibody used for immunoprophylaxis in organ transplantation. It was assessed in a randomized, double-blind, placebo-controlled efficacy trial in de novo liver allograft recipients who received 40 mg of basiliximab (20 mg on days 0 and 4) in addition to baseline immunosuppression with cyclosporine (INN, ciclosporin) microemulsion and corticosteroids. Serial blood samples (8.3 +/- 1.4 per patient) were collected during 12 weeks after transplantation from 184 basiliximab-treated patients, and empirical Bayes estimates of each patient's disposition parameters were derived. Demographic-clinical covariates were explored with regression methods. Basiliximab clearance was 55 +/- 26 mL/h, the distribution volume was 9.7 +/- 4.2 L, and the half-life was 8.7 +/- 6.7 days. Patient weight, age, sex, ethnicity, history of alcoholism, hepatitis C seropositivity, and notable postoperative bleeding had no clinicall...
Dysfunction in the physiological pathways of programmed cell death may promote proliferation of m... more Dysfunction in the physiological pathways of programmed cell death may promote proliferation of malignant cells, and correction of such defects may selectively induce apoptosis in cancer cells. We measured the levels of ceramide, a candidate lipid mediator of apoptosis, in human metastatic colorectal cancer and tested in vitro and in vivo effects of various ceramide analogues in inducing apoptosis in metastatic colon cancer. Human colon cancer showed a > 50% decrease in the cellular content of ceramide when compared with normal colon mucosa. Application of ceramide analogues and ceramidase inhibitors induced rapid cell death through activation of various proapoptotic molecules, such as caspases and release of cytochrome c. Ceramidase inhibition increases the ceramide content of tumor cells, resulting in maximum activation of the apoptotic cascade. Normal liver cells were completely resistant to inhibitors of ceramidases. Treatment of nude mice with B13, the most potent ceramidase...
Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society, 2001
Biliary complications after orthotopic liver transplantation (OLT) lead to considerable morbidity... more Biliary complications after orthotopic liver transplantation (OLT) lead to considerable morbidity and occasional mortality after surgery. Bile duct strictures secondary to localized lymphoproliferative disorder of the porta hepatis is rare, with only 12 cases reported in the English literature. Posttransplant lymphoproliferative disorder develops in up to 9% of liver allograft recipients. We describe 2 adult patients who developed Epstein-Barr virus-associated localized B-cell lymphoma of donor-tissue origin confined to the porta hepatis 3 and 5 months after OLT. Both patients were administered cyclosporine (CyA) and prednisone as primary immunosuppression. One patient was administered basiliximab as induction therapy. Neither patient had CyA trough levels greater than 250 ng/mL. Both patients were treated with a hepatojejunostomy, 75% reduction in immunosuppression therapy, and acyclovir. One patient had complete involution of the tumor, and the second patient had an 80% reduction ...
We describe the unusual case of a patient who developed recurrent right upper quadrant pain 25 yr... more We describe the unusual case of a patient who developed recurrent right upper quadrant pain 25 yr after cholecystectomy. A cystic lesion containing a calculus was identified on transabdominal ultrasound, initially suggesting the possibility of gallbladder duplication. Endoscopic retrograde cholangiography identified this lesion as a massively dilated cystic duct stump. Surgical resection led to complete resolution of symptoms. Recurrent cholelithiasis involving the cystic duct stump may lead to massive dilatation, and must be considered in the differential diagnosis of postcholecystectomy syndrome.
Canadian journal of surgery. Journal canadien de chirurgie, 1993
To determine the efficacy of laparoscopic cholecystectomy (LC) in the treatment of gallstone dise... more To determine the efficacy of laparoscopic cholecystectomy (LC) in the treatment of gallstone disease, all patients who underwent elective surgery for cholelithiasis during three consecutive periods (1989, 1990 and 1991) were studied. There were 121 patients in each period. All patients in the first period underwent open cholecystectomy (OC), whereas 70 (58%) patients underwent laparoscopic procedures in the second period (OC-LC). LC was the treatment of choice in the third period. Multiple factors, including sex, age, clinical and biochemical presentation of the disease and modified Apache II score were comparable among the three groups. The authors found significant differences in length of hospitalization (6.4 +/- 4.2 days in the OC group, 3.6 +/- 2.4 days in the OC-LC group and 2.4 +/- 1.7 days in the LC group, p < 0.01 when compared with the OC group) and return to work after surgery (5.8 +/- 2.8 weeks, 2.8 +/- 1.2 weeks and 1.3 +/- 1.8 weeks respectively, p < 0.01 when co...
Lack of uniform reporting of negative outcomes makes interpretation of surgical literature diffic... more Lack of uniform reporting of negative outcomes makes interpretation of surgical literature difficult. We attempt to define and classify negative outcomes by differentiating complications, sequelae, and failures. Complications and sequelae result from procedures, adding new problems to the underlying disease. However, complications are unexpected events not intrinsic to the procedure, whereas sequelae are inherent to the procedure. Failures are events in which the purpose of the procedure is not fulfilled. We propose a classification of complications based on four grades: Grade I complications are alterations from the ideal postoperative course, non-life-threatening, and with no lasting disability. Complications of this grade necessitate only bedside procedures and do not significantly extend hospital stay. Grade II complications are potentially life-threatening but without residual disability. Within grade II complications a subdivision is made according to the requirement for invas...
Gallstone ileus as a complication of endoscopic sphincterotomy (ES) is exceptional, and this is o... more Gallstone ileus as a complication of endoscopic sphincterotomy (ES) is exceptional, and this is only the second reported case. The present case is unique in that there was no previous instrumentation to the papilla, the bowel was obstructed and perforated, and the patient survived. This case again points out the danger of performing ES for large common bile duct stones. When a large stone is not extracted after ES, close monitoring is mandatory until unequivocal stone passage through the intestine is proven. In both cases reported so far, the lack of adequate monitoring after failure of stone extraction by ES was critical to the severity of gallstone ileus.
Revista de gastroenterología del Perú : órgano oficial de la Sociedad de Gastroenterología del Perú
HELLP syndrome is a rare condition related to pregnancy; however, it can cause complications such... more HELLP syndrome is a rare condition related to pregnancy; however, it can cause complications such as a ruptured subcapsular hepatic hematoma. In most cases, this is managed surgically, but the mortality rate is high, up to 50% of all patients. We present a case with conservative management by percutaneous embolization of the right hepatic artery with a successful outcome and we propose a modern treatment algorithm.
Very few areas in medicine have seen as many controversies as the evaluation and treatment of pat... more Very few areas in medicine have seen as many controversies as the evaluation and treatment of patients with liver diseases. Many novel therapies, often marketed before conclusive demonstration of their efficacy, have been developed to enable selective destruction of liver tumors to minimize the risk of liver failure associated with major surgery. Whether these techniques are effective and result in
Of 1192 patients treated for breast cancer, four had extrahepatic gastro-intestinal metastases as... more Of 1192 patients treated for breast cancer, four had extrahepatic gastro-intestinal metastases as first clinical manifestation of the tumour dissemination. One woman presented with gastric metastases mimicking a linitis plastica. Another had metastases localized to the rectum also mimicking a linitis plastica. Two women had peritoneal and retroperitoneal metastases that caused, in one case, a right hydronephrosis. Histology of the four primary tumours showed invasive lobular carcinoma (ILC) mixed with invasive ductal carcinoma in two. However, ILC exclusively was found at the site of the gastro-intestinal metastases involving the serosal layer (two cases) and extending to the submucosa (one case) or to the mucosal stroma (one case). Thus, when a women with previous history of invasive lobular breast cancer experiences gastro-intestinal symptoms, particular attention should be paid to the large and deep biopsy of lesions to ascertain the histological type and whether oestrogen or progesterone receptors differ from those of the primary breast lesion. Since survival is extremely variable (one woman is alive 7 years after the discovery of gastro-intestinal metastases), treatment including surgery, hormonal manipulation and chemotherapy with the expectation of a cure is often justifiable, particularly if no other extensive metastases are present.
... Correspondence: Pierre-Alain Clavien, MD, PhD, Professor of Surgery, Zurich University Hospit... more ... Correspondence: Pierre-Alain Clavien, MD, PhD, Professor of Surgery, Zurich University Hospital, Zurich 8091, Switzerland ... bleeding from submucosal gastric collaterals secondary to occlusion of the proximal segment of the splenic artery, possibly from a blunt abdominal trauma ...
The purpose of this study was to compare the use of phased array MR imaging of the liver at 1.5 T... more The purpose of this study was to compare the use of phased array MR imaging of the liver at 1.5 T with and without ferumoxides with dual-phase helical CT for the detection of hepatic lesions in candidates for hepatic surgery. Patients with known or suspected hepatic lesions who were eligible for surgery underwent dual-phase helical CT at 20 and 70 sec after the start of contrast material injection and phased array MR imaging using fast spin-echo T2-weighted imaging and gradient-echo T1-weighted imaging before and after ferumoxides infusion of 0.56 mg of iron per kilogram of body weight. Three observers who were unaware of the surgical findings separately reviewed the CT scans and unenhanced and enhanced MR images of 24 patients who completed the protocol. The observers&amp;amp;#39; findings were compared with results obtained at surgery using intraoperative sonography and having histopathologic confirmation. Statistical analysis was performed using a segment-by-segment analysis. Eighty-two lesions were found at surgery. The sensitivity of CT, unenhanced MR imaging, and enhanced MR imaging for blinded observers was 60.4%, 62.0%, and 68.2%, respectively. The specificity was 89.2%, 81.9%, and 81.6%, respectively. Five lesions in three patients were not detected preoperatively using any of the techniques. MR imaging found additional lesions not detected on CT in four patients; CT detected one additional lesion not seen on MR imaging. Ferumoxides-enhanced MR imaging of the liver shows a trend toward increased sensitivity compared with dual-phase helical CT. Specificity of helical CT was superior to that of enhanced MR imaging for most observers.
We aimed to determine the rate of hepatitis E virus (HEV) infection, a recently increasingly reco... more We aimed to determine the rate of hepatitis E virus (HEV) infection, a recently increasingly recognized disease in the Western world, in liver transplant patients by direct molecular testing of liver tissue. A RT-PCR assay was designed for detecting the HEV open reading frame (ORF) 2/3 gene region in formalin-fixed, paraffin-embedded tissues, and applied to all liver biopsies (n=683) taken 4 weeks or later from all patients (n=282) after liver transplantation of two large academic centers. HEV-RNA was detected in ten biopsies from four different patients (rate: 1%). Histology in early HEV infection was variable including cases with only few hepatocellular apoptoses, no or only minute inflammation. Hepatitis lasted for at least 6 months in 3/4 patients. Serologic testing for HEV-RNA in a subcohort (159 patients) was positive in five patients (rate: 3%), resulting in an overall HEV detection rate of 3% (8/282). In case both liver tissue and sera of a patient were available from the same time period, all cases tested positive in one material were also tested positive in the other material, respectively. All patients had de novo autochthonous infection with HEV genotype 3. Our data confirm that HEV infection is a relevant cause of liver injury after liver transplantation. Molecular testing for HEV in routinely processed transplant liver biopsies is powerful for evaluating patients with elevated transaminases of unknown origin. Histology of HEV infection under immunosuppression in the early phase is distinct from HEV infection in immunocompetent individuals.
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Papers by Pierre-alain Clavien