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© 2020 Elsevier B.V. Brain metastases manifest the advanced stage of breast cancer disease with poor prognosis for patient survival. Recent reports demonstrate that some therapeutic agents can activate the expression of several breast cancer-associated genes, whose products are involved in the onset and development of brain metastases. In this study, we discovered a functional link between KISS1 and E-cadherin that could be observed in both primary brain metastatic lesions and paired cell lines, such as parental CN34TGL and MDA-MB-231 and their respective brain metastatic subclones CN34Brm2Ctgl and MDA-MB-231Br. Remarkably, expression of KISS1 and E-cadherin genes consistently showed an inverse correlation in all of the above cell/tissue types. While E-cadherin expression was strongly upregulated in metastatic clones isolated from blood and brain, the levels of this protein in parental MDA-MB-231 cell line was low. Furthermore, E-cadherin upregulation can be artificially induced in MDA-MB-231Br and CN34Brm2Ctgl cell populations by knocking down KISS1 expression directly or through overexpressing the miR345 mimic. In the aggregate, our data suggest that the tumor microenvironment, which controls breast cancer spreading via miR345-regulated KISS1 expression, might modulate metastatic spreading by a mechanism(s) involving upregulation of E-cadherin production.

© 2019 Wiley Periodicals, Inc. Background: The management of patients with incidentally discovered metastatic thyroid cancer in cervical lymph nodes in neck dissection specimens for other pathologies is unclear. Methods: Retrospective review of neck dissection specimens for nonthyroid malignancy during a 30-year period was undertaken to identify incidental metastatic papillary thyroid cancer (PTC). Results: Twenty-six patients had an incidental finding of PTC in lymph node(s) in neck dissection specimens. Subsequent ultrasound of the thyroid showed nodules in 20 patients. Eleven (42%) underwent total thyroidectomy, 1 (4%) had a lobectomy, and 14 (54%) were kept under active surveillance only. At a median follow-up of 48 months (range 10-189 months), all patients who had undergone surgery and those under surveillance were free of PTC recurrence. Conclusion: Evaluation for detection of a primary thyroid tumor is essential in all patients with incidentally discovered metastatic PTC. Decision regarding surgery or surveillance is dependent on clinical and radiological tumor features and patient factors.

© 2019, Indian Association of Surgical Oncology. The role of surgery in the management of metastatic gastric cancer (MGC) remains unclear. The aim of this study was to investigate the surgical and oncologic outcomes of gastrectomy in patients with MGC. The study included prospectively collected data of patients with MGC operated at four medical centers in Yerevan, Armenia, between 2000 and 2014. Armenian National Center of Oncology Registry and hospital records were used to obtain survival data. Factors associated with performing gastrectomy in patients with MGC were analyzed by using the logistic regression model. The Kaplan-Meier method was applied for survival analysis, and the Cox regression model with backward selection was used for multivariate analysis. A total number of 733 patients were operated for gastric cancer including 112 (15.3%) with MGC. Of those, 70 underwent gastrectomy, while 42 had exploratory laparotomy or bypass. Morbidity and mortality were similar after gastrectomy and exploratory laparotomy/bypass (18.6 vs 21.4%, p = 0.71 and 2.9 vs 7.1% p = 0.36, respectively). Female gender, involvement of N1 and/or N2 lymph node stations, and differentiated adenocarcinoma were associated with opting for gastrectomy. Gastrectomy with synchronous resection of distant metastases resulted in postoperative outcomes similar to those following gastrectomy without synchronous organ resection. Median follow-up was 6 months. Eighteen (16.1%) patients received chemotherapy. Median survival following gastrectomy and exploratory laparotomy/bypass were 7 and 4 months (p = 0.015), respectively. The use of chemotherapy following gastrectomy significantly improved survival compared with gastrectomy only (14 vs 6 months, p = 0.01). In the multivariable analysis, chemotherapy and nodal stage correlated with survival after gastrectomy. Gastrectomy for MGC is associated with satisfactory surgical outcomes and can be combined with synchronous resection of distant metastases in selected patients. Gastrectomy results in longer survival compared with exploratory laparotomy/bypass, especially when followed by chemotherapy.

© 2019 The Author(s). Background: Liver resection is a treatment of choice for colorectal and neuroendocrine liver metastases, and laparoscopy is an accepted approach for surgical treatment of these patients. The role of liver resection for patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM), however, is still disputable. Outcomes of laparoscopic liver resection for this group of patients have not been analyzed. Material and methods: In this retrospective study, patients who underwent laparoscopic liver resection for NCNNLM at Oslo University Hospital between April 2000 and January 2018 were analyzed. Perioperative and oncologic data of these patients were examined. Postoperative morbidity was classified using the Accordion classification. Kaplan-Meier method was used for survival analysis. Median follow-up was 26 (IQR, 12-41) months. Results: Fifty-one patients were identified from a prospectively collected database. The histology of primary tumors was classified as adenocarcinoma (n = 16), sarcoma (n = 4), squamous cell carcinoma (n = 4), melanoma (n = 16), gastrointestinal stromal tumor (n = 9), and adrenocortical carcinoma (n = 2). The median operative time was 147 (IQR, 95-225) min, while the median blood loss was 200 (IQR, 50-500) ml. Nine (18%) patients experienced postoperative complications. There was no 90-day mortality in this study. Thirty-five (68%) patients developed disease recurrence or progression. Seven (14%) patients underwent repeat surgical procedure for recurrent liver metastases. One-, three-, and five-year overall survival rates were 85%, 52%, and 38%, respectively. The median overall survival was 37 (95%CI, 25 to 49) months. Conclusion: Laparoscopic liver resection for NCNNLM results in good outcomes and should be considered in patients selected for surgical treatment.

© 2017 Elsevier B.V. KISS1 tumor suppressor protein regulates cancer cell invasion via MMP9 metalloproteinase. Downregulation of KISS1 gene expression promotes progression of breast cancer and melanoma, resulting in the development of distant metastases. In the current study, we investigated whether restoration of KISS1 expression in KISS1-deficient human metastatic breast cancer cells holds potential as an advanced anticancer strategy. To this end we engineered an infectivity-enhanced conditionally-replicative human adenovirus type 5 encoding KISS1 as an “arming” transgene in the Ad5 E3 region for an ectopic KISS1 expression in transduced cancer cells. The oncolytic potential of the vector was examined using brain-invading metastatic clones of CN34 and MDA-MB-231 breast cancer cells, which supported high levels of AdKISS1 replication, correlating with a robust CRAd-mediated cytotoxicity. Secretion of cellular factors responsible for tumor angiogenesis, cell-to-cell communication and anti-tumoral immune responses upon KISS1 expression in breast cancer cells was analyzed by a RayBiotech Kiloplex Quantibody array. Overall, our results indicate that KISS1 transgene expression provides an important benefit for CRAd-mediated cytotoxicity in breast cancer cells and holds potential as an anticancer treatment in conjunction with oncolytic virotherapy of breast and other metastatic cancers.

Liver resection remains the method of choice for treatment of colorectal liver metastases with good long-term results. Regional lymph nodes involvement is significant negative prognostic factor. Moreover, it has been considered as a contraindication for liver resection for a long time. The role of lymphadenectomy remains controversial. Current state of this problem is reviewed in the article. Liver regional lymph nodes involvement takes place in 10-20% of cases. PET/CT is the most sensitive method of preoperative diagnosis. Involvement of liver regional lymph nodes is currently not absolute contraindication for liver resection. Routine lymphadenectomy does not make sense, and, perhaps, is justified only within scientific trials for more accurate disease staging. Indications for lymphadenectomy are suspicious changes of lymph nodes revealed by preoperative visualization methods or by intraoperative exploration. Modern chemotherapy regimens allow to reconsider the prognostic importance of liver regional lymph node metastases and to extend indications for liver resections.

© 2018 Russian Electronic Journal of Radiology.All right reserved. Purpose: In recent years, whole-body MRI have been increasingly used in the field of oncological radiology owing to its advantages such as: yield of high-quality diagnostic information in relatively short scan time, lack of radioisotope or intravenous contrast use, and comparingly low examination cost in contrast to traditional nuclear medicine techniques. Aim of this article is to bring the overview of whole-body MRI as a technique and current applications of its use in oncological radiology.

© 2018 Ima-Press Publishing House. All Rights Reserved. Up to 15% of patients with secondary brain tumors of unknown primary are admitted to a neurosurgery department. Identification of a primary tumor site on the basis of surgical material immunophenotyping in routine clinical practice has a significant potential; however, this requires systematization. Objective: to detect the primary focus of brain carcinoma. Patients and methods: Surgical specimens from 7 patients with brain tumor of unknown primary were investigated using light optical microscopy and an immunohistochemical (IHC) panel including EMA, CK AE1/3, CK7, CK5/6, GFAP, S-100, Vimentin, p63, TTF-1, Uroplakin III (UPIII), CDX2, and Her2/neu. Results and discussion: A study using the IHC panel made it possible to obtain the following tumor phenotypes in the patients: CK5/6+, p63+, CK7+, UPIII+ (urothelial cancer) (n=3); CK5/6-, CK7+, TTF-1+, CDX2- (lung adenocarcinoma) (n=2); CK5/6+, p63+, CK7-, UPIII, TTF-1- (squamous cell carcinoma) (n=1), and CK5/6-, CK7+, TTF-1-, CDX2-, Her2/neu+ (breast cancer) (n=1). Evidence of the primary focus of the tumors was subsequently confirmed by instrumental techniques in all cases when cancer of the breast, lung and urinary system was directly sought. The findings were used to elaborate an algorithm for the differential diagnostic immunophenotyping of brain metastases. Conclusion: The primary focus of brain carcinoma was detected in all cases on the proposed IHC panel. The systematized algorithm for differential diagnostic immunophenotyping can be used in clinical practice.