Multimodal Treatment of Resectable Esophageal Cancer.

BACKGROUND: The current guidelines for the treatment of esophageal cancer recommend a multimodal approach that includes chemotherapy, targeted therapy and immunotherapy, radiation, and surgery. Despite advances in treatment, rates of treatment failure, pathologic incomplete response, tumor metastasis, and death remain unacceptably high. METHODS: This study was a narrative literature review using the terms "resectable esophageal cancer" and "multimodal therapy" to identify prospective trials of neoadjuvant radiation and chemotherapy, individually or combined with surgery, for esophageal cancer. Trials performed between 1984 and 2022 were identified and analyzed. CLINICALTRIALS: gov was queried to identify ongoing studies. RESULTS: Twenty-one clinical studies were identified: 15 randomized controlled trials and 6 prospective nonrandomized trials. The results of the randomized trials suggest that multimodal therapy-in the form of neoadjuvant chemotherapy in combination with radiation or chemotherapy alone, followed by surgery-is associated with better rates of local disease control and partial clinical response and, potentially, longer survival than is surgery alone. Immunotherapy is an emerging option for the treatment of patients with esophageal cancer. CONCLUSIONS: The treatment of patients with resectable esophageal cancer is rapidly evolving. Although previous treatment options have had only limited benefits for patients, significant progress has been made during last 3 decades. The results of the available studies suggest that advances in the treatment of esophageal cancer have the potential to improve survival in these patients; however, questions remain regarding mechanisms of action, patient selection, and the use of personalized approaches that are based on genetics.

Clinical and radiological septic joint analysis of spontaneous sternoclavicular joint infections: achieving the best outcomes-a systems engineering approach.

OBJECTIVES: Spontaneous sternoclavicular joint infection (SSCJI) is a rare and poorly understood disease process. This study aims to identify factors guiding effective management strategies for SSCJI by using data mining. METHODS: An Institutional Review Board-approved retrospective review of patients from 2 large hospitals (2010-2022) was conducted. SSCJI is defined as a joint infection without direct trauma or radiation, direct instrumentation or contiguous spread. An interdisciplinary team consisting of thoracic surgeons, radiologists, infectious disease specialists, orthopaedic surgeons, hospital information experts and systems engineers selected relevant variables. Small set data mining algorithms, utilizing systems engineering, were employed to assess the impact of variables on patient outcomes. RESULTS: A total of 73 variables were chosen and 54 analysed against 11 different outcomes. Forty-seven patients [mean age 51 (22-82); 77% male] met criteria. Among them, 34 underwent early joint surgical resection (<14 days), 5 patients received delayed surgical intervention (>14 days) and 8 had antibiotic-only management. The antibiotic-only group had comparable outcomes. Indicators of poor outcomes were soft tissue fluid >4.5 cm, previous SSCJI, moderate/significant bony fragments, HgbA1c >13.9% and moderate/significant bony sclerosis. CONCLUSIONS: This study suggests that targeted antibiotic-only therapy should be considered initially for SSCJI cases while concurrently managing comorbidities. Patients displaying indicators of poor outcomes or no symptomatic improvement after antibiotic-only therapy should be considered for surgical joint resection.

Circumferential tracheal replacement with silicone stent supported, cryopreserved aortic homograft.

Treatment of long-segment tracheal defects remains a challenge in thoracic surgery with no standard surgical option. Aortic allografts have been used for this purpose with varying degrees of success. In a patient that suffered anastomotic dehiscence after tracheal resection with primary anastomosis, we performed complete tracheal resection and replacement using a stented circumferential aortic allograft. Currently, this patient is able to breathe normally without tracheostomy assistance 22 months postoperatively. Our report is the first in the English literature of long-term survival without tracheostomy dependence and close interval follow-up after circumferential tracheal resection and replacement with a cryopreserved aortic allograft.

Metabolic signatures of thymomas: potential biomarkers and treatment targets.

OBJECTIVES: A study of tumour metabolic reprogramming has revealed disease biomarkers and avenues for therapeutic intervention. Metabolic reprogramming in thymoma is currently understudied and largely unknown. This study utilized metabolomics and isotope tracing with 13C-glucose to metabolically investigate thymomas, adjacent thymic tissue and benign thymic lesions. METHODS: From 2017 to 2021, 20 patients with a suspected thymoma were recruited to this prospective Institutional Review Board approved clinical trial. At the time of surgery, 11 patients were infused with 13C-glucose, a stable, non-radioactive tracer which reports the flow of carbon through metabolic pathways. Samples were analysed by mass spectrometry to measure the abundance of >200 metabolites.13C enrichment was measured in patients who received 13C-glucose infusions. RESULTS: Histological analysis showed that 9 patients had thymomas of diverse subtypes and 11 patients had benign cysts. In our metabolomic analysis, thymomas could be distinguished from both adjacent thymus tissue and benign lesions by metabolite abundances. Metabolites in pyrimidine biosynthesis and glycerophospholipid metabolism were differentially expressed across these tissues.13C-glucose infusions revealed differential labelling patterns in thymoma compared to benign cysts and normal thymus tissue. The lactate/3PG labelling ratio, a metabolic marker in aggressive lung tumours correlated with lactate uptake, was increased in thymomas (1.579) compared to normal thymus (0.945) and benign masses (0.807) (thymic tissue versus tumour P = 0.021, tumour versus benign P = 0.013). CONCLUSIONS: We report metabolic biomarkers, including differential 13C labelling of metabolites from central metabolism, that distinguish thymomas from benign tissues. Altered glucose and lactate metabolism warrant further investigation and may provide novel therapeutic targets for thymoma.

Longitudinal ultrasound imaging and network modeling in rats reveal sex-dependent suppression of liver regeneration after resection in alcoholic liver disease.

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5-7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow rates were seen in most animals, with ethanol-fed males showing higher peak portal flow than any other experimental group. A computational model of liver regeneration was used to evaluate the contribution of physiological stimuli and estimate the animal-specific parameter intervals. The results implicate lower metabolic load, over a wide range of cell death sensitivity, in matching the model simulations to experimental data of ethanol-fed male rats. However, in the ethanol-fed female rats and controls of both sexes, metabolic load was higher and in combination with cell death sensitivity matched the observed volume recovery dynamics. We conclude that adaptation to chronic ethanol intake has a sex-dependent impact on liver volume recovery following liver resection, likely mediated by differences in the physiological stimuli or cell death responses that govern the regeneration process. Immunohistochemical analysis of pre- and post-resection liver tissue validated the results of computational modeling by associating lack of sensitivity to cell death with lower rates of cell death in ethanol-fed male rats. Our results illustrate the potential for non-invasive ultrasound imaging to assess liver volume recovery towards supporting development of clinically relevant computational models of liver regeneration.

Esophagectomy for End-Stage Achalasia.

Esophagectomy for achalasia is reserved for patients with end-stage disease for whom prior treatment has failed. Esophagectomy can be performed safely through a variety of techniques. Conduit options include stomach, colon, and small intestine. There are many potential complications following esophagectomy. Outcomes of esophagectomy for achalasia are good when performed in experienced surgical centers.

Intraoperative cytopathology of thoracic surgery (ICTS). A captivating, worthwhile, and rewarding service line.

Intraoperative cytopathology for thoracic surgeons is a service that has not been utilized to its full potential in most institutions. It has the advantage of a rapid turnaround time, low costs, high accuracy, real time communication with the surgeon, on-site visualization of the lesion before excision, simplicity, and safety. Our experience, common cytologic findings of the most frequent thoracic tumors encountered during ICTS, hints about the service, and models for implementation and maintenance are presented. This review is aimed to present our experience and perspective about intraoperative cytopathology for thoracic surgeons.

Update on Management of Squamous Cell Esophageal Cancer.

PURPOSE OF THE REVIEW: Esophageal cancer is the sixth most common cause of cancer death globally. Squamous cell carcinoma of the esophagus (ESCC) is the predominant histologic type in the world. Treatment strategies have evolved in the last decade and new paradigms are replacing traditional approaches at all stages of cancer. This review will summarize the epidemiology, diagnosis, staging, and treatment of esophageal squamous cell carcinoma. RECENT FINDINGS: Novel approaches to screening may be cost-effective in regions with a high incidence of ESCC. Multi-disciplinary evaluation and treatment has become the standard of care. Endoscopic resection may be an option for early stage ESCC. Minimally invasive esophagectomy can be performed safely as a primary therapy or after-induction chemoradiation. Several recent studies have found a survival benefit to immunotherapy for patients with metastatic or persistent disease. Multi-disciplinary evaluation and multi-modal therapy including cytotoxic chemotherapy, radiation, surgery, and immunotherapy have improved survival compared to surgery alone.

Left hand necrosis as the initial presentation of disseminated mucormycosis: A case report and literature review.

Cutaneous mucormycosis typically occurs as a primary infection following traumatic inoculation or as a secondary disseminated disease in immunocompromised patients with hematologic malignancy or organ transplantation. We describe an unusual case of a poorly controlled type 1 diabetic patient presenting with wet gangrene of the hand due to angioinvasive dissemination from a primary pulmonary infection, with additional suspected foci of cardiac and central nervous system involvement. Despite combined medical and surgical treatment, the patient ultimately died due to complications of her infection. This case and the associated literature review of secondary cutaneous mucormycosis highlight that invasive fungal infections can present peripherally, and identifying the primary source is important in order to promptly pursue aggressive combined medical and surgical treatment for this highly fatal disease.

Assessing Human Immunodeficiency Virus (HIV) Prevention Through Knowledge and Condom Use Among Female Sex Workers at the Border of Haiti and Dominican Republic.

Geographic border studies are relatively scare, but have the potential to inform bilateral health policies that affect the well-being of female sex workers (FSWs) who work at these borders as well as those individuals who solicit their services, both groups being at high risk for human immunodeficiency virus (HIV). We applied bivariate and multivariate techniques to examine FSWs' HIV knowledge and condom use across three partner types, at the Haiti Dominican Republic border, using data from the Study on Sex Workers (n = 241, 2014). Condom use was significantly lower among FSWs on the Haitian side of the border compared to the Dominican side, yet levels of HIV knowledge were similar; specifically, 81% of respondents on the Dominican side reported using condoms every time they had sex with a client, compared to 38% of peers in Haiti (p < 0.001). After introducing controls, FSWs in Haiti continued to have lower odds of using condoms with clients (p < 0.001), noncommercial partners (p < 0.001), and regular partners (p < 0.05) compared to peers in the Dominican Republic. This unique border study highlights disparities in FSWs' condom use regardless of HIV knowledge. The lack of consistent condom use by FSWs in Haiti has the potential to exacerbate the HIV epidemic at the border and impact both nations' HIV incidence rates.

Lemierre's syndrome treated operatively.

Lemierre's syndrome (LS) is a pharyngeal infection complicated by infectious jugular vein thrombosis and septic emboli. Most commonly caused by Fusobacterium necrophorum, it may result in metastatic infection, especially when antibiotic treatment is delayed. Patients with LS are often healthy adults between 16 and 30 years who present with prolonged symptoms of pharyngitis, lateral neck pain, and fever. Other symptoms may include shortness of breath, tachycardia, and hypotension. When administered promptly, antibiotics can act as an effective treatment. However, complications may arise that require additional intervention. Herein, we report a case of LS in a young adult, complicated by severe pleural effusions that required surgical decortication.

Tumour necrosis factor in infectious disease.

TNF signals through two distinct receptors, designated TNFR1 and TNFR2, which initiate diverse cellular effects that include cell survival, activation, differentiation, and proliferation and cell death. These cellular responses can promote immunological and inflammatory responses that eradicate infectious agents, but can also lead to local tissue injury at sites of infection and harmful systemic effects. Defining the molecular mechanisms involved in TNF responses, the effects of natural and experimental genetic diversity in TNF signalling and the effects of therapeutic blockade of TNF has increased our understanding of the key role that TNF plays in infectious disease.

Tumour necrosis factor and cancer.

Tumour necrosis factor (TNF) was originally described as a circulating factor that can induce haemorrhagic necrosis of tumours. It is now clear that TNF has many different functions in cancer biology. In addition to causing the death of cancer cells, TNF can activate cancer cell survival and proliferation pathways, trigger inflammatory cell infiltration of tumours and promote angiogenesis and tumour cell migration and invasion. These effects can be explained by the diverse cellular responses TNF can initiate through distinct signal transduction pathways, opening the way for more selective targeting of TNF signalling in cancer therapy.

Factors controlling material deposition in the CVD of nickel sulfides, selenides or phosphides from dichalcogenoimidodiphosphinato complexes: deposition, spectroscopic and computational studies.

The series of nickel dichalcogenoimidodiphosphinates [Ni{(i)Pr(2)P(X1)NP(X2)(i)Pr(2)}(2)]: X1 = S, X2 = Se (1), X1 = X2 = S (2), and X1 = X2 = Se (3) have been successfully used as single-source precursors (SSPs) to deposit thin films of nickel sulfide, selenide or phosphide; the material deposited depended on both temperature and method used for the deposition. Aerosol-assisted (AA) chemical vapour deposition (CVD) and low-pressure (LP) CVD were used. The as-deposited films were characterised by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS). A variety of phases including: Ni(2)P, Ni(0.85)Se and NiS(1.03) were deposited under different conditions. The mechanism of decomposition to the phosphide, selenide, or sulfide was studied by pyrolysis gas chromatography mass spectrometry (Py-GC-MS) and modelled by density functional theory (DFT).

Evidence-based practice guidelines for plasma transfusion.

BACKGROUND: There is little systematically derived evidence-based guidance to inform plasma transfusion decisions. To address this issue, the AABB commissioned the development of clinical practice guidelines to help direct appropriate transfusion of plasma. STUDY DESIGN AND METHODS: A systematic review (SR) and meta-analysis of randomized and observational studies was performed to quantify known benefits and harms of plasma transfusion in common clinical scenarios (see accompanying article). A multidisciplinary guidelines panel then used the SR and the GRADE methodology to develop evidence-based plasma transfusion guidelines as well as identify areas for future investigation. RESULTS: Based on evidence ranging primarily from moderate to very low in quality, the panel developed the following guidelines: 1) The panel suggested that plasma be transfused to patients requiring massive transfusion. However, 2) the panel could not recommend for or against transfusion of plasma at a plasma : red blood cell ratio of 1:3 or more during massive transfusion, 3) nor could the panel recommend for or against transfusion of plasma to patients undergoing surgery in the absence of massive transfusion. 4) The panel suggested that plasma be transfused in patients with warfarin therapy-related intracranial hemorrhage, 5) but could not recommend for or against transfusion of plasma to reverse warfarin anticoagulation in patients without intracranial hemorrhage. 6) The panel suggested against plasma transfusion for other selected groups of patients. CONCLUSION: We have systematically developed evidence-based guidance to inform plasma transfusion decisions in common clinical scenarios. Data from additional randomized studies will be required to establish more comprehensive and definitive guidelines for plasma transfusion.

Extensive contribution of embryonic stem cells to the development of an evolutionarily divergent host.

The full potential of embryonic stem (ES) cells to generate precise cell lineages and complex tissues can be best realized when they are differentiated in vivo-i.e. in developing blastocysts. Owing to various practical and ethical constraints, however, it is impossible to introduce ES cells of certain species into blastocysts of the same species. One solution is to introduce ES cells into blastocysts of a different species. However, it is not known whether ES cells can contribute extensively to chimerism when placed into blastocysts of a distantly related species. Here, we address this question using two divergent species, Apodemus sylvaticus and Mus musculus, whose genome sequence differs by approximately 18% from each other. Despite this considerable evolutionary distance, injection of Apodemus ES cells into Mus blastocysts led to viable chimeras bearing extensive Apodemus contributions to all major organs, including the germline, with Apodemus contribution reaching approximately 40% in some tissues. Immunostaining showed that Apodemus ES cells have differentiated into a wide range of cell types in the chimeras. Our results thus provide a proof of principle for the feasibility of differentiating ES cells into a wide range of cell types and perhaps even complex tissues by allowing them to develop in vivo in an evolutionarily divergent host-a strategy that may have important applications in research and therapy. Furthermore, our study demonstrates that mammalian evolution can proceed at two starkly contrasting levels: significant divergence in genome and proteome sequence, yet striking conservation in developmental programs.