An evaluation of the quality and content of web-based stoma information.

AIM: Although the internet is commonly the first port of call for medical information, it provides unregulated data of variable quality. We aimed to evaluate commonly accessed web-based information on intestinal stomas using validated and novel scoring systems. METHOD: The keywords 'stoma', 'colostomy', 'ileostomy' and 'bowel bag' were entered into the most commonly used internet search engines (Google, Bing and Yahoo). The first ten websites from each search were analysed using the validated Journal of the American Medical Association (JAMA) benchmark criteria and DISCERN scoring systems. A novel stoma-specific score was devised and applied. RESULTS: Forty-three unique websites were identified. The majority (49%) were from nonprofit or governmental agencies and 9% were from commercial entities. The mean total DISCERN score for all websites was 42.4 ± 10.2 (maximum possible score = 75). The mean JAMA and stoma-specific scores were 2.1 ± 1.0 (maximum possible score = 4) and 12.9 ± 6.1 (maximum possible score = 27). The lowest JAMA scores were in the category of attribution, with 70% of websites lacking references for the information provided. A total of 88% displayed disclosure/paid advertiser information. Surgery was described in 67%. An image or diagram was provided in 58% and in 72% a stoma therapist/nurse was mentioned. Information on when to seek medical help was provided in 51%. CONCLUSION: Web-based information on stomas is of variable content and quality. Authorship and information sources are often unclear. Only half provided information on when to seek medical help for complications including high output and dehydration. These findings should be highlighted to patients who utilize the internet to obtain information on stomas.

AKT as Locus of Cancer Unknown Primary Site.

Cancer of unknown primary site is a metastasis developed by the positive feedback loops of primary cancer forming extreme cancer robustness. Such robustness occurs only in metastatic cancer or in relapsed lymphoma, myeloma, plasmocytoma, or leukemia. However, when it develops in primary cancer, hypoxic microenvironment generates positive feedback loops which hyperactivate AKT locus, forming extreme robustness that forcing cancer cells to migrate to the distant site, but primary cancer loosing that property or remains silent. Positive loops are the force and principal mechanism of metastasis development. A cancer cell is converted normal cell. Conversion occurs at the AKT genomic locus. Thus, cancer is genomic disease rather than disease of the specific organs. Targeting such locus by the locus chemotherapy (redox balance change) rather than by organ specific therapy results in conversion of positive loops into negative and disappearance of extreme robustness and malignant phenotype of the cancer unknown primary origin.

Metastatic Clear Cell Carcinoma of Unknown Primary Origin in an Elderly Female Patient With Paraneoplastic Hypercalcemia.

Metastatic clear cell carcinoma (mCCC) is a rare histological subtype of cancer with ovarian and renal origins most common primary sites. Cancer of unknown primary origin (CUP) is a rare type of cancer in the United States and the most common histologic subtypes are adenocarcinoma, squamous cell cancer, and neuroendocrine cancer. We are presenting a rare case of an 86-year-old female patient with mCCC of unknown origin, biopsy and staining showed renal and ovarian in the differential of primary cancer type. However, the patient did not survive the aggressive nature of mCCC and was unable to get any trials of chemotherapy. Primary sites of adenocarcinoma of unknown origin are most common in the breast, lung, pancreas, prostate, colon, and liver. In most cases, empiric chemotherapy with platinum-based agents is the standard of care but needs more data to manage CUP, making it difficult to identify the primary site.

Updated Incidence, Treatment and Survival of a Nationwide Cohort of Patients with Peritoneal Metastases of Unknown Origin.

The aim of this study was to investigate the incidence, treatment and survival of patients with peritoneal metastases (PM) of unknown origin. All Dutch patients diagnosed in 2017 and 2018 with PM of unknown origin (PM-CUP) were evaluated. Data were extracted from the Netherlands Cancer Registry (NCR). Patients with PM-CUP were categorized into the following histological subtypes: 1) adenocarcinoma, 2) mucinous adenocarcinoma, 3) carcinoid, 4) unspecified carcinoma and 5) other. Treatments were compared between the different histological subtypes in patients with PM-CUP. Overall survival (OS) was calculated using the Kaplan-Meier method for all patients with cancer of unknown origin and between histological subtypes in patients with PM-CUP. Significant differences in OS were assessed by using the log-rank test. In total, 3026 patients were diagnosed with cancer of unknown origin, 513 (17%) among them were diagnosed with PM-CUP. Most PM-CUP patients received best supportive care only (76%), whereas 22% received systemic treatment and 4% underwent metastasectomy. Median OS was 1.1 months for all patients with PM-CUP but varied from 0.6 months to 30.5 months depending on the underlying histology. In this study, PM-CUP were diagnosed in 17% of all patients with cancer of unknown primary and the reported survival in this cohort was extremely poor. Since survival differed among histological subtypes and recently more treatment options became available for a selected group of patients with peritoneal malignancies, it is of great importance to identify the histology of the metastases and whenever possible the primary tumor.

To Treat or Not to Treat Poorly Differentiated Adenocarcinoma of Unknown Origin.

This case illustrates that although advances have been made with diagnosis and treatment of adenocarcinoma of unknown origin with targeted therapy, more research needs to be done on poorly differentiated adenocarcinoma that initially presents with extensive metastases. In this patient's case, it was beneficial and ethical to reduce the toxicity and emotional burden and thus limit further investigation into her adenocarcinoma. However, it is imperative to recognize that only a small subset of adenocarcinoma of unknown origin are responsive to current therapies and more research is required for the many cases that present with poorly differentiated adenocarcinoma and widespread metastasis.

Clinical Implications of Noncoding Indels in the Surfactant-Encoding Genes in Lung Cancer.

Lung cancer arises from the accumulation of genetic mutations, usually in exons. A recent study identified indel mutations in the noncoding region of surfactant-encoding genes in lung adenocarcinoma cases. In this study, we recruited 94 patients with 113 lung cancers (88 adenocarcinomas, 16 squamous cell carcinomas, and nine other histologies) who had undergone surgery in our department. A cancer panel was designed in-house for analyzing the noncoding regions, and targeted sequencing was performed. Indels in the noncoding region of surfactant-encoding genes were identified in 29/113 (25.7%) cases and represent the precise cell of origin for the lung cancer, irrespective of histological type and/or disease stage. In clinical practice, these indels may be used as clonal markers in patients with multiple cancers and to determine the origin of cancer of unknown primary site.

Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site.

Cancer of unknown primary (CUP) is a malignant widespread metastatic disease without an identifiable primary site after extensive clinical investigation. Recently, a decline is observed in the diagnosis of CUP, mainly due to improvement in detection of the primary tumors, thus decreasing the unknown primaries. Worldwide, CUP is the sixth to eighth most common malignancy, accounting for 2.3% to 5% of a new cancer diagnosis. CUP is third to fourth most common cause of death due to cancer-related mortality. The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. High risk for developing CUP is seen in heavy smokers (26 or more cigarettes/day) and individuals with the lowest quartiles of waist circumference. A weak association is observed with the use of alcohol consumption and low level of education. Human papillomavirus DNA plays a role in those with squamous cell carcinoma of unknown primaries in head and neck regions. In the diagnosis of CUP, comprehensive medical history, complete physical examination (including genitourinary, rectal exam, and breast examination in women) and necessary laboratory tests are crucial. Whole-body positron emission tomography-computed tomography (PET/CT) is the investigation of choice to assess the entire body for CUP. Multiparametric 3T-MRI (MP-MRI) is used to examine the local soft tissue status, helps in the staging of the tumor, and to determine the extent of involvement of tissue for medical as well as prognostic purposes. Immunohistochemistry outlines the specific markers, including caudal-related homeobox protein (CDX2), homeobox protein Nkx-3.1 (NKX3-1), paired box gene 8 (PAX8), special AT-rich sequence-binding protein 2 (SATB2), thyroid transcription factor 1 (TTF-1), and splicing factor 1 (SF1) with the focus on the effectiveness of lineage-restricted transcription factors. Patients response to treatment can be evaluated by the gene expression profiling (GEP) test that also predicts tissue of origin (TOO). Tumor identified through gene profiling is sensitive to platinum/taxane therapy, others that are not TOO tumors are resistant to platinum/taxane. The new therapeutic method based on molecular profiling is associated with higher treatment response. In comprehensive genomic profiling, it is observed that there is at least one clinically appropriate genomic alteration in CUP that can influence the targeted therapy. The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site.

Transoral tongue base mucosectomy for the identification of the primary site in the work-up of cancers of unknown origin: Systematic review and meta-analysis.

BACKGROUND: The use of transoral robotic surgery (TORS) and laser microsurgery (TLM) in the diagnosis and identification of the site of the unknown primary has become increasingly common. This systematic review and meta-analysis aims to assess the use and efficacy of TORS and TLM for this indication. METHOD: Systematic review and meta-analysis of studies employing TORS or TLM in diagnosis of the unknown primary tumor site in patients with cervical nodal metastases of squamous cell origin. MEDLINE, EMBASE and CINHAL were searched from inception to July 2018 for all studies that used TORS and or TLM in identifying the unknown primary. RESULTS: 251 studies were identified, of which 21 were eligible for inclusion. The primary tumour was identified by TORS/TLM in 78% of patients (433 out of 556). Tongue base mucosectomy (TBM) identified the primary in 222 of 427 cases (53%). In patients with negative physical examination, diagnostic imaging and PETCT, TBM identified the primary in 64% (95% CI 50, 79) cases. In patients who had negative CT/MRI imaging, negative PETCT and negative EUA and tonsillectomy, TBM identified a tongue base primary in 78% (95% CI 41, 92) cases. Haemorrhage, the commonest complication, was reported in 4.9% cases. Mean length of stay varied between 1.4 and 6.3 days. CONCLUSION: Tongue base mucosectomy, performed by TORS or TLM, is highly efficacious in identifying the unknown primary in the head and neck region.

Prediction of Primary Tumors in Cancers of Unknown Primary.

A cancer of unknown primary (CUP) is a metastatic cancer for which standard diagnostic tests fail to identify the location of the primary tumor. CUPs account for 3-5% of cancer cases. Using molecular data to determine the location of the primary tumor in such cases can help doctors make the right treatment choice and thus improve the clinical outcome. In this paper, we present a new method for predicting the location of the primary tumor using gene expression data: locating cancers of unknown primary (LoCUP). The method models the data as a mixture of normal and tumor cells and thus allows correct classification even in impure samples, where the tumor biopsy is contaminated by a large fraction of normal cells. We find that our method provides a significant increase in classification accuracy (95.8% over 90.8%) on simulated low-purity metastatic samples and shows potential on a small dataset of real metastasis samples with known origin.

A Nordic survey on the management of head and neck CUP.

CONCLUSION: The management of Head and Neck Cancer of Unknown Primary (HNCUP) patients varies both between centres within and also between the Nordic countries. This study contributes to a continuing discussion of how to improve the accuracy of diagnosis and quality of treatment of HNCUP patients. OBJECTIVES: The initiative for this study was based on the lack of common guidelines for diagnostic procedures and for treatment of HNCUP patients in the Nordic countries constituting a region having a rather homogeneous population. METHOD: A structured questionnaire was sent to all university hospitals in the five Nordic countries. RESULTS: Four of the five Nordic countries use either national guidelines or specific protocols when handling HNCUP. The main diagnostic tools are PET-CT, fine needle aspiration, endoscopic evaluation with biopsies, and most often bilateral tonsillectomy. At 21 of 22 university hospitals the treatment decision is made at a multidisciplinary conference. Three of seven Swedish centres use only radiotherapy or chemoradiotherapy to treat N+ HNCUP patients. Robotic surgery for biopsy of the tongue base is beginning to become an alternative to targeted biopsies in Sweden and Finland. Narrow Band Imaging is used only in Finland.

The migration ability of stem cells can explain the existence of cancer of unknown primary site. Rethinking metastasis.

Cancers of unknown primary site are metastatic cancers for which primary tumors are not found after detailed investigations. In many cases, the site of origin is not identified even on postmortem examination. These cancers are the fourth most common cause of cancer death. The biological events involved in the development of this type of cancers remain unknown. This manuscript discusses that, like metastatic cells, stem cells have a natural ability to migrate. A cancer of unknown primary site would form when deregulated, premalignant or cancerous stem cells migrated away from their natural tissue and gave rise to a cancer in a new site before or without generating a tumor in their original tissue. It is important to realize that forming a tumor in a tissue is not a prerequisite for stem cells to migrate away from that tissue. This view is in accordance with recent observations that strongly support the tumorigenesis model in which cancer arises from normal stem cells. Evidence has accumulated that cancer stem cells may play a key role in cancer progression and resistance to therapy. Successful treatment of cancer, including that of unknown primary site, may therefore require the development of therapies against cancer stem cells.