Evaluation of the Validity of Endoscopic Transpapillary Gallbladder Drainage for Acute Cholecystitis Based on the Tokyo Guidelines 2018.

GOALS: We evaluated the validity of endoscopic transpapillary gallbladder drainage (ETGBD) as a bridging therapy prior to elective Lap-C for the patients with acute cholecystitis (AC). BACKGROUND: The Tokyo Guidelines 2018 recommend early laparoscopic cholecystectomy (Lap-C) for patients with AC, however, some patients require the preoperative drainage because of inadequate for early Lap-C du to background and comorbidities. STUDY: We performed a retrospective cohort analysis using data from our hospital records from 2018-2021. In total, 71 cases of 61 patients with AC underwent ETGBD. RESULTS: The technical success rate was 85.9%. Patients in the failure group had more complicated branching of the cystic duct. The length of time until feeding was started and until WBC levels normalized, and the length of hospital stay were significantly shorter in the success group. The median waiting period for surgery was 39 days in the ETGBD success cases. The median operating time, amount of bleeding, and length of postoperative hospital stay were 134 min, 83.2g, and 4 days, respectively. In patients who underwent Lap-C, the waiting period for surgery and the operating time were similar between the ETGBD success and failure groups. However, the temporary discharge period after drainage and the length of postoperative hospital stay were significantly longer in the patients with ETGBD failure. CONCLUSIONS: Our study revealed that ETGBD has equivalent efficacy prior to elective Lap-C despite some challenges that lower its success rate. Preoperativ ETGBD can improve patient quality of life by eliminating the need for a drainage tube.

Cost-effectiveness analysis of initial nonoperative management versus emergency laparoscopic appendectomy for acute complicated appendicitis.

BACKGROUND: The evidence regarding the safety and efficacy of nonoperative management is growing. However, the best treatment strategy for acute complicated appendicitis remains controversial. We aimed to evaluate the cost-effectiveness of treatment strategies for complicated appendicitis patients. This study sought to determine the most cost-effective strategy from the health care-payer's perspective. METHODS: The primary outcome was an incremental cost effectiveness ratio (ICER) using nonoperative management with or without interval laparoscopic appendectomy (ILA) as the intervention compared with operative management with emergency laparoscopic appendectomy (ELA) alone as the control. Model variables were abstracted from a literature review, and from data obtained from the hospital records of Tochigi Medical Center. Cost-effectiveness was evaluated using an ICER. We constructed a Markov model to compare treatment strategies for complicated appendicitis in otherwise-healthy adults, over a time horizon of a single year. Uncertainty surrounding model parameters was assessed via one-way- and probabilistic-sensitivity analyses. Threshold analysis was performed using the willingness-to-pay threshold set at the World Health Organization's criterion of $107,690. RESULTS: Three meta-analysis were included in our analysis. Operative management cost $6075 per patient. Nonoperative management with interval laparoscopic appendectomy (ILA) cost $984 more than operative management and produced only 0.005 more QALYs, resulting in an ICER of $182,587. Nonoperative management without ILA cost $235 more than operative management, and also yielded only 0.005 additional QALYs resulting in an ICER of $45,123 per QALY. Probabilistic sensitivity analysis with 1000 draws resulted in average ICER of $172,992 in nonoperative management with ILA and $462,843 in Nonoperative management without ILA. The threshold analysis demonstrated that regardless of willingness-to-pay, nonoperative management without ILA would not be most cost-effective strategy. CONCLUSIONS: Nonoperative management with ILA and Nonoperative management without ILA were not cost-effective strategies compared with operative management to treat complicated appendicitis. Based on our findings, operative management remains the standard of care and nonoperative management would be reconsidered as a treatment option in complicated appendicitis from economic perspective.

Tooth Loss as a Predictor of Postoperative Complications and Prognosis in Patients with Colorectal Cancer.

PURPOSE: We hypothesized that preoperative tooth loss could predict general health conditions, including inflammation, postoperative complications (POCs), and overall survival (OS), in patients with colorectal cancer (CRC) and other gastrointestinal cancers. METHODS: Data of patients who underwent curative surgical resection for CRC during 2017-2021 at our hospital were retrieved. The primary outcomes were POCs, whereas the secondary endpoint was OS. According to the Japanese database, patients within each age range with more than the age-adjusted average number of teeth were classified as the Oral N (normal) group, whereas those with less than the age-adjusted average number of teeth were classified as the Oral A (abnormal) group. The relationship between tooth loss and POCs was assessed using a logistic regression model. RESULTS: Overall, 146 patients were enrolled, with 68 (46.6%) and 78 (53.4%) patients in the Oral N and A groups, respectively. In the multivariate analysis, the Oral A group was an independent risk factor for POCs [hazard ratio (HR), 5.89; 95% confidence interval (CI), 1.81-19.1; p < 0.01]. Similarly, univariate analysis revealed that the Oral A group tended to be associated with OS (HR, 4.57; 95% CI, 0.99-21.2; p = 0.052), but the association was not statistically significant. CONCLUSION: In CRC patients who underwent curative resection, tooth loss was a predictor of POCs. Although further investigations are needed, our results support the use of tooth loss as a simple and essential preoperative evaluation system.

Clinical complete response maintained for more than 5 years after aggressive chemoradiotherapy for advanced rectal cancer with necrotizing fasciitis: a case report.

We report the case of a 65-year-old male diagnosed with advanced rectal cancer associated with necrotizing fasciitis (NF). Since radical surgery, total pelvic exenteration with sacrectomy, was rejected because of detrimental effects on quality of life, chemoradiotherapy (CRT) was chosen as anti-cancer treatment after urgent debridement. Although CRT was paused unintentionally just after delivering the total dose of radiation owing to the relapse of NF, the patient has maintained clinical complete response (cCR) without any distant metastasis for >5 years. Advanced rectal cancer is recognized as an NF risk factor. No definitive treatment strategies have been reported for NF-inducing rectal cancer; however, some reports have demonstrated curative extended surgery. Thus, CRT may be a less-invasive treatment option for NF-inducing rectal cancer, whereas severe adverse effects including re-infection after debridement should be closely monitored.

Spontaneous Biloma Resulting from Intrahepatic Bile Duct Perforation Coexisting with Intrahepatic Cholelithiasis and Cholangiocarcinoma: A Case Report and Literature Review.

BACKGROUND Spontaneous biloma is a rare non-traumatic disease in which an extrahepatic or intrahepatic bile duct perforates spontaneously with no discernable cause. We present the details of a patient with spontaneous biloma resulting from intrahepatic bile duct perforation with concurrent intrahepatic cholelithiasis and cholangiocarcinoma. CASE REPORT A 74-year-old woman was admitted to our hospital with symptoms of abrupt epigastralgia, nausea, and fever. Physical examination revealed epigastric tenderness, guarding, and rebound tenderness. Laboratory test results were normal, except for elevated leukocytes, and C-reactive protein, total bilirubin, and blood urea nitrogen concentrations. Carcinoembryonic antigen and carbohydrate antigen 19-9 concentrations were also elevated. Abdominal computed tomography revealed perihepatic fluid and ascites, with common bile duct dilatation and localized cholangiectasia of B2 with areas of slight high density, which indicated an intraabdominal abscess and intrahepatic cholelithiasis. Spontaneous intrahepatic bile duct perforation was subsequently diagnosed by cholangiography via endoscopic nasobiliary drainage. Left hepatic lobectomy was performed to treat the intrahepatic cholelithiasis and spontaneous biloma. Intraoperatively, a perforation was identified at the edge of the lateral segment of the left triangular ligament, through which bile had been leaking. Histopathology revealed intraductal cholangiocellular carcinoma with intrahepatic cholangiolithiasis. The patient's postoperative course was excellent, and she was discharged on postoperative day 16. However, cancer dissemination to the peritoneum was identified 8 months after surgery. CONCLUSIONS Treatment for patients with intrahepatic cholelithiasis should involve aggressive surgery because of the associated carcinogenicity. This approach reduces the risk of dissemination secondary to intrahepatic bile duct perforation.

Characterization of beta-lactam antibiotic-induced vancomycin-resistant MRSA (BIVR) in a patient with septicemia during long-term vancomycin administration.

It was reported that some methicillin-resistant Staphylococcus aureus (MRSA) show resistance to vancomycin (VCM) and beta-lactam antibiotics; thus, they are termed beta-lactam antibiotic-induced VCM-resistant MRSA (BIVR). The VCM resistance of MRSA is induced by the administration of beta-lactam antibiotics, but this phenomenon can be difficult to detect in the clinical laboratory. We detected the BIVR strain in a 64-year-old man who had had a ventilator tube inserted directly into the windpipe during long-term VCM therapy. The patient was diagnosed with MRSA pneumonia and septicemia on July 5, 2007, and sulbactam/ampicillin (SBT/ABPC) was administered for 5 days. However, the fever recurred, and administration of VCM was resumed for 7 days from July 19. Fever developed again, and VCM was administered again for 14 days from September 30. BIVR and VCM-low-sensitive MRSA were isolated from blood on October 18 and 22, although the VCM trough concentration was 10.2 microg/ml. On October 27, we changed to a combination of fosfomycin (FOM) and arbekacin (ABK), and thereafter the fever quickly decreased and the clinical symptoms abated. We isolated five MRSA strains from the blood of the patient, three strains of VCM-sensitive MRSA, one strain of BIVR, and one strain of a VCM-low-sensitive MRSA. The DNA band patterns determined by pulsed-field gel electrophoresis were completely identical except for the VCM-low-sensitive MRSA, which was missing one band. Furthermore, the VCM-low-sensitive MRSA became sensitive to beta-lactam antibiotics. Our results indicate the possibility that long-term VCM therapy is one of the factors that allow BIVR or VCM-low-sensitive MRSA to emerge, and this allows VCM therapy for MRSA to fail.

Immunological tolerance-related genes in a spontaneous tolerant model of rat liver transplantation explored by suppression subtractive hybridization.

Natural immunological tolerance can be induced in certain types of allogeneic liver transplantation in rats. To screen for genes associated with the induction of tolerance, suppression subtractive hybridization was performed in the rat liver transplantation model between a DA donor and PVG recipient combination where spontaneous immunological tolerance is known to occur without any immunosuppressive treatment. As a result, 112 genes were cloned from a DA liver graft that survived for 20 days in the fully allogeneic PVG recipient. After confirmation of the expression intensity using an in-house manufactured DNA array with cDNAs from the DA graft, 36 genes were classified in the highly expressed group and 26 moderately expressed group. In the first group, there were 8 immunoglobulin-related genes and 6 MHC class II-related genes, suggesting the existence of an underlying rejection response. Among those genes, an antiapoptotic gene in the p38 MAP kinase pathway, heme oxygenase gene (HO-1), and a ras cascade gene, IQ motif containing GTPase activating protein 1 (Iqgapl), retained biological significance. The results suggested that the molecular response to a liver graft tends to be antiapoptotic and to terminate the rejection response. Unfortunately, there was no gene identified that qualified as a putative immunosuppressive protein, liver suppressor factor-1 (LSF-1). The panel of genes identified in the present work will be a useful panel of candidate genes to investigate the induction of spontaneous tolerance.

Potential asbestos exposure among patients with primary lung cancer in Japan.

OBJECTIVE: To investigate the extent of asbestos exposure among patients with primary lung cancer in Japan. METHODS: A retrospective estimation of potential asbestos-exposed individuals, as determined by the presence of pleural plaques identified on chest computed tomography (CT), was conducted on 885 pathologically confirmed primary lung cancer patients (mean age 71.3 years, 641 males). All patients were diagnosed at 29 hospitals across Japan between 2006 and 2007. Since these hospitals belong to the Japan Federation of Democratic Medical Institutions (MIN-IREN), an organization of medical institutions for workers, the study subjects may contain a higher proportion of workers than the general population. RESULTS: Pleural plaques were identified in 12.8% of subjects (15.8% in males and 4.9% in females), consisting exclusively of cases older than 50 years. They were found most frequently on the chest wall pleura (96.5%), followed by the diaphragm (23.9%) and mediastinum (9.7%). Calcifications were seen in 47 cases (41.6%). The highest prevalence of pleural plaques was seen among workers from construction-related fields (37.7%). No distinct lung cancer histology was observed in patients with pleural plaques. Coexistence of pleural plaques and small irregular opacities was observed in 2.5% of subjects. CONCLUSION: In a Japanese population representing more workers than general Japanese, 12.8% of patients with primary lung cancer may have experienced asbestos exposure at some time in the past. Special medical attention should be paid to individuals with a history of employment in construction-related occupations, as workers in this sector showed the highest prevalence of pleural plaques.

TIRC7 is induced in rejected human kidneys and anti-TIRC7 mAb with FK506 prolongs survival of kidney allografts in rats.

TIRC7 delivers essential signals during immune activation as antibodies targeting TIRC7 inhibit lymphocyte proliferation and Th1 cytokine expression in vitro and prolonged kidney and heart allograft survival in vivo. Immunohistochemical analysis of biopsy specimens from human renal allografts undergoing rejection despite treatment with Calcineurin inhibitors (CI) showed elevated TIRC7 expression. Accordingly, with a view to clinical application, we evaluated the therapeutic effect of a chimerized anti-TIRC7 mAb in combination with Tacrolimus (FK506) using a rat kidney transplantation model (DA to Lewis). The combination of sub-therapeutic doses of both compounds significantly (p<0.05) prolonged the median graft survival to 19.5 days compared to monotherapy with FK506 (median survival, 7d) or mAb against TIRC7 (7d). These results suggest a potential synergism of anti-TIRC7 mAb and FK506 action, which could be developed into a novel combination therapy in the clinic by lowering side effects of present CI treatment. Moreover, the identification of TIRC7 in graft infiltrating lymphocytes might serve as a diagnostic marker to detect allograft rejection.

TIRC7 pathway as a target for preventing allograft rejection.

A number of leukocyte surface molecules play an essential role during immune activation. Targeting of these molecules utilizing antibodies serves as a specific therapeutic approach for the treatment of a variety of human diseases. Antibodies targeting a number of leukocyte surface molecules were shown to induce tolerance to transplants in several animal models. A novel membrane molecule, T-cell immune response cDNA 7 (TIRC7), has been shown to be an essential protein in the regulation of lymphocyte activation. TIRC7 does not share any homology with other known membrane proteins expressed during the course of lymphocyte activation and does not belong to any of the known costimulatory, cytokine, chemokine or receptor families. TIRC7, a highly conserved protein across species, is expressed in immune tissues such as spleen, lymph nodes, and T and B lymphocytes. Antibodies against extracellular domains of TIRC7 prolong allograft survival in rat and mouse transplantation models. The prevention of rejection is mediated at least partially via induction of cytotoxic T lymphocyte antigen 4 (CTLA4) in T cells. Functional cellular assays utilizing TIRC7-deficient mice splenocytes show that TIRC7 does have an impact not only on T-cell, but also on B-cell response. Subtherapeutic amounts of FK506 and anti-TIRC7 monoclonal antibody prolong graft survival, suggesting synergistic effects with calcineurin inhibitors. Targeting TIRC7 with monoclonal antibody might serve as a promising therapeutic strategy for preventing allograft rejection in humans and treatment of other immune-related diseases. Acutely rejected human kidney allografts show strong expression of TIRC7 despite treatment with calcineurin inhibitors. Therefore, monitoring TIRC7 expression may facilitate an early diagnostic tool of acute rejection. TIRC7 seems to belong to a group of targets with dual roles in disease pathogenesis, so-called theranostics, which can be utilized to treat and diagnose diseases.

Gastric cancer recognized by metastasis to the ureter.

Although ureteral obstruction is rarely noted in patients with gastric cancer at an advanced stage or at autopsy, the condition caused by authentic ureteral metastasis of gastric cancer is extremely rare. We experienced a case of gastric cancer in a 51-year-old woman who showed bilateral ureteral metastasis. The patient initially complained of right flank pain, caused by right ureteral obstruction, and was referred to our hospital, where she underwent a right nephroureterectomy, with suspicion of primary ureteral neoplasm. Histopathological examination of the resected specimen showed that metastatic growth of adenocarcinoma in the ureteral wall had caused the obstruction, and the subsequent extensive search for the primary lesion revealed asymptomatic gastric cancer. Soon after the nephroureterectomy, the patient developed left hydronephrosis, possibly caused by left ureteral metastasis, and a left percutaneous nephrostomy was performed. She then received chemotherapeutic reagents. However, she finally developed peritoneal carcinomatosis, and died of the disease about 1 year after the onset of the disease. In this report, we also review true ureteral metastasis from the stomach, and discuss the clinicopathologic features.

[Risk factors for low back pain among taxi drivers in Japan].

We conducted a questionnaire study on low back pain (LBP) and working conditions among male taxi drivers employed in the company in Fukuoka city in order to investigate the occurrence of LBP and occupational factors related to LBP among taxi drivers. The study was undertaken through two questionnaires, the first conducted in 1999 (n = 280, first cross-sectional study), the second conducted in 2001 (n = 284, second cross-sectional study). The questionnaire results were used to conduct two analyses: 1) the one-year prevalence of LBP and the relationship between LBP and occupational factors in the second cross-sectional study, and 2) the incidence of LBP and the relationship between LBP and occupational factors from the first to the second cross-sectional study in the longitudinal study. The incidence cases were defined as subjects who met the following conditions: those who had never experienced LBP at the time of the first study but had experienced LBP during the previous year at the time of the 2nd study. The one-year prevalence (45.8%) of LBP among taxi drivers was comparable to rates reported for other occupational drivers in which LBP occurs frequently. This result indicates that LBP is an important health problem for taxi drivers, and an urgent occupational safety and health management issue. The two-year incidence of LBP among the taxi drivers was estimated at 25.9%. LBP was significantly related with the suitability of the driver's seat pan, total mileage on the taxi (total mileage), the level of uncomfortable vibrations on the road, job stress and time employed as a taxi driver. Importantly, the prevalence of LBP increased with increasing total mileage, a finding which had not previously been reported. The findings of this study also suggest that ergonomic problems with the driver's seat pan, whole-body vibration (WBV) and job stress may contribute to LBP among taxi drivers. Further study is needed to confirm how total mileage contributes to LBP. Furthermore, WBV during normal use of taxies should be measured in order to evaluate the association between WBV and LBP.

[Work-relatedness of asthma among outpatients].

The American Thoracic Society (ATS) issued a statement in 2002 that approximately 15% of adult asthma was likely to be work related and emphasized the importance of prevention for occupational asthma. However, the occupational contribution of the burden of asthma has been not understood, because there are very few epidemiological studies in the general population in Japan that examined the population attributable risk (PAR) of asthma due to occupational exposures. Assessing this component of the burden of asthma can better inform preventive strategies. Therefore, we examined the PAR of adult asthma due to occupational exposures among outpatients by using the National Institute for Occupational Safery and Health (NIOSH) criteria. Additionally we examined characteristics of cases of work-related asthma. The results indicate that the PAR of asthma due to occupational exposures is 22.7%, a value comparable to previous reports in Western countries. Therefore, we thought that it suggested that the prevalence of work-related asthma in Japan is similar to Western countries. Five patients met the criteria for having "probable OA", and their occupations were pest control industry, florist, hairdresser and pet groomer. Two patients (40%) changed their jobs due to asthma, which suggests that work-related asthma materially affects continuation of employment. Four patients (80%) had asthma despite leaving their jobs, which suggests that it is crucial to prevent work-related asthma.

Partial duplication of MSH2 spanning exons 7 through 14 in Lynch syndrome.

BACKGROUND: Lynch syndrome, also referred to as hereditary nonpolyposis colorectal cancer, is the most common form of hereditary colorectal cancer, and is associated with a high incidence of multiple primary neoplasms in various organs. METHODS: A 79-year-old woman (patient 1) diagnosed with ascending colon cancer had a history of previous carcinomas of the uterus, stomach, uroepithelial tract, and colon. One year later, she developed a brain tumor (glioblastoma). A 54-year-old female (patient 2) was diagnosed with endometrial cancer and sigmoid colon cancer. Both patients underwent genetic evaluations independently. RESULTS: No mutations were found in an exon-by-exon analysis of genomic DNA by polymerase chain reaction (PCR) and reverse transcription (RT)-PCR. However, multiplex ligation-dependent probe amplification (MLPA) identified genomic duplication spanning from exon 7 to exon 14 of the MSH2 gene in both patients. Due to the presence of this characteristic gene duplication, their pedigrees were investigated further, and these showed that they are paternal half-sisters, consistent with paternal inheritance. CONCLUSION: Large genomic duplication from intron 6 through intron 14 in MSH2 is a very rare cause of Lynch syndrome and is difficult to identify with conventional methods. MLPA may be an alternative approach for detecting large-scale genomic rearrangements.

Low-frequency oscillation of instantaneous heart rate in newly hatched chicks.

Instantaneous heart rate (IHR) of chickens began to fluctuate on days 13-14 of incubation and heart rate (HR) fluctuations became augmented towards hatching and increased further after hatching. IHR fluctuations of newly hatched chicks have been categorized into three types: type I HR variability (HRV), which is high-frequency oscillation; type II HRV, which is low-frequency oscillation; and type III HR irregularities (HRI), which are irregular HR accelerations. The present experiment was carried out to investigate the origin of type II HR oscillations. Following previous evidence, we assumed that the low-frequency oscillation of HR in newly hatched chicks was related to thermoregulation and changed by environmental temperature. Eventually, type II HRV was produced or augmented by exposure of hatchlings to lowered ambient temperature and was abolished by exposure to elevated environmental temperature. The hatchlings that were exposed to large temperature decreases tended to increase their HR more than those exposed to small temperature decreases, and vice versa. The HR oscillation accompanied by an elevation of HR baseline in response to cooling may be a phenomenon related to thermoregulation in chick hatchlings.

Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage.

PURPOSE: To describe the clinical features and to present results of new diagnostic methods to help define the cause of the clinical syndrome of intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage (IHAPSH). DESIGN: Retrospective review of patients with IHAPSH at presentation seen in 3 centers in Hawaii and Japan. METHODS: We analyzed data including patient demographics, presenting symptoms, initial and final visual acuities, biomicroscopic findings, fundus photographs, and results of available ancillary testing, including fluorescein angiography, B-scan ultrasonography, and optical coherence tomography. RESULTS: There were 10 eyes of 9 patients (7 female and 2 male, 8 Asian and 1 white) aged 14 to 79 years. All patients experienced an acute onset of visual symptoms. Eight eyes had mild to severe myopia (-2.50 diopters [D] to -9.50 D), and 8 eyes had a tilted disc. Hemorrhage within the disc and adjacent subretinal hemorrhage were located nasally in 6 eyes, superiorly in 2 eyes, and temporally in 2 eyes. Vitreous hemorrhage was noted in 6 of 10 eyes. Posterior vitreous evaluation by biomicroscopy (10 eyes), by B-scan ultrasonography (4 eyes), and by optical coherence tomography (2 eyes) revealed no evidence of vitreopapillary traction, except for a follow-up optical coherence tomography in 1 eye showing localized vitreoretinal separation with residual attachment to the optic disc 10 months after presentation. Fluorescein angiography showed mild disc staining in 4 of 8 eyes. Hemorrhage spontaneously resolved within 1 to 7 months, and there were no recurrent hemorrhages with an average follow-up of 13.5 months (range, 2-31 months). Visual acuities maintained or improved to 20/25 or better in 8 eyes. The other 2 eyes had unrelated poor vision. CONCLUSIONS: Intrapapillary hemorrhage with adjacent peripapillary subretinal hemorrhage is more common in myopic eyes and spontaneously resolves without treatment. The unique structural architecture of the elevated nasal edge of the myopic tilted disc and the choroidal blood supply of the prelaminar optic nerve may predispose patients to bleeding from the optic discs, which may be spontaneous or may be precipitated by acute disc edema, Valsalva maneuver, or vitreopapillary traction.

Standardization of ischemic hepatic failure in pigs as a model for bioartificial liver assessment.

PURPOSE: A standard protocol of ischemic liver failure in pigs was examined to establish a system for assessing the efficacy of a bioartificial liver, based on clinical practice. METHODS: The portal blood flow was extracorporeally bypassed into the cervical jugular vein, using a centrifugal blood pump. The portal vein and hepatic artery were then ligated. RESULTS: The maintenance protocol was established as follows: (1) the concentration of the inhaled anesthetic was decreased by 0.2% when the systolic blood pressure was <100 mmHg; (2) the volume of an infusion containing 5% glucose was increased to 10 ml/kg per hour when central venous pressure was <5 mmHg; (3) 20 ml of 50% glucose was injected intravenously when the blood glucose was <50 mg/dl; (4) 2000 units of heparin was injected intravenously when the activated clotting time was <150 s; (5) sodium bicarbonate was given when the blood pH was <7.3; (6) tidal volume was increased by 1 ml/kg when the pCO(2) was >80 mmHg; (7) oxygen was increased by 25% when the pO(2) was <100 mmHg. No vasopressors were used in the experiment. CONCLUSION: Our protocol reduced the operating time and minimized the risk of data deviation that can arise from variations in operating techniques and individual animal conditions. This experimental model is also easy to use as a bridge to transplantation.