H. Oya

The differential effect of stress on natural killer T (NKT) and NK cell function

When C57Bl/6 mice were exposed to restraint stress for 12 h or 24 h, lymphocytopenia was induced in the liver, spleen, and thymus. We examined which types of lymphocytes were sensitive or resistant to such stress by a immunofluorescence test. T cells of thymic origin were sensitive while NKT and NK cells were resistant. In contrast to the increase in the proportion of NK cells, NK activity of liver lymphocytes against YAC‐1 targets decreased at 24 h after stress. On the other hand, their NKT cytotoxicity against syngeneic thymocytes increased in parallel with an increase in their proportion. In perforin −/– B6 mice and B6‐gld/gld (Fas ligand−) mice, NK cells were found to mediate cytotoxicity through perforin while NKT cells mediated self‐reactive cytotoxicity through Fas ligand. These results suggest that stress increases the proportion of both NK and NKT cells, but that NK cytotoxicity is suppressed while self‐reactive NKT cytotoxicity is not, due to a diversity of their functional mechanisms.

Clinical and cardiac features of patients with subarachnoid haemorrhage presenting with out-of-hospital cardiac arrest

BACKGROUND Subarachnoid haemorrhage (SAH) is known as one of the aetiologies of out-of-hospital cardiac arrest (OHCA). However, the mechanisms of circulatory collapse in these patients have remained unclear. METHODS AND RESULTS We examined 244 consecutive OHCA patients transferred to our emergency department. Head computed tomography was performed on all patients and revealed the existence of SAH in 14 patients (5.9%, 10 females). Among these, sudden collapse was witnessed in 7 patients (50%). On their initial cardiac rhythm, all 14 patients showed asystole or pulseless electrical activity, but no ventricular fibrillation (VF). Return of spontaneous circulation (ROSC) was obtained in 10 of the 14 patients (14.9% of all ROSC patients) although all resuscitated patients died later. The ROSC rate in patients with SAH (71%) was significantly higher than that of patients with either other types of intracranial haemorrhage (25%, n=2/8) or presumed cardiovascular aetiologies (22%, n=23/101) (p<0.01). On electrocardiograms, ST-T abnormalities and/or QT prolongation were found in all 10 resuscitated patients. Despite their electrocardiographic abnormalities, only 3 patients showed echocardiographic abnormalities. CONCLUSIONS The frequency of SAH in patients with all causes of OHCA was about 6%, and in resuscitated patients was about 15%. The initial cardiac rhythm revealed no VF even though half had a witnessed arrest. A high ROSC rate was observed in patients with SAH, although none survived to hospital discharge.

The Majority of Lymphocytes in the Bone Marrow, Thymus and Extrathymic T Cells in the Liver Are Generated In Situ from Their Own Preexisting Precursors

Parabiotic pairs of B6.Ly5.1 and B6.Ly5.2 mice were used to investigate how lymphocytes in various organs and various lymphocyte subsets mixed with partner cells. The origin of partner cells was determined by using anti‐Ly5.1 mAb in conjunction with immunofluorescence tests. Parabiosis was also produced after the irradiation of B6.Ly5.2 mice at various doses to prepare an immunosuppressive partner. Irrespective of irradiation, lymphocytes and other hematopoietic cells in the bone marrow and lymphocytes in the thymus showed a low mixture of partner cells in comparison with those of all other organs tested. On the other hand, lymphocytes in the blood, spleen, and lymph nodes became a half‐and‐half mixture of their own cells and partner cells by 14 days after parabiosis. Among lymphocyte subsets, intermediate CD3 cells (i.e., CD3int cells) and NKT cells (i.e., NK1.1+ subset of CD3int cells) in the liver also showed a low mixture of partner cells. The present results raise the possibility that lymphocytes in the bone marrow and thymus, and extrathymic T cells in the liver might be in situ generated from their own preexisting precursor cells. Another observation was that, after irradiation, partner cells showed accelerated mixture even if they showed a low mixture under non‐irradiated conditions. However, only lymphocyte subsets with the same phenotype as those of preexisting cells entered the corresponding sites.

Disparate effect of beige mutation on cytotoxic function between natural killer and natural killer T cells

Beige mice lack natural killer (NK) cytotoxicity, although NK cells are normally present. In recent studies, NK T cells have been newly identified. We therefore examined the number and function of NK T cells in beige mice. The number of NK T cells was at a normal level in the liver of beige mice. NK cytotoxicity was decreased in the liver of these mice, whereas NK T cytotoxicity was intact. When immunochemical staining for perforin was conducted, the majority of NK cells and the minority of NK T cells in beige mice carried a giant granule, containing perforin, in the cytoplasm. In the case of control B6 mice, the majority of NK cells and the minority of NK T cells had multiple, dispersed granules containing perforin. These results suggest that NK T cytotoxicity is unaffected by the beige mutation, owing to their cytotoxicity being mediated without the secretion system of perforin.

Magnetic Compression Anastomosis for Bile Duct Stenosis After Donor Left Hepatectomy: A Case Report

Magnetic compression anastomosis (MCA) provides a minimally invasive treatment creating a nonsurgical, sutureless enteric anastomosis in conjunction with an interventional radiologic technique by using 2 high-power magnets. Recently, the MCA technique has been applied to bile duct strictures after living donor liver transplantation or major hepatectomy. Herein we described use of MCA for bile duct stenosis 5 months after donor left hepatectomy in a 24-year-old man who presented with a stricture at the porta hepatis and intrahepatic bile duct dilatation. Unsuccessful transpapillary biliary drainage and balloon dilatation through a percutaneous transhepatic biliary drainage (PTBD) route led to the MCA. A 4-mm-diameter cylindrical samarium-cobalt (Sm-Co) daughter magnet with a long nylon wire was placed at the superior site of the obstruction through the PTBD route. A 5-mm-diameter Sm-Co parent magnet with an attached nylon handle was endoscopically inserted into the common bile duct and placed at the inferior site of obstruction. The 2 magnets were attracted, sandwiching the stricture and establishing a reanastomosis. In conclusion, the MCA technique was a unique procedure for choledochocholedochostomy in a patient with bile duct stenosis after donor hepatectomy.

Method for spontaneous constriction and closure of portocaval shunt using a ligamentum teres hepatis in small-for-size graft liver transplantation.

Background. We have developed a new portocaval (PC) shunt creation technique for use in small-for-size (SFS) graft liver transplantations. PC shunts are already used to avoid SFS graft syndrome in cases of adult-to-adult living donor liver transplantation (LDLT), but the current method of creating these shunts is subject to two problems: reportal hypertension and liver dysfunction after premature ligation of the PC shunt; and graft atrophy and liver dysfunction because of the loss of portal venous flow late in the recovery period after LDLT. Methods. Our new technique avoids these two problems simultaneously by using the interposed obliterated ligamentum teres hepatis (LTH) to create the PC shunt, then obstructing the PC shunt after regeneration of the liver graft. Results. We have used this technique in four cases. In all cases, portal venous pressures after shunting were lower than those before shunting, and PC shunts with lower portal pressure were obstructed faster than that with higher portal pressure. Conclusion. Our results suggest that the LTH can function as a shape memory graft to reduce portal venous flow after regeneration of the graft liver. Using the LTH to create a PC shunt might help to prevent both SFS graft syndrome early in the recovery period after LDLT and loss of portal venous flow late in the recovery period.

Successful Super-Small-for-Size Graft Liver Transplantation by Decompression of Portal Hypertension via Splenectomy and Construction of a Mesocaval Shunt: A Case Report

We performed a successful super-small-for-size graft liver transplantation by decompressing portal hypertension via splenectomy and a mesocaval shunt. A 46-year-old woman with Child-Pugh class C liver cirrhosis associated with Wilsons disease underwent a living donor liver transplantation (LDLT). The donor had an anomalous portal vein, hepatic vein, and bile duct, so we had to use the right lateral segment for the graft. Preoperative computed tomographic (CT) volumetry showed the volume of this area to be 433 mL; graft-to-recipient weight ratio (GRWR) was 0.72; and graft-to-standard liver volume (GV/SLV) was 39.0%. However, the real volume of the resected right lateral segment was 281 g; GRWR was 0.47; and GV/SLV was 25.3%--a super-small-for-size graft. After implantation, congestion of the small graft was severe due to excessive portal hypertension. Therefore, we tried decompressing the portal vein. First, we performed splenectomy which reduced the portal pressure which remained excessive. Second, a mesocaval shunt was constructed decreasing the portal pressure from 38 to 30 cm H2O. Additionally, we initiated continuous portal injection of prostaglandin E1. The postoperative course was not smooth, but the general status slowly recovered. Over 25 cm H2O of portal hypertension was observed until postoperative day 21 when it improved. At last, the recipient was discharged on postoperative day 156. Accurate preoperative CT volumetry is important to obtain sufficient graft volume. Our case may be one of the smallest-for-size grafts that was successfully transplanted. Management of excessive portal hypertension is important for LDLT, especially using a small-for-size graft. Splenectomy and construction of a mesocaval shunt may be useful strategies to decompress the portal vein.

Feasibility of Auxiliary Partial Living Donor Liver Transplantation for Fulminant Hepatic Failure as an Aid for Small-for-Size Graft : Single Center Experience

Auxiliary partial orthotopic liver transplantation (APOLT) or heterotopic auxiliary partial liver transplantation (HAPLT) was initially indicated for potentially reversible fulminant hepatic failure (FHF). We started auxiliary partial living donor liver transplantation (LDLT) for FHF in February 2002. Since then, 5 FHF patients (3 females and 2 males) underwent auxiliary partial LDLT: 3 cases of APOLT and 2 cases of HAPLT. All of them received a small-for-size graft: graft-to-recipient weight ratio (GRWR) < or = 1.0%. The etiologies of FHF were hepatitis B virus (HBV) in 1, Wilsons disease in 1, and unknown origin in 3 cases. Three were the acute type and 2 the subacute type of FHF. Median age was 45 years (range, 14-54 years). Blood type was identical in all cases. A left lobe graft was used in 4 instances and a right lobe graft in 1 case. Median GRWR was 0.74 (range, 0.42-0.85). Median follow-up was 42 months (range, 3 days to 70 months). Three of 5 patients (60%) were alive (at 42, 67, and 70 months) and 1 was free of immunosuppression after sufficient recovery of the native liver. Two cases succumbed: 1 at postoperative day 3 because of cytomegalovirus pneumonia and 1 at 10 months after APOLT because of sepsis. Complications were seen in all 5 patients: Relaparotomy for hemostasis in 3, decompression surgery of the abdominal cavity in 1, rehepaticojejunostomy in 1, and biliary strictures in 2 cases. Auxiliary partial LDLT may be a choice as an aid for a small-for-size graft in FHF.

Long-Term Follow-up Study of Biliary Reconstructions and Complications After Adult Living Donor Liver Transplantation: Feasibility of Duct-to-Duct Reconstruction With a T-Tube Stent

The aim of this study was to analyze the feasibility of duct-to-duct biliary reconstruction (hepaticohepaticostomy) with a T-tube stent (HH-T) after adult living donor liver transplantation (LDLT) based on long-term follow-up. We retrospectively evaluated 63 primary adult LDLTs who had survived >1 month from March 1999 to January 2008. We compared the incidence of bile leaks and biliary strictures (BS) in 3 groups of patients: Roux-en-Y hepaticojejunostomy (HJ; n = 18); duct-to-duct hepaticohepaticostomy with external stents except a T-tube (HH; n = 26); and HH-T (n = 19). Median follow-up was longer among the HJ (63 months) than the other groups (32 months in HH and 25 months in HH-T; P = .04). Bile leaks developed in 8 of the HJ cases (44%); 9 of the HH cases (33%); and 1 of the HH-T cases (5%; P = .02). All cases with bile leaks (n = 18) were treated using continuous drainage, 15 of them (83%) successfully. BS developed in 4 HJ cases (22%); 12 HH cases (46%), and 4 HH-T cases (21%; P = .12). Intervention for BS (n = 20) was successful in 10 cases (50%) via an endoscopic approach and 6 cases (30%) via a percutaneous transhepatic approach. Operative management for BS was required in 4 cases (20%). Biliary reconstruction using HH-T may be effective to prevent bile leaks after LDLT. However, HH-T may not decrease the incidence of BS after adult LDLT.

Catheter-directed continuous thrombolysis following aspiration thrombectomy via the ileocolic route for acute portal venous thrombosis: report of two cases

Although acute portal venous thrombosis (PVT) is a potentially life-threatening complication that occurs after hepatobiliary surgery with portal vein (PV) reconstruction or splenectomy, no effective or universal treatments have yet been established. Transjugular or transhepatic catheter-directed thrombolysis has recently been reported to be effective for treating acute PVT. However, the efficiency of this treatment for complete PV occlusion might be limited because a poor portal venous flow prevents thrombolytic agents from reaching and dissolving thrombi. Moreover, the use of the transjugular or transhepatic route might not be suitable in patients who have undergone major hepatectomy or in those with ascites due to an increased risk of residual liver injury or intra-abdominal bleeding following puncture to the residual liver. We herein describe the cases of two patients with almost total PV occlusion caused by massive thrombi that formed after hepatobiliary surgery, who were successfully treated with catheter-directed continuous thrombolysis following aspiration thrombectomy via the ileocolic route. This treatment should be considered beneficial for treating selected patients such as the two patients described herein.