Evaluation of diagnostic algorithm and therapeutic interventions for intra-abdominal desmoid tumors

Desmoid-type fibromatosis (DF) is a distinctly rare condition, mostly of younger adults, characterized by the development of locally aggressive tumors of mesenchymal origin. Desmoid tumors (DT) arise either sporadically or in association with FAP (familial adenomatous polyposis), although certain risk factors have also been identified, including pregnancy and antecedent surgical trauma. They can emerge from any connective tissue including muscle, fascia and aponeurosis and are therefore classified, according to location, as intra-abdominal, of the abdominal wall and extra-abdominal. Despite the lack of metastasizing potential, the course can be unpredictable. Various mutations of APC and β-catenin genes, among others, play a catalytic role in the pathogenesis of this neoplastic entity. Surgery has lost its traditional role as first line treatment of the disease and several other treatment methods are being considered. Cytotoxic chemotherapy, non-cytotoxic systemic therapy and targeted therapy have been revealed as part of different treatment regimens. Recent progress regarding DT biology and molecular pathways has led to the development of promising novel biological agents. In any case, a multidisciplinary approach is required and is gradually employed, espe-cially in intra-abdominal DTs. In this review, we aim to present current knowledge on DF and summarize current treatment regimens as well as their effectiveness, with emphasis on the intraperitoneal type of DT.     

Abdominal tumors in patients with neurofibromatosis type I: Genotype-phenotype relationships

BackgroundGastrointestinal stromal tumors have been detected in 25% of the necropsies performed on NF1 patients, but have been reported only in 7% of NF1 patients in the largest series. Such data imply an important gap between the true presence of tumors and those diagnosed. Few genotype-phenotype relationships have been described but to date none referring to abdominal tumors.ObjectivesEvaluate retrospectively the efficacy of a regular and proactive follow-up of NF1 patients to early diagnose abdominal tumors and report their mutations.MethodsCohort study performed between 2010 and 2020, with 43 NF1 adult patients followed at our Dermatology department.ResultsEight abdominal tumors were diagnosed in six patients, meaning that 14% of the followed patients developed an abdominal tumor. Five patients (83%) were asymptomatic. Five (83.3%) had a family history of NF1 with abdominal tumors (patients 1,2 and 3,4,5 were relatives).ConclusionsAlthough currently gastrointestinal routine screening investigations for asymptomatic patients are not recommended in the guidelines, the family aggregation in our series suggests it should be considered a close follow-up of the relatives of a patient with an NF1-related abdominal tumor. Also, for the first time, two mutations [c.2041C > T (p.Arg681Ter) and c.4537C > T (p.Arg1513*)] have been associated with family aggregation of abdominal tumors in NF1 patients.     

Curcumin Encapsulated into Biocompatible Co-Polymer PLGA Nanoparticle Enhanced Anti-Gastric Cancer and Anti-Helicobacter Pylori Effect

Background: The current disadvantages (high cost, toxicity, resistance) of chemotherapy for gastric cancer opted people for alternative therapy from natural source. Curcumin (natural product) possess multiple biological activities but low bio-availability limits their uses as therapeutic. The Nano-formulation of curcumin increased the bioavailability and productivity of anti-cancer and anti-bacterial properties. The present study was initiated to determine the anti-cancer and anti-bacterial effect of Nano curcumin against gastric cancer and H. pylori. Methods: Curcumin loaded PLGA nanoparticles (CUR-NPs) was prepared by single emulsion solvent evaporation method. The MIC were determined using agar dilution method to find the anti-H. Pylori activity of Nano curcumin. The cytotoxicity of Nano curcumin was evaluated by MTT assay and the apoptotic effect (cell cycle arrest and morphology change) was shown by PI staining and microscopy. Results: The MIC of nanocurcumin and curcumin for all four H. pylori strains were 8 µg/ml and 16 µg/ml respectively. The inhibition rate of gastric cancer cells after treatment with curcumin was increased from 6% to 67% for 24h, from 8% to 75% for 48h, from 10% to 83% for 72h. In case of nanocurcumin, the inhibition rate increased from 7% to 69% for 24h, 11% to 87% for 48h and 16% to 97% for 72h. The IC50 of curcumin and Nano-curcumin were 24.20 µM and 18.78 µM respectively for 72 h. The population of cells in sub-G0 population increased from 4.1% in the control group to 24.5% and 57.8% when treated with curcumin and nanocurcumin respectively. After 72h of treatment with nanocurcumin, the apoptotic cells population increased as compared to native curcumin treated cells. Conclusion: The Nano curcumin might be used as a potential therapeutics against gastric cancer and H. Pylori. There is need of further in vivo study in order to validate CUR-NPs activity.     

Analysis of the correlation between P27 expression and Helicobacter pylori infection in gastric cancer

We aimed to explore the correlation between P27 expression and Helicobacter pylori (H. pylori) infection in gastric cancer, so as to provide evidence for understanding the pathogenesis of gastric cancer caused by H. pylori infection. A total of 82 samples of gastric cancer tissues and 56 samples of tumor-adjacent normal tissues collected from the gastrectomy were enrolled in this study. Then, 14C-urease breathing test was carried out to evaluate the infection of H. pylori in gastric cancer tissues, the expression of P27 in the tissue samples was detected by the immunohistochemistry staining, and the correlation between the H. pylori infection and P27 expression in gastric cancer was analyzed. Of 82 gastric cancer patients, there were 53 patients with H. pylori infection (64.63%). Among the patients with highly or moderately differentiated gastric cancer, the expression of P27 was much higher than that of patients with poorly differentiated gastric cancer (p < 0.01). Besides, comparison of the P27 expression between males and females, among different age groups, tumor sizes, TNM stages, tumor infiltration degrees, or lymph node metastasis, showed no significant differences (p > 0.05). Analysis of the correlation revealed that P27 expression was negatively correlated with the infection of H. pylori (p < 0.01). Multifactorial logistics regression analysis indicated that tumor differentiation was a risk factor of P27-positive expression in gastric cancer tissues (p < 0.01). In addition, P27 expression in the gastric cancer tissues was lower than that in the tumor-adjacent normal tissues (p < 0.01). In gastric cancer patients, expression of P27 is correlated with H. pylori infection which, via downregulating P27, can cause the cancerization of gastric mucosa, and P27, for its role in the development and progression of gastric cancer, is a potential auxiliary indicator for clinical diagnosis whether gastric cancer is complicated with H. pylori infection. So, P27 is a key indicator for diagnosis, treatment, and prognostic evaluation of disease in the advanced stage.     

携带同源重组修复相关基因突变的消化道肿瘤的临床特点

目的:探讨消化道肿瘤中同源重组修复相关基因(homologous recombination repair related gene，HRR)突变的发生情况及临床意义。方法:共92例消化道肿瘤患者，79例患者进行了血液标本HRR检测，53例患者进行了组织标本HRR检测，40例患者同时行血液和组织的HRR基因检测，收集患者基因检测结果及临床相关资料。结果:在79例患者血液标本检测中发现10例（12.6%）有临床意义HRR突变，在53例患者组织标本检测中发现9例（17.0%）有临床意义HRR突变。40例同时行血液和组织的HRR基因检测患者中常见的有临床意义HRR突变为CDK12突变4例（10.0%）、ATM突变3例（7.5%）、BRCA1突变2例（5.0%）。13例有临床意义HRR突变患者中常见共存突变为TP53突变10例（76.9%）、APC突变5例（38.5%）、PIK3CA突变4例（30.8%）。40例患者中13例患者血液和/或组织中有临床意义HRR突变，27例患者血液和组织中均无任何临床意义HRR突变且两组相比，有临床意义HRR突变组肿瘤突变负荷（tumor mutational burden，TMB）为6.17(2.24～11.52)，而未携带HRR突变组TMB为0.4(0～3.75)，差异有统计学意义（P＜0.05）。40例患者组织检测中7例HRR有临床意义的突变，33例无HRR突变，血液检测中10例HRR有临床意义的突变，30例无HRR突变，一致性检验的Kappa值为0.333（P=0.031）。结论:携带有临床意义HRR突变的消化道肿瘤患者TMB更高，血液和组织检测HRR突变有较好的一致性。     

Pulmonary metastases in urogenital cancers: Surgical treatment and outcomes

IntroductionMetastasis is remaining one of the major problems in cancer treatment. Like many other malignancies, urogenital tumors originating from kidney, prostate, testes, and bladder tend to metastasize to the lungs.The aim of this retrospective study is to evaluate the operative results and prognosis of pulmonary metastasectomy in patients with primary urogenital tumors.MethodsThis study was approved by the local ethical committee. We retrospectively analyzed the surgical and oncological results of patients who underwent lung resections for urogenital cancer metastases in our department between 2002 and 2018. Demographic data and clinicopathological features were extracted from the medical records. Survival outcomes according to cancer subtypes and early postoperative results of VATS and thoracotomy were analyzed.Results22 out of 126 patients referred for pulmonary metastasectomy to our department had metastases from urogenital tumors. These patients consisted of 17 males and five females. Their metastasis originated from renal cell carcinoma (RCC; n = 9), bladder tumor (n = 7), testis tumors (n = 4), and prostate cancer (n = 2). There was no intraoperative complication. Postoperative complications were seen in 2 patients.ConclusionsAlthough pulmonary metastasectomy in various types of tumors is well known and documented, the data is limited for metastases of urogenital cancers in the literature. Despite the limitations of this study, we aim to document our promising results of pulmonary metastasectomy in patients with primary urogenital tumors and wanted to emphasize the role of minimally invasive approaches.