Pancreatic malignancies can be subdivided into endocrine and non-endocrine processes. Of the non-endocrine tumours, ductal carcinoma is the most common, and the ductal carcinomas can be further subdivided into adenocarcinomas and squamous cell carcinomas. The adenocarcinomas constitute most of the non-endocrine pancreatic malignancies, and the treatment options for these, although limited in efficacy, are relatively well established. The squamous cell carcinoma pathology is a rare entity, and few reports of it are found in the literature. As a result, treatment options for squamous cell carcinoma of the pancreas are poorly understood. Here, we report the presentation of a 48-year-old woman with metastatic squamous cell carcinoma of the pancreas. The subsequent investigations, treatment, and outcome are described.
Metabolomic profiling of nine trained ultramarathon runners completing an 80.5 km self-paced treadmill-based time trial was carried out. Plasma samples were obtained from venous whole blood, collected at rest and on completion of the distance (post-80.5 km). The samples were analyzed by using high-resolution mass spectrometry in combination with both hydrophilic interaction (HILIC) and reversed phase (RP) chromatography. The extracted putatively identified features were modeled using Simca P 14.1 software (Umetrics, Umea, Sweden). A large number of amino acids decreased post-80.5 km and fatty acid metabolism was affected with an increase in the formation of medium-chain unsaturated and partially oxidized fatty acids and conjugates of fatty acids with carnitines. A possible explanation for the complex pattern of medium-chain and oxidized fatty acids formed is that the prolonged exercise provoked the proliferation of peroxisomes. The peroxisomes may provide a readily utilizable form of energy through formation of acetyl carnitine and other acyl carnitines for export to mitochondria in the muscles; and secondly may serve to regulate the levels of oxidized metabolites of long-chain fatty acids. This is the first study to provide evidence of the metabolic profile in response to prolonged ultramarathon running using an untargeted approach. The findings provide an insight to the effects of ultramarathon running on the metabolic specificities and alterations that may demonstrate cardio-protective effects.
Cachexia is a multifactorial wasting syndrome associated with high morbidity and mortality in patients with cancer. Diagnosis can be difficult and, in the clinical situation, usually relies upon reported weight loss. The ‘omics’ technologies allow us the opportunity to study the end points of many biological processes. Among these, blood-based metabolomics is a promising method to investigate the pathophysiology of human cancer cachexia and identify candidate biomarkers. In this study, we performed liquid chromatography mass spectrometry (LC/MS)-based metabolomics to investigate the metabolic profile of cancer-associated weight loss. Non-selected patients undergoing surgery with curative intent for upper gastrointestinal cancer were recruited. Fasting plasma samples were taken at induction of anaesthesia. LC/MS analysis showed that 6 metabolites were highly discriminative of weight loss. Specifically, a combination profile of LysoPC 18.2, L-Proline, Hexadecanoic acid, Octadecanoic acid, Phenylalanine and LysoPC 16:1 showed close correlation for eight weight-losing samples (≥5% weight loss) and nine weight-stable samples (<5%weight loss) between predicted and actual weight change (r = 0.976, p = 0.0014). Overall, 40 metabolites were associated with ≥5% weight loss. This study provides biological validation of the consensus definition of cancer cachexia (Fearon et al.) and provides feasible candidate markers for further investigation in early diagnosis and the assessment of therapeutic intervention.
Patients with oral cavity cancers often present late to seek medical care. Surgery is usually the preferred upfront treatment. However, surgical resection cannot be achieved in many cases with advanced disease without major impact on patient’s quality of life. On the other hand, radiotherapy (RT) and chemotherapy (CT) have not been employed routinely to replace surgery as curative treatment or to facilitate surgery as neoadjuvant therapy. The optimal care of these patients is challenging when surgical treatment is not feasible. In this review, we aimed to summarize the best available evidence-based treatment approaches for patients with locally advanced oral cavity cancer. Surgery followed by RT with or without CT is the standard of care for locally advanced oral cavity squamous cell carcinoma. In the case of unresectable disease, induction CT prior to surgery or chemoradiotherapy (CRT) can be attempted with curative intent. For inoperable patients or when surgery is expected to result in poor functional outcome, patients may be candidates for possibly curative CRT or palliative RT with a focus on quality of life.
ABSTRACT. Mutations in codons 12/13 of K-ras exon 2 are associated with reduced benefit from anti-epidermal growth factor receptor antibody treatment for metastatic colorectal cancer (CRC). Here, we evaluated the frequency of K-ras mutations and their relationship with clinicopathological features and treatment outcomes in Saudi Arabian patients with CRC. The genetic status of K-ras was determined in 300 patients diagnosed with CRC. Clinical information was collected retrospectively. K-ras was wild-type in 58% and mutated in 42% of the tumors. Most mutations were at codon 12 (89%) and were associated with metastasis [odds ratio (OR) = 1.38 (95%CI = 1.14-1.67] and occurrence of >40 µg/L carcinoembryonic antigen (CEA) [OR = 1.33 (1.1-1.74)] during diagnosis. Patients in stages I-III of the disease with wild-type K-ras tumors had a median relapse free survival (RFS) of 29 months in contrast to 22 months for those with the mutated K-ras tumor (P = 0.0357). In multivariate analysis, only the stage of the disease significantly predicted RFS (P = 0.001). Patients in stage IV of CRC with the wild-type K-ras tumor did not reach the median overall survival (OS), whereas patients with the mutated K-ras tumor survived for 23.5 months (P = 0.044). CEA level >40 µg/L (P = 0.004) and status of K-ras (P = 0.044) were independent predictors of OS. This is the largest study investigating K-ras mutations in patients with CRC in the Middle East. Mutations were associated with advanced stage of CRC, higher serum CEA, shorter RFS and OS.
Human coronaviruses (HCoVs) have become evident sources of human respiratory infections with new emerging HCoVs as a significant cause of morbidity and mortality. The common four coronaviruses (229E, HKU1, NL63, and OC43) are known to cause respiratory illness in humans, but their clinical impact is poorly described in the literature. We analyzed the data of all patients who tested positive for at least one of the four HCoVs from October 2015 to January 2020 in a tertiary care center. HCoVs were detected in 1062 specimens, with an incidence rate of 1.01%, out of all documented respiratory illnesses. Detection of these viruses was reported sporadically throughout the years, with a peak of occurrence during winter seasons. OC43 had the highest incidence (53.7%), followed by NL63 (21.9%), HKU1 (12.6%), and 229E (11.8%). Most of these infections were community-acquired, with symptoms of both upper and lower respiratory tract. Co-detection with other viruses were observed, mostly with rhinovirus. 229E was the most frequent (26.4%) HCoV in patients requiring intensive care, while NL63 and 229E were the most common in patients requiring invasive ventilation. The highest 30-day mortality rate was observed in patients infected with 229E (6.4%). HCoVs are common circulating pathogens that have been present for decades, with 229E being the most virulent in this study cohort.
Background: Colorectal cancer (CRC) is a significant healthcare burden worldwide and in the Middle East (ME). KRAS mutation confers resistance to epidermal growth factor receptor (EGFR) inhibitors in the treatment of advanced CRC. Data regarding the rate of KRAS mutation from the ME are scattered and scarce. We aim to collect and review all sizable studies evaluating the frequency of KRAS mutations in CRC patients from the ME. Method:A Pubmed and Google Scholar search was conducted using keywords including KRAS, K-ras, colorectal cancer and Middle East, along with names of each ME country. Studies including over 90 patients were included in the review.Result: Eleven studies containing more than 90 patients were identified. Among all eleven studies, KRAS mutation rate ranged from 13 to 56%. Five studies reported KRAS mutation rate in M1 stage either exclusively or as part of subgroup analysis. In these studies, mutations were found in 8-45% of cases. KRAS mutations were associated with female gender, M1 stage and high CEA in 3, 2, and 1 studies respectively. Conclusion:There is a broad range of variability in KRAS mutation rate reported in different studies from the ME. This may have been due to small number of patients in the studies and lack of centralized testing for KRAS mutations. Larger and more coordinated studies from the ME population are required to ascertain the accuracy of KRAS mutation rate.
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