小儿原发性膀胱输尿管返流的诊断与手术治疗(附39例报告)

目的：总结小儿原发性膀胱输尿管返流（PVUR）诊治经验。方法：回顾分析PVUR39例的诊治资料,1例4月龄婴儿做膀胱造口,2例患侧及1例对侧并发肾发育异常者共做3例肾切除,1例上尿路正常者用药物治疗,余35例均行膀胱内、外的横向推进抗返流输尿管膀胱再植术。结果：35例（92％）术后效果满意,2例双侧病变者第一次手术仅做严重的一侧,术后尿内持续有脓细胞,复查时原对侧Ⅰ、Ⅱ度返流增重,经再次手术治愈。1例手术后仍不能挖掘尿路感染,经患肾穿刺造瘘后好转。结论：外科矫治PVUR（Ⅳ-Ⅴ）的手术成功率,双 侧病变一期完成双侧手术。6月龄以内的PVUR（Ⅳ-Ⅴ）应做膀胱造口,周岁后应考虑抗返流的输 尿管膀胱再植术。     

Linkage of Gitelman syndrome to the thiazide-sensitive sodium-chloride cotransporter gene with identification of mutations in Dutch families

Gitelman syndrome is a mostly autosomal recessive disorder affecting the renal tubular function associated with hypokalemia and hypomagnesemia. Functional studies point to a defect in the distal renal tubule in the thiazide-sensitive, electroneutral sodium-chloride cotransporter (TSC). Based upon the localization of a 2.6 cDNA encoding the human TSC to chromosome 16q13, polymorphic markers spanning the region from 16p12 to 16q21 were tested for linkage to the Gitelman syndrome locus in three Dutch families with autosomal recessive inheritance of this disorder. Using two-point linkage analysis, a maximum LOD score (Z_max of 4.49 (at Θ = 0.00) was found for the marker D16S408. One crucial recombination event places the Gitelman syndrome locus distal to D16S419 at 16q12-13. Subsequently we have tested our group of Gitelman patients for mutations in the human TSC gene. Two mutations were identified in three Gitelman families. Our study confirms that the human TSC gene is involved in Gitelman syndrome. Patients from three Gitelman families reveal two identical human TSC mutations, suggesting these families share a common ancestor. Received April 19, 1996; received in revised form and accepted May 24, 1996     

Conservative treatment and anti-reflux surgery in adults with vesico-ureteral reflux: effect on urinary-tract infections, renal function and loin pain in a long-term follow-up study.

STUDY PURPOSE: To investigate the long-term effects in adults of conservative treatment and anti-reflux surgery for vesico-ureteral reflux on urinary-tract infections, renal function, and loin pain. METHODS: Of 115 adult patients with vesico-ureteral reflux diagnosed between 1968 and 1984, conservative treatment was given to 46 patients (36 women) and anti-reflux surgery was performed in 57 patients (52 women). The remaining 12 patients underwent nephrectomy or heminephrectomy and were excluded from the study. The anti-reflux surgical methods used were the Politano-Leadbetter procedure in 44 patients (73 ureters) and the Hutch procedure in 19 patients (25 ureters). Six of these patients were operated on with both methods. RESULTS: The frequency of acute pyelonephritis was significantly reduced after anti-reflux surgery (P < 0.0001) as well as after diagnosis of vesico-ureteral reflux in the group given conservative treatment (P or < 0.001). The frequency of lower-urinary-tract infections was not altered in either group. Surgery had no effect on significant albuminuria (Albustix > or = 2+) or on progressive renal functional deterioration. Forty-three patients reported recurrent loin pain at the time of diagnosis or anti-reflux surgery. Only one of the 12 patients in the conservative group, compared with 29 of the 31 patients in the anti-reflux surgery group, obtained relief from loin pain during the follow-up. Nine patients in the anti-reflux surgery group reported restitution of reduced general well-being after surgery. These patients had experienced weariness and/or headache before surgery. Vesico-ureteral reflux was eliminated more frequently (P < 0.01) in the patients operated on by the Politano-Leadbetter procedure (94%) than in those operated on by the Hutch procedure (68%). CONCLUSIONS: Loin pain is common in adults with vesico-ureteral reflux and is effectively eliminated by anti-reflux surgery. Anti-reflux surgery should be considered in adults with vesico-ureteral reflux and very frequent acute pyelonephritic attacks only if conservative treatment has failed to alleviate these symptoms. Anti-reflux surgery is not indicated with the aim of arresting renal functional deterioration.     

Pathology and Genetics of Diffuse Gliomas in Adults

The current World Health Organization (WHO) classification of tumors of the central nervous system (CNS) is essentially a lineage-oriented classification based on a presumable developmental tree of CNS. A four-tiered WHO grading scheme has been successfully applied to a spectrum of diffusely infiltrative astrocytomas, but it is not fully applicable to other gliomas, including oligodendrogliomas and ependymomas. Recent genetic studies have revealed that the major categories of gliomas, such as circumscribe astrocytomas, infiltrating astrocytomas/oligodendrogliomas, and glioblastoma, roughly correspond to major genetic alterations, including isocitrate dehydrogenases (IDHs) 1/2 mutations, TP53 mutations, co-deletion of chromosome arms 1p/19q, and BRAF mutation/fusion. These genetic alterations are clinically significant in terms of the response to treatment(s) and/or the prognosis. It is, thus, rational that future classification of gliomas should be based on genotypes, rather than phenotypes, although the genetic features of each tumor are not sufficiently understood at present to draw a complete map of the gliomas, and genetic testing is not yet available worldwide, particularly in Asian and African countries. This review summarizes the current concepts of the WHO classification, as well as the current understanding of the major genetic alterations in glioma and the potential use of these alterations as diagnostic criteria.     

Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity

 Studies on polymorphisms of candidate genes and their association with bone mineral density (BMD) have been reported in many populations, but few have been reported in Chinese populations. We investigated polymorphisms of the following five commonly used markers of four prominent BMD candidate genes with the purpose of identifying useful genetic markers for osteoporosis genetic research in Chinese: the Sp1 and RsaI polymorphisms of the collagen type 1 alpha l (Col1a1) gene, the −174G/C promoter polymorphism of the interleukin 6 (IL-6) gene, the Asn363Ser polymorphism of the glucocorticoid receptor (GR) gene, and the T → C polymorphism in intron 5 of the transforming growth factor β₁ (TGF-β₁) gene. We evaluated these polymorphisms using PCR-RFLP in samples of at least 124 random individuals. We compared the polymorphisms of these five markers with other populations using the χ² test and Fisher's exact two-tailed test. For the RsaI polymorphism, only three heterozygotes but no variant homozygote were identified. For the −174G/C polymorphic site, only one GC heterozygote and no CC homozygote were found. Alleles s, Ser, and A ₁ at the Sp1, Asn363Ser, and T → C marker sites that have been found to be polymorphic in other populations were not found in Chinese. Significant differences of allele and genotype frequency distributions were observed at these polymorphisms (P < 0.001) after comparing with other populations. Our results suggest that variant alleles of the five markers are absent or too rare to be useful genetic makers in Chinese, despite the fact that they have been commonly used as polymorphic markers in osteoporosis genetic research in other populations. Received: April 22, 2002 / Accepted: July 2, 2002 Acknowledgments. The study was partially supported by the Hunan Province Special Professor Start-up Fund (25000612), Chinese National Science Foundation (CNSF) Outstanding Young Scientist Award (30025025), CNSF Grant (30170504), a grant from Huo Ying-Dong Education Foundation, and a Seed Fund from the Ministry of Education of P.R. China (25000106). Some investigators (R.R.R., V.D., H.W.D.) were partially supported by grants from the Health Future Foundation of USA, grants of National Health Institute (K01 AR02170-01, R01 GM60402-01A1), grants from the State of Nebraska Cancer and Smoking Related Disease Research Program, and U.S. Department of Energy grant (DE-FG03-00ER63000/A00). We thank all the study subjects for volunteering to participate in the study. Offprint requests to: H.-W. Deng     

Mutations in the <Emphasis Type="Italic">ROBO2</Emphasis> and <Emphasis Type="Italic">SLIT2</Emphasis> genes are rare causes of familial vesico-ureteral reflux

Familial clustering of vesico-ureteral reflux (VUR) suggests that genetic factors play an important role in the pathogenesis of this condition. The SLIT2 protein and its receptor, ROBO2, have key functions in the formation of the ureteric bud. Two recent studies have found that ROBO2 gene missense mutations are associated with VUR. In the study reported here, we investigated the genetic contribution of the SLIT2 and ROBO2 genes in non-syndromic familial VUR by mutation screening of 54 unrelated patients with primary VUR. Direct sequencing of all 26 exons and the exon–intron boundaries revealed six ROBO2 gene variants, two of which were new. Direct sequencing of all 37 exons and the exon–intron boundaries identified 20 SLIT2 gene variants, two of which were new. One variant, c.4253C > T, which was found in two families, leads to an amino acid substitution in a relatively well-conserved amino acid, p.Ala1418Val, which was predicted to cause an altered secondary structure but to have little impact on the three-dimensional structure. This missense variant did not segregate with VUR in these two families and was not found in 96 control subjects. We conclude that gene variants in ROBO2 and SLIT2 are rare causes of VUR in humans. Our results provide further evidence for the genetic heterogeneity of this disorder.     

Testosterone enanthate therapy is effective and independent of SRD5A2 and AR gene polymorphisms in boys with micropenis

PURPOSE: We report penile length (PL) responses to testosterone enanthate (TE) therapy for micropenis, and the relevance of the V89L polymorphism of SRD5A2 encoding the 5alpha-reductase type 2 and CAG repeat length polymorphism of AR encoding the androgen receptor. MATERIALS AND METHODS: A total of 53 Japanese boys with micropenis (less than -2.0 SD) 0 to 13 years old who had no SRD5A2 or AR mutation were examined. TE was given at a dosage of 25 mg intramuscularly, and PL was measured at least 4 weeks after the injection. The 2 polymorphisms were determined by direct sequencing. RESULTS: PLs became -2.0 SD or greater in all the boys after TE therapy (1 injection in 4 boys, 2 in 28, 3 in 19 and 4 in 2), with a significant increase in the medians of PLs (from 2.5 to 3.5 cm, p <0.0001) and SD score, (from -2.6 to -0.7, p <0.0001). The increment in actual PL at the first injection ranged from 0.2 to 1.5 cm (median 0.6) and was independent of age (r = 0.22, p = 0.12) and body surface area (r = 0.11, p = 0.43), while that in PL SD score at the first injection ranged from 0.3 to 2.5 (1.0) and was inversely correlated with age (r = -0.33, p = 0.02) and body surface area (r = -0.37, p = 0.008). The actual PL increment at the first injection was also unrelated to initial PL (r = -0.03, p = 0.81). The median of actual PL increments at the first injection was similar among boys with V/V, V/L and L/L genotypes of SRD5A2 (0.6 cm in 18, 0.7 cm in 30 and 0.5 cm in 5, respectively, p = 0.77), and between boys with and without long CAG repeats (26 or greater) of AR (0.65 cm in 6 and 0.6 cm in 47, respectively, p = 0.77). In addition, there was no significant correlation between actual PL increment at the first injection and CAG repeat length (r = 0.06, p = 0.67). CONCLUSIONS: Our results suggest that administration of 25 mg TE is effective for micropenis in prepubertal boys with no SRD5A2 or AR mutation, with variable but significant PL increments, and that the penile responsiveness to TE therapy is independent of the V89L and the CAG repeat length polymorphisms.     

The cumulative incidence of significant gastroesophageal reflux in patients with congenital diaphragmatic hernia-a systematic clinical, pH-metric, and endoscopic follow-up study

Background

Gastroesophageal reflux (GER) is common in patients with congenital diaphragmatic hernia (CDH). Gastroesophageal reflux may occur early after the primary repair of CDH and require antireflux surgery (ARS). It is unknown how many patients will be severely affected later on. We conducted an objective long-term follow-up for the cumulative incidence of CDH-associated GER based on symptoms, pH-metry, and histology.

Materials and Methods

From March 1990 to July 2006, we admitted 33 newborn patients with CDH. Twenty-six patients (79%) (male 13, left-sided 21) survived. Extracorporeal membrane oxygenation was required in one patient and patch closure in 10 patients. The follow-up consisted of assessment of GER symptoms at 6 months, 1 year, 3 years, 5 years, and 10 years; endoscopy; and pH-metry for all patients at 1 year and to selected patients (with symptoms or complications of GER) from 3 to 10 years after the primary closure of CDH. Gastroesophageal reflux was considered significant (sGER) when a symptomatic patient required ARS, had endoscopic biopsies showing at least moderate esophagitis, or total and preprandial reflux index of more than 10% and 5%, respectively.

Main Results

The incidence of sGER (patients with sGER/total amount assessed) at 6 months, 1 year, 3 years, 5 years, and 10 years was 27% (7/26), 42% (11/26), 53% (8/15), 53% (8/15), and 55% (5/9), respectively. During a median follow-up of 60 months (range, 12-195 months), 12 (46%) of 26 patients had sGER and 4 (15%) required ARS. After the assessment at 1 year, only one new case of sGER appeared. Endoscopic and/or pH-metric assessment covered 100% of the patients at 1 year follow-up, but later on only 70%.

Conclusion

One year after the primary closure of CDH, the incidence of sGER was 42%. After 1 year follow-up, only one new case of sGER was found, and ARS was not required. In patients who required ARS manifested before 6 months.     

Long‐ and short‐term outcomes in renal allografts with deceased donors: A large recipient and donor genome‐wide association study

Improvements in immunosuppression have modified short‐term survival of deceased‐donor allografts, but not their rate of long‐term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short‐ and long‐term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large‐scale genome‐wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant‐pairs with replication in 5866 complete pairs. We studied deceased‐donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long‐ or short‐term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.     

Differential excretion of urinary proteins in children with vesicoureteric reflux and reflux nephropathy

We studied 40 children with a history of vesicoureteric reflux (VUR) without evidence of renal scarring, 93 children with a history of VUR and renal scarring and 10 children with previous urinary tract infections in whom the urinary tract was radiologically normal. Urine retinol-binding protein (RBP), albumin andN-acetyl--d-glucosaminidase (NAG) were measured in each child. All were free from infection at the time of the analysis. Urinary RBP and NAG levels were significantly elevated (P<0.001) in the group of children with renal scarring. Elevated RBP levels were detected in 51% of children with bilateral renal scarring compared with 7% of children with unilateral scarring. Urine RBP excretion increased progressively according to the type of scarring, best determined by the type of scarring of the less affected kidney. In children with renal scarring, elevated NAG levels were seen mostly in the 65 children with bilateral scarring and severe reflux. Urine albumin excretion was elevated in 10 children, 9 with bilateral scarring, all of whom had elevated RBP excretion. Urine protein excretion was unaffected by the presence or absence of persisting VUR. There was a strong negative correlation between glomerular filtration rate and RBP excretion (r=–0.69). We conclude that evidence of tubular dysfunction is common in children with bilateral renal scarring and usually precedes any glomerular protein leak. Tubular dysfunction may be the consequence of relative nephron hyperperfusion in the presence of bilateral scarring.     

The lectin-like domain of thrombomodulin is a drug candidate for both prophylaxis and treatment of liver ischemia and reperfusion injury in mice

Ischemia and reperfusion injury (IRI) can occur in any tissue or organ. With respect to liver transplantation, the liver grafts from donors by definition experience transient ischemia and subsequent blood reflow. IRI is a problem not only in organ transplantation but also in cases of thrombosis or circulatory disorders such as mesenteric ischemia, myocardial, or cerebral infarction. We have reported that recombinant human soluble thrombomodulin (rTM), which is currently used in Japan to treat disseminated intravascular coagulation (DIC), has a protective effect and suppresses liver IRI in mice. However, rTM may not be fully safe to use in humans because of its inherent anticoagulant activity. In the present study, we used a mouse liver IRI model to explore the possibility that the isolated lectin-like domain of rTM (rTMD1), which has no anticoagulant activity, could be effective as a therapeutic modality for IRI. Our results indicated that rTMD1 could suppress ischemia and reperfusion-induced liver damage in a dose-dependent manner without concern of associated hemorrhage. Surprisingly, rTMD1 suppressed the liver damage even after IR insult had occurred. Taken together, we conclude that rTMD1 may be a candidate drug for prevention of and therapy for human liver IRI without the possible risk of hemorrhage.     

图像处理和人工神经网络在肺癌细胞病理诊断中的应用

目的探求基于计算机图像处理和人工神经网络的“肺癌早期细胞病理电脑诊断系统”（lung cancer diagnosing system，LCDS）在肺癌临床细胞病理诊断中的应用价值。方法运用LCDS对512例经皮肺穿刺标本的细胞学涂片进行检测评判和综合分析，并对其中手术治疗的362例进行LCDS细胞病理诊断与术后组织病理诊断对比分析研究。结果LCDS能运用图像处理和专家系统完成对肺部病灶癌细胞和非癌细胞的识别诊断，进而运用人工神经网络能完成肺鳞癌、腺癌、小细胞癌等主要病理类型的细胞病理诊断，与临床组织病理或细胞病理诊断结果对比，总符合率为91．80％。其中362例接受外科手术者以术后组织病理诊断结果为标准，LCDS检测诊断的敏感性为94．79％（291／307例），特异性为90．91％（50／55例），准确性为94．20％（341／362例）。结论LCDS所采用的诊断模型是实用而有效的，具有诊断准确率高、易于操作培训等优势，有可能为肺癌早期细胞病理诊断提供又一实用有效的手段。     

Treatment of chronic antibody mediated rejection with intravenous immunoglobulins and rituximab: A multicenter,prospective, randomized,double‐blind clinical trial

There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo‐controlled, double‐blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010‐023746‐67). Patients with transplant glomerulopathy and anti‐HLA donor‐specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m² and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m²) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions, and DSA at 1 year. The planned sample size was 25 patients per group. During 2012‐2015, 25 patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (?4.2 ± 14.4 vs. ?6.6 ± 12.0 mL/min per 1.73 m², P‐value = .475), increase of proteinuria (+0.9 ± 2.1 vs. +0.9 ± 2.1 g/day, P‐value = .378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA.     

Comparative study between trapezium resection and tendon interposition with and without ligamentplasty in the management of carpometacarpal arthrosis of the thumb

Purpose

Treating arthrosis in the base of the thumb has been a highly controverted subject. Many surgeries have been described, such as the isolated trapezium resection; resection with interposition with and without ligament plasty; arthrodesis, and arthroplasties. The purpose of this paper is to compare the two techniques which are currently the most used in this treatment.

Methods

A prospective study has been made to compare the surgical results between the trapezium resection with tendon interposition (tenoarthroplasty) — 22 cases — and tenoarthroplasty associated to ligament plasty—24 cases. Objective evaluation was done by measuring opponence, movements of the metacarpophalangeal joint, pinch and grasp strength, radiographic measurement of the distance between the base of first metacarpal and the scaphoid, and measurement of the angle between the first and the second metacarpals. Subjective evaluation was done with a DASH questionnaire, visual analog scale to evaluate pain and patient satisfaction.

Results and conclusion

After application of the criteria described and using Student ‘t’ tests for statistical analysis, the authors concluded that the ligament reconstruction has no advantage over the simple resection and tendon interposition in carpometacarpal arthrosis of the thumb.     

Comparison of cross-sectional renal function measurements in African Americans with hypertensive nephrosclerosis and of primary formulas to estimate glomerular filtration rate

Renal function measurements were obtained in 1,703 African Americans with presumed hypertensive nephrosclerosis who were screened for entry into the African-American Study of Hypertension and Kidney Disease (AASK). We examined the effect of race on relationships involving renal variables by comparing African Americans enrolled into the AASK with non-African Americans enrolled into the Modification of Diet in Renal Disease (MDRD) study. We examined the effect of gender on renal variables by comparing African American men and women. We compared various methods for estimating glomerular filtration rate (GFR) with iodine 125-labeled (¹²⁵I)-iothalamate GFR. AASK data were also used to derive a new formula for estimating GFR in African Americans. After adjusting for age, sex, and baseline GFR, African American patients on the AASK study were heavier and had larger body surface areas and body mass indices than either MDRD African Americans or non-African Americans. African Americans had greater serum creatinine levels and urinary creatinine excretions for any given level of GFR. Mean GFR was greater in African American men than African American women (59.7 versus 51.7 mL/min/1.73 m²), although serum creatinine levels were also greater in men (1.91 versus 1.73 mg/dL). Seventy-eight percent of women with serum creatinine levels between 1.2 and 1.5 mg/dL had GFRs less than 65 mL/min/1.73 m². For African Americans in the AASK, GFR was overestimated by the 24-hour creatinine clearance and underestimated by the Cockcroft-Gault formula. A prediction formula developed in the MDRD study more accurately predicted GFR in AASK patients than these measurements. AASK data were also used to derive a new five-term formula for estimating GFR that was slightly more accurate in the African Americans in the AASK than the MDRD formula (median percentage of error, 12.4% for the MDRD formula versus 12.1% for the AASK formula). Important differences exist in renal variables between African Americans and non-African Americans and between African American men and African American women. Formulas using demographic data and readily measured serum values estimate ¹²⁵I-iothalamate GFR. © 2001 by the National Kidney Foundation, Inc.     

Efficacy and safety of everolimus with reduced tacrolimus in living‐donor liver transplant recipients: 12‐month results of a randomized multicenter study

In a multicenter, open‐label, study, 284 living‐donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non‐inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference –0.7% (90% CI ?5.2%, 3.7%); P < .001 for non‐inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non‐inferiority (P < .001 for non‐inferiority), but not superiority and was similar between groups overall (mean ?8.0 vs. ?12.1 mL/min/1.73 m², P = .108), and in patients continuing randomized treatment (?8.0 vs. ?13.3 mL/min/1.73 m², P = .046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC‐treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non‐inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432.     

Isolated v‐lesion in kidney transplant recipients: Characteristics,association with DSA,and histological follow‐up

Isolated v‐lesion (IvL) represents a rare and challenging situation in renal allograft biopsies because it is unknown whether IvL truly represents rejection, antibody‐ or T cell–mediated, or not. This multicentric retrospective study describes the clinicopathological features of IvL with an emphasis on the donor‐specific antibody (DSA) status, histological follow‐up, and graft survival. Inclusion criteria were the presence of v‐lesion with minimal interstitial (i ≤ 1) and microvascular inflammation (g + ptc≤1). C4d‐positive biopsies were excluded. We retrospectively found 33 IvL biopsies in 33 patients, mainly performed in the early posttransplantation period (median time 27 days) and clinically indicated in 66.7%. A minority of recipients (5/33, 15.2%) had DSA at the time of biopsy. IvL was treated by anti‐rejection therapy in 21 cases (63.6%), whereas 12 (36.4%) were untreated. Seventy percent of untreated patients and 66% of treated patients showed favorable histological evolution on subsequent biopsy. Kidney graft survival in IvL was significantly higher than in a matched cohort of antibody‐mediated rejection with arteritis. In conclusion, IvL is not primarily antibody‐mediated and may show a favorable evolution. The heterogeneity of IvL pathophysiology on early biopsies should prompt DSA testing as well as close clinical and histological follow‐up in all patients with IvL.     

Face transplantation: A longitudinal histological study focusing on chronic active and mucosal rejection in a series with long-term follow-up

The 2007 Banff working classification of skin-containing Tissue Allograft Pathology addressed only acute T cell–mediated rejection in skin. We report the longitudinal long-term histological follow-up of six face transplant recipients, focusing on chronic and mucosal rejection. We identified three patterns suggestive of chronic rejection (lichen planus-like, vitiligo-like and scleroderma-like). Four patients presented lichen planus-like and vitiligo-like chronic rejection at 52 ± 17 months posttransplant with severe concomitant acute T cell–mediated rejection. After lichen planus-like rejection, two patients developed scleroderma-like alterations. Graft vasculopathy with C4d deposits and de novo DSA led to subsequent graft loss in one patient. Chronic active rejection was frequent and similar patterns were noted in mucosae. Concordance between 124 paired skin and mucosal biopsies acute rejection grades was low (κ = 0.2, p = .005) but most grade 0/I mucosal rejections were associated with grade 0/I skin rejections. We defined discordant (grade≥II mucosal rejection and grade 0/I skin rejection) (n = 55 [70%]) and concordant (grade≥II rejection in both biopsies) groups. Mucosal biopsies of the discordant group displayed lower intra-epithelial GranzymeB/FoxP3 ratios suggesting a less aggressive phenotype (p = .08). The grading system for acute rejection in mucosa may require phenotyping. Whether discordant infiltrates reflect a latent allo-immune reaction leading to chronic rejection remains an open question.     

全腹腔镜与内镜联合腹腔镜治疗胆总管结石并胆囊良性疾病的对比研究

[摘 要] 目的 对比分析全腹腔镜与内镜联合腹腔镜治疗胆总管结石合并胆囊良性疾病的临床疗效,探讨最佳微创治疗方案。方法 回顾性分析四川绵阳四〇四医院2014年5月至2017年5月收治的122例胆总管结石合并胆囊良性疾病患者的临床资料,根据手术方案分为腹腔镜胆囊切除+胆总管探查取石组（LC+LCBDE,n=75）,和十二指肠镜下乳头切开术（EST）+LC组（EST+LC,n=47）。其中LC+LCBDE组又分为经胆囊管胆总管探查组（LTCBDE,n=30）、胆道一期缝合组（n=21）、T管引流组（n=24）。对比分析各组围手术期结果。结果 LC+LCBDE组与EST+LC组比较,手术时间、术后禁食时间及术后并发症发生率无统计学差异（P＞0.05）;LC+LCBDE组术中失血量更多[（22.36±5.89）mL vs （18.74±6.58）mL]、术后住院时间更长[ （7.90±2.91）d vs （5.40±2.51）d]、但总费用更少[ （19 467.72±1 916.39）元 vs （24 882.89±2 477.21）元],差异均有统计学意义（P＜0.05）。LC+LCBDE组内比较,LTCBDE组、胆道一期缝合组手术时间和术中失血量与T管引流组比较无统计学差异（P＞0.05）;LTCBDE组、胆道一期缝合组术后禁食时间[ （28.44±10.69）h、 （32.67±12.61）h vs （33.94±11.75）h]、腹腔引流时间[（2.02±0.64）d、 （2.19±0.71）d vs （3.68±0.94）d]、术后住院时间[（5.10±1.04）d、 （6.61±1.16）d vs （9.81±1.26）d]短于T管引流组（P＜0.05）,住院费用[（18 743.57±1 952.64）元、 （21 035.94±2 268.68）元 vs （19 242.90±1 549.71）元]少于T管引流组（P＜0.05）;术后并发症发生率（0、19% vs 25.0%）也均低于T管引流组,且LTCBDE组与T管引流组比较有统计学差异（P＜0.05）。结论 （1）相对于内镜联合腹腔镜,全腹腔镜避免了分次手术,适应证更宽,术后并发症更轻且住院费用更少,值得推荐;（2）全腹腔镜中,LTCBDE及胆道一期缝合均能达到一次性封闭胆管的目的,能让患者获得更大的治疗收益,临床上应根据胆囊管或胆总管的具体情况优先选择。     

Antigen‐Specificity of T Cell Infiltrates in Biopsies With T Cell–Mediated Rejection and BK Polyomavirus Viremia: Analysis by Next Generation Sequencing

This study interrogates the antigen‐specificity of inflammatory infiltrates in renal biopsies with BK polyomavirus (BKPyV) viremia (BKPyVM) with or without allograft nephropathy (BKPyVN). Peripheral blood mononuclear cells (PBMC) from five healthy HLA‐A0101 subjects were stimulated by peptides derived from the BKPYV proteome or polymorphic regions of HLA. Next generation sequencing of the T cell–receptor complementary DNA was performed on peptide‐stimulated PBMC and 23 biopsies with T cell–mediated rejection (TCMR) or BKPyVN. Biopsies from patients with BKPyVM or BKVPyVN contained 7.7732 times more alloreactive than virus‐reactive clones. Biopsies with TCMR also contained BKPyV‐specific clones, presumably a manifestation of heterologous immunity. The mean cumulative T cell clonal frequency was 0.1378 for alloreactive clones and 0.0375 for BKPyV‐reactive clones. Samples with BKPyVN and TCMR clustered separately in dendrograms of V‐family and J‐gene utilization patterns. Dendrograms also revealed that V‐gene, J‐gene, and D‐gene usage patterns were a function of HLA type. In conclusion, biopsies with BKPyVN contain abundant allospecific clones that exceed the number of virus‐reactive clones. The T cell component of tissue injury in viral nephropathy appears to be mediated primarily by an “innocent bystander” mechanism in which the principal element is secondary T cell influx triggered by both antiviral and anti‐HLA immunity.