Neutralization of blood group A-antigen by a novel anti-A antibody: overcoming ABO-incompatible solid-organ transplantation

BACKGROUND: The major barrier to ABO-incompatible solid-organ transplantation is acute humoral rejection. It is known to be triggered by antidonor blood group A/B antibodies, which might bind to A/B-antigen on the endothelium of the graft. Various strategies to reduce antiblood group antibody by overcoming ABO-incompatible transplantation have been tried. However, antigen-suppressing procedures have not been performed. METHODS: We produced a novel anti-A antibody (K7508) by immunizing mice with salivary mucin of a blood group A individual, thereby clarifying that blood group A-antigen is expressed in endothelial cells of the liver. We investigated whether K7508 can mask A-antigen on the cells in vitro. Next, we immunized mice with A-antigen-expressing cells coated with K7508 or its Fab fragment, and measured anti-A antibody production in the mice. RESULTS: Blood group A-antigen-expressing cells, such as blood group A-red blood cells (A-RBCs) and A431 cells, coated with K7508 were not recognized by another anti-A antibody in flow cytometry, indicating that A-antigen was masked by K7508 in vitro. The A-antigen on the paraffin-embedded liver tissue was also masked by K7508. Furthermore, the production of anti-A antibody in mice immunized with A-antigen-expressing cells coated with K7508 or its Fab fragment was significantly suppressed compared to that in mice immunized with non-coated cells alone, indicating that A-antigen was neutralized by K7508 in vivo. CONCLUSIONS: The neutralization of blood group antigen by antiblood group antibody and especially its Fab fragment might represent one strategy to overcome ABO-incompatible organ transplantation.     

Value of Multidetector-row Computed Tomography in Diagnosis of Portal Vein Invasion by Perihilar Cholangiocarcinoma

BACKGROUND: Although knowledge of cancer invasion of the portal bifurcation is vitally important in planning an operation for perihilar cholangiocarcinoma, the diagnostic capability of multidetector-row computed tomography (MDCT) for this purpose has not been assessed. We evaluated how well MDCT could identify cancer invasion of the portal bifurcation by perihilar cholangiocarcinoma. METHODS: Between April 2003 and June 2005, perihilar cholangiocarcinoma was resected in 87 patients, 83 of whom underwent MDCT within 1 month before the surgery. Three-dimensional volume-rendered (3DVR) and multiplanar reformation (MPR) images were examined for evidence of portal vein invasion. Agreement with intraoperative and pathologic findings was assessed. Portal bifurcation findings by 3DVR and MPR were classified into no portal vein stenosis, unilateral stenosis, or more extensive stenosis, and also into tumor contact with the bifurcation in no, one of two, or two projections. RESULTS: For macroscopic portal vein invasion, sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were 81.5, 91.1, 81.5, 91.1, and 88.0% in 3D portography and 96.3, 92.6, 86.7, 98.1, and 94.0% in MPR, respectively. Findings by both 3DVR and MPR were significantly correlated with depth of cancer invasion (p < 0.001). CONCLUSION: MDCT is useful in assessing cancer invasion of the portal vein bifurcation by perihilar cholangiocarcinoma.     

Retroportal Hepaticojejunostomy for Extended Resection of Hilar Bile Ducts

High hepatic duct resection sometimes is unavoidable in achieving curative resection of hilar cholangiocarcinoma, as tumor cells can extend further than expected along the bile ducts from the macroscopically evident cancer. In patients undergoing left hemihepatectomy with caudate lobectomy whose bile duct must be severed at the subsegmental bile duct levels, the orifices of the posterior bile ducts would lie behind the right portal vein. Conventional hepaticojejunostomy would be risky in such cases because an anastomosis performed in the usual manner would be subjected to strain. Instead, between 2002 and 2004, three patients underwent retroportal hepaticojejunostomy using a jejunal limb mobilized and positioned behind the hepatoduodenal ligament. Primary tumors were classified as type IV in the Bismuth–Corlette classification. Tension-free hepaticojejunal anastomosis was performed successfully in all three patients; insufficiency of the hepaticojejunostomy did not develop. Neither early nor late complications directly related to this method occurred. Retroportal hepaticojejunostomy, thus, permits more peripheral resection of the hepatic duct while providing a sufficient operative field for safe, tension-free anastomosis. This technique is very useful for patients undergoing left hemihepatectomy requiring high hilar resection of the bile duct.     

Reconstruction of the middle hepatic vein tributaries draining segments V and VIII of a right liver graft by using the recipient’s own middle hepatic vein and vascular closure staples

A right liver graft lacking the middle hepatic vein can result in congestion of the anterior segment. We describe a method of reconstructing the middle hepatic vein tributaries by using the recipient’s own middle hepatic vein with vascular closure staples. During a living donor right liver transplantation, the middle hepatic vein tributaries draining segments V (V5) and VIII (V8) of the right lobe graft were reconstructed using the recipient’s own middle hepatic vein and secured with vascular closure staples. Computed tomography showed good venous outflow from the middle hepatic vein and no congestion or atrophy of the anterior segment of the right liver grafts. Thus, using the recipient’s own middle hepatic vein is a suitable option for reconstructing the middle hepatic vein tributaries (V8 and V5) in right-liver living donor transplantation and the application of vascular closure staples helps to accomplish this.     

Follicular lymphoma of the extrahepatic bile duct mimicking cholangiocarcinoma

We report a case of a 33-year old man who presented with symptoms and signs of an acute biliary tract obstruction with jaundice and abdominal pain. Diagnostic imaging studies revealed a biliary stricture of the hepatic confluence, and a mass at the hepatic hilum which obstructed the extrahepatic bile duct from the outside. At laparotomy, there was 3-cm-size nodule at the hilum which presented with a rubbery consistency. We performed extrahepatic bile duct resection and right and left hepaticojejunostomy. Histological examination of the resected specimen revealed follicular lymphoma, which consisted of medium cleaved follicle-like cells, grade 1 of 3 according to the revised European-American classification of lymphoid neoplasms proposed by International Lymphoma Study Group. Postoperative follow-up of more than 1 year has been completely uneventful, without any symptoms or signs of disease recurrence. This is the second case report of follicular lymphoma of the extrahepatic bile duct.     

Hydrodynamic evaluation of axillary artery perfusion for normal and diseased aorta

Axillary artery perfusion is an attractive alternative to reduce the frequency of atheroembolism in extensive atherosclerotic aorta and aortic aneurysms. This study was conducted to evaluate the flow dynamics of axillary artery perfusion. Transparent glass models of a normal aortic arch and an aortic arch aneurysm were used to evaluate hydrodynamic properties. Streamline analysis and distribution of the shear stress was evaluated using a particle image velocity method. In the normal aortic arch model, rapid flow of 80 cm/s from the right axillary artery ran out from the brachiocephalic artery and grazed the lesser curvature of the aortic arch. There was secondary reversed flow in the ascending aorta. Flow from left axillary perfusion went straight to the descending aorta. In the aortic arch aneurysm model, flow from both axillary arteries hit the lesser curvature of the aortic arch and went into the ascending aorta with vortical flow. Distribution of shear stress was high along the jet from the ostium of the brachiocephalic artery and left subclavian artery. Flow in the aortic arch and the ascending aorta was unexpectedly rapid. Special care must be taken when the patient has frail atheroma around arch vessels or the lesser curvature of the aortic arch during axillary artery perfusion.     

Anterior lumbar interbody fusion using two standard cylindrical threaded cages, a single mega-cage, or dual nested cages: a biomechanical comparison

Our purpose was: (1) to compare the biomechanical properties of an interbody reconstruction using two standard threaded cages (18-mm diameter), a reconstruction using a single mega-cage (24-mm diameter), and a reconstruction using dual nested cages (22-mm diameter); and (2) to quantify the surface area of the cancellous bone bed exposed by reaming for the cages. Each motion segment was tested according to a nondestructive biomechanical loading sequence (compression, flexion, extension, lateral bending, axial torsion). Load was applied first to the intact motion segment and again after the insertion of cages, and stiffness values were calculated at each step. After the testing, each specimen was bisected through the disc and the surface area of the vascular bed was calculated. Comparison of the biomechanical properties of the three reconstructions showed that the dual nested cages produced the stiffest reconstruction. However, when the standard cages were compared with the nested cages, there was no significant difference, and compared with the mega-cage, the only difference was in flexion. The surface area of cancellous bone exposed by reaming for each of the three reconstructions showed the greatest value with the dual nested cages. These findings, together with the improved safety afforded by the nested or mega-cage, suggest that they are appropriate alternatives to the standard dual threaded cage reconstruction. Received: May 16, 2000 / Accepted: October 25, 2000     

Persistent subclinical rejection associated with nodular B-cell infiltrates in a renal transplant recipient

Abstract:  Recently, B-cell infiltrates in acute rejection grafts have attracted interest as an indicator of refractory rejection. Here, we report a case of deceased donor renal transplantation in a Japanese recipient operated overseas in which the recipient suffered from persistent tubulointerstitial rejection episodes associated with B-cell infiltrates. A 59-yr-old man with end-stage renal disease caused by immunoglobulin A nephropathy underwent deceased donor renal transplantation overseas in December 2005. The initial post-operative course was uneventful. The patient was referred to our hospital one month after transplantation. He maintained stable renal function throughout the follow-up period. The maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil and methylprednisolone. His serum creatinine concentration remained around 1.0 mg/dL, with no evidence of proteinuria. However, a discrepancy was detected between the renal function and the pathological findings. The pathology showed subclinical tubulointerstitial rejection with nodular B-cell infiltrates refractory to aggressive antirejection therapy. A steroid pulse and 15-deoxyspergualin were ineffective and the patient developed interstitial fibrosis and tubular atrophy by one yr after the transplantation, with persistent tubulitis and B-cell infiltrates. We treated the refractory rejection with B-cell infiltrates with a single 200 mg/body dose of rituximab and obtained an improvement. The pathological findings after administering rituximab consisted of mild tubulitis classified as Banff borderline, and elimination of the nodular B-cell infiltrates. At present, 20 months after renal transplantation, the patient continues to maintain stable renal function, with a good serum creatinine concentration (0.87 mg/dL).     

Beneficial Effect of Partial Portal Decompression Using the Inferior Mesenteric Vein for Intractable Gastroesophageal Variceal Bleeding in Patients With Liver Cirrhosis

BACKGROUND: Use of the inferior mesenteric vein (IMV) for partial portal decompression has not been recommended as a first-line option for intractable gastroesophageal variceal bleeding because of the thin diameter of the vein. Although these indications remain relevant, few reports have compared partial portal decompression using the IMV with other therapies. We propose that partial portal decompression using the IMV is a useful alternative treatment for intractable variceal bleeding. METHODS: We performed partial portal decompression using the IMV in eight patients with intractable variceal bleeding that had been uncontrolled using medical and endoscopic therapies. All patients were classified into Child's class B or C. The surgical data, morbidity, and mortality were assessed. RESULTS: Mean portal venous pressure significantly decreased from 26.9 +/- 2.0 mmHg before the surgery to 19.8 +/- 3.9 mmHg after the surgery. The operative mortality rate was 0%. The mean duration of hospital stay was 25.5 +/- 13.3 days. Although one patient experienced recurrent bleeding, shunt patency was well maintained in all patients during the follow-up period (mean 28.9 +/- 14.1 months). Six patients are still alive and well without ascites or hepatic encephalopathy. Two of the Child's class C patients who underwent emergency shunt died owing to hepatic decompensation. CONCLUSION: Partial portal decompression using the IMV can be a safe, effective way to treat intractable variceal bleeding in patients with liver cirrhosis. However, use of the shunt procedure may have the most survival benefits for cirrhotic patients with preserved liver function.