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1.
Med Oncol ; 41(6): 140, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713310

RESUMO

Glioblastoma (GBM) is an extremely aggressive primary brain tumor with poor prognosis, short survival time post-diagnosis and high recurrence. Currently, no cure for GBM exists. The identification of an effective therapeutic modality for GBM remains a high priority amongst medical professionals and researches. In recent studies, inhalant cannabidiol (CBD) has demonstrated promise in effectively inhibiting GBM tumor growth. However, exactly how CBD treatment affects the physiology of these tumor cells remains unclear. Stress granules (SG) (a sub-class of biomolecular condensates (BMC)) are dynamic, membrane-less intracellular microstructures which contain proteins and nucleic acids. The formation and signaling of SGs and BMCs plays a significant role in regulating malignancies. This study investigates whether inhaled CBD may play an intervening role towards SGs in GBM tumor cells. Integrated bioinformatics approaches were preformed to gain further insights. This includes use of Immunohistochemistry and flow cytometry to measure SGs, as well as expression and phosphorylation of eukaryotic initiation factor-2α (eIF2α). The findings of this study reveal that CBD receptors (and co-regulated genes) have the potential to play an important biological role in the formation of BMCs within GBM. In this experiment, CBD treatment significantly increased the volume of TIAR-1. This increase directly correlated with elevation in both eIF2α expression and p-eIF2α in CBD treated tissues in comparison to the placebo group (p < 0.05). These results suggest that inhalant CBD significantly up-regulated SGs in GBM, and thus support a theory of targeting BMCs as a potential therapeutic substrate for treating GBM.


Assuntos
Neoplasias Encefálicas , Canabidiol , Glioblastoma , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Canabidiol/farmacologia , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Grânulos de Estresse/metabolismo , Grânulos de Estresse/efeitos dos fármacos , Linhagem Celular Tumoral , Fator de Iniciação 2 em Eucariotos/metabolismo
2.
Ann Nucl Med ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750330

RESUMO

OBJECTIVES: This study aims to evaluate the utility of F-18 FDG PET/CT in the non-invasive diagnosis of autoimmune pancreatitis (AIP) and differentiating it from pancreatic cancer (CaP) based on the amount and pattern of FDG uptake, as well as involvement of extra-pancreatic sites. METHODS: A systematic search was conducted using PubMed, Scopus, Cochrane Library and Google Scholar. Only those studies that compared the findings of F-18 FDG PET/CT in terms of SUVmax, pattern of FDG uptake and presence of FDG-avid extra-pancreatic sites in both AIP and CaP were included. Studies were qualitatively assessed for risk of bias and publication bias. The diagnostic performance of parameters on PET/CT was examined through pooled sensitivity, specificity, diagnostic odd's ratio (DOR) and summary receiver operator characteristic (SROC) curve analysis. RESULTS: Six studies were included with a total of 580 patients. 178 patients had AIP (Age 18-90 years, male, M: female, F ratio-8.4:1) and 402 patients had CaP (Age 22-88 years, M:F ratio-1.5:1). Type of AIP was reported in only 3 studies, with the included cases predominantly being type 1 AIP. All studies were retrospective with heterogeneity and a risk on patient selection and index test. The FDG uptake, expressed as SUVmax, was lower in AIP with a weighted mean difference of -3.11 (95% confidence interval, CI: -5.28 to -0.94). To diagnose AIP, the pooled sensitivity, specificity and DOR of diffuse pattern of FDG uptake were 0.59 (95% CI: 0.51-0.66), 0.89 (95% CI: 0.86-0.92) and 21.07 (95% CI: 5.07-88.32), respectively, with an area under curve (AUC) of 0.717 on SROC analysis. The pooled sensitivity, specificity and DOR of FDG-avid extra pancreatic sites were 0.55 (95% CI: 0.45-0.65), 0.58 (95% CI: 0.52-0.64) and 2.33 (95% CI: 1.40-3.89), respectively, with an AUC of 0.632. CONCLUSION: On F-18 FDG PET/CT, a pancreatic lesion of AIP has a lower SUVmax value than CaP. A diffuse pattern of FDG uptake and presence of an extra-pancreatic FDG-avid site are nearly 21 times and twice more likely in AIP than CaP, respectively.

3.
Emerg Radiol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780718

RESUMO

PURPOSE: To formulate and evaluate the diagnostic performance and utility of a new CT difficulty score in predicting difficult laparoscopic surgery in cases of gallbladder (GB) perforation. METHODS: This prospective single centre study included a total of 48 diagnosed cases of GB perforation on CT between December 2021 and June 2023, out of which 24 patients were operated. A new 6-point CT difficulty scoring system was devised to predict difficult laparoscopic approach, based on patterns of inflammation around the perforated GB that were found to be surgically relevant. The pre-operative imaging findings on CT were studied in detail and correlation coefficients of various imaging findings were calculated to predict difficult surgery. RESULTS: On CECT, the type of perforation, according to the revised Niemeier's classification could be exactly delineated in all 48 patients. A CT difficulty score of ≥ 3 was found to a good predictor difficult laparoscopic approach, with statistical significance (p = 0.001), sensitivity of 94.44%, specificity of 83.33%, PPV of 94.44% and NPV of 83.33%. Inflammatory changes around duodenum showed maximum correlation coefficient of 0.744 (p = 0.0001), around colon showed a correlation coefficient of 0.657 (p = 0.0005), and in the omentum had a correlation coefficient of 0.5 (p = 0.013)). Inter-observer agreement was also calculated for various findings and it was found to have moderate to strong agreement (κ value 0.5-1.0). CONCLUSION: The CT difficulty scoring system can be an effective tool in predicting difficult laparoscopic surgery in cases of GB perforation in an emergency setting which can help in decision making and improved patient outcome.

4.
Geroscience ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733547

RESUMO

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions.

5.
Front Immunol ; 15: 1302163, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38515752

RESUMO

Mechanistic understanding of antibiotic persistence is a prerequisite in controlling the emergence of MDR cases in Tuberculosis (TB). We have reported that the cholesterol-induced activation of VapC12 ribonuclease is critical for disease persistence in TB. In this study, we observed that relative to the wild type, mice infected with ΔvapC12 induced a pro-inflammatory response, had a higher pathogen load, and responded better to the anti-TB treatment. In a high-dose infection model, all the mice infected with ΔvapC12 succumbed early to the disease. Finally, we reported that the above phenotype of ΔvapC12 was dependent on the presence of the TLR4 receptor. Overall, the data suggests that failure of a timely resolution of the early inflammation by the ΔvapC12 infected mice led to hyperinflammation, altered T-cell response and high bacterial load. In conclusion, our findings suggest the role of the VapC12 toxin in modulating the innate immune response of the host in ways that favor the long-term survival of the pathogen inside the host.


Assuntos
Mycobacterium tuberculosis , Toxinas Biológicas , Tuberculose , Animais , Camundongos , Imunidade Inata , Fenótipo
6.
J Minim Invasive Surg ; 27(1): 23-32, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38494183

RESUMO

Purpose: This study examines the impacts of omitting nasogastric tube (NGT) placement following cervical esophagogastric anastomosis (CEGA) in Enhanced Recovery After Surgery (ERAS) protocols, comparing outcomes to those from early NGT removal. Methods: In a retrospective cohort of esophagectomy patients treated for esophageal cancer, participants were divided into two groups: group 1 had the NGT inserted post-CEGA and removed by postoperative day 3, while group 2 underwent the procedure without NGT placement. We primarily investigated anastomotic leak rates, also analyzing hospital stay duration, pulmonary complications, and NGT reinsertion. Results: Among 50 esophageal squamous cell carcinoma patients, 30 in group I were compared with 20 in group II. The baseline demographic and tumor characteristics were similar between both groups. The overall incidence of anastomotic leak was 14.0%, comparable in both groups (16.7% vs. 10.0%, p = 0.63). The postoperative hospital stay was significantly shorter in the no NGT group (median of 7 days vs. 6 days, p = 0.03) with similar major morbidity (Clavien-Dindo grade ≥IIIa; 13.3% vs. 5.0%, p = 0.63). There was no 30-day mortality, and one patient in each group had reinsertion of NGT for conduit dilatation. Conclusion: The exclusion of an NGT across CEGA after esophagectomy did not influence the anastomotic leak rate with comparable complications and a shorter hospital stay.

7.
Cancers (Basel) ; 16(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38339232

RESUMO

Colorectal cancer (CRC) is one of the most heterogeneous and deadly diseases, with a global incidence of 1.5 million cases per year. Genomics has revolutionized the clinical management of CRC by enabling comprehensive molecular profiling of cancer. However, a deeper understanding of the molecular factors is needed to identify new prognostic and predictive markers that can assist in designing more effective therapeutic regimens for the improved management of CRC. Recent breakthroughs in single-cell analysis have identified new cell subtypes that play a critical role in tumor progression and could serve as potential therapeutic targets. Spatial analysis of the transcriptome and proteome holds the key to unlocking pathogenic cellular interactions, while liquid biopsy profiling of molecular variables from serum holds great potential for monitoring therapy resistance. Furthermore, gene expression signatures from various pathways have emerged as promising prognostic indicators in colorectal cancer and have the potential to enhance the development of equitable medicine. The advancement of these technologies for identifying new markers, particularly in the domain of predictive and personalized medicine, has the potential to improve the management of patients with CRC. Further investigations utilizing similar methods could uncover molecular subtypes specific to emerging therapies, potentially strengthening the development of personalized medicine for CRC patients.

8.
PLoS One ; 19(2): e0297925, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358978

RESUMO

Nematophagous fungi are the best alternatives to chemical nematicides for managing nematodes considering environmental health. In the current study, activity of metabolites from ten isolates of Purpureocillium lilacinum (Thom) Luangsa-ard (Hypocreales: Ophiocordycipitaceae) and two isolates of Paecilomyces variotii Bainier (Eurotiales: Trichocomaceae), were examined to inhibit the hatching of Meloidogyne incognita (Kofoid & White) Chitwood (Tylenchida: Heteroderidae) eggs. At 100%, 50%, and 25% concentrations, respectively, the culture filtrate of the isolate P. lilacinum 6887 prevented 97.55%, 90.52%, and 62.97% of egg hatching. Out of all the isolates, Pl 6887, Pl 6553, and Pl 2362 showed the greatest results in the hatching inhibition experiment.Gas chromatography-mass spectrometry (GC-MS) analysis revealed a variety of nematicidal compounds from different isolates. A total of seven nematicidal compounds, including four very potent nematicidal fatty acids were found in the isolate Pl 6553. Secondary metabolites of the same isolate possess the highest M. incognita juvenile mortality, i.e., 43.33% and 92% after 48 hrs of treatment at 100 and 200 ppm concentrations, respectively. Significant difference was observed in juvenile mortality percentage among the isolate having highest and lowest nematicidal compounds. Nematicidal fatty acids like myristic and lauric acid were found for the first time in P. lilacinum. Multiple vacuole-like droplets were found inside the unhatched eggs inoculated with the culture filtrate of isolate Pl 6887, and also in the juveniles that perished in the ethyl acetate extract of isolate Pl 6553.


Assuntos
Byssochlamys , Hypocreales , Tylenchoidea , Animais , Cromatografia Gasosa-Espectrometria de Massas , Hypocreales/metabolismo , Antinematódeos/farmacologia , Antinematódeos/metabolismo , Tylenchoidea/metabolismo , Ácidos Graxos
9.
J Xray Sci Technol ; 32(2): 253-269, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38189732

RESUMO

BACKGROUND: The coronavirus disease 2019 is a serious and highly contagious disease caused by infection with a newly discovered virus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE: A Computer Aided Diagnosis (CAD) system to assist physicians to diagnose Covid-19 from chest Computed Tomography (CT) slices is modelled and experimented. METHODS: The lung tissues are segmented using Otsu's thresholding method. The Covid-19 lesions have been annotated as the Regions of Interest (ROIs), which is followed by texture and shape extraction. The obtained features are stored as feature vectors and split into 80:20 train and test sets. To choose the optimal features, Whale Optimization Algorithm (WOA) with Support Vector Machine (SVM) classifier's accuracy is employed. A Multi-Layer Perceptron (MLP) classifier is trained to perform classification with the selected features. RESULTS: Comparative experimentations of the proposed system with existing eight benchmark Machine Learning classifiers using real-time dataset demonstrates that the proposed system with 88.94% accuracy outperforms the benchmark classifier's results. Statistical analysis namely, Friedman test, Mann Whitney U test and Kendall's Rank Correlation Coefficient Test has been performed which indicates that the proposed method has a significant impact on the novel dataset considered. CONCLUSION: The MLP classifier's accuracy without feature selection yielded 80.40%, whereas with feature selection using WOA, it yielded 88.94%.


Assuntos
COVID-19 , Máquina de Vetores de Suporte , Humanos , Animais , COVID-19/diagnóstico por imagem , Baleias , SARS-CoV-2 , Algoritmos , Redes Neurais de Computação , Tomografia Computadorizada por Raios X , Teste para COVID-19
10.
Tuberculosis (Edinb) ; 145: 102477, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38211498

RESUMO

Mycobacterium tuberculosis (Mtb) has evolved sophisticated surveillance mechanisms to neutralize the ROS-induces toxicity which otherwise would degrade a variety of biological molecules including proteins, nucleic acids and lipids. In the present study, we find that Mtb lacking the Rv0495c gene (ΔRv0495c) is presented with a highly oxidized cytosolic environment. The superoxide-induced lipid peroxidation resulted in altered colony morphology and loss of membrane integrity in ΔRv0495c. As a consequence, ΔRv0495c demonstrated enhanced susceptibility when exposed to various host-induced stress conditions. Further, as expected, we observed a mutant-specific increase in the abundance of transcripts that encode proteins involved in antioxidant defence. Surprisingly, despite showing a growth defect phenotype in macrophages, the absence of the Rv0495c enhanced the pathogenicity and augmented the ability of the Mtb to grow inside the host. Additionally, our study revealed that Rv0495c-mediated immunomodulation by the pathogen helps create a favorable niche for long-term survival of Mtb inside the host. In summary, the current study underscores the fact that the truce in the war between the host and the pathogen favours long-term disease persistence in tuberculosis. We believe targeting Rv0495c could potentially be explored as a strategy to potentiate the current anti-TB regimen.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Proteínas de Bactérias/metabolismo , Tuberculose/microbiologia , Oxirredução , Homeostase/fisiologia
11.
J Am Chem Soc ; 146(4): 2319-2324, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38251829

RESUMO

Intrinsically disordered proteins (IDPs) are highly dynamic biomolecules that rapidly interconvert among many structural conformations. These dynamic biomolecules are involved in cancers, neurodegeneration, cardiovascular illnesses, and viral infections. Despite their enormous therapeutic potential, IDPs have generally been considered undruggable because of their lack of classical long-lived binding pockets for small molecules. Currently, only a few instances are known where small molecules have been observed to interact with IDPs, and this situation is further exacerbated by the limited sensitivity of experimental techniques to detect such binding events. Here, using experimental nuclear magnetic resonance (NMR) spectroscopy 19F transverse spin-relaxation measurements, we discovered that a small molecule, 5-fluoroindole, interacts with the disordered domains of non-structural protein 5A from hepatitis C virus with a Kd of 260 ± 110 µM. Our analysis also allowed us to determine the rotational correlation times (τc) for the free and bound states of 5-fluoroindole. In the free state, we observed a rotational correlation time of 27.0 ± 1.3 ps, whereas in the bound state, τc only increased to 46 ± 10 ps. Our findings imply that it is possible for small molecules to engage with IDPs in exceptionally dynamic ways, in sharp contrast to the rigid binding modes typically exhibited when small molecules bind to well-defined binding pockets within structured proteins.


Assuntos
Proteínas Intrinsicamente Desordenadas , Ressonância Magnética Nuclear Biomolecular/métodos , Proteínas Intrinsicamente Desordenadas/química , Espectroscopia de Ressonância Magnética , Conformação Proteica
12.
J Minim Access Surg ; 20(2): 196-200, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37282438

RESUMO

BACKGROUND: Although fast-track treatment pathways are well established in colorectal surgeries, their role in oesophageal resections has not been well studied. This study aims to prospectively evaluate the short-term outcomes of enhanced recovery after surgery (ERAS) protocol in patients undergoing minimally invasive oesophagectomy (MIE) for oesophageal malignancy. PATIENTS AND METHODS: We studied a prospective cohort of 46 consecutive patients from January 2019 to June 2022 who underwent MIE for oesophageal malignancy. The ERAS protocol mainly consists of pre-operative counselling, pre-operative carbohydrate loading, multimodal analgesia, early mobilisation, enteral nutrition and initiation oral feed. Principal outcome measures were the length of post-operative hospital stay, complication rate, mortality rate and 30-day readmission rate. RESULTS: The median (interquartile range [IQR]) age of patients was 49.5 (42, 62) years, and 52.2% were female. The median (IQR) post-operative day of intercoastal drain removal and initiation of oral feed was 4 (3, 4) and 4 (4, 6) days, respectively. The median (IQR) length of hospital stay was 6 (6.0, 7.25) days, with a 30-day readmission rate of 6.5%. The overall complication rate was 45.6%, with a major complication (Clavien-Dindo ≥3) rate of 10.9%. Compliance with the ERAS protocol was 86.9%, and the incidence of major complications was associated with failure to follow the protocol ( P = 0.000). CONCLUSIONS: ERAS protocol in minimally invasive oesophagectomy is feasible and safe. This may result in early recovery with shortened length of hospital stay without an increase in complication and readmission rates.

13.
Med J Armed Forces India ; 79(Suppl 1): S325-S328, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144643

RESUMO

Echinococcal liver cysts are predominantly located in the right lobe of the liver and are mostly asymptomatic. A frank intra-biliary rupture (IBR) of hydatid cyst is uncommon, having variable clinical presentation and treatment options. We present a case of a 60-year-old male patient who presented with pain in the upper abdomen associated with vomiting but without jaundice. On investigations, he was diagnosed to have a left lobe hepatic hydatid cyst (HHC) with IBR for which left hepatectomy with bile duct exploration was performed. It highlights the benign nature of the disease for which seldom major hepatectomies have to be performed.

14.
Med J Armed Forces India ; 79(Suppl 1): S329-S332, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144664

RESUMO

Mucinous adenocarcinoma of jejunum is a rare tumor of the gastrointestinal tract. Patients usually present after fifth decade of their life with non-specific symptoms. Delayed diagnosis is commonplace and often the reason for advanced disease and poor prognosis. These tumors may masquerade as other common malignancies, with a conclusive diagnosis only after the final histopathological examination. We present a case of jejunal mucinous adenocarcinoma, disguised as cecal malignancy, in an old female patient, managed with radical resection and adjuvant chemotherapy. The report reiterates that the mucinous variant of jejunal adenocarcinoma is a rare pathology with an unusual advanced presentation.

15.
Artigo em Inglês | MEDLINE | ID: mdl-37803192

RESUMO

INTRODUCTION: Diffuse esophageal leiomyomatosis is a rare esophageal tumor characterized by circumferential thickening of smooth muscle layers of the entire esophagus. CLINICAL CASE: Herein, we describe the case of a 19-year-old girl, who presented with a history of long-standing dysphagia. On evaluation she was found to have diffuse esophageal leiomyomatosis and was managed successfully by thoracoscopy-assisted esophagectomy with intra-nodal indocyanine green injection. DISCUSSION: In this report, we discuss the pre-operative workup and our surgical approach to managing this rare entity. We also discuss the available literature on the subject and the lessons learnt in managing this complex condition.

16.
Structure ; 31(11): 1360-1374, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-37848030

RESUMO

Biomolecular nuclear magnetic resonance (NMR) spectroscopy and artificial intelligence (AI) have a burgeoning synergy. Deep learning-based structural predictors have forever changed structural biology, yet these tools currently face limitations in accurately characterizing protein dynamics, allostery, and conformational heterogeneity. We begin by highlighting the unique abilities of biomolecular NMR spectroscopy to complement AI-based structural predictions toward addressing these knowledge gaps. We then highlight the direct integration of deep learning approaches into biomolecular NMR methods. AI-based tools can dramatically improve the acquisition and analysis of NMR spectra, enhancing the accuracy and reliability of NMR measurements, thus streamlining experimental processes. Additionally, deep learning enables the development of novel types of NMR experiments that were previously unattainable, expanding the scope and potential of biomolecular NMR spectroscopy. Ultimately, a combination of AI and NMR promises to further revolutionize structural biology on several levels, advance our understanding of complex biomolecular systems, and accelerate drug discovery efforts.


Assuntos
Inteligência Artificial , Descoberta de Drogas , Ressonância Magnética Nuclear Biomolecular/métodos , Reprodutibilidade dos Testes , Conformação Molecular
17.
Proc Natl Acad Sci U S A ; 120(41): e2310910120, 2023 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-37782780

RESUMO

Enzymes are known to sample various conformations, many of which are critical for their biological function. However, structural characterizations of enzymes predominantly focus on the most populated conformation. As a result, single-point mutations often produce structures that are similar or essentially identical to those of the wild-type enzyme despite large changes in enzymatic activity. Here, we show for mutants of a histone deacetylase enzyme (HDAC8) that reduced enzymatic activities, reduced inhibitor affinities, and reduced residence times are all captured by the rate constants between intrinsically sampled conformations that, in turn, can be obtained independently by solution NMR spectroscopy. Thus, for the HDAC8 enzyme, the dynamic sampling of conformations dictates both enzymatic activity and inhibitor potency. Our analysis also dissects the functional role of the conformations sampled, where specific conformations distinct from those in available structures are responsible for substrate and inhibitor binding, catalysis, and product dissociation. Precise structures alone often do not adequately explain the effect of missense mutations on enzymatic activity and drug potency. Our findings not only assign functional roles to several conformational states of HDAC8 but they also underscore the paramount role of dynamics, which will have general implications for characterizing missense mutations and designing inhibitors.


Assuntos
Mutação de Sentido Incorreto , Conformação Proteica , Ressonância Magnética Nuclear Biomolecular/métodos , Catálise
18.
Ochsner J ; 23(3): 243-247, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711471

RESUMO

Background: Esophageal carcinosarcoma is an uncommon histologic variant of esophageal malignancy, occurring in approximately 0.5% to 2.8% of patients. Esophageal carcinosarcoma usually involves the middle and lower esophagus and consists of both epithelial and mesenchymal components. Case Report: A 54-year-old male presented with painless progressive dysphagia associated with loss of weight for 2 months. Esophagogastroduodenoscopy suggested an ulceroproliferative polypoidal growth in the lower thoracic esophagus. Biopsies from the growth showed leiomyosarcoma with tumor cells immunopositive for vimentin, h-Caldesmon, and smooth muscle actin and negative for pan-cytokeratin. Imaging suggested a heterogeneously enhancing polypoidal growth arising in the lower third of the esophagus. Thoracoscopic-assisted McKeown esophagectomy with gastric pull-up and standard 2-field lymphadenectomy was performed. A minor epithelial component was identified on final pathologic examination in addition to the leiomyosarcoma found on the preoperative biopsy. This epithelial component was invasive squamous cell carcinoma and was positive for pan-cytokeratin and p40, both of which were negative in the sarcomatous component. The patient received 4 cycles of adjuvant chemotherapy (carboplatin and paclitaxel). However, he developed a recurrence in the left cervical lymph node 4 months after adjuvant treatment and died 2 months after the diagnosis of recurrence. Conclusion: Carcinosarcoma can be easily missed in the presence of predominantly sarcomatous components even on immunohistochemical analysis. These tumors may be associated with poor prognosis and may have early recurrence despite surgery and adjuvant treatment.

19.
Ochsner J ; 23(3): 251-256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711472

RESUMO

Background: Gangliocytic paraganglioma (GP) is a rare tumor that most commonly arises from the duodenum and is characterized pathologically by 3 cell types: epithelioid, spindle, and ganglion cells. GP is often difficult to differentiate from a neuroendocrine tumor on the basis of preoperative imaging, and the diagnosis is based on final histopathologic and immunohistochemical analysis. Case Report: We report the case of a 28-year-old male who presented with pain in the abdomen, bilious vomiting, and weight loss. Imaging showed a mass involving the first and second part of the duodenum that was likely a neuroendocrine or gastrointestinal stromal tumor. He underwent robotic-assisted pancreatoduodenectomy, and the final pathology report identified GP with lymph node metastasis. The patient was doing well at 1-year follow-up. Conclusion: GP is often a histologic surprise as most cases are diagnosed in postoperative histopathology. While GP has a more benign course than a neuroendocrine tumor, radical surgical resection is warranted in cases of diagnostic dilemma, suspicion of malignancy, or lymph node metastasis. Robotic-assisted pancreatoduodenectomy is a feasible option.

20.
J Minim Invasive Surg ; 26(3): 151-154, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37712315

RESUMO

Hepaticojejunostomy is currently the best treatment for post-cholecystectomy biliary strictures. Laparoscopic repair has not gained popularity due to difficult reconstruction. We present case of 43-year-old-female with Bismuth type 2 stricture following laparoscopic converted open cholecystectomy with bile duct injury done elsewhere. Position was modified Llyod-Davis position and four 8-mm robotic ports (including camera) and 12-mm assistant port were placed. The procedure included noticeable steps such as adhesiolysis, identification of gallbladder fossa, identification of common hepatic duct, lowering of hilar plate etc. Operating and console time were 420 and 350 minutes and blood loss was 100 mL. Patient was discharged on postoperative day 4. Robotic repair (hepaticojejunostomy) of biliary tract stricture after cholecystectomy is safe and feasible with good outcomes.

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