Evaluation of a Sentinel Lymph Node Biopsy with Patent Blue in Locally Advanced Gastric Cancer

Background: A sentinel lymph node (SLN) biopsy is an interesting issue in the field of surgical oncology and has recently been introduced to the treatment of gastric cancer. The purpose of this study is to assess accuracy, sensitivity, specificity, and false negative rates (FNRs) of SLN biopsies, and to ascertain whether or not this procedure is useful for locally advanced gastric cancer.Methods: From December 2013 to March 2014, 22 patients with gastric cancer were enrolled in this study. After laparotomy, patent blue was injected around the tumor subserosaly, resection was then done, and SLNs were detected on a back table. Afterward, D2 dissection was carried out. Finally, SLNs and other specimens were submitted for permanent pathology.Results: SLNs were detected in 20 of 22 patients. The total number of SLNs was 87. SLNs were positive in 7 patients, and the total number of positive SLNs was 17. In three patients, the SLNs were negative, whereas other LNs were positive, with an FNR of 15%. 18 patients received neoadjuvant. Complete pathologic responses with negative LNs were seen in 3 patients. Accuracy, sensitivity, specificity, and negative predictive values were 80%, 66%, 90%, and 76%, respectively.Conclusions: This research demonstrated that SLN mapping in advanced gastric cancer is an appropriate method with acceptable levels of accuracy, sensitivity, and negative predictive values, even in those patients who received neoadjuvant treatment

Metastatic Merkel Cell Carcinoma of the Pancreas: A Case Report

Background: Merkel cell carcinoma (MCC) is a malignant primary cutaneous neuroendocrine tumor with high propensity for local recurrence and distant metastasis. It commonly involves skin, brain, bone, liver and lung. Distant metastasis to the gastrointestinal tract, including pancreas, is very rare.Presentation of Case: In this article we report a case of a 59 year old male with history of left gluteal skin MCC which presented with metastatic involvement of body of pancreas 5 months after the diagnosis of primary tumor.Conclusion: Although MCC metastases to pancreas is rare, it should be kept in mind in patients with abdominal complaints and past history of MCC

Clinical improvement of diabetes mellitus type 1 by b-D-mannuronic acid (M2000) in a breast cancer patient — as a case report

A 56 years old female with breast cancer (BC) and poor controlled diabetes mellitus type 1 (DM1) which has registered in a clinical trial for assessment of thera­peutic efficacy of b-D-mannuronic acid (M2000) on pre-surgical BC patients is described in this case report. After receiving M2000, the patient was followed for 9 weeks. During this period, cancer mass details, fast­ing blood glucose (FBG) levels, 2-hour post-prandial blood glucose (2HPP), blood uric acid (BUA) level and urine analysis (UA) were continuously controlled. After 9 weeks of treatment with M2000, her FBG, BUA and UA decreased significantly. This finding was exactly in accordance with our published experimental data about the anti-diabetic effect of M2000 in an animal model. Therefore, it might be concluded that M2000 is probably able to improve DM1 by reducing FBG level, BUA level, glycosuria, ketonuria and proteinuria

Abnormal anti-Müllerian hormone level may be a trigger for breast cancer in young women: A case-control study

Background: Anti-Müllerian hormone (AMH) is a known sensitive biomarker for fertility and ovarian reserve. The results of in vivo and human studies showed inconsistency with respect to the relation between AMH and breast cancer. Objective: To compare the AMH level of young Iranian women with early breast cancer who have not received any treatment compared to that of healthy women. Materials and Methods: In this case-control study, 58 breast cancer cases were recruited from the breast oncology clinic of two university hospitals. They were diagnosed with an in situ or invasive breast cancer before any anticancer treatment between August 2018 and April 2019. Healthy controls (n = 58) were selected from women referred to a gynecologic outpatient clinic without any symptoms of cancer or infertility. AMH was measured by the AMH enzyme-linked immunosorbent assay kits in one laboratory. Results: Final analysis showed that the AMH means of case and control were not statistically significant (3.36 ± 2.95 vs 3.13 ± 1.79). However, the lower and higher AMH level categories are more prevalent in breast cancer compared to the control. Pearson’s correlation test showed that the AMH level was negatively correlated with age (r = -0.44, p< 0.001). The results of logistic regression analysis considering confounding factors showed the positive association between breast cancer and lower (Odds Ratio [OR] = 5.98, p = 0.02) and higher quartile of AMH level (OR = 4.95, p = 0.01). Conclusion: Our results suggest that abnormal AMH level is more frequent in young breast cancer patients. Further investigation considering AMH determinants is required. Key words: Anti-Müllerian hormone, Breast cancer, Biomarkers, Ovarian reserve

Expression and Clinical Significance of IRE1-XBP1s, p62, and Caspase-3 in Colorectal Cancer Patients

Background: Three main cell signaling pathways including the endoplasmic reticulum stress (ERS) response, autophagy, and apoptosis play critical roles in both cell survival and death. They were found to crosstalk with one another during tumorigenesis and cancer progression. This study aimed to investigate the expression of the spliced form of X-box binding protein 1 (XBP1s), p62, and caspase-3, as the essential biomarkers of ERS, autophagy, and apoptosis in patients with colorectal cancer (CRC), as well as the correlation between their expression and clinicopathological data. Methods: This retrospective study was conducted on formalin-fixed paraffin-embedded (FFPE) blocks, which were collected from patients and their tumor margins, from the tumor bank of Imam Khomeini Hospital (Tehran, Iran) from 2017 to 2019. Tissue microarray (TMA) was used to measure the XBP1s, p62, and caspase-3 biomarkers. Data were analyzed using SPSS software version 20, and P≤0.05 was considered statistically significant. Results: Evaluating the total of 91 patients, a significant relationship was found between XBP1s expression and TNM stage (P=0.003), primary tumor (pT) (P=0.054), and the degree of differentiation (P=0.006); and between caspase-3 with pT (P=0.004), and lymphovascular invasion (P=0.02). However, no significant correlation was found between p62 and clinicopathological data. Furthermore, a positive relationship between XBP1s and p62 was confirmed (correlation coefficient: 22.2% and P=0.05).Conclusion: Our findings indicated that XBP1s could be considered as a target for therapy in personalized medicine

The Role of Open Diagnostic Peritoneal Lavage in the Evaluation of Peritoneal Cytology for Advanced Gastric Cancer: An Old Diagnostic Modality with New Usage

Background: Positive peritoneal cytology is a critical factor in prognosis. Peritoneal lavage is associated with long-term survival in patients with gastric cancer. Diagnostic peritoneal lavage (DPL) is a method for diagnosing visceral injury in trauma patients. This study aimed to investigate the usage of DPL in staging the work-up of patients with gastric cancer. Method: In this prospective study, we enrolled gastric cancer patients referring to Cancer Institute; they underwent DPL and washing specimen was sent for cytology review. After DPL, all patients underwent staging laparoscopy (SL) via the same abdominal incision. Results: DPL and SL were successful in all patients. There were six (11%) cases of peritoneal seeding discovered in SL; all of these patients had positive peritoneal cytology on DPL. Also, four patients showed positive cytology in the absence of positive SL. Thus, sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of DPL were 100 % (95% CI: 54.1-100), 91.6 % (95%: 79.2-97.5), 100 % (95%CI: 85.3-100), and 60 % (95%CI: 37-79.3). The accuracy of DPL in determining the peritoneal dissemination of gastric cancer was 92.31% (95% CI: 81.5-97.9). Conclusion: DPL had an excellent ability to find peritoneal dissemination in a gastric cancer patient, which is of great value in the setting of low-resource countries

Enabling informed policymaking for chronic kidney disease with a registry:Initiatory steps in Iran and the path forward

Objectives: Chronic kidney disease (CKD) registries have been used for more than half a century. Iran lacks a comprehensive registry to capture data of all CKD patients for an informed care planning and policy making. We aimed to identify the objectives and possible challenges for developing a CKD registry and also to define its minimum data set (MDS) in our healthcare context.Methods: This was a mixed-method study conducted in Iran from fall 2016 till summer 2017. The qualitative part included document analysis and 26 semi-structured interviews with 17 clinicians and managers involved in CKD care. This data was analyzed using the "grounded theory". Then, a modified Delphi survey was conducted. Percentages and mode values were used for analysis.Results: Our participants' leading interest in a CKD registry was centered on providing a coordinated, good-quality care for all CKD stages with particular emphasis to capture events and monitor trends for patients in earlier stages. They highlighted the required financial, technical and human resources as main challenges for a smooth registry implementation. Furthermore, a clinically oriented MDS comprising of 168 elements (with a majority having more than 90% agreement with mode 2) was extracted. It mainly collects demographics, medical history, encounter sessions, diagnostic examinations, medications, vaccinations and mortality data.Conclusions: We reported the initiatory steps taken to establish a CKD registry in an Iranian healthcare context. We focused on the information needs and priorities of our main stakeholders and based our intended registry on addressing those needs. We hope this approach will facilitate its endorsement and advance the efforts for a sustainable, good-quality CKD care. (C) 2018 Fellowship of Postgraduate Medicine. Published by Elsevier Ltd. All rights reserved

The integrative multi-omics approach identifies the novel competing endogenous RNA (ceRNA) network in colorectal cancer

Circular RNAs (circRNA) are known to function as competing endogenous RNA (ceRNA) in various cancers by regulating microRNAs (miRNA). However, in colorectal cancer (CRC), the precise pathological role of circ000240/miRNA/mRNA remains indeterminate. The expression level of hsa_circ_000240 was evaluated using qRT-PCR in matching pairs of CRC tumor and adjacent normal tissue samples in our laboratory. Then, to determine whether hsa_circ_000240 acted as a ceRNA in CRC, the linked miRNAs and gene targets were retrieved. Topological analysis of candidate genes using a network approach identified the most critical hub genes and subnetworks related to CRC disease. Microarray and bulk RNA sequencing analyses were utilized to comprehensively evaluate the expression levels of both miRNA and mRNA in CRC. Single-cell RNA-seq analysis was also used to evaluate the significant overall survival (OS) genes at the cellular level. ATAC-seq data provided insights into candidate genes' accessible chromatin regions. The research uncovered a considerable upregulation of hsa_circ_000240 in CRC tissues. Three miRNAs interacted with the target circRNA. One thousand six hundred eighty intersected genes regulated by three miRNAs were further identified, and the relevant functionality of identified neighbor genes highlighted their relevance to cancer. The topological analysis of the constructed network has identified 33 hub genes with notably high expression in CRC. Among these genes, eight, including CHEK1, CDC6, FANCI, GINS2, MAD2L1, ORC1, RACGAP1, and SMC4, have demonstrated a significant impact on overall survival. The utilization of single-cell RNA sequencing unequivocally corroborated the augmented expression levels of CDC6 and ORC1 in individuals with CRC, alongside their noteworthy connection with the infiltration of immune cells. ATAC-seq analyses revealed altered accessibility regions in Chr2, 4, and 12 for CDC6 and ORC1 high-expression. Correlation analysis of CDC6 and ORC1 further highlighted the association of candidate gene expression with exhaustion markers such as CTLA4, CD247, TIGIT, and CD244. The candidate genes exhibit a positive correlation with chromatin remodeling and histone acetylation. These epigenetic modifications play a significant role in influencing the cancer progression following expression of CDC6 and ORC1 in CRC. Additionally, results showed that the methylation rate of the promoter region of CDC6 was elevated in CRC disease, confirming the functional importance of CDC6 and their interaction with hsa_circ_000240 and associated ceRNA in CRC. In conclusion, this study highlights hsa_circ_000240's role as a ceRNA in CRC. It opens new avenues for further dissection of CDC6, ORC1, and underlying novel epigenetics and immunotherapy targets for CRC therapy

Assessment of sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer in two subgroups: Initially node negative and node positive converted to node negative – A systemic review and meta-analysis

Background: Neoadjuvant chemotherapy (NAC) is increasingly used to treat patients with breast cancer, but the reliability of sentinel lymph node biopsy (SLNB) following chemotherapy is in doubt. In this meta-analysis, we aimed to evaluate studies that examine the results of SLNB after NAC to assess identification rate (IR) and false-negative rate (FNR). Materials and Methods: Systemic searches were performed in the PubMed, ISI Web of Sciences, Scopus, and Cochrane databases from January 1, 2000, to November 30, 2016, for studies of SLNB after NAC for breast cancer and followed by axillary lymph node (LN) dissection in two subgroups: initially node negative and node positive converted to node negative. Two reviewers independently review quality of included studies. A random-effects model was used to pool IR and FNR with 95% confidence intervals (CI), and heterogeneity among studies was assessed by I2 and Q-test. Results: A total of 23 studies with 1521 patients in the initially node-negative subgroup and 13 studies with 1088 patients in the node-positive converted to node-negative subgroup, were included in this meta-analysis with IR and FNR of 94% (95% CI: 92–96) and 7% (95% CI: 5–9) in the initially node-negative subgroup and 89% (95% CI: 85–94) and 13% (95% CI: 7–18) in the node-positive converted to node-negative subgroup, respectively. Conclusion: Our meta-analysis showed acceptable IR and FNR in initially node-negative group and it seems feasible in these patients, but these parameters did not reach to predefined value in node-positive converted to node-negative group, and thus, it is not recommended in these patients

Oesophageal perforation during neo-adjuvant brachytherapy for oesophageal squamous cell carcinoma

Neo-adjuvant brachytherapy (NBT) for oesophageal cancer is under rapid development in recent years and more reports are required to elucidate its complications and drawbacks. Here, we report a case treated for NBT whose oesophagus was perforated during the procedure and mention necessary precautions to avoid it. A 73 year old male whose upper gastrointestinal endoscopy showed a lesion extending from 29 cm to 33 cm of the incisors with a histology of poorly differentiated squamous cell carcinoma, without metastases. Endoscopic ultrasonography diagnosed a T3 N0 grade tumour. He was selected for NBT and neo-adjuvant chemotherapy. The patient received 5 Gy in the first session of NBT, but in the second session before receiving the same dosage his control chest X-ray showed the tip of the catheter to be out of the oesophageal tract. After confirmation of the perforation by Gastrografin, we performed total oesophagectomy combined with a gastric pull-up procedure. To our best knowledge, our case is the first reported complication related to the direct effect of the catheter and tissue manipulation rather than the radiation beam. Weakness in the oesophageal wall due to tumour involvement makes it prone to perforation by any rigid catheter