Malignant Transformation of Intra-Cranial Epithelial Cysts: Systematic Article Review

Summary Introduction: Epidermoid and dermoid cysts are among the most benign intra cranial tumors. Their malignant transformation into squamous cell carcinoma is rare. The authors reviewed the literature. Materials and Methods: MEDLINE and SCIENCE DIRECT searches, and examination of the references in the selected articles yielded 74 patients, 52 of whom fulfilled Garcia’s criteria and were selected for the study. Survival analyses were performed to determine whether survival differences were of statistical significance, and P < 0.05 was considered as significant. Results: Malignant transformation is characterized by a rapid onset of symptoms, recurrence, leptomeningeal carcinomatosis (LC), and tumor enhancement at Computed Tomography Scan or Magnetic Resonance Imaging (87.8 showed this radiological feature). In this review, the SCCs were classified in five groups– (1) Initial malignant transformation of a benign cyst; (2) malignant transformation from a remnant cyst; (3) malignant transformation of a dermoid and epithelial cyst; (4) malignant transformation with leptomeningeal carcinomatosis; (5) other malignancies arising from benign cysts. The median survival was 9 months. Statistics show that LC was of poor prognosis and radiotherapy, although not statistically significant, seems effective against such lesions, with a median survival of 26 months as opposed to 3 months (P=0.077). Conclusion: Although rare, malignant transformation of intracranial epithelial cysts has a poor prognosis and surgery followed by radiotherapy seems to be the best therapeutic modality.     

Clinical Factors as a Component of the Personalized Treatment Approach to Advanced Pancreatic Cancer: a Systematic Literature Review

Introduction

Pancreatic cancer is often diagnosed at late stages, where disease is either locally advanced unresectable or metastatic. Despite advances, long-term survival is relatively non-existent.

Discussion

This review article discusses clinical factors commonly encountered in practice that should be incorporated into the decision-making process to optimize patient outcomes, including performance status, nutrition and cachexia, pain, psychological distress, medical comorbidities, advanced age, and treatment selection.

Conclusion

Identification and optimization of these clinical factors could make a meaningful impact on the patient’s quality of life.

     

Familial Pancreatic Cancer: Challenging Diagnostic Approach and Therapeutic Management

Background

Familial predisposition characterizes up to 10 % of the patients with pancreatic cancer (PC). Although many syndromes have been associated with an increased risk for PC, familial pancreatic cancer (FPC) accounts for the majority of hereditary cases. FPC is defined by families with at least a pair of first-degree relatives (FDRs) who have been diagnosed with PC and do not fulfill the criteria of other inherited tumor syndromes.

Methods and Results

Genetic counseling is of great importance to estimate the prevalence and recommend further molecular testing. Regarding the screening program for individuals with increased risk for PC, a consortium summit stated that candidates for screening are FDRs of patients with PC from a familial kindred with at least two affected FDRs, patients with Peutz–Jeghers syndrome and p16, BRCA2, and hereditary nonpolyposis colorectal cancer (HNPCC) mutation carriers. It was also agreed that initial screening should include endoscopic ultrasonography (EUS) and/or magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) instead of computed tomography (CT) or endoscopic retrograde cholangiopancreatography (ERCP).

Conclusions

However, the optimal age of initial screening remains undefined. Furthermore, a multidisciplinary assessment is required to determine whether surgical interventions should be performed at high-volume specialty centers. The aim of this study is to collect all the recent information considering the genetic basis, screening protocols, and treatment of FPC in order to provide an update on the current contemporary concepts of therapeutic management of the disease.     

碳离子和质子治疗胰腺癌安全性和有效性的系统评价及Meta分析

目的评价碳离子和质子治疗胰腺癌(PaC)的安全性和有效性。方法检索数据库纳入碳离子和质子治疗PaC的临床研究,检索时间为自建库至2019年6月。两位研究者独立筛选文献、提取资料。采用STATA 12.0和MetaAnalyst Beta 3.13软件进行Meta分析。结果共纳入8篇文献,包含459例PaC患者。效应模型Meta分析显示,碳离子和质子治疗PaC的2、3、5级胃肠道溃疡发生率分别为7%、2%、0;2、3、4级厌食症发生率分别为6%、3%、0;1、2年总生存率(OS)分别为77%、45%;2年局部控制率为81%;1年无局部进展率为88%;1年局部复发率为15%。碳离子和质子治疗PaC的2、3、2～3级胃肠道溃疡发生率分别为6.8%、1.5%、9.2%和3.5%、8.3%、6.1%(均P>0.05);1、2年OS分别为77.1%、44.4%和77.6%、49.7%(P均>0.05)。结论碳离子和质子治疗PaC安全有效,两者的安全性和有效性相似。     

MRI as an Alternative to Second Look Mastoid Surgery

The main goal of surgery of cholesteatoma is eradication of the disease and revision surgery is indicated when a dry and safe ear has not been achieved. Residual cholesteatoma usually occurs at the sites that are difficult to reach with an operating microscope, such as posterior tympanum and anterior epitympanic recess. Computed tomography can be performed to delineate the extent of disease. High-resolution computed tomography scanning is important for planning for surgery and is indicated for all revision mastoid operations. Magnetic resonance imaging is superior to computed tomography in tissue characterization for diagnosis of recurrent cholesteatoma. To evaluate the cases of recurrent cholesteatoma comparing the intraoperative surgical findings with the preoperative MRI radiological findings and if the preoperative MRI can replace the second look surgery for cholesteatoma. This study was applied on 60 patients that have a recurrent cholesteatoma after previous mastoid surgery. A preoperative radiological evaluation was done by Magnetic resonance, surgical management was done by canal wall up or canal wall down mastoidectomy to exclude residual disease. Then, radiological, and surgical findings correlation was done. Diffusion-weighted MRI successfully detected 42 cases out of the 45 cases of surgically proved cholesteatoma, it has accuracy 95%, sensitivity 93.33%, specificity 100%, PPV 100% and NPV 83.33%. MRI is better than CT in tissue characterization for diagnosis of recurrent cholesteatoma, and can replace the unnecessary second look surgery of cholesteatoma     

Gemcitabine in Combination with a Second Cytotoxic Agent in the First-Line Treatment of Locally Advanced or Metastatic Pancreatic Cancer: a Systematic Review and Meta-Analysis

Background

It remains controversial whether the addition of a second cytotoxic agent can further improve the therapeutic effect of gemcitabine monotherapy in advanced or metastatic pancreatic cancer (LA/MPC).

Objective

The objective of the present systematic review and meta-analysis was to investigate the efficacy and safety of gemcitabine-based doublet chemotherapy regimens compared to single-agent gemcitabine in the first-line treatment of unresectable LA/MPC.

Methods

We searched for randomized controlled trials (RCTs) of gemcitabine monotherapy versus gemcitabine in combination with a second cytotoxic agent in patients with LA/MPC. The last search date was December 31, 2016.

Results

Twenty-seven RCTs were identified and included in the present systematic review and meta-analysis, involving a total of 7343 patients. The meta-analysis showed that gemcitabine-based combination therapy significantly improved overall survival (OS) (HR: 0.89; 95% confidence interval (CI): 0.85-0.94; P?<?0.0001), progression-free survival (PFS) (HR: 0.80; 95% CI: 0.73-0.88; P?<?0.0001), and overall response rate (ORR) (RR: 1.83; 95% CI: 1.62-2.07; P?<?0.0001) in comparison to single-agent gemcitabine. Subgroup analysis suggested that the antitumor activity differed between gemcitabine-based combination regimens: doublet regimens of gemcitabine plus a taxoid, and gemcitabine plus a fluoropyrimidine, in particular an oral fluoropyrimidine, resulted in a significant OS benefit for the patients. However, the combination of gemcitabine with other cytotoxic agents, such as platinum compounds or topoisomerase inhibitors failed to reduce the mortality risk. Combination therapy caused more grade 3/4 toxicities, including neutropenia, thrombocytopenia, vomiting, diarrhea, and fatigue.

Conclusions

Gemcitabine-based doublet regimens demonstrated superiority over gemcitabine monotherapy in overall efficacy, but were associated with increased toxicity. Different gemcitabine-based combinations showed different antitumor activity, and doublet regimens of gemcitabine in combination with a taxoid or a fluoropyrimidine, in particular an oral fluoropyrimidine provided significant survival benefits in the first-line treatment of unresectable LA/MPC.

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A Systematic Approach of Data Collection and Analysis in Medical Imaging Research

Background: Obtaining the right image dataset for the medical image research systematically is a tedious task. Anatomy segmentation is the key step before extracting the radiomic features from these images. Objective: The purpose of the study was to segment the 3D colon from CT images and to measure the smaller polyps using image processing techniques. This require huge number of samples for statistical analysis. Our objective was to systematically classify and arrange the dataset based on the parameters of interest so that the empirical testing becomes easier in medical image research. Materials and Methods: This paper discusses a systematic approach of data collection and analysis before using it for empirical testing. In this research the image were considered from National Cancer Institute (NCI). TCIA from NCI has a vast collection of diagnostic quality images for the research community. These datasets were classified before empirical testing of the research objectives. The images in the TCIA collection were acquired as per the standard protocol defined by the American College of Radiology. Patients in the age group of 50-80 years were involved in various clinical trials (multicenter). The dataset collection has more than 10 billion of DICOM images of various anatomies. In this study, the number of samples considered for empirical testing was 300 (n) acquired from both supine and prone positions. The datasets were classified based on the parameters of interest. The classified dataset makes the dataset selection easier during empirical testing. The images were validated for the data completeness as per the DICOM standard of the 2020b version. A case study of CT Colonography dataset is discussed. Conclusion: With this systematic approach of data collection and classification, analysis will be become more easier during empirical testing.     

Pain Relief after Stereotactic Radiotherapy of Pancreatic Adenocarcinoma: An Updated Systematic Review

Severe pain is frequent in patients with locally advanced pancreatic ductal adenocarcinoma (PDCA). Stereotactic body radiotherapy (SBRT) provides high local control rates in these patients. The aim of this review was to systematically analyze the available evidence on pain relief in patients with PDCA. We updated our previous systematic review through a search on PubMed of papers published from 1 January 2018 to 30 June 2021. Studies with full available text, published in English, and reporting pain relief after SBRT on PDCA were included in this analysis. Statistical analysis was carried out using the MEDCALC statistical software. All tests were two-sided. The I² statistic was used to quantify statistical heterogeneity (high heterogeneity level: >50%). Nineteen papers were included in this updated literature review. None of them specifically aimed at assessing pain and/or quality of life. The rate of analgesics reduction or suspension ranged between 40.0 and 100.0% (median: 60.3%) in six studies. The pooled rate was 71.5% (95% CI, 61.6–80.0%), with high heterogeneity between studies (Q² test: p < 0.0001; I² = 83.8%). The rate of complete response of pain after SBRT ranged between 30.0 and 81.3% (median: 48.4%) in three studies. The pooled rate was 51.9% (95% CI, 39.3–64.3%), with high heterogeneity (Q² test: p < 0.008; I² = 79.1%). The rate of partial plus complete pain response ranged between 44.4 and 100% (median: 78.6%) in nine studies. The pooled rate was 78.3% (95% CI, 71.0–84.5%), with high heterogeneity (Q² test: p < 0.0001; I² = 79.4%). A linear regression with sensitivity analysis showed significantly improved overall pain response as the EQD2α/β:10 increases (p: 0.005). Eight papers did not report any side effect during and after SBRT. In three studies only transient acute effects were recorded. The results of the included studies showed high heterogeneity. However, SBRT of PDCA resulted reasonably effective in producing pain relief in these patients. Further studies are needed to assess the impact of SBRT in this setting based on Patient-Reported Outcomes.     

Association Between Pancreatitis and Subsequent Risk of Pancreatic Cancer: a Systematic Review of Epidemiological Studies

This study aimed to summarize published epidemiological evidence for the relationship between pancreatitis and subsequent risk of pancreatic cancer (PC). We searched Medline and Embase for epidemiological studies published by February 5th, 2014 examining the risk of PC in pancreatitis patients using highly inclusive algorithms. Information about first author, year of publication, country of study, recruitment period, type of pancreatitis, study design, sample size, source of controls and attained age of subjects were extracted by two researchers andStata 11.0 was used to perform the statistical analyses and examine publication bias. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with the random effects model. A total of 17 articles documenting 3 cohort and 14 case-control studies containing 14,667 PC cases and 17,587 pancreatitis cases were included in this study. The pooled OR between pancreatitis and PC risk was 7.05 (95%CI: 6.42-7.75). Howeever, the pooled ORs of case-control and cohort studies were 4.62 (95%CI: 4.08-5.22) and 16.3 (95%CI: 14.3-18.6) respectively. Therisk of PC was the highest in patients with chronic pancreatitis (pooled OR=10.35; 95%CI: 9.13-11.75), followed by unspecified type of pancreatitis (pooled OR=6.41; 95%CI: 4.93-8.34), both acute and chronic pancreatitis (pooled OR=6.13; 95%CI: 5.00-7.52), and acute pancreatitis (pooled OR=2.12; 95%CI: 1.59-2.83). The pooledOR of PC in pancreatitis cases diagnosed within 1 year was the highest (pooled OR=23.3; 95%CI: 14.0-38.9); and the risk in subjects diagnosed with pancreatitis for no less than 2, 5 and 10 years were 3.03 (95%CI: 2.41-3.81), 2.82 (95%CI: 2.12-3.76) and 2.25 (95%CI: 1.59-3.19) respectively. Pancreatitis, especially chronic pancreatitis, was associated with a significantly increased risk of PC; and the risk decreased with increasing duration since diagnosis of pancreatitis.     

二代测序获得胰腺癌患者肿瘤相关基因变异图谱分析

摘 要：［目的］ 了解胰腺癌患者的基因变异情况,为胰腺癌的个体化治疗提供探索依据。［方法］ 收集58例原发胰腺恶性肿瘤患者,利用二代基因测序技术（NGS）检测肿瘤组织和体细胞的基因变异情况,绘制基因变异图谱,并结合临床资料进行分析。［结果］ 53例胰腺腺癌患者中最常见的突变基因是KRAS、TP53、CDKN2A、SMAD4、ARID1A、RNF43（突变发生频率在10%以上）等。原发灶和转移灶、不同性别的样本之间,基因变异基本相似。肿瘤相关重要通路,如 MAPK通路变异89.0%,G1/S通路变异84.9%,HRD相关通路变异17.0%,TGF-β信号通路变异35.8%,SWI/SNF复合物通路变异46.0%。其中54.7%的患者至少有1个潜在可用药靶点。免疫生物标志物方面高肿瘤突变负荷（TMB-H）占1/52（1.9%),可分析的52例患者全部为微卫星稳定（MSS）。［结论］该研究中胰腺癌患者的全肿瘤相关基因测序情况,在主要的突变基因和潜在可用药靶点基因上,与国外报道相似,少数低频率突变的基因差异有待扩大样本量进一步验证。超50%的患者存在潜在可用药靶点,为胰腺癌的靶向免疫治疗提供了个体化治疗依据。     

Cysts of the larynx : A clinicopathologic study of nine cases

In this only report from India, nine patients with laryngeal cysts have been diagnosed in the 24 year period from Jan 1971 through Jan 1996 representing 0.01 % of 1,05,279 general biopsies and 1.16% of 774 laryngeal biopsies received. The patients were mainly male with a mean age of 48.87 years. They presented with laryngeal obstructive symptoms. Six of the patients were chronic cigarette smokers. None had history of voice abuse. Laryngoscopic examination showed solitary cysts situated in the supraglottic region in seven cases and in the true vocal cords in two. Using modified DeSanto’s classification of laryngeal cysts putforth by Newman et al (1984), four were ductal, three saccular and one of tonsillar type. However, one of the cysts having features of an epidermoid cyst could not fit into the classification. The major proposed classifications of laryngeal cysts which are in practice have resulted in much confusion for both clinicians and pathologists and these have been studied in depth and their implications discussed here.     

The Utility of Second Look Microlaryngoscopy after Trans Oral Laser Resection of Laryngeal Cancer

In the past few decades more and more number of tumors of the glottis and supraglottis are been treated with single stage transoral laser microsurgery (TOLS). TOLS for the treatment of glottic and supraglottic carcinoma with anterior commissure (A-com) and/paraglottic space involvement is associated with a high rate of recurrence. We prospectively evaluated the outcomes of laser microsurgery and the impact of second look operation in these patients. Twenty-three patients with glottic and supraglottic carcinoma underwent transoral laser micro resection of the lesions. Subsequently five patients underwent second look microlaryngeal evaluation 6–8 months later for non-satisfactory healing, poor voice, and or suspicion of recurrent disease. Patients with A-com involvement and or paraglottic space involvement were followed up longitudinally for the effectiveness and timing of second look microsurgery. After initial transoral laser micro resection, all patients achieved microscopically clear resection margins. At second look microlaryngeal evaluation, local recurrence was found in four of 23 patients. Of these, two patients were salvaged by second look surgery and are disease free, whereas in two others, the larynx had to be subjected to open surgical intervention. One of two had extensive local recurrent tumor and underwent total laryngectomy with neck dissection followed by post-operative radiotherapy. Tracheohyoidopexy was done with successful functional and oncologic outcome for another patient who had local recurrence for the third time. Only the patient who underwent total laryngectomy with neck dissection was subjected to adjuvant post-operative radiotherapy. Finally, larynx was saved in 21 out of 23 patients.