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1.
Ann Surg Oncol ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797790

RESUMO

BACKGROUND: Ileal neuroendocrine tumors (i-NETs) are characterized by their multifocality and bulky mesenteric mass. Having shown that minimally invasive surgery (MIS) utilizing a hand-access port device has favorable short-term outcomes and achieves the goals of surgery for i-NETs, we sought to analyze long-term survival outcomes of MIS. METHODS: One hundred and sixty-eight patients who underwent resection of primary i-NETs at a single institution between January 2007 and February 2023 were retrospectively studied. Patients were categorized into the MIS or open surgery cohorts on an intention-to-treat basis. Open surgery was selected mainly based on the need for hepatectomy or bulky mesenteric mass resection. Overall survival was analyzed using log-rank tests with propensity score matching (PSM) and Cox proportional hazards regression. PSM was performed to reduce standardized mean differences of the variables to <0.2. RESULTS: Overall, 129 (77%) patients underwent MIS and 39 (23%) underwent open surgery. Twenty-seven MIS patients were converted to an open procedure. The median follow-up time was 49 months (interquartile range 23-87 months). In the PSM cohorts, overall survival did not differ significantly between the MIS and open surgery cohorts {median 99 months (95% confidence interval [CI] 91-not applicable [NA]) vs. 103 months (95% CI 86-NA), p = 0.77; hazard ratio 0.87 (95% CI 0.33-2.2), p = 0.77}. CONCLUSIONS: MIS is an alternative to open surgery for i-NETs, achieving similar short- and long-term oncological outcomes. Bulky mesenteric mass and a plan for concurrent liver resection are potential criteria for open surgery.

2.
Ann Surg Oncol ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879670

RESUMO

BACKGROUND: In 2023 alone, it's estimated that over 64,000 patients will be diagnosed with PDAC and more than 50,000 patients will die of the disease. Current guidelines recommend neoadjuvant therapy for patients with borderline resectable and locally advanced PDAC, and data is emerging on its role in resectable disease. Neoadjuvant chemotherapy may increase the number of patients able to receive complete chemotherapy regimens, increase the rate of microscopically tumor-free resection (R0) margin, and aide in identifying unfavorable tumor biology. To date, this is the largest study to examine surgical outcomes after long-duration neoadjuvant chemotherapy for PDAC. METHODS: Retrospective analysis of single-institution data. RESULTS: The routine use of long-duration therapy in our study (median cycles: FOLFIRINOX = 10; gemcitabine-based = 7) is unique. The majority (85%) of patients received FOLFIRINOX without radiation therapy; the R0 resection rate was 76%. Median OS was 41 months and did not differ significantly among patients with resectable, borderline-resectable, or locally advanced disease. CONCLUSIONS: This study demonstrates that in patients who undergo surgical resection after receipt of long-duration neoadjuvant FOLFIRINOX therapy alone, survival outcomes are similar regardless of pretreatment resectability status and that favorable surgical outcomes can be attained.

3.
World J Surg Oncol ; 22(1): 77, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468341

RESUMO

BACKGROUND: Metastatic melanoma to the small bowel is an aggressive disease often accompanied by obstruction, abdominal pain, and gastrointestinal bleeding. With advancements in melanoma treatment, the role for metastasectomy continues to evolve. Inclusion of novel immunotherapeutic agents, such as checkpoint inhibitors, into standard treatment regimens presents potential survival benefits for patients receiving metastasectomy. CASE PRESENTATION: We report an institutional experience of 15 patients (12 male, 3 female) between 2014-2022 that underwent small bowel metastasectomy for metastatic melanoma and received perioperative systemic treatment. Median age of patients was 64 years (range: 35-83 years). No patients died within 30 days of their surgery, and the median hospital length of stay was 5 days. Median overall survival in these patients was 30.1 months (range: 2-115 months). Five patients died from disease (67 days, 252 days, 426 days, 572 days, 692 days postoperatively), one patient died of non-disease related causes (1312 days postoperatively), six patients are alive with disease, and three remain disease free. CONCLUSIONS: This case series presents an updated perspective of the utility of metastasectomy for small bowel metastasis in the age of novel immunotherapeutic agents as standard systemic treatment. Small bowel metastasectomy for advanced melanoma performed in conjunction with perioperative systemic therapy is safe and appears to promote long-term survival and enhanced quality of life.


Assuntos
Melanoma , Metastasectomia , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Melanoma/terapia , Melanoma/patologia , Qualidade de Vida , Imunoterapia , Intestino Delgado/patologia , Estudos Retrospectivos
4.
Ann Surg Oncol ; 30(12): 7738-7747, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37550449

RESUMO

BACKGROUND: Clinically-relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) is a major postoperative complication and the primary determinant of surgical outcomes. However, the majority of current risk calculators utilize intraoperative and postoperative variables, limiting their utility in the preoperative setting. Therefore, we aimed to develop a user-friendly risk calculator to predict CR-POPF following PD using state-of-the-art machine learning (ML) algorithms and only preoperatively known variables. METHODS: Adult patients undergoing elective PD for non-metastatic pancreatic cancer were identified from the ACS-NSQIP targeted pancreatectomy dataset (2014-2019). The primary endpoint was development of CR-POPF (grade B or C). Secondary endpoints included discharge to facility, 30-day mortality, and a composite of overall and significant complications. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated and a user-friendly risk calculator was then developed. RESULTS: Of the 8666 patients who underwent elective PD, 13% (n = 1160) developed CR-POPF. XGBoost was the best performing model (AUC = 0.72), and the top five preoperative variables associated with CR-POPF were non-adenocarcinoma histology, lack of neoadjuvant chemotherapy, pancreatic duct size less than 3 mm, higher BMI, and higher preoperative serum creatinine. Model performance for 30-day mortality, discharge to a facility, and overall and significant complications ranged from AUC 0.62-0.78. CONCLUSIONS: In this study, we developed and validated an ML model using only preoperatively known variables to predict CR-POPF following PD. The risk calculator can be used in the preoperative setting to inform clinical decision-making and patient counseling.

5.
Ann Surg Oncol ; 30(8): 5119-5129, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37140748

RESUMO

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare malignancy with a historically poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an effective therapy for patients with peritoneal malignancies. A contemporary analysis of trends in management of and survival from MPM is warranted. METHODS: Patients with MPM were identified from the National Cancer Database (2004-2018). Patients were categorized by treatment (CRS-HIPEC, CRS-chemotherapy, CRS only, chemotherapy only, no treatment), and joinpoint regression was employed to compute the annual percent change (APC) in treatment over time. Multivariable Cox proportional hazards models were used to analyze factors associated with survival. RESULTS: Of 2683 patients with MPM, 19.1% underwent CRS-HIPEC, and 21.1% received no treatment. Joinpoint regression revealed a statistically significant increase in the proportion of patients undergoing CRS-HIPEC over time (APC 3.21, p = 0.01), and a concurrent decrease in the proportion of patients who underwent no treatment (APC - 2.21, p = 0.02). Median overall survival was 19.5 months. Factors independently associated with survival included CRS-HIPEC, CRS, histology, sex, age, race, Charlson Comorbidity Index, insurance, and hospital type. Although there was a strong association between year of diagnosis and survival on univariate analysis (2016-2018 HR 0.67, p < 0.001), this association was attenuated after adjustment for treatment. CONCLUSIONS: CRS-HIPEC is increasingly employed as a treatment for MPM. In parallel, there has been a decrease in patients receiving no treatment with an increase in overall survival. These findings suggest that patients with MPM may be receiving more appropriate therapy; however, a substantial proportion of patients may remain undertreated.


Assuntos
Hipertermia Induzida , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneais , Humanos , Mesotelioma/patologia , Neoplasias Peritoneais/patologia , Neoplasias Pulmonares/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Taxa de Sobrevida , Estudos Retrospectivos
6.
World J Surg ; 47(3): 750-758, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36402918

RESUMO

BACKGROUND: Hand-assisted laparoscopic distal pancreatectomy (HALDP) is suggested to offer similar outcomes to pure laparoscopic distal pancreatectomy (LDP). However, given the longer midline incision, it is unclear whether HALDP increases the risk of postoperative hernia. Our aim was to determine the risk of postoperative incisional hernia development after HALDP. METHODS: We retrospectively collected data from patients undergoing HALDP or LDP at a single center (2012-2020). Primary endpoints were postoperative incisional hernia and operative time. All patients had at minimum six months of follow-up. Outcomes were compared using unadjusted and multivariable regression analyses. RESULTS: Ninety-five patients who underwent laparoscopic distal pancreatectomy were retrospectively identified. Forty-one patients (43%) underwent HALDP. Patients with HALDP were older (median, 67 vs. 61 years, p = 0.02). Sex, race, Body Mass Index (median, 27 vs. 26), receipt of neoadjuvant chemotherapy, gland texture, wound infection rates, postoperative pancreatic fistula, overall complications, and hospital length-of-stay were similar between HALDP and LDP (all p > 0.05). In unadjusted analysis, operative times were shorter for HALDP (164 vs. 276 min, p < 0.001), but after adjustment, did not differ significantly (MR 0.73; 0.49-1.07, p = 0.1). Unadjusted incidence of hernia was higher in HALDP versus LDP (60% vs. 24%, p = 0.004). After adjustment, HALDP was associated with an increased odds of developing hernia (OR 7.52; 95% CI 1.54-36.8, p = 0.014). After propensity score matching, odds of hernia development remained higher for HALDP (OR 4.62; 95% CI 1.28-16.65, p = 0.031) p = 0.03). CONCLUSIONS: Compared with LDP, HALDP was associated with increased likelihood of postoperative hernia with insufficient evidence that HALDP shortens operative times. Our results suggest that HALDP may not be equivalent to LDP.


Assuntos
Hérnia Incisional , Laparoscopia , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/complicações , Hérnia Incisional/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Laparoscopia/métodos , Duração da Cirurgia , Tempo de Internação
7.
Ann Surg Oncol ; 29(3): 1566-1574, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34724124

RESUMO

BACKGROUND: Guidelines recommend limiting minimally invasive pancreaticoduodenectomy (MIPD) to high-volume centers. However, the definition of high-volume care remains unclear. We aimed to objectively define a minimum number of MIPD performed annually per hospital associated with improved outcomes in a contemporary patient cohort. PATIENTS AND METHODS: Resectable pancreatic adenocarcinoma patients undergoing MIPD were included from the National Cancer Database (2010-2017). Multivariable modeling with restricted cubic splines was employed to identify an MIPD annual hospital volume threshold associated with lower 90-day mortality. Outcomes were compared between patients treated at low-volume (≤ model-identified cutoff) and high-volume (> cutoff) centers. RESULTS: Among 3079 patients, 141 (5%) died within 90 days. Median hospital volume was 6 (range 1-73) cases/year. After adjustment, increasing hospital volume was associated with decreasing 90-day mortality for up to 19 (95% CI 16-25) cases/year, indicating a threshold of 20 cases/year. Most cases (82%) were done at low-volume (< 20 cases/year) centers. With adjustment, MIPD at low-volume centers was associated with increased 90-day mortality (OR 2.7; p = 0.002). Length of stay, positive surgical margins, 30-day readmission, and overall survival were similar. On analysis of the most recent two years (n = 1031), patients at low-volume centers (78.2%) were younger and had less advanced tumors but had longer length of stay (8 versus 7 days; p < 0.001) and increased 90-day mortality (7% versus 2%; p = 0.009). CONCLUSIONS: The cutpoint analysis identified a threshold of at least 20 MIPD cases/year associated with lower postoperative mortality. This threshold should inform national guidelines and institution-level protocols aimed at facilitating the safe implementation of this complex procedure.


Assuntos
Adenocarcinoma , Laparoscopia , Neoplasias Pancreáticas , Adenocarcinoma/cirurgia , Hospitais , Humanos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos
8.
J Surg Res ; 277: A25-A35, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35307162

RESUMO

Emotional regulation is increasingly gaining acceptance as a means to improve well-being, performance, and leadership across high-stakes professions, representing innovation in thinking within the field of surgical education. As one part of a broader cognitive skill set that can be trained and honed, emotional regulation has a strong evidence base in high-stress, high-performance fields. Nevertheless, even as Program Directors and surgical educators have become increasingly aware of this data, with emerging evidence in the surgical education literature supporting efficacy, hurdles to sustainable implementation exist. In this white paper, we present evidence supporting the value of emotional regulation training in surgery and share case studies in order to illustrate practical steps for the development, adaptation, and implementation of emotional regulation curricula in three key developmental contexts: basic cognitive skills training, technical skills acquisition and performance, and preparation for independence. We focus on the practical aspects of each case to elucidate the challenges and opportunities of introducing and adopting a curricular innovation into surgical education. We propose an integrated curriculum consisting of all three applied contexts for emotional regulation skills and advocate for the dissemination of such a longitudinal curriculum on a national level.


Assuntos
Regulação Emocional , Liderança , Competência Clínica , Currículo
9.
Biochem Biophys Res Commun ; 522(4): 1003-1008, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-31812243

RESUMO

Astrocytes regulate various brain functions, for which Ca2+ release from the endoplasmic reticulum (ER) often play crucial roles. Because astrocytic ER Ca2+ release is robust and frequent, the ER Ca2+ refilling mechanism should be critical for ongoing Ca2+ signaling in astrocytes. In this study, we focused on the putative functional significance of store-operated Ca2+ entry (SOCE) in ER Ca2+ refilling. We expressed the ER luminal Ca2+ indicator G-CEPIA1er in astrocytes in acute cortical slices to directly monitor the decrease and recovery of ER Ca2+ concentration upon spontaneous or norepinephrine-induced Ca2+ release. Inhibition of SOCE significantly slowed the recovery of ER Ca2+ concentration after Ca2+ release in astrocytes. This delayed recovery resulted in a prolonged decrease in the ER Ca2+ content in astrocytes with periodic spontaneous Ca2+ release, followed by the attenuation of cytosolic Ca2+ responses upon Ca2+ release. Therefore, our results provide direct evidence for the physiological significance of SOCE in ER Ca2+ refilling after ER Ca2+ release.


Assuntos
Astrócitos/metabolismo , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Córtex Cerebral/metabolismo , Retículo Endoplasmático/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Camundongos Endogâmicos C57BL , Norepinefrina/farmacologia
10.
J Surg Res ; 256: 476-485, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32798995

RESUMO

BACKGROUND: Synchronous colorectal cancer liver metastasis (CRLM) has been viewed as being more aggressive and having shorter survival than metachronous disease. Advances in CRLM management led us to examine differences in treatment characteristics of synchronous versus metachronous CRLM patients along with survival and recurrence. MATERIALS AND METHODS: A retrospective review of hepatic resection for CRLM at a tertiary academic medical center was performed for two periods: a historic cohort from 1992 to 2010 (n = 121), and a modern cohort (n = 179) from 2012 to 2018. Clinical variables were compared between the patient groups, and survival outcomes were characterized. RESULTS: Five-year disease-specific survival for the modern synchronous group compared to the historic synchronous group was 71.7% versus 44.3% (P = 0.02). Modern metachronous versus modern synchronous 5-y disease-specific survival rates were 49.8% versus 71.7% (P = 0.31). Compared to the historic cohort, the modern one had significantly different timing of hepatic resection (P < 0.01) with increased use of liver-first (30.1% versus 7.5%) and simultaneous liver-colon resections (24.1% versus 10.4%), along with greater use of neoadjuvant chemotherapy (96.4% versus 65.6%; P < 0.01). Significantly more patients in the modern synchronous cohort had disease-free or alive-with-disease status at last follow-up, compared to the historic group (P < 0.01), and experienced less disease recurrence (62.7% versus 77.6%; P < 0.05). CONCLUSIONS: Modern synchronous CRLM patients who underwent hepatic resection experienced significantly improved survival compared to a historic cohort. We postulate that increased use of neoadjuvant chemotherapy and liver-first/simultaneous liver-colon resections in the modern synchronous cohort contributed to improved survival.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/estatística & dados numéricos , Neoplasias Hepáticas/mortalidade , Terapia Neoadjuvante/estatística & dados numéricos , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Quimioterapia Adjuvante/estatística & dados numéricos , Colectomia/estatística & dados numéricos , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estudos Retrospectivos , Taxa de Sobrevida
11.
J Surg Oncol ; 122(2): 204-211, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32291778

RESUMO

BACKGROUND AND OBJECTIVES: We classified the extent of mesenteric mass (MM) involvement that predicts challenging mesenteric lymph node dissection (mLND) by minimally invasive surgery (MIS) for ileal neuroendocrine tumors (i-NETs). METHODS: Patients who underwent surgery for i-NETs were retrospectively reviewed. MM involvement was classified as region-0: no MM; region-1: >2 cm from the origins of the ileocolic artery/vein; region-2: ≤2 cm from the origins; and region-3: more proximal superior mesenteric artery/vein. Logistic regression analysis was used to evaluate the predictive value of MM regions for gross positive mesenteric margin (mR2) and/or conversion among the MIS cohort. The open surgery cohort was used as a reference for mR2 rates. RESULTS: Of 108 patients, 83 patients (77%) underwent MIS. MMs in region-2 and region-3 were independent risk factors for mR2 and/or conversion (odds ratio [95% confidence interval]: 4.25 [1.17-16.4] and 8.51 × 107 [11.0-], respectively, against regions-0 and 1]. mR2 rates of MIS and open surgery cohorts per region did not differ significantly (4% and 7% for regions-0 and 1; 17% and 25% for region-2; and 100% and 83% for region-3). CONCLUSIONS: The novel stratification of MM regions was predictive of challenging mLND by MIS. Surgeons should have a low threshold for conversion for MMs in proximal regions.


Assuntos
Neoplasias do Íleo/patologia , Neoplasias do Íleo/cirurgia , Linfonodos/patologia , Linfonodos/cirurgia , Mesentério/patologia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Estudos de Coortes , Humanos , Excisão de Linfonodo , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Valor Preditivo dos Testes , Estudos Retrospectivos
12.
J Surg Oncol ; 121(2): 330-336, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31828813

RESUMO

BACKGROUND AND OBJECTIVES: We developed objective measurements of preoperative and residual tumor volume, and debulking rate, to evaluate their prognostic value for neuroendocrine liver metastasis (NELM). METHODS: Seventy-three patients who underwent surgery for NELM were analyzed retrospectively. Indices of preoperative and postoperative residual tumor volume (pre-volume index [VI] and post-VI) were calculated as the sum of the cubes of individual tumor diameters on preoperative and postoperative imaging, respectively. The debulking rate (%) was calculated as 100 - 100 × post-VI/pre-VI. The classification and regression trees method was used to classify pre-VI and post-VI. RESULTS: Overall survival (OS) was discriminated by preoperative tumor volume (5-year OS rates, 87.8% for low pre-VI and 60.1% for high pre-VI; P = .037) and residual tumor volume (5-year OS rates, 88.1% for low post-VI and 24.8% for high post-VI; P < .001). In contrast, debulking rates of 100%, ≥90%, and <90% did not discriminate OS (5-year OS rates, 88.0%, 61.9%, and 58.9%, respectively, not significant). In multivariate analysis, residual tumor volume (high post-VI, hazard ratio, 6.40; 95% confidence interval, 1.45-32.3) was an independent prognostic factor for OS. CONCLUSIONS: Objective measurement of tumor volume demonstrates that residual tumor volume is prognostic after surgery for NELM.

13.
HPB (Oxford) ; 22(10): 1496-1503, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32340857

RESUMO

BACKGROUND: Ampullary stenosis following Roux-en-Y gastric bypass (RYGB) is increasingly encountered. We describe cases of biliary obstruction from ampullary stenosis and choledocholithiasis to illustrate the associated diagnostic and interventional challenges with this condition. METHODS: We reviewed medical records of patients with prior RYGB who underwent a biliary access procedure or surgery for non-malignant disease from January 2012-December 2018. RESULTS: We identified 15 patients (4 male, 11 female; mean age 53.7 years) who had RYGB on average 11.7 years (range 1-32) years before diagnosis of biliary obstruction. Fourteen patients reported abdominal pain, 5 had nausea/emesis, 12 had elevated liver function tests, and 6 had ascending cholangitis. Mean common bile duct (CBD) diameter at presentation was 16.9 mm (range 4.0-25.0 mm). Operations included 3 transduodenal ampullectomies (2 with biliary bypass), 2 CBD explorations with stone extraction, 1 laparoscopic cholecystectomy alone, 1 Whipple procedure, 1 balloon enteroscopy with sphincterotomy, and 7 transgastric endoscopic retrograde cholangiopancreatography. All ampulla pathology was benign in patients who underwent resection. At follow-up (mean 15.4 months; range 0.23-44.5 months), 12/15 (80%) reported symptom resolution or improvement. DISCUSSION: Ampullary stenosis after RYGB presents challenges for diagnostic evaluation and intervention, often requiring multi-disciplinary expertise. The underlying pathology remains to be elucidated.


Assuntos
Coledocolitíase , Derivação Gástrica , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/cirurgia , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/cirurgia , Constrição Patológica , Feminino , Derivação Gástrica/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
Glia ; 67(1): 113-124, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30306640

RESUMO

Accumulating evidence indicates that astrocytes are actively involved in the physiological and pathophysiological functions of the brain. Intracellular Ca2+ signaling, especially Ca2+ release from the endoplasmic reticulum (ER), is considered to be crucial for the regulation of astrocytic functions. Mice with genetic deletion of inositol 1,4,5-trisphosphate receptor type 2 (IP3 R2) are reportedly devoid of astrocytic Ca2+ signaling, and thus widely used to explore the roles of Ca2+ signaling in astrocytic functions. While functional deficits in IP3 R2-knockout (KO) mice have been found in some reports, no functional deficit was observed in others. Thus, there remains a controversy regarding the functional significance of astrocytic Ca2+ signaling. To address this controversy, we re-evaluated the assumption that Ca2+ release from the ER is abolished in IP3 R2-KO astrocytes using a highly sensitive imaging technique. We expressed the ER luminal Ca2+ indicator G-CEPIA1er in cortical and hippocampal astrocytes to directly visualize spontaneous and stimulus-induced Ca2+ release from the ER. We found attenuated but significant Ca2+ release in response to application of norepinephrine to IP3 R2-KO astrocytes. This IP3 R2-independent Ca2+ release induced only minimal cytosolic Ca2+ transients but induced robust Ca2+ increases in mitochondria that are frequently in close contact with the ER. These results indicate that ER Ca2+ release is retained and is sufficient to increase the Ca2+ concentration in close proximity to the ER in IP3 R2-KO astrocytes.


Assuntos
Astrócitos/metabolismo , Sinalização do Cálcio/fisiologia , Retículo Endoplasmático/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/deficiência , Animais , Astrócitos/química , Retículo Endoplasmático/química , Hipocampo/química , Hipocampo/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/análise , Receptores de Inositol 1,4,5-Trifosfato/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
J Surg Oncol ; 120(8): 1311-1317, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31613999

RESUMO

BACKGROUND AND OBJECTIVES: Ileal neuroendocrine tumors (i-NETs) frequently metastasize to mesenteric lymph nodes and the liver. Regional lymphadenopathy is associated with desmoplasia of the mesentery forming a large mesenteric mass (LMM). Although the latest American Joint Committee on Cancer TNM staging (8th edition) defined LMM >2 cm as N2, the prognostic impact of LMM is ill-defined. We evaluated whether LMM is prognostic for patients with i-NETs. METHODS: This single-institution, retrospective cohort study included 106 patients who underwent resection of i-NETs between 2007 and 2018. Overall survival (OS) and liver progression-free survival (LPFS) were compared between patients with and without LMM. RESULTS: LMM was present in 66 patients (62%) and was not associated with the presence or absence of liver metastasis (P = .969) or the extent of liver involvement (P = .938). OS and LPFS differed significantly between patients with and without LMM (5-year OS rates of 64.8% and 92.9%, respectively, P = .011; 3-year LPFS rates of 45.3% and 67.5%, respectively, P = .025). In multivariate analysis, LMM was an independent prognostic factor for both OS (hazard ratio: 4.69, 95% confidence interval: 1.63-17.6) and LPFS (1.99, 1.08-3.88). CONCLUSION: LMM >2 cm is prognostic for OS and LPFS and represents aggressive tumor biology.


Assuntos
Neoplasias do Íleo/mortalidade , Neoplasias do Íleo/patologia , Linfonodos/patologia , Mesentério/patologia , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Idoso , Estudos de Coortes , Feminino , Humanos , Neoplasias do Íleo/cirurgia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/cirurgia , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos
19.
Pancreatology ; 17(5): 732-737, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28733148

RESUMO

BACKGROUND & OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is employed for the management of refractory pain in chronic pancreatitis (CP) with the prospect of partial beta cell preservation. The primary aim of this study is to evaluate the prevalence and predictors of abdominal pain and opioid use following TPIAT. METHODS: A single center cohort study of all adult patients who underwent TPIAT from 2011 to 2015 for CP. Postoperative pain outcomes included: opioid use, ongoing abdominal pain and new characteristic abdominal pain. Multiple logistic regression analysis was used to evaluate known and potential predictors of postoperative pain outcomes. RESULTS: During the study period, 46 patients underwent TPIAT. Following surgery, 89% of patients had resolution of their pre-operative abdominal pain; however, 83% of patients developed a new characteristic abdominal pain. Opioid independence was achieved in 46% of patients. Acute recurrent pancreatitis (ARP) (OR: 11.66; 95%CI: 1.47-92.39; p = 0.02) but not pain duration >3 years or ≥ 5 ERCPs was independently associated with resolution of pre-operative abdominal pain on multiple logistic regression. None of these factors were associated with cessation of opioid use. CONCLUSION: While the majority of patients have resolution of their initial abdominal pain following TPIAT, many will also develop a new characteristic abdominal pain and only half of all patients achieve opioid independence. ARP is the only independent factor associated with positive postoperative pain outcomes and should be considered a standard criterion for patient selection.


Assuntos
Analgésicos Opioides/uso terapêutico , Transplante das Ilhotas Pancreáticas/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor/tratamento farmacológico , Pancreatectomia/efeitos adversos , Pancreatite/cirurgia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Ann Surg Oncol ; 23(2): 375-81, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26561404

RESUMO

BACKGROUND: Liver resection is a key therapeutic strategy to improve survival in patients with colorectal cancer liver metastases. Underutilization may negatively affect outcomes. Using a Web-based survey and standardized imaging scenarios, this study assessed medical oncologists' (MOs) perceptions of resectability, preferences for chemotherapy sequencing, and referral for surgical consultation in a static patient profile of good performance status and no extrahepatic spread but varying bulk and distribution of disease. METHODS: A total of 190 US-based MOs were surveyed. A single patient profile was created and combined with 10 different sets of liver computed tomographic images displaying a broad spectrum of metastases. Assessments of resectability and ranking were compared with the results obtained from an expert panel of 3 hepatic surgeons. RESULTS: The expert hepatic surgeons designated 8 scans resectable, 1 borderline resectable/convertible, and 1 unresectable. In the 8 resectable cases, 34.4 % of MOS perceived the case to be initially resectable, 41.7 % potentially resectable after chemotherapy response, and 23.9 % unresectable. Increasing number of lesions, larger tumor diameter, and bilateral disease were associated with lower resectability perception (P < 0.01). Among those cases considered resectable by MOs, they preferred initial resection (54.2 %) over neoadjuvant chemotherapy (38.4 %). Initial referral for surgical consultation was generally favored only for cases considered initially resectable by MOs. CONCLUSIONS: This study confirms both potential discrepancies between MOs' and hepatic surgeons' perception of resectability and underutilization of early surgical consultation for patients with potentially resectable colorectal cancer liver metastases and underscores the importance of an evaluation that includes an experienced hepatic surgeon.


Assuntos
Neoplasias Colorretais/cirurgia , Cirurgia Geral/normas , Neoplasias Hepáticas/cirurgia , Oncologia/normas , Padrões de Prática Médica/normas , Neoplasias Colorretais/patologia , Hepatectomia , Humanos , Relações Interprofissionais , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Cuidados Pré-Operatórios , Encaminhamento e Consulta , Inquéritos e Questionários
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