Comments on methods and results in: Sherman et al., "Segregation analysis of balanced pericentric inversions in pedigree data"

The analysis by Sherman et al. (1986), its basis and results have been examined. The analysis relies on general methods, which may give acceptable results under the special conditions considered by the authors, but will usually produce more or less misleading results. The program POINTER (Lalouel & Morton 1981) is shown to be based partly on a chain of irrelevant arguments for the actual context. The so-called "conventional ascertainment rules" (Morton et al. 1983) are shown to produce misleading results in cases where their assumptions are not satisfied. The mean risk for unbalanced offspring is underestimated because of an erroneous ascertainment correction. The segregation frequencies are found to be different in three national samples, contrary to the claim by Sherman et al. Only a small proportion of all information available in the data has been utilized. Alternative and more appropriate models, hypotheses and procedures have been suggested. The frequent use of packages with computer programmes of standard statistical procedures in nonstandard situations with data from collaborative studies in human cytogenetics is discussed.     

Correlates of genetic risk for non-syndromic cleft lip with or without cleft palate

Mitchell LE, Risch N. Correlates of genetic risk for non-syndromic cleft lip with or without cleft palate. Clin Genet 1993: 43: 255–260. © Munksgaard, 1993 Multivariate analysis was used to determine which characteristics: sex of the proband, sibling sex, severity of the proband's defect or family history, are the best predictors of recurrence risk among siblings of individuals with non-syndromic cleft lip with or without cleft palate (CL \pm P). Sibling recurrence risks are not significantly related to the sex of the proband. Severity of the proband's defect, classified by the extent of the lip defect (unilateral versus bilateral), was found to be a significant predictor of sibling recurrence, whereas involvement of the palate in the proband's defect was not. A positive family history of clefting (i.e. at least one affected first-degree relative in addition to the proband) and the sex of the sibling were also found to be significant predictors of sibling recurrence. The associations between sibling risk and family history, and sibling risk and bilaterality of the proband's defect appear to be mildly confounded. After adjusting for the effects of family history, the risk to siblings of probands with bilateral lip defects is twice the risk to siblings of probands with unilateral defects (O.R. = 2.00; 95% C.I. 1.25-3.19). A positive family history of clefting increases the risk to siblings by greater than 4-fold (O.R. =4.49; 95% C.I. 2.74-7.35), after adjusting for the extent of the proband's lip defect. These results provide a rational strategy for identifying subsets of the ‘at risk’ population which have markedly different recurrence risks. This information is important for genetic counseling, since it allows for more precise estimation of sibling recurrence risks in individual cases. Furthermore, our findings indicate that the power to detect linkage between a genetic marker or a candidate gene and CL \pm P will increase if the study population is ascertained through individuals with bilcteral clefts of the lip, rather than through individuals with either unilateral or bilateral CL \pm P.     

Paternal mosaicism for a novel PBX1 mutation associated with recurrent perinatal death: Phenotypic expansion of the PBX1‐related syndrome

Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra‐renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one‐day‐old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Further investigation by droplet digital PCR revealed that the mutation had occurred post‐zygotically in the father, with different variant allele frequencies of the mosaic PBX1 mutation in blood (10%) and sperm (20%). Interestingly, the father had subclinical hydronephrosis in childhood. With an expected recurrence risk of one in five, chorionic villus sampling and prenatal diagnosis for the PBX1 mutation identified recurrence in a subsequent pregnancy. The family opted to continue the pregnancy and the second affected sibling was stillborn at 35 weeks, presenting with similar severe bilateral diaphragmatic eventration, microsplenia, and complete sex reversal (46, XY female). This study highlights the importance of follow‐up studies for presumed de novo and low‐level mosaic variants and broadens the phenotypic spectrum of developmental abnormalities caused by PBX1 mutations.     

CT与MRI在诊断原发性肝癌介入术后病灶残留及复发中的应用

目的:对原发性肝癌患者介入术后接受CT、MRI诊断病灶残留及复发的临床价值进行系统研究与探讨。方法:选择本院2018年12月~2019年12月收治的90例行介入术原发性肝癌患者作为实验对象,数字奇偶法分组后探究每组诊断效果。对照组(45例)应用CT诊断;观察组(45例)应用MRI诊断。对比两组患者残留及复发病灶数量。结果:观察组残留及复发病灶数量为(66.44±3.75)个,较之于对照组,差异具有统计学研究意义(P<0.05)。结论:原发性肝癌患者接受介入手术治疗后,在诊断病灶残留与复发中,MRI诊断优势更明显。     

卵巢癌肿瘤标志物研究进展

卵巢癌是妇科三大恶性肿瘤之一,由于疾病早期没有明显的临床症状,发现时多已进展为晚期,且约80%的晚期患者在治疗后3年内复发,因此卵巢癌成为妇科恶性肿瘤中死亡率最高的肿瘤。早期有效的筛查及预后评估机制对卵巢癌的诊断及治疗有重要意义。CA125是监测卵巢癌病程和转归的重要标志物,然而其特异性不足,其他标志物包括HE4、CA199对卵巢癌的诊断和预后也缺乏敏感性和特异性。因此,寻找和鉴定新的分子标志物用于早期筛查和诊断卵巢癌以及评估预后至关重要。本文基于目前卵巢癌生物标志物最新研究进行综述。     

复发性坏死性粘膜腺周围炎的中药治疗疗效观察

目的：对复发性坏死性粘膜腺周围炎根据四诊合参进行辩证施治,探讨减少其复发的有效治疗方法。方法．68例患者随机分组,对照组16例局部用药,治疗组52例局部用药配合全身中药调理。结果：对照组有效率为68．75％,复发率为87．5％,治疗组有效率为96．15％,复发率为28．85％。结论：通过内外兼治,能缩短溃疡发作时期,延长间歇期,减少复发,还能通过全身调理,增强病人体质状况,提高抗病能力。     

不同中国肝癌分期肝癌根治性切除术后的临床效果及预后因素分析

目的探讨不同中国肝癌分期(CNLC)肝癌接受根治性切除术后的临床效果及长期生存的预后因素。方法回顾性分析2010年1月至2019年12月南京医科大学第一附属医院肝胆中心单一治疗组收治的行肝癌根治术的549例肝细胞癌(HCC)患者的临床病理学资料。男性462例(84.2%),女性87例(15.8%);中位年龄57岁(范围:21~84岁)。观察患者的术前变量、术中及术后情况、术后病理学检查结果等。采用门诊与电话相结合的方式进行随访。采用寿命表法进行生存率的估计,采用Kaplan-Meier法绘制总体生存和无瘤生存曲线,采用Log-rank检验比较不同组别生存过程的差异,采用多因素Cox回归模型分析影响预后的主要因素。结果 549例HCC患者中,CNLC Ⅰa期200例(36.4%),CNLC Ⅰb 期148例(27.0%),CNLC Ⅱa期49例(8.9%),CNLC Ⅱb期32 例(5.8%),CNLC Ⅲa期101例(18.4%),CNLC Ⅲb期19例(3.5%)。患者1、3、5、10年总体生存率分别为83.8%、69.0%、54.2%、37.7%,1、3、5年无瘤生存率分别为61.0%、44.2%、36.0%。CNLC Ⅰa期患者的1、3、5年总体生存率和无瘤生存率分别为97.3%、90.6%、80.5%和83.9%、65.0%、54.0%;CNLC Ⅰb期患者的1、3、5年总体生存率和无瘤生存率分别为87.9%、71.0%、47.7%和58.4%、42.3%、33.4%;CNLC Ⅱa和Ⅱb期患者的5年总体生存率(Ⅱa期:37.2%,Ⅱb期:44.3%)与CNLC Ⅰb期类似。CNLC Ⅲb期患者 1、3、5年总体生存率和无瘤生存率分别为35.3%、13.2%、0和23.5%、0、0。单因素分析结果显示,术前合并症状、术前甲胎蛋白水平、术前总蛋白水平、术前AST水平、术前总胆红素水平、术中出血量、术中或术后输血、术后并发症、肿瘤最大径和数目、微血管侵犯、大血管侵犯、肿瘤分化程度是HCC患者长期生存(≥5年)的预后因素(P值均<0.05)。多因素分析结果显示,术前AST水平、术中出血量、肿瘤数目、肿瘤最大径、大血管侵犯和肿瘤分级是HCC患者长期生存的独立预后因素(P值均<0.05)。结论不同CNLC的HCC患者具有不同的复发模式及预后。经过严格术前评估的CNLC Ⅱa~Ⅲb期HCC患者可从外科根治切除术中获得生存获益。术前AST水平、术中出血量、肿瘤数目、肿瘤最大径、大血管侵犯和肿瘤分化程度是影响HCC患者长期生存的独立预后因素。     

Clinical Outcome of Cytoreductive Surgery Prior to Bevacizumab for Patients with Recurrent Glioblastoma: A Single-center Retrospective Analysis

Bevacizumab (BEV) is a key anti-angiogenic agent used in the treatment for recurrent glioblastoma multiforme (GBM). The aim of this study was to investigate whether cytoreductive surgery prior to treatment with BEV contributes to prolongation of survival for patients with recurrent GBM. We retrospectively analyzed the treatment outcomes of 124 patients with recurrent GBM who were initially treated with the Stupp protocol between 2006 and 2019. Given that BEV has only been available in Japan since 2013, we grouped the patients into two groups according to the time of first recurrence: the pre-BEV group (N = 51) included patients who had recurrence before BEV approval, and the BEV group (N = 73) included patients with recurrence after BEV approval. The overall survival after first recurrence (OS-R) was analyzed according to the treatment strategy. Among 124 patients, 27 patients (19.4%) received cytoreductive surgery. There were nine cases in the pre-BEV group and 18 cases in the BEV group. Although the mean extent of resection for both groups was almost equal, OS-R was significantly different. The median OS-R was 8.1 m in the pre-BEV group and 16.3 m in the BEV group (P = 0.007). Multivariate analysis revealed that the unavailability of BEV postoperatively (P = 0.03) and decreasing performance status by surgery (P = 0.01) were significant poor prognostic factors for survival after surgery. With the advent of BEV, cytoreductive surgery might provide superior survival benefit at the time of GBM recurrence, especially in cases where surgery can be performed without deteriorating the patient’s condition.     

青年乳腺癌患者拼贴画心理疗法的实施

目的探讨拼贴画心理疗法在青年乳腺癌患者癌症复发恐惧干预中的应用效果。方法将87例青年乳腺癌患者按照住院时间分为对照组43例和观察组44例。对照组实行常规健康教育,观察组在对照组基础上实施拼贴画心理疗法,干预前及干预12周后采用癌症患者恐惧疾病进展简化量表、医院焦虑抑郁量表、Herth希望量表进行评价。结果干预12周后,观察组癌症复发恐惧、焦虑、抑郁评分显著低于对照组,希望评分显著高于对照组(P<0.05,P<0.01)。结论拼贴画心理疗法有利于缓解青年乳腺癌患者负性情绪,并提升其希望水平。     

甲状腺癌术后复发再手术难点与对策

分化型甲状腺癌预后良好。甲状腺癌复发需行以再次手术为主的综合治疗。与初次手术相比,再次手术风险明显增大,并发症发生率和严重程度均升高。因此,再次手术前应进行充分的检查评估,并做好充分的知情同意。中央区的再次手术,难点在于把握手术指征、术中复发淋巴结的定位、术中喉返神经和甲状旁腺的保护以及周围器官结构受侵的处理。术前超声引导下纳米炭注射能够可靠帮助术中定位。术中神经监测技术可以帮助喉返神经的辨认。如需要切除喉返神经,尽可能同期修复。术中对于上位甲状旁腺区减少扰动、仔细在标本中辨认寻找甲状旁腺、必要时甲状旁腺自体移植可以尽量保护甲状旁腺。而侵犯气管、喉、食管时,则需要部分喉切除、气管切除和重建等技术。颈侧区的再次手术,难点在于颈淋巴结清扫容易遗漏部位的再次切除、咽旁等少见复发位置的处理,以及神经和大血管受侵的处理。颈侧区复发的转移淋巴结仍以规范的区域淋巴结清扫为主要治疗方法。对于少见部位的复发应熟悉局部解剖,减少副损伤。神经受侵时,尽量保留有功能的神经。必要时可以切除颈内静脉。上纵隔位置的复发主要通过上纵隔淋巴结清扫完成。胸骨劈开的开放入路显露较好,可切除范围较大,相对比较安全,但创伤较大。腔镜辅助的上纵隔淋巴结清扫创伤较小,需要一定技术储备。复发甲状腺癌经积极治疗预后较好。再次手术建议由经验丰富的专科医师来完成。术后辅助多学科综合治疗能提高再次手术的疗效。