Papillary thyroid carcinoma with a high tumor mutation burden has a poor prognosis

BackgroundTumor mutation burden (TMB) as a prognostic marker for immunotherapy has shown prognostic value in many cancers. However, there is no systematic investigation on TMB in papillary thyroid carcinoma (PTC).MethodsBased on the somatic mutation data of 487 PTC patients from The Cancer Genome Atlas (TCGA), TMB was calculated, and we classified the samples into high-TMB (H-TMB) and low-TMB (L-TMB) groups. Bioinformatics methods were used to explore the characteristics and potential mechanism of TMB in PTC.ResultsHigh TMB predicts shorter progression-free survival (PFS) (P < 0.001). TMB was positively correlated with age, stage, tumor size, metastasis, the male sex and tall cell PTC. Compared to the L-TMB group, the H-TMB group presented with lower immune cell infiltration, a higher proportion of tumor-promoting immune cells (M0 macrophages, activated dendritic cells and monocytes) and a lower proportion of antitumor immune cells (M1 macrophages, CD8⁺ T cells and B cells). Additionally, the characteristics displayed by different TMB groups were not driven by critical driver mutations such as BRAF and RAS.ConclusionsPTC patients with high TMB have a worse prognosis. By stratifying PTC patients according to their TMB, advanced PTC patients who are candidates for immunotherapy could be selected.     

超声引导下细针穿刺检测甲状腺乳头状癌 ret/PTC基因重组突变

目的了解ret／PTC基因突变与超声、病理诊断在甲状腺乳头状癌诊断中的关系。方法术前超声检查，并在超声引导下细针穿刺，活体取材进行病理诊断和逆转录聚合酶链（RT-PCR）方法检测ret／PTC基因突变。结果在34例超声与病理诊断的甲状腺乳头状癌（PTC）患者中，16例分子生物学检测发现ret／PTC基因突变（47％），其中8例为PTC-1基因突变（50％），2例PTC-2基因突变（12．5％），2例PCT-3基因突变（12．5％），3例PTC-1和PTC-2突变同时存在（18．75％），1例PTC-1和PTC-3突变同时存在（6．25％）。结论ret／PTC基因重组突变可存在于散发的甲状腺乳头状癌中，主要表现PTC-1型。应用超声引导下细针穿刺与甲状腺乳头状癌基因突变的检测相结合是早期诊断甲状腺乳头状癌的有效方法。     

阻塞性黄疸:PTC下胆管钳夹活检的技术方法学研究

目的探索切实可行的胆管病理学检查新途径.资料与方法连续92例阻塞性黄疸患者接受经皮肝穿刺胆管造影(PTC)和经皮肝穿胆管引流(PTCD)治疗.PTCD过程中,影像监测下经皮经肝胆管穿刺,向胆管内引入活检钳对梗阻段钳夹活检,行组织病理学检查.统计学分析用χ2检验或Fisher确切概率计算法,以α=0.05作为检验水准.结果 92例钳夹活检患者90例成功获得组织块,技术成功率97.83%(90/92).钳夹活检敏感性为88.04%,63例胆管癌性恶性肿瘤钳夹活检敏感性较25例非胆管癌性恶性肿瘤高(93.65%比72.00%,P＜0.05).结论PTC下胆管钳夹活检操作简单,创伤小,敏感性高,是一种值得推广的胆管病理学诊断新途径.     

1—氰基—2—苯甲酰—1,2—二氢异喹啉的合成

采用1,1,2-三氯乙烷作溶剂,三乙胺作相转移催化剂合成了吡喹酮的重要中间体1-氰基-2-苯甲酰-1,2-二氢异喹啉。本法单耗低,产物质量好。Reissert 反应收率由文献报道的82%提高至90%。     

Warthin-like tumour of the thyroid gland: RET/PTC expression indicates it is a variant of papillary carcinoma

AIMS: Three cases with features of so-called 'Warthin-like tumour' of the thyroid (WaLTT) are described, in order to evaluate its relationship with papillary carcinoma (PC). METHODS AND RESULTS: We performed an histological and immunohistochemical study with emphasis on RET/PTC expression. The most striking features are represented by marked lymphocytic infiltration in the stalks of papillae and by oxyphilic metaplasia of epithelium, resembling Warthin tumour of the salivary gland. In all cases, we found nuclear features reminiscent of PC. The neoplastic cells were strongly positive for Leu M1 and epithelial membrane antigen (EMA), less for thyroglobulin and negative for calcitonin. The lymphocytic infiltrate was composed of a mixed population of B and T-cells with sparse S100-positive Langerhans cells. An interesting finding was the strong positivity with the antibody against RET/PTC. CONCLUSION: All clinicopathological data along with the presence of the extensive lymphocytic infiltrate could imply a more favourable prognosis. The expression of RET/PTC fusion gene adds support to the hypothesis that this tumour is a variant of PC, probably related to the oncocytic variant of PC.     

Percutaneous transhepatic cholangiography for choledocholithiasis after laparoscopic gastric bypass surgery

INTRODUCTIONGallstones are a common condition in bariatric patients after a laparoscopic Roux-en-Y gastric bypass (LRYGB). The management of ductal stones is challenging due to the altered gastrointestinal anatomy. Various techniques have been reported to manage bile duct stones.PRESENTATION OF CASEWe present the successful percutaneous trans hepatic management of common bile duct stones after LRYGB.One year after a LRYGB for morbid obesity, a 59-year-old female presented with acute cholecystitis. One month after laparoscopic cholecystectomy a 1 cm calculus was found within the distal CBD and patient underwent a percutaneous trans hepatic cholangiography under local anesthetic. This involved a right sided anterior segmental duct puncture. With the sphincter dilated to 10 mm, a balloon catheter was used to push the stone into the duodenum leaving an internal- external drain. Patient recovered completely at follow up.DISCUSSIONPatients with morbid obesity have a higher incidence of gallstones. After LRYGB, the altered anatomy does not allow the conventional endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis.Various techniques have been reported as means of managing bile duct stones in LRYGB patients. These include a double balloon enteroscope-assisted ERCP, laparoscopic transgastric ERCP, laparoscopic or open biliary surgery and interventional radiology. We report a non-surgical approach using percutaneous transhepatic technique under local anesthetic that resulted effective and could be applied more extensively.CONCLUSIONDue to the increase of global obesity, bariatric centers need to strategically plan resources such as interventional radiology in order to manage post LRYGB choledocholithiasis safely, efficiently and in a cost effective manner.     

The role of aquaporin-1 in idiopathic and drug-induced intracranial hypertension

Idiopathic intracranial hypertension is a common disorder affecting mainly healthy, young, overweight women. The pathogenesis of this condition is unknown, but it has been shown to follow treatment with several compounds including corticosteroids and vitamin A derivatives. This paper will offer a novel hypothesis and insight on the pathogenesis of drug induced intracranial hypertension following a review and analysis of the literature. Both corticosteroids and vitamin A derivatives have been shown to upregulate the expression of aquaporin 1, a water channel protein. Aquaporin 1 is widely distributed in the human brain and is associated with water secretion into the subarachnoid space. Aquaporin 1 was also shown to participate in the regulation of weight. Agents used for treating idiopathic intracranial hypertension reduce aquaporin 1 expression. Based on these observations, we propose that aquaporin 1 has a pathogenetic role in drug induced idiopathic intracranial hypertension. Over expression of this gene causes increased intracranial pressure, and downregulation reduces pressure and alleviates the symptomatology and complications of idiopathic intracranial hypertension.     

The relationship between taste sensitivity to phenylthiocarbamide and anhedonia

It has been proposed that taste sensitivity to bitter compounds such as, phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP), represents a genetic marker for an increased vulnerability to depressive illness. Previous explorations of this idea have proven equivocal. This study refines and further explores this idea by focusing specifically on anhedonia (diminished hedonic capacity), a key symptom in some depressive illness, linked also with sensory pleasure. It is hypothesized that diminished PTC taste sensitivity will be associated with more general decrements in hedonic capacity (anhedonia). An opportunity sample of 198 university students were assessed using paper strips impregnated with PTC, the same participants also completed a widely used assessment of hedonic capacity, the Snaith-Hamilton Pleasure Scale (SHAPS). Hedonic capacity scores positively correlated with PTC taste sensitivity; specifically, heightened hedonic capacity was associated with heightened sensitivity to the bitter taste of PTC. Furthermore, modest differences were observed between those least (non-tasters) and most (supertasters) sensitive to PTC, with non-tasters reporting significantly lower hedonic capacity scores than supertasters. PTC taste sensitivity may represent a peripheral risk factor for anhedonia.     

Association between the HLA-G molecule and lymph node metastasis in papillary thyroid cancer

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and can present as lymph node metastasis in 30 to 65% of cases when initially diagnosed. High frequency recurrence, distant metastasis and treatment resistance can be found in cases of PTC so early diagnosis and treatment are critical for improved prognosis and better survival rates. The characterization of new biomarkers has proved useful for the diagnosis and follow-up of these patients. HLA-G is a non-classical HLA class I molecule whose expression in cancer cells has been associated with tumor evasion of immune response. Therefore, the aim of this study was to investigate the HLA-G expression and its clinical significance in PTC. Paraffin-embedded thyroid biopsies of 70 PTC patients (40 of whom had presented with metastasis) were evaluated. HLA-G-staining was observed in tumor cells in PTC, and the HLA-G expression was significantly associated with an increased occurrence of lymph node metastasis (p = 0.0006) and capsular invasion (p = 0.02). This preliminary data shows the HLA-G expression in thyroid carcinoma specimens for the first time and suggests that this expression could impair efficient anti-tumor immunity in PTC. This would indicate that HLA-G could have an independent prognostic value in PTC, principally for tumor recurrence.     

BRAFV600E突变对甲状腺乳头状癌HMGB1及MMP-9表达的影响

目的探究BRAF^V600E突变对甲状腺乳头状癌(PTC)高迁移率族蛋白1(HMGB1)及基质金属蛋白酶-9(MMP-9)表达的影响。方法选取2018年1月至2019年11月在本院行甲状腺全切除术或次全切除术的116例PTC患者及匹配癌组织标本作为PTC组,另择同时期体检正常的30例健康人作为对照组。检测PTC患者BRAFV600E基因类型,免疫组化法及Western blot法检测PTC患者甲状腺癌组织中HMGB1、MMP-9表达情况,酶联免疫吸附法检测受试者血清HMGB1、MMP-9水平,并收集PTC患者临床资料。结果 116例PCT患者检出59例BRAF^V600E突变型、57例为BRAFV600E野生型,PTC患者BRAF^V600E突变型为50.86%(59/116)。免疫组化法分析结果显示BRAFV600E突变型HMGB1、MMP-9阳性表达率均显著高于BRAFV600E野生型,差异有统计学意义(P<0.05);Western blot法检测结果显示BRAFV600E突变型HMGB1表达量、MMP-9表达量显著高于BRAF^V600E野生型,差异有统计学意义(P<0.05)。PTC组BRAF^V600E突变型及BRAF^V600E野生型血清HMGB1、MMP-9水平均显著高于对照组,差异有统计学意义(P<0.05),PTC患者BRAFV600E突变型与BRAF^V600E野生型在血清HMGB1、MMP-9水平上比较,差异无统计学意义(P>0.05)。BRAF^V600E突变型TNM分期Ⅲ~Ⅳ期、包膜浸润、多发病灶、淋巴结转移占比显著高于BRAF^V600E野生型,差异有统计学意义(P<0.05)。二元Logistic结果显示,合并包膜浸润、多发病灶、组织HMGB1阳性、组织MMP-9阳性均是BRAF^V600E突变型的影响因素(P<0.05)。结论 PTC患者BRAF^V600E突变型组织HMGB1、MMP-9阳性表达率显著高于BRAF^V600E野生型,且组织HMGB1阳性、MMP-9阳性是BRAF^V600E突变型的影响因素。