Primary and recurrent regional metastases for lateralized oral cavity squamous cell carcinoma

ObjectivesMap regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence.Materials and methodsRetrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997–2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression.ResultsRegional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2–3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9–9.3; T4 vs. T1: HR 2.3, 95% CI 1.2–4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2–16.1), upper alveolus (HR 3.2, 95% CI 1.0–4.7) or with LVI (HR 2.0, 95% CI 1.0–3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases.ConclusionsFor lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3–4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection.     

A Pilot First-in-Human Study of Embrace,a Polyethylene Glycol-Based Liquid Embolic Agent,in the Embolization of Malignant and Benign Hypervascular Tumors

PurposeTo investigate the safety and efficacy of an aqueous polyethylene glycol-based liquid embolic agent, Embrace Hydrogel Embolic System (HES), in the treatment of benign and malignant hypervascular tumors.Materials and MethodsA prospective, single-arm, multicenter study included 8 patients, 5 males and 3 females, with a median age of 58.5 years (30–85 years), who underwent embolization in 8 tumors between October 2019 and May 2020. Technical success was defined as successful delivery of HES to the index vessel, with disappearance of >90% of the targeted vascular enhancement or, for portal vein embolization, occlusion of the portal branches to the liver segments for future resection. The volume of HES administered, ease of use (5 point Likert scale), administration time, and adverse events (AEs) were recorded. Evaluation was performed at 7, 30, and 90 days via clinical assessment and blood testing, and follow-up imaging was performed at 30 days.ResultsEight patients were enrolled, and 10 embolizations were performed in 8 lesions. Tumors included hepatocellular carcinoma (n = 4), renal angiomyolipoma (n = 3), and intrahepatic cholangiocarcinoma (n = 1). Technical success was 100%, and the average ease of use was 3.3 ± 1.0 SD. The HES delivery time was 1–28 minutes (median, 16.5 minutes), and the HES volume injected was 0.4–4.0 mL (median, 1.3 mL). All patients reached 30-day follow-up with imaging, and 6 patients reached 90-day follow-up. There were 3 serious AEs in 2 patients that were unrelated to the embolic agent.ConclusionHES resulted in a 100% embolization technical success rate. The product ease of use was acceptable, and no target vessel recanalization was noted on follow-up imaging at 30 days.     

The role of extra-hepatic bile duct resection in the surgical management of gallbladder carcinoma. A first meta-analysis

ObjectiveTo systematically evaluate the clinicopathological and prognostic value of extra-hepatic bile duct resection (EHBDR) in the surgical management of patients with gallbladder carcinoma (GBC), especially in non-jaundiced patients.MethodsPubMed, EMBASE and the Cochrane Library were searched up to March 1^st 2021 for comparative studies between bile duct resected and non-resected groups. RevMan5.3 and Stata 13.0 software were used for the statistical analyses.ResultsEHBDR did not correlate with a better overall survival (OS) (P = 0.17) or disease-free survival (P = 0.27). No survival benefit was also observed in patients with T2N1 (P = 0.4), T3N0 (P = 0.14) disease and node-positive patients (P = 0.75), rather, EHBDR was even harmful for patients with T2N0 (P = 0.01) and node-negative disease (P = 0.02). Significantly higher incidences of recurrent disease (P = 0.0007), postoperative complications (P < 0.00001) and positive margins (P = 0.02) were detected in the bile duct-resected group. The duration of postoperative hospital stay between the two groups was comparable (P = 0.58). Selection bias was also detected in our analysis that a significantly higher proportion of advanced lesions with T3-4 or III-IV disease was observed in the bile duct-resected group (P < 0.00001). EHBDR only contributed to a greater lymph yield (P = 0.01).ConclusionEHBDR has no survival advantage for patients with GBC, especially for those with non-jaundiced disease. Considering the unfairness of comparing OS between jaundiced patients receiving EHBDR with non-jaundiced patients without EHBDR, we could only conclude that routine EHBDR in non-jaundiced patients is not recommended and future well-designed studies with more specific subgroup analyses are required for further validation.     

姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义

目的:探讨姑息性胃切除联合术后化疗评分在腹膜转移的胃癌患者预后评估中的临床意义。方法:回顾性分析2010年1月至2016年12月7年间收治的287例发生腹膜转移的胃癌患者的临床病理资料。通过χ2检验分析评分与患者临床病理因素间的关系。通过Kaplan-Meier法绘制生存曲线，Log-rank检验比较患者生存率的差异；采用Cox比例风险回归模型对患者进行预后分析。结果:与评分中得分为2分和1分的患者相比，得分为0分的患者肿瘤侵润至T4b 期的患者较少［31%(18/58)比50.8%(63/124)、56.2%(59/105)，P=0.039］。全组患者的中位生存时间仅为8.7月。对患者进行单因素预后分析结果显示，血清白蛋白浓度（≤40 g/L），腹水，腹膜转移范围较大，肿瘤T分期较晚，评分得分较高的患者预后较差（均P＜0.05）。将上述因素纳入Cox多因素分析结果显示:评分［HR（95%CI）:1.384（1.165~1.644），P=0.000］，血清白蛋白浓度［HR（95%CI）:0.759（0.593~0.971），P=0.028］，肿瘤T分期［HR（95%CI）:1.493（1.216~1.832），P=0.000］是患者预后的独立危险因素。结论:评分对于胃癌伴腹膜转移患者的预后生存评估具有重要的临床意义。     

Rucaparib in the landscape of PARP inhibition in ovarian cancer

Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.     

Influences of simulated gastrointestinal environment on physicochemical properties of gold nanoparticles and their implications on intestinal epithelial permeability

Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H₂O₂. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.     

Percutaneous renal mass biopsy: historical perspective,current status,and future considerations

Introduction: Percutaneous renal mass biopsy has evolved over the last decade with improvements on previous pitfalls including low tissue yield, high non-diagnostic rates, and complications. As understanding of tumor biology and natural history of renal cortical neoplasms has improved, percutaneous renal mass biopsy is poised to have an expanding role in an area characterized by individualized management and refined risk stratification.

Areas covered: This review summarizes the evolution of renal mass biopsy to its current state with respect to outcomes, indications, and clinical guidelines.

Expert opinion: With improved understanding of differential biological potential of renal cortical neoplasms combined with technical improvements in diagnostic yield and accuracy, utilization of renal mass biopsy is becoming an important adjunct to patient care in a broad range of clinical scenarios, including active surveillance, thermal ablation, and use of primary systemic therapy in localized and advanced settings.     

甲状腺乳头状癌前上纵隔淋巴结转移临床病理特征初步分析

目的 探讨肿瘤位置、最大直径及甲状腺外浸等临床病理特征与甲状腺癌前上纵隔淋巴结转移的关系。 方法 研究分析初次手术治疗的60例甲状腺乳头状癌患者临床及病理资料,运用检验临床病理特征与前上纵隔淋巴结阳性率的相关性。 结果 肿块位置、最大直径、数量、腺体外侵、受累腺叶数及Ⅵ区淋巴结转移等特征,以及患者年龄等相关因素中,只有VI区淋巴结对前上纵隔淋巴结状态有影响;60例患者前上纵隔淋巴结转移率为10/60(16.67%)。相关因素的前上纵隔淋巴结转移率对比:≥55岁vs <55岁(20% vs 16.36%, P<0.05);肿块位于下极 vs 上极 vs 中极(P>0.05);最大直径≥1.5 cm vs 最大直径<1.5 cm(18.18% vs 15.79, P>0.05);单灶 vs 多灶(21.88% vs 10.71%, P>0.05);单叶 vs 多叶(17.5% vs 15%, P>0.05);男性vs女性(20% vs 15.55%, P>0.05); Ⅵ区淋巴结阳性vs 阴性(24.43% vs 3.57%, P<0.05); 结论 总体来说,甲状腺乳头状癌前上纵隔淋巴结转移率较低。本研究发现VI区淋巴结状态可能与前上纵隔淋巴结转移相关,未来仍需大样本前瞻性的研究验证。     

Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.