Publications by authors named "Sham J"

Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

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Background And Objectives: Few data exist to guide optimal communication practices for surgical oncologists. VitalTalk, an evidence-based communication skills training model for clinicians, offers the five-step ADAPT tool for discussing prognosis. This study aimed to characterize surgeon communication of pancreatic cancer prognosis using VitalTalk's ADAPT framework.

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Background: Postoperative pancreatic fistulas lead to substantially increased morbidity, mortality, and healthcare costs after pancreatectomy. Studies have reported conflicting data on the role of prophylactic somatostatin analogs in the reduction of postoperative pancreatic fistula. Current practice patterns, surgeon beliefs, and barriers to using these drugs in the Americas is not known.

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Background: For open minor hepatectomy, morbidity and recovery are dominated by the incision. The robotic approach may transform this "incision dominant procedure" into a safe outpatient procedure.

Study Design: We audited outpatient (less than 2 midnights) robotic hepatectomy at 6 hepatobiliary centers in 2 nations to test the hypothesis that the robotic approach can be a safe and effective short-stay procedure.

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Poorly differentiated pancreatic neuroendocrine carcinomas (pNECs) are rare, highly aggressive neoplasms. Frequently metastatic at diagnosis, prognosis is poor with median overall survival estimated to be less than 1 year. Although multidisciplinary management, including systemic medications and locoregional therapies aimed at reducing and preventing symptoms caused by mass effect, is the mainstay of treatment for patients with metastatic well-differentiated pancreatic neuroendocrine tumors, rapid progression, organ dysfunction, and poor performance status often preclude initiation of even single-modality palliative chemotherapy for patients with metastatic pNEC, limiting the use of and recommendation for multidisciplinary management.

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  • Clinical evidence points to a connection between pulmonary hypertension (PH) and coronary artery (CA) disease, with serotonin, reactive oxygen species, and calcium signaling being crucial factors in this relationship.
  • A study on rats indicates that the NOX-TRPM2 pathway plays a significant role in the remodeling of coronary arteries associated with pulmonary hypertension.
  • Findings show that NOX1/4 and TRPM2 contribute to increased cell proliferation and metabolic changes in CA smooth muscle cells, ultimately leading to mitochondrial dysfunction, but inhibiting NOX1/4 can mitigate these effects.
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The carotid bodies (CBs) have been implicated in glucose abnormalities in obesity via elevation of activity of the sympathetic nervous system. Obesity-induced hypertension is mediated by insulin receptor (INSR) signaling and by leptin, which binds to the leptin receptor (LEPR) in CB and activates transient receptor potential channel subfamily M member 7 (TRPM7). We hypothesize that in mice with diet-induced obesity, hyperglycemia, glucose intolerance, and insulin resistance will be attenuated by the CB denervation (carotid sinus nerve dissection, CSND) and by knockdown of , and gene expression in CB.

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  • Pancreatic ductal adenocarcinoma (PDA) is a highly deadly cancer, with standard treatment leading to a median survival of only 24 months; this study aimed to explore a multiagent perioperative therapy to enhance survival rates.
  • In a phase 2 trial, patients received a combination of chemotherapy and radiation before and after surgery; results showed a median overall survival of 31.6 months, increasing to 58.1 months for those who completed the surgery.
  • The study suggests that the examined perioperative therapy could offer a promising new treatment strategy for patients with potentially resectable PDA, potentially improving outcomes significantly.
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Arginine vasopressin (AVP) induces an increase in intracellular Ca concentration ([Ca]) with an oscillatory pattern in isolated perfused kidney inner medullary collecting duct (IMCD). The AVP-induced Ca mobilization in inner medullary collecting ducts is essential for apical exocytosis and is mediated by the exchange protein directly activated by cyclic adenosine monophosphate (Epac). Murine principal kidney cortical collecting duct cells (mpkCCD) is the cell model used for transcriptomic and phosphoproteomic studies of AVP signaling in kidney collecting duct.

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Background: Pancreatic neuroendocrine tumors (PanNETs) exhibit heterogenous behavior, whereby some small tumors are aggressive with a propensity for metastasis. Detection of somatic mutations associated with aggressive biology may help with patient stratification and surgical decision-making in patients with well-differentiated PanNETs. Using next-generation sequencing (NGS), we investigated the feasibility of detecting somatic mutations in endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA) specimens and determining the mutational concordance between the EUS-FNA specimens and the primary tumors.

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Surgery is considered for patients without metastatic disease and with resectable primary tumor. Pre-operatively, high quality imaging is reviewed to determine the likely extent of resection, specifically including the need for potential en-bloc resection of adjacent organs. In cases where up-front surgical approach would expose the patient to excessive morbidity (such as bilateral nephrectomy, multi-visceral resection, or prohibitively high risk of positive margins), neoadjuvant chemotherapy and/or chemoradiotherapy is considered.

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Background: The National Comprehensive Cancer Network recommends genetic testing in patients with potentially hereditary breast, ovarian, pancreatic, and prostate cancers (HBOPP). Knowledge of genetic mutations impacts decisions about screening and treatment.

Methods: A retrospective cohort study of 28,586 HBOPP patients diagnosed from 2013 to 2019 was conducted using a linked administrative-cancer database in the Seattle-Puget Sound SEER area.

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Sleep-disordered breathing (SDB) affects over 50% of obese individuals. Exaggerated hypoxic chemoreflex is a cardinal trait of SDB in obesity. We have shown that leptin acts in the carotid bodies (CB) to augment chemoreflex and that leptin activates the transient receptor potential melastatin 7 (TRPM7) channel.

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Article Synopsis
  • KRAS variant alleles can influence the biological behavior of pancreatic ductal adenocarcinomas (PDA), affecting patient prognosis and treatment options.
  • A study at the University of Washington analyzed advanced PDA patients, revealing that specific KRAS mutations, particularly G12R, were linked to better overall and progression-free survival compared to other variants.
  • However, having PI3K pathway mutations alongside KRAS G12R diminished this survival advantage, suggesting that the KRAS/PI3K genomic profile can help predict treatment responses in PDA patients.
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Background: Pulmonary arterial hypertension maintains rapid cell proliferation and vascular remodeling through metabolic reprogramming. Recent studies suggested that circRNAs play important role in pulmonary vascular remodeling and pulmonary arterial smooth muscle cells proliferation. However, the relationship between circRNA, cell proliferation, and metabolic reprogramming in pulmonary arterial hypertension has not been investigated.

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  • Uterine serous cancer (USC) is a highly aggressive form of uterine cancer that often leads to treatment-resistant disease, highlighting the need for new therapies.
  • A novel biomarker, ryanodine receptor 1 (RYR1), was identified as having a negative impact on patient outcomes, prompting researchers to investigate its role in cancer progression and the potential for FDA-approved drugs to target it.
  • The study found that high levels of RYR1 correlate with advanced disease and that inhibiting RYR1 improves cancer cell behaviors, with the repositioned drug dantrolene demonstrating effectiveness in reducing USC progression in models.
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Background: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a significant contributor to morbidity after pancreatectomy. Somatostatin analogues have shown variable efficacy in the prevention of CR-POPF. Lanreotide is a somatostatin analogue ideally suited for perioperative use due to its long half-life and favorable side effect profile.

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  • Mortality rates after pancreatic surgery have decreased to less than 5%, but postoperative complications (morbidity) remain high, affecting 15% to 65% of patients.
  • The most significant issue causing these complications is a postoperative pancreatic fistula (POPF), which can result in severe conditions like abscesses, hemorrhage, sepsis, and even death.
  • Current models for studying POPF are limited and ineffective, prompting researchers to develop a new rat model that reliably induces POPF by cutting the common pancreatic duct, which could improve understanding and treatment options.
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  • Hepatocellular carcinoma (HCC) is a serious global health issue with few effective treatments for advanced stages, prompting research into targeted therapies like α-therapy which involves delivering α-particle-emitting radionuclides, such as Th, specifically to cancer cells.
  • The study focuses on developing a Th-labeled antibody (Th-octapa-αGPC3) that targets Glypican-3 (GPC3), a protein often overexpressed in HCC, showing high efficiency in labeling and maintaining stability in vitro.
  • In preclinical tests involving mice with HCC, Th-octapa-αGPC3 effectively accumulated in tumors while sparing normal tissue, leading to a significant tumor reduction at specific
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Pancreatic ductal adenocarcinoma (PDAC) is often a lethal malignancy with limited preoperative predictors of long-term survival. The purpose of this study was to evaluate the prognostic utility of preoperative CT radiomics features in predicting postoperative survival of patients with PDAC. A total of 153 patients with surgically resected PDAC who underwent preoperative CT between 2011 and 2017 were retrospectively identified.

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The transient receptor potential canonical (TRPC) channels have been implicated in various types of malignancies including gastric cancer (GC). However, the detailed mechanisms of TRPC channels underlying cell proliferation and apoptosis of GC cells remain largely unknown. Here, we report that TRPC3 was highly expressed in clinical GC specimens and correlated with GC malignant progression and poor prognosis.

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Chloride channels play an important role in regulating smooth muscle contraction and proliferation, and contribute to the enhanced constriction of pulmonary arteries (PAs) in pulmonary hypertension (PH). The intracellular Cl concentration ([Cl]), tightly regulated by various Cl transporters, determines the driving force for Cl conductance, thereby the functional outcome of Cl channel activation. This study characterizes for the first time the expression profile of Cl transporters/exchangers in PA smooth muscle and provides the first evidence that the intracellular Cl homeostasis is altered in PA smooth muscle cells (PASMCs) associated with chronic hypoxic PH (CHPH).

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