Is neoadjuvant chemotherapy followed by surgery the appropriate treatment for esophagogastric signet ring cell carcinomas? A systematic review and meta-analysis

BackgroundThe impact of neoadjuvant chemotherapy (nCTX) on survival and tumor response in patients with esophagogastric signet ring cell carcinoma (SRCC) is still controversial.MethodsTwo independent reviewers performed a systematic literature search in Medline, CENTRAL, and Web of Science including prospective and retrospective two-arm non-randomized and randomized controlled studies (RCTs). Data was extracted on overall survival (OS) and tumor regression in resected esophagogastric SRCC patients with or without nCTX. Survival data was analyzed using published hazard ratios (HR) if available or determined it from other survival data or survival curves. OS and histopathological response rates by type of tumor (SRCC vs. non-SRCC) were also investigated.ResultsOut of 559 studies, ten (1 RCT, 9 non-RCTs) were included in this meta-analysis (PROSPERO CRD42022298743) investigating 3,653 patients in total. The four studies investigating survival in SRCC patients treated with nCTX + surgery vs. surgery alone showed no survival benefit for neither intervention, but heterogeneity was considerable (HR, 1.01; 95% CI, 0.61–1.67; p = 0.98; I2 = 89%). In patients treated by nCTX + surgery SRCC patients showed worse survival (HR, 1.45; 95% CI, 1.21–1.74; p < 0.01) and lower rate of major histopathological response than non-SRCC patients (OR, 2.47; 95% CI, 1.78–3.44; p < 0.01).ConclusionThe current meta-analysis could not demonstrate beneficial effects of nCTX for SRCC patients. Histopathological response to and survival benefits of non-taxane-based nCTX seem to be lower in comparison to non-SRC esophagogastric cancer. However, certainty of evidence is low due to the scarcity of high-quality trials. Further research is necessary to determine optimal treatment for SRCC patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/, PROSPERO (CRD42022298743)

Evening Telegram, 1891-06-17

The Evening Telegram began publication in St. John's on 3 April 1879 and remains in print today under the title The Telegram. It was published daily except Sunday through to 1958, the frequency changing thereafter. -- The total collection has been split into several parts; this portion contains the years 1879-1899. -- Not published: 9 June - 31 August 1892, 2-10 January 1894. Missing issue ranges: 3-7 April 1879, 5-6 May 1880, 29-31 December 1880, 31 March - 19 April 1881, 25-30 June 1895. In addition, these individual issues are missing from 1880: 16 January, 2 April, 17 April, 24 April, 11 May, 28 May, 11 October, 22 October, 13 November, 7 December

Mitoferrin2 is a synthetic lethal target for chromosome 8p deleted cancers

Abstract Background Somatic copy number alterations are a hallmark of cancer that offer unique opportunities for therapeutic exploitation. Here, we focused on the identification of specific vulnerabilities for tumors harboring chromosome 8p deletions. Methods We developed and applied an integrative analysis of The Cancer Genome Atlas (TCGA), the Cancer Dependency Map (DepMap), and the Cancer Cell Line Encyclopedia to identify chromosome 8p-specific vulnerabilities. We employ orthogonal gene targeting strategies, both in vitro and in vivo, including short hairpin RNA-mediated gene knockdown and CRISPR/Cas9-mediated gene knockout to validate vulnerabilities. Results We identified SLC25A28 (also known as MFRN2), as a specific vulnerability for tumors harboring chromosome 8p deletions. We demonstrate that vulnerability towards MFRN2 loss is dictated by the expression of its paralog, SLC25A37 (also known as MFRN1), which resides on chromosome 8p. In line with their function as mitochondrial iron transporters, MFRN1/2 paralog protein deficiency profoundly impaired mitochondrial respiration, induced global depletion of iron-sulfur cluster proteins, and resulted in DNA-damage and cell death. MFRN2 depletion in MFRN1-deficient tumors led to impaired growth and even tumor eradication in preclinical mouse xenograft experiments, highlighting its therapeutic potential. Conclusions Our data reveal MFRN2 as a therapeutic target of chromosome 8p deleted cancers and nominate MFNR1 as the complimentary biomarker for MFRN2-directed therapies

Spectral characterization of intraoperative renal perfusion using hyperspectral imaging and artificial intelligence

Abstract Accurate intraoperative assessment of organ perfusion is a pivotal determinant in preserving organ function e.g. during kidney surgery including partial nephrectomy or kidney transplantation. Hyperspectral imaging (HSI) has great potential to objectively describe and quantify this perfusion as opposed to conventional surrogate techniques such as ultrasound flowmeter, indocyanine green or the subjective eye of the surgeon. An established live porcine model under general anesthesia received median laparotomy and renal mobilization. Different scenarios that were measured using HSI were (1) complete, (2) gradual and (3) partial malperfusion. The differences in spectral reflectance as well as HSI oxygenation (StO2) between different perfusion states were compelling and as high as 56.9% with 70.3% (± 11.0%) for “physiological” vs. 13.4% (± 3.1%) for “venous congestion”. A machine learning (ML) algorithm was able to distinguish between these perfusion states with a balanced prediction accuracy of 97.8%. Data from this porcine study including 1300 recordings across 57 individuals was compared to a human dataset of 104 recordings across 17 individuals suggesting clinical transferability. Therefore, HSI is a highly promising tool for intraoperative microvascular evaluation of perfusion states with great advantages over existing surrogate techniques. Clinical trials are required to prove patient benefit