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1.
Ann Surg Oncol ; 30(9): 5815-5825, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37285095

RESUMO

BACKGROUND: Anastomotic leak after esophagectomy is associated with significant morbidity and mortality. Our institution began performing laparoscopic gastric ischemic preconditioning (LGIP) with ligation of the left gastric and short gastric vessels prior to esophagectomy in all patients presenting with resectable esophageal cancer. We hypothesized that LGIP may decrease the incidence and severity of anastomotic leak. METHODS: Patients were prospectively evaluated following the universal application of LGIP prior to esophagectomy protocol in January 2021 until August 2022. Outcomes were compared with patients who underwent esophagectomy without LGIP from a prospectively maintained database from 2010 to 2020. RESULTS: We compared 42 patients who underwent LGIP followed by esophagectomy with 222 who underwent esophagectomy without LGIP. Age, sex, comorbidities, and clinical stage were similar between groups. Outpatient LGIP was generally well tolerated, with one patient experiencing prolonged gastroparesis. Median time from LGIP to esophagectomy was 31 days. Mean operative time and blood loss were not significantly different between groups. Patients who underwent LGIP were significantly less likely to develop an anastomotic leak following esophagectomy (7.1% vs. 20.7%, p = 0.038). This finding persisted on multivariate analysis [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.03-0.42, p = 0.029]. The occurrence of any post-esophagectomy complication was similar between groups (40.5% vs. 46.0%, p = 0.514), but patients who underwent LGIP had shorter length of stay [10 (9-11) vs. 12 (9-15), p = 0.020]. CONCLUSIONS: LGIP prior to esophagectomy is associated with a decreased risk of anastomotic leak and length of hospital stay. Further, multi-institutional studies are warranted to confirm these findings.


Assuntos
Neoplasias Esofágicas , Precondicionamento Isquêmico , Laparoscopia , Humanos , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Fístula Anastomótica/cirurgia , Estômago/cirurgia , Neoplasias Esofágicas/complicações , Laparoscopia/métodos , Precondicionamento Isquêmico/efeitos adversos , Precondicionamento Isquêmico/métodos , Estudos Retrospectivos , Anastomose Cirúrgica/efeitos adversos
2.
Dig Dis Sci ; 67(10): 4732-4741, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35001242

RESUMO

BACKGROUND: Observational studies demonstrate a protective effect of statins on the development and progression of esophageal adenocarcinoma. The role of statins in the prevention of reflux-induced esophageal changes remains unknown. AIMS: Using a mixed gastroduodenal reflux mouse model, we hypothesized that oral administration of simvastatin would attenuate reflux-induced mucosal changes of the distal esophagus. METHODS: Human Barrett's (CPB) and esophageal adenocarcinoma (FLO1 and OE19) cells were treated with simvastatin. Cell proliferation and apoptosis were evaluated using the MTS proliferation and annexin V apoptosis assays, respectively. A reflux mouse model was generated by performing a side-to-side anastomosis between the gastroesophageal junction and first portion of the duodenum (duodeno-gastroesophageal anastomosis, DGEA). DGEA mice were fed a standard or simvastatin-containing diet following surgery. Mice were euthanized 6 weeks post-operatively. RESULTS: Simvastatin significantly decreased proliferation and increased apoptosis in all cell lines. Compared to control animals, mice undergoing DGEA who were fed a standard diet demonstrated a fourfold increase in mucosal thickness and significant increase in proliferating cells (p < 0.0001). DGEA mice fed a simvastatin-containing diet had an attenuated response to reflux, with a significant reduction in mucosal hyperplasia and proliferation (p < 0.0001). DGEA mice fed a simvastatin-containing diet demonstrated significant upregulation of procaspase-3 (p = 0.009) and cleaved caspase-3 (p = 0.034) in the distal esophagus. CONCLUSIONS: We demonstrate for the first time a reduction in reflux-induced histologic changes of the distal esophagus following oral administration of simvastatin in vivo. These findings identify simvastatin as a potential preventative agent to inhibit the development and progression of reflux-induced esophageal injury.


Assuntos
Adenocarcinoma , Esôfago de Barrett , Neoplasias Esofágicas , Esofagite Péptica , Refluxo Gastroesofágico , Inibidores de Hidroximetilglutaril-CoA Redutases , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Animais , Anexina A5 , Esôfago de Barrett/tratamento farmacológico , Esôfago de Barrett/patologia , Caspase 3 , Modelos Animais de Doenças , Neoplasias Esofágicas/patologia , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/patologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Camundongos , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico
3.
J Minim Access Surg ; 16(4): 438-440, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32978357

RESUMO

BACKGROUND: Endophytic submucosal masses at anatomically difficult locations such as lesser curve of the stomach, juxta-gastroesophageal junction and duodenum are challenging to resect laparoscopically due to proximity of vital structures and difficulty to visualise them. To overcome these limitations, we describe a technique of endoscopic tattooing with indocyanine green (ICG) injection into the lesion allowing easy identification and oncological resection in a minimally invasive manner. PATIENTS AND METHODS: The technique of endoscopic tattooing of the lesion and robotic transgastric eversion resection technique is described in patients with gastrointestinal tumours at difficult anatomical location. RESULTS: Gastric gastrointestinal stromal tumours at the lesser curve (n = 3) and gastroesophageal junction (n = 1) were resected using this technique successfully. CONCLUSION: The use of intraoperative ICG tattooing of endophytic submucosal lesions at difficult locations can facilitate minimally invasive oncologic resection. This technique allows the surgeon to be more comfortable to approach complex lesions safely to improve patient outcomes.

6.
Surg Endosc ; 32(4): 1834-1839, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29052065

RESUMO

BACKGROUND: Minimally invasive surgery (MIS) use for ventral hernia repair has increased over the last decade. Whether outcomes are improved by robotic assistance remains a subject of debate. The aim of this study is to evaluate outcomes (including cost, complications, length of stay (LOS), and pain medication utilization) in patients who underwent an open (OVHR), laparoscopic (LVHR), or robotic (RVHR) ventral hernia repair (VHR). METHODS: The Vizient database was queried using ICD-9 procedure and diagnosis codes for patients who underwent VHR from January 2013 to September 2015. Complications, 30-day readmission, mortality, LOS, cost, and intra-hospital opiate utilization were analyzed using IBM SPSS v.23.0.0.0. Median tests with post hoc pairwise comparisons, Fischer's exact, and Pearson's chi-squared test with Bonferroni correction were applied where appropriate, with α = 0.05. RESULTS: 46,799 patients (OVHR: N = 39,505, LVHR: N = 6829, RVHR: N = 465) met the criteria and patients in each group had similar demographics (Table 1). OVHR was associated with significant increased overall complications, 30-day readmission, LOS, and postoperative pain use compared to RVHR or LVHR. OVHR had higher mortality and postoperative infection rates than LVHR. RVHR had significantly higher rates of complications and postoperative infections compared to LVHR, although there was no difference in mortality, 30-day readmission, LOS, and postoperative pain medication use. Mean direct cost of surgery was significantly higher for RVHR, followed by OVHR and LVHR. CONCLUSIONS: Overall patient outcomes were improved in the LVHR and RVHR groups compared to the open approach. However, RVHR patients did not have significant improvement compared with the LVHR group in either short-term outcomes or opiate medication used. While RVHR surgery was the most expensive modality, OVHR was also significantly costlier than LVHR, which was the least expensive. Long-term data on recurrence could not be evaluated and should be studied to determine the role of robotic surgery in VHR and recurrence rates.


Assuntos
Hérnia Ventral/cirurgia , Herniorrafia/instrumentação , Laparoscopia , Complicações Pós-Operatórias/cirurgia , Procedimentos Cirúrgicos Robóticos , Adulto , Bases de Dados Factuais , Feminino , Herniorrafia/métodos , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/etiologia
7.
Anticancer Res ; 43(8): 3411-3418, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37500147

RESUMO

BACKGROUND/AIM: The primary mode of therapy for individuals with locally advanced esophageal adenocarcinoma (EAC) is neoadjuvant chemotherapy, commonly 5-Fluorouracil (5-FU). However, approximately 30% of these patients develop resistance to therapy. Glypican-1 (GPC-1) has been identified as one of the key drivers of chemoresistance in cancer; however, its role in EAC cells has not been explored. The objective of the present study was to evaluate the role of GPC-1 in chemoresistance to 5-FU in EAC cells. MATERIALS AND METHODS: Cell viability to 5-FU was measured with CCK-8 assay, and GPC-1 expression was validated using western blot. 5-FU resistant cell lines were generated. The effect of lentivirus-mediated GPC-1 knockdown on FLO-1 cell viability, cell cycle, and apoptosis was evaluated. RESULTS: 5-FU resistant EAC cells showed increased GPC-1 expression and knockdown of GPC-1 increased cell death and apoptosis. Importantly, the knockdown of GPC-1 enhanced the antitumor effects of 5-FU in vitro via down-regulating AKT/ERK/ß-catenin signaling. CONCLUSION: Silencing GPC-1 has the potential to augment the efficacy of 5-FU chemotherapy in resistant EAC tumors.


Assuntos
Adenocarcinoma , Fluoruracila , Humanos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Glipicanas/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Apoptose , Proliferação de Células
8.
J Gastrointest Surg ; 27(8): 1587-1593, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37237090

RESUMO

INTRODUCTION: Endoscopic transoral outlet reduction (TORe) has emerged as a safe and effective treatment option for weight regain after Roux-en-Y Gastric Bypass (RYGB). Factors that predict successful weight loss after TORe are incompletely understood. The aims of this study were to evaluate procedural factors and patient factors that may affect percent total body weight loss (%TBWL) after TORe. METHODS: A retrospective cohort study was performed on patients after TORe. The primary outcomes were %TBWL at 6 and 12 months based on four procedural factors: purse-string (PS) vs. non-purse-string (NPS) suture pattern, gastric pouch sutures (N), change in the diameter of the gastrojejunal anastomosis, and change in the length of the gastric pouch. Secondary outcomes included patient factors that affected weight loss. RESULTS: Fifty-one patients underwent TORe. Weight loss for completers was 11.3 ± 7.6% and 12.2 ± 9.2% at 6 and 12 months. There was a correlation between %TBWL and change in pouch length at 6 and 12 months and number of sutures in the pouch at 6 months. The difference in %TBWL between PS and NPS groups at 6 months (PS, n=21, 12.3 ± 8.5% and NPS, n=8, 8.7 ± 3.7%) and 12 months (PS, n=21, 13.5 ± 9.2% and NPS, n=5, 7.0 ± 7.9%) did not reach statistical significance. For secondary outcomes, depression was associated with %TBWL. CONCLUSION: Change in pouch length and number of sutures in the pouch correlated positively while depression correlated negatively with weight loss after TORe. Further studies are needed to understand these effects.


Assuntos
Derivação Gástrica , Obesidade Mórbida , Humanos , Aumento de Peso , Estudos Retrospectivos , Técnicas de Sutura , Endoscopia , Derivação Gástrica/efeitos adversos , Resultado do Tratamento , Redução de Peso , Obesidade Mórbida/cirurgia , Reoperação
9.
J Gastrointest Surg ; 27(2): 213-221, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36443554

RESUMO

INTRODUCTION: A new postoperative esophagectomy care pathway was recently implemented at our institution. Practice pattern change among provider teams can prove challenging; therefore, we sought to study the barriers and facilitators toward pathway implementation at the provider level. METHODS: This qualitative study was guided by the Theoretical Domains Framework (TDF) to study the adoption and implementation of a post-esophagectomy care pathway. Sixteen in-depth interviews were conducted with providers involved with the pathway. Matrix analysis was used to analyze the data. RESULTS: Providers included attending surgeons (n = 6), advanced practice providers (n = 8), registered dietitian (n = 1), and clinic staff (n = 1). TDF domains that were salient across our findings included knowledge, beliefs about consequences, social influences, and environmental context and resources. Identified facilitators included were electronic health record tools, such as note templates including pathway components and a pathway-specific order set, patient satisfaction, and preliminary data indicating clinical benefits such as a reduced anastomotic leak rate. The major barrier reported was a hesitance to abandon previous practice patterns, most prevalent at the attending surgeon level. CONCLUSION: The TDF enabled us to identify and understand the individuals' perceived barriers and facilitators toward adoption and implementation of a postoperative esophagectomy pathway. This analysis can help guide and improve adoption of surgical patient care pathways among providers.


Assuntos
Procedimentos Clínicos , Esofagectomia , Humanos , Pesquisa Qualitativa , Satisfação do Paciente
10.
Transl Cancer Res ; 12(11): 3129-3146, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38130302

RESUMO

Background: Studies have shown that there is a connection between estrogen receptor (ER) and glucocorticoid receptor (GR), which can impact the epithelial-mesenchymal transition (EMT) process and contribute to endocrine resistance in breast cancer. However, the specific mechanism is unclear. It is crucial to investigate this mechanism further. Methods: This study aimed to confirm the role of GR in breast cancer endocrine resistance. Based on our hypothesis, GR is linked to a gene involved in the EMT process, and thus contributes to endocrine resistance in breast cancer. We obtained survival data and GR expression data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). Additionally, we gathered GR expression data from Gene Expression Omnibus (GEO). Using Cytoscape, we constructed a protein-protein interaction (PPI) network and identified key genes. Data of Vimentin, E-cad, and Wnt/ß-catenin expression were obtained from The Cancer Genome Atlas (TCGA). We used the co-expression method to identify key proteins. UALCAN and cBioPortal were utilized to verify the function of the key protein. Results: In ER+ breast cancer, GR (P=3.12780899271121E-08) and zinc finger E-box binding homeobox 1 (ZEB1) (P=1.716157E-01) were lowly expressed and down-regulated genes of GR differentially expressed genes were enriched in cell adhesion molecules. We screened for the key protein ZEB1 and found high levels of it was positively associated with prolonged recurrence-free survival (RFS) in patients receiving endocrine therapy (P=0.0024), while high levels of E-cad were negatively associated (P=0.0038). GR expression was positively associated with ZEB1 (Spearman =0.29, P=8.50e-21), negatively associated with E-cad (Spearman =-0.13, P=5.17e-5), and negatively associated with the SETD1B (Spearman =-0.14, P=1.527e-5), a gene downstream of ZEB1. In contrast, ZEB1 expression was negatively correlated with E-cad (Spearman =-0.081, P=3.132e-3) and negatively correlated with SET domain-containing 1B (SETD1B) (Spearman =-0.177, P=9.07e-11). Conclusions: In ER+ breast cancers, GR expression is suppressed, and the EMT process is inhibited by suppressing ZEB1 expression and thus promoting E-cad expression. For the investigation of endocrine medication resistance in breast cancer, it is crucial to identify the mechanisms by how GR participates in the EMT process.

11.
Mol Cell Oncol ; 10(1): 2238873, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37649964

RESUMO

Poorly differentiated esophageal adenocarcinoma (PDEAC) has a dismal prognosis. Glypican-1(GPC-1) is known to be upregulated in several cancer types in contrast to healthy tissues, rendering it as a biomarker. Nevertheless, the potential therapeutic targeting of GPC-1 has not been explored in PDEAC. There is accumulating evidence that GPC-1, via upregulation of PI3K/Akt/ERK signaling, plays a crucial role in the progression and chemoresistance in cancer. Pictilisib, a class I pan PI3K inhibitor, has shown promising antitumor results in clinical trials, however, has not gained widespread success due to acquired drug resistance. This study investigated the role of GPC-1 in chemo-resistant PDEAC and appraises the impact of targeted silencing of GPC-1 on the antitumor effects of Pictilisib in PDEAC cell lines. Immunohistochemistry assays in PDEAC tissue specimens demonstrated a pronounced intensity of staining with GPC-1. Upregulation of GPC-1 was found to be correlated with advanced stage and poor prognosis. In-vitro studies examined the influence of GPC-1 knockdown and Pictilisib, both as individual agents and in combination, on cytotoxicity, cell cycle distribution, apoptosis, and gene expression profiles. Silencing GPC-1 alone showed significantly reduced cell viability, migration, colony formation, epithelial-mesenchymal transition, and stemness in PDEAC cells. Significantly, knockdown of GPC-1 combined with low-dose Pictilisib led to enhancement of cytotoxicity, cell cycle arrest, and apoptosis in ESO-26 and OE-33 cells. In the xenograft mouse model, the combination of Pictilisib and GPC-1 knockdown exhibited synergy. These findings suggest that GPC-1 represents a promising target to augment chemosensitivity in esophageal adenocarcinoma.

12.
Surg Laparosc Endosc Percutan Tech ; 32(3): 404-408, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35648420

RESUMO

INTRODUCTION: Data is limited on hybrid transoral incisionless fundoplication (TIF) and hiatal hernia repair in giant paraoesophageal hernia (GPEH). We aimed to assess the safety, patient satisfaction, and symptom resolution following a hybrid paraoesophageal hernia (PEH) repair and TIF in patients with GPEH. PATIENTS AND METHODS: All single-session hybrid TIF combined with minimally invasive PEH repair performed between February 2020 and June 2021 were evaluated. Procedures were performed in the operating room under general anesthesia with robotic or laparoscopic PEH repair followed by TIF. RESULTS: Twelve patients underwent combined surgical hiatal hernia repair and TIF. Primary presenting symptoms included heartburn (75.0%), dysphagia (41.7%), and chronic anemia from Cameron's ulcers (16.7%). The mean hernia defect size was 5.0 cm (range 3.0 to 6.0 cm). Hiatal hernia repairs were performed robotically in 7 patients and laparoscopically in 5 patients. The total mean operative time was 254 minutes (range: 180 to 390 min). One patient reported postoperative dysphagia requiring endoscopic dilation postdischarge with a resolution of symptoms. No gas-bloat symptoms were reported. All patients reported complete resolution of presenting symptoms at the time of follow-up. Postoperative mean follow-up for 4 patients at 6 months with upper endoscopy and pH testing showed an intact valve with no evidence of esophagitis or acid reflux. CONCLUSIONS: In our experience, hybrid hiatal hernia repair and TIF is a safe and effective therapeutic option for patients with GPEH. This hybrid procedure allows for more expeditious completion of the repair and results in lower rates of postfundoplication dysphagia and gas-bloat. Furthermore, this approach requires a less extensive surgical dissection on the greater curvature of the stomach, thereby minimizing the risk of vagal nerve injury and bleeding from the short gastric vessels.


Assuntos
Transtornos de Deglutição , Hérnia Hiatal , Assistência ao Convalescente , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Fundoplicatura/métodos , Hérnia Hiatal/cirurgia , Herniorrafia , Humanos , Alta do Paciente , Estômago/cirurgia
13.
Semin Thorac Cardiovasc Surg ; 34(4): 1324-1335, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34534678

RESUMO

Dysregulation of toll-like receptor (TLR) signaling within the gastrointestinal epithelium has been associated with uncontrolled inflammation and tumorigenesis. We sought to evaluate the role of TLR4 in the development of gastroesophageal reflux-mediated inflammation and mucosal changes of the distal esophagus. Verified human esophageal Barrett's cells with high grade dysplasia (CPB) and esophageal adenocarcinoma cells (OE33) were treated with deoxycholic acid for 24 hours. Cells were pretreated with a TLR4-specific inhibitor peptide 2 hours prior to deoxycholic acid treatment. Inflammatory markers were evaluated using immunoblotting and enzyme-linked immunosorbent assay. A surgical reflux mouse model was generated by performing a side-to-side anastomosis between the second portion of the duodenum and the gastroesophageal junction. Control animals underwent laparotomy with incision and closure of the esophagus superior to the gastroesophageal junction (sham procedure). Esophageal sections were evaluated using hematoxylin and eosin staining and immunohistochemistry. Deoxycholic acid increased expression of inflammatory markers including intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin 8. Pretreatment with a TLR4 inhibitor significantly decreased deoxycholic acid-induced inflammatory marker expression. C3H/HeNCrl mice demonstrated a significant increase in mucosal hyperplasia and proliferation following DGEA compared to sham procedure. TLR4 mutant mice (C3H/HeJ) undergoing DGEA demonstrated an attenuated hyperplastic and proliferative response compared to C3H/HeNCrl mice. Inhibition of TLR4 signaling attenuates reflux-induced inflammation in vivo. These findings identify TLR4 inhibition as a potential therapeutic target to halt the progression of pathologic esophageal changes developing in the setting of chronic gastroesophageal reflux disease.


Assuntos
Esôfago de Barrett , Neoplasias Esofágicas , Refluxo Gastroesofágico , Camundongos , Humanos , Animais , Receptor 4 Toll-Like , Camundongos Endogâmicos C3H , Resultado do Tratamento , Neoplasias Esofágicas/patologia , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/patologia , Inflamação/complicações , Ácido Desoxicólico , Esôfago de Barrett/complicações , Esôfago de Barrett/metabolismo
14.
J Gastrointest Oncol ; 13(5): 2082-2104, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388647

RESUMO

Background: Glypican 1 (GPC1) is a heparan sulphate proteoglycan cell membrane protein. It is implicated in driving cancers of the breast, brain, pancreas, and prostate; however, its role in esophagogastric cancer (EGAC) remains unexplored. The aim of the study was to investigate and elucidate the molecular mechanistic of GPC1 in human EGAC. Methods: Thirty tissue and 120 microarray sections of EGAC were evaluated with Anti-GPC1 immunohistochemistry. Loss and gain of GPC1 function were performed using lentivirus transfection in EGAC cell lines. Mechanistically, AKT/GSK/ß-catenin pathway was evaluated using AKT inhibitor MK-2206 and Wnt/ß-catenin stimulant LiCl. Results: GPC1 overexpression was found in 102 cases (68%). Overexpression of GPC1 correlated with lymph node metastasis, poor differentiation and decreased overall survival. Lentivirus mediated GPC1 knockdown resulted in decreased cell proliferation, migration, invasion, and colony formation. Knockdown caused G0/G1 cell cycle arrest, increased apoptosis, and reduced epithelial mesenchymal transition (EMT). GPC1 mediated its effects by activation of AKT/GSK/ß-catenin pathway. Conclusions: This is the first descriptive study to decipher the role of GPC1 in EGAC. Our results suggest that GPC1 regulates cell proliferation and growth and may serve as an attractive oncotarget in EGAC.

15.
Mol Pharm ; 8(3): 958-68, 2011 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-21491930

RESUMO

Cholestasis is a significant risk factor for immediate hepatic failure due to ischemia reperfusion (I/R) injury in patients undergoing liver surgery or transplantation. We recently demonstrated that inhibition of Hedgehog (Hh) signaling with cyclopamine (CYA) before I/R prevents liver injury. In this study we hypothesized that Hh signaling may modulate I/R injury in cholestatic rat liver. Cholestasis was induced by bile duct ligation (BDL). Seven days after BDL, rats were exposed to either CYA or vehicle for 7 days daily before being subjected to 30 min of ischemia and 4 h of reperfusion. Expression of Hh ligands (Sonic Hedgehog, Patched-1 and Glioblastoma-1), assessment of liver injury, neutrophil infiltration, cytokines, lipid peroxidation, cell proliferation and apoptosis were determined. Significant upregulation of Hh ligands was seen in vehicle treated BDL rats. I/R injury superimposed on these animals resulted in markedly elevated serum alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin accompanied with increased neutrophil recruitment and lipid peroxidation. Preconditioning with CYA reduced the histological damage and serum liver injury markers. CYA also reduced neutrophil infiltration, proinflammatory cytokines such as TNF-α and IL-1ß expression of α-smooth muscle actin and type 1 collagen resulting in reduced fibrosis. Furthermore CYA treated animals showed reduced cholangiocyte proliferation, and apoptosis. Hepatoprotection by CYA was conferred by reduced activation of protein kinase B (Akt) and extracellular signal regulated kinase (ERK). Endogenous Hh signaling in cholestasis exacerbates inflammatory injury during liver I/R. Blockade of Hh pathway represents a clinically relevant novel approach to limit I/R injury in cholestatic marginal liver.


Assuntos
Colestase/complicações , Hepatopatias/tratamento farmacológico , Traumatismo por Reperfusão/tratamento farmacológico , Alcaloides de Veratrum/uso terapêutico , Animais , Interleucina-1beta/metabolismo , Ligadura , Ratos , Traumatismo por Reperfusão/etiologia , Fator de Necrose Tumoral alfa/metabolismo
17.
Gastrointest Endosc Clin N Am ; 31(1): 205-218, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33213796

RESUMO

The management of Barrett's-related neoplasia has benefited from advances in endoscopic assessment, resection, and ablation, along with improved pathologic and radiographic staging. The development of specialized, high-volume esophageal multidisciplinary teams, with improvements in patient selection, preparation, perioperative care, minimally invasive operative approaches, and enhanced recovery after surgery programs, has contributed to improved outcomes for patients undergoing esophagectomy for Barrett's-related neoplasia.


Assuntos
Esôfago de Barrett/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagoscopia/métodos , Esôfago/cirurgia , Esôfago de Barrett/complicações , Neoplasias Esofágicas/etiologia , Humanos
18.
J Robot Surg ; 15(5): 821-826, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33389628

RESUMO

Morgagni hernia (MH) is a rare diaphragmatic hernia which needs surgical repair. The conventional reconstruction involves reduction of hernia, closure of the defect and placement of an intraperitoneal onlay mesh often using robotic platform for ease of dissection and suturing the mesh (r-IPOM). We propose a novel robotic preperitoneal repair (r-TAPP) of MH in four cases and compare them with conventional r-IPOM technique. Between August 2017 and August 2020 nine patients underwent repair of MH. Five cases underwent repair by r-IPOM (group I). For the other four cases, r-TAPP was used (group II). Among the nine cases, the mean age was 53 years in group I and 55 years in group II, mean defect size was 33 mm in group I and 55 mm in group II. Operative time was longer in group II compared to group I (220 min vs 135 min, p = 0.022). Mean length of hospital stay was 1.3 days in group I compared to group II (4.5 and 4.5 vs 1.3 days, p = 0.03). There was statistically significant difference in reduced post-operative pain and time to return to work in group II compared to group I. There was no difference in complications, 30-day readmissions or recurrence of hernia between the two groups. We conclude that compared to the conventional r-IPOM repair, the r-TAPP technique is associated with less pain, early discharge, and faster return to work, translating into overall cost savings for the hospital.


Assuntos
Hérnia Inguinal , Hérnias Diafragmáticas Congênitas , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Hérnia Inguinal/cirurgia , Hérnias Diafragmáticas Congênitas/cirurgia , Herniorrafia , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Telas Cirúrgicas
19.
Surg Laparosc Endosc Percutan Tech ; 31(3): 385-388, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33655895

RESUMO

INTRODUCTION: Approximately 5% of patients who have undergone prior Heller myotomy and Roux en Y gastric bypass progress to end-stage achalasia (ESA). Surgical options for ESA are often limited to esophagectomy for management of severe dysphagia or life-threatening aspiration episodes. Mediastinoscopy-assisted transhiatal esophagectomy (MATHE) by a small left neck incision combined with an abdominal incision, without using a transthoracic approach, has been reported to reduce pulmonary complications. We herein present the first report of MATHE in 2 consecutive patients with ESA and gastric bypass. MATERIALS AND METHODS: Between August 2017 and September 2020, 2 patients who had undergone Heller myotomy and Roux en Y gastric bypass underwent MATHE for ESA. Transhiatal esophagectomy with mediastinoscopy-assisted dissection was performed. The remnant stomach was used as the conduit in both cases. The embedded Supplemental Digital Content 1 (http://links.lww.com/SLE/A269) reports our novel technique. RESULTS: Both cases were completed laparoscopically without conversion to laparotomy or thoracotomy. Median length of hospital stay was 9 days (range, 6 to 11 d). Postoperatively, 1 patient developed a cervical anastomotic leak, which healed with conservative management. No other major complications were observed. CONCLUSIONS: MATHE can be safely performed in patients with a history of gastric bypass and ESA without requiring thoracoscopic mobilization of the esophagus. Further studies are required to validate reproducibility of our technique as an alternative to using a thoracic incision.


Assuntos
Acalasia Esofágica , Neoplasias Esofágicas , Derivação Gástrica , Acalasia Esofágica/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Mediastinoscopia , Reprodutibilidade dos Testes
20.
Asian J Endosc Surg ; 14(3): 648-652, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33200531

RESUMO

INTRODUCTION: Morgagni hernia (MH) is a rare, congenital diaphragmatic hernia. We developed a novel robotic-assisted technique to repair MH which enables dissection into the preperitoneal space, facilitating closure of the diaphragmatic defect and placement of a synthetic mesh. MATERIALS AND SURGICAL TECHNIQUE: Between August 2017 and August 2020, 8 consecutive patients with MH were repaired by robotic-assisted transabdominal preperitoneal (r-TAPP) approach. A preperitoneal plane is developed at the level of the falciform ligament and extended toward the diaphragmatic defect. The pocket is dissected inferior to the defect to allow 3 to 5 cm overlap of synthetic mesh. Excision of the hernia sac followed by closure of defect is performed. A synthetic mesh is deployed in the preperitoneal space with wide overlap. This technique using the robot provides superior optics and ergonomics for dissection while isolating the mesh from underlying viscera and avoiding the need for suturing or tacking of the mesh. Data of patients who underwent r-TAPP were reviewed. Mean operating time was 113 minutes. Mean pain visual analog scale score was 5/2 on post-operative days 1/7. Average hospital stay was 1.8 days. One patient developed superficial cellulitis related to the abdominal drain. There were no procedure-related complications, 30-day readmissions, or hernia recurrences at a mean follow-up of 10 months. DISCUSSION: A robotic-assisted preperitoneal approach is a novel, safe, and anatomically justified alternative technique for MH repair that may lead to improved post-operative outcomes.


Assuntos
Hérnias Diafragmáticas Congênitas , Herniorrafia/métodos , Procedimentos Cirúrgicos Robóticos , Idoso , Feminino , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Peritônio/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Telas Cirúrgicas
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