The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric ...cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors. Postoperative chemotherapy is included as an option after a modified D2 lymph node dissection for this group of patients. Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by fluorescence in situ hybridization for IHC 2+.
Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of ...the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.
Esophageal and esophagogastric junction cancers Ajani, Jaffer A; Barthel, James S; Bentrem, David J ...
Journal of the National Comprehensive Cancer Network,
2011-Aug-01, Letnik:
9, Številka:
8
Journal Article
Ocular manifestations of ectodermal dysplasia Landau Prat, Daphna; Katowitz, William R; Strong, Alanna ...
Orphanet journal of rare diseases,
05/2021, Letnik:
16, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The ectodermal dysplasias (EDs) constitute a group of disorders characterized by abnormalities in two or more ectodermal derivatives, including skin, hair, teeth, and sweat glands. The purpose of the ...current study was to evaluate ocular manifestations in pediatric patients with ED.
Retrospective case series including consecutive ED subjects who were treated in the ophthalmology department at the Children's Hospital of Philadelphia over a 12-year period (2009-2020). Main Outcome Measures were ocular and ocular adnexal abnormalities.
Thirty subjects were included: 20 males (67%), mean age of 4.5 years (range 0.3-18). Patients with different subtypes were included, with the hypohidrotic ED and ectrodactyly-ectodermal dysplasia-clefting variants being most prevalent. Most common findings were: lacrimal drainage obstruction in 12 (40%) including punctal agenesis in 10 (33%), refractive errors in 13 (43%) and amblyopia in 6 (20%). A new finding of eyelid ptosis or eyelash ptosis was demonstrated in 11 subjects (37%), mostly associated with TP63 or EDA1 genes variants.
Ectodermal dysplasias are associated with various ocular pathologies and amblyopia in the pediatric population. We report a possible genetic association between lash ptosis and EDA1 gene, and eyelid ptosis and TP63 or EDA1 genes variants.
IMPORTANCE: Adrenalectomy is the definitive treatment for multiple adrenal abnormalities. Advances in technology and genomics and an improved understanding of adrenal pathophysiology have altered ...operative techniques and indications. OBJECTIVE: To develop evidence-based recommendations to enhance the appropriate, safe, and effective approaches to adrenalectomy. EVIDENCE REVIEW: A multidisciplinary panel identified and investigated 7 categories of relevant clinical concern to practicing surgeons. Questions were structured in the framework Population, Intervention/Exposure, Comparison, and Outcome, and a guided review of medical literature from PubMed and/or Embase from 1980 to 2021 was performed. Recommendations were developed using Grading of Recommendations, Assessment, Development and Evaluation methodology and were discussed until consensus, and patient advocacy representation was included. FINDINGS: Patients with an adrenal incidentaloma 1 cm or larger should undergo biochemical testing and further imaging characterization. Adrenal protocol computed tomography (CT) should be used to stratify malignancy risk and concern for pheochromocytoma. Routine scheduled follow-up of a nonfunctional adrenal nodule with benign imaging characteristics and unenhanced CT with Hounsfield units less than 10 is not suggested. When unilateral disease is present, laparoscopic adrenalectomy is recommended for patients with primary aldosteronism or autonomous cortisol secretion. Patients with clinical and radiographic findings consistent with adrenocortical carcinoma should be treated at high-volume multidisciplinary centers to optimize outcomes, including, when possible, a complete R0 resection without tumor disruption, which may require en bloc radical resection. Selective or nonselective α blockade can be used to safely prepare patients for surgical resection of paraganglioma/pheochromocytoma. Empirical perioperative glucocorticoid replacement therapy is indicated for patients with overt Cushing syndrome, but for patients with mild autonomous cortisol secretion, postoperative day 1 morning cortisol or cosyntropin stimulation testing can be used to determine the need for glucocorticoid replacement therapy. When patient and tumor variables are appropriate, we recommend minimally invasive adrenalectomy over open adrenalectomy because of improved perioperative morbidity. Minimally invasive adrenalectomy can be achieved either via a retroperitoneal or transperitoneal approach depending on surgeon expertise, as well as tumor and patient characteristics. CONCLUSIONS AND RELEVANCE: Twenty-six clinically relevant and evidence-based recommendations are provided to assist surgeons with perioperative adrenal care.
Abstract
Coral reefs are subject to degradation by multiple environmental stressors which are predicted to intensify. Stress can alter ecosystem composition, with shifts from hard coral to macroalgae ...dominated reefs often accompanied by an increase in soft corals and sponges. Such changes may alter net ecosystem metabolism and biogeochemistry by shifting the balance between photosynthesis, respiration, calcification and dissolution. We deployed high temporal resolution pH and dissolved oxygen (DO) sensors at four Caribbean reef sites with varying covers of hard and soft corals, sponges and macroalgae. The resultant data indicated that the strength of the “metabolic pulse”, specifically the co‐variation in daily pH and DO oscillations, was driven by the net balance of light ‐dependent and ‐independent metabolism. pH and DO were positively correlated over the diel cycle at coral dominated sites, suggesting that photosynthesis and respiration were the major controlling processes, and further indicated by agreement with a simple production:respiration model. Whereas, at a site with high macroalgal cover, pH and DO decoupling was observed during daylight hours. This indicates that an unidentified light‐driven process altered the expected pH:DO relationship. We hypothesize that this could be mediated by the higher levels of macroalgae, which either stimulated bacterial‐mediated carbonate dissolution via the production and release of allelopathic compounds or retained oxygen, evolved during photosynthesis, in the gaseous form in seawater (ebullition). Our work demonstrates that high resolution monitoring of pH and DO provides insight into coral reef biogeochemical functioning and can be key for understanding long‐term changes in coral reef metabolism.
Plain Language Summary
Coral reefs are regarded as the rainforests of the sea, supporting 25% of marine species and millions of people worldwide. Yet, they are facing a number of threats including rising sea surface temperature, decreasing ocean pH, overfishing and increased competition with algae. As coral reefs experience stress, the relative abundance of hard coral, algae, soft corals and sponges can change. A healthy reef is generally thought of as one with a high proportion of hard coral as their skeletons form the backbone of the reef environment. Under stress, however, a reef can transition from hard coral to algae dominated with significant implications for the entire reef ecosystem. In this paper, we suggest that the reef metabolism, which is driven by benthic composition, drives the natural variability and the relationship between pH and dissolved oxygen (DO) over a 24‐hr cycle. Our data suggest that the daily range in pH and DO is larger at sites with more hard coral and less algae, and the relationship between pH and DO is stronger. High resolution measurements of pH and DO using autonomous sensors could potentially reveal vital information on ecosystem functioning and may be valuable tools in monitoring changes in coral reefs.
Key Points
High resolution data indicated that photosynthesis and respiration mainly drove pH and dissolved O
2
(DO) daily variability in reef systems
Diel ranges in pH and DO and their co‐variation may be linked to reef metabolism and benthic ecosystem composition
Punctal atresia or agenesis (PA) is a rare congenital anomaly characterized by the absence or closure of the tear duct puncta, potentially linked to systemic genetic anomalies. The necessity of a ...genetic workup based solely on the presence of PA remains uncertain. This study investigates a cohort of PA patients, examining the prevalence and types of associated syndromes.
A retrospective medical records review of all patients diagnosed with PA at the Children's Hospital of Philadelphia between 2009-2023 was conducted, analyzing medical histories and genetic testing results. Primary outcomes included the prevalence of systemic syndromes, while secondary outcomes focused on the variety of associated syndromes.
Forty-four patients were included, of which 31 were male (70%) with a mean ± SD age 3.3 ± 3.3 years. Overall, 87 puncta in the study cohort were affected, and 26 cases (59%) were bilateral. Systemic abnormalities or genetic syndromes were identified in 19 patients (43%), with the most common being Ectodermal Dysplasia and Down syndrome. Additional rare syndromes were demonstrated. No significant association was found between systemic abnormalities and gender, bilaterality, or the number of puncta involved.
A high incidence of systemic syndromes (43%) was observed in the study cohort. In individuals with PA who also exhibit extraocular disease, systemic evaluation and genetic workup should be considered. Syndromic diagnoses identified in our cohort also include: Branchio-oto-renal syndrome, 22q11.2 deletion syndrome, 1q21.1 microdeletion syndrome, NF1, monosomy 4q and trisomy 6q, which represent novel associations. The lack of correlation between PA's phenotypic severity and systemic abnormalities highlights the need to obtain a comprehensive medical history and consider a systemic workup in PA patients.
Tissue-specific antigens can serve as targets for adoptive T cell transfer-based cancer immunotherapy. Recognition of tumor by T cells is mediated by interaction between peptide–major ...histocompatibility complexes (pMHCs) and T cell receptors (TCRs). Revealing the identity of peptides bound to MHC is critical in discovering cognate TCRs and predicting potential toxicity. We performed multimodal immunopeptidomic analyses for human prostatic acid phosphatase (PAP), a well-recognized tissue antigen. Three physical methods, including mild acid elution, coimmunoprecipitation, and secreted MHC precipitation, were used to capture a thorough signature of PAP on HLA-A*02:01. Eleven PAP peptides that are potentially A*02:01-restricted were identified, including five predicted strong binders by NetMHCpan 4.0. Peripheral blood mononuclear cells (PBMCs) from more than 20 healthy donors were screened with the PAP peptides. Seven cognate TCRs were isolated which can recognize three distinct epitopes when expressed in PBMCs. One TCR shows reactivity toward cell lines expressing both full-length PAP and HLA-A*02:01. Our results show that a combined multimodal immunopeptidomic approach is productive in revealing target peptides and defining the cloned TCR sequences reactive with prostatic acid phosphatase epitopes.
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