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1.
Surg Endosc ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39271509

RESUMEN

BACKGROUND: Although per oral endoscopic myotomy (POEM) has shown to be beneficial for the treatment of achalasia, it can be difficult to predict who will have a robust and long-lasting response. Historically, it has been shown that higher lower esophageal sphincter pressures have been associated with poorer responses to alternative endoscopic therapies such as Botox therapy and pneumatic dilation. This study was designed to evaluate if modern preoperative manometric data could similarly predict response to therapy after POEM. METHODS: This was a retrospective study of 237 patients who underwent POEM at a single institution over a period of 13 years (2011-2023) and who had a high-resolution manometry performed preoperatively and an Eckardt symptom score performed both preoperative and postoperatively. The achalasia type and integrated relaxation pressures (IRP) were tested for potential correlation with the need for any further achalasia interventions postoperatively as well as the degree of Eckardt score reduction using a linear regression model. RESULTS: The Achalasia type on preoperative manometry was not predictive for further interventions or degree of Eckardt score reduction (p = 0.76 and 0.43, respectively). A higher IRP was not predictive of the need for further interventions, however, it was predictive of a greater reduction in postoperative Eckardt scores (p = 0.03) as shown by the non-zero regression slope. CONCLUSION: In this study, achalasia type was not a predictive factor in the need for further interventions or the degree of symptom relief. Although IRP was not predictive of the need for further interventions, a higher IRP did predict better symptomatic relief postoperatively. This result is opposite that of other endoscopic treatment modalities (Botox and pneumatic dilation). Therefore, patients with higher IRP on preoperative high-resolution manometry would likely benefit from POEM which provides significant symptomatic relief postoperatively.

2.
Surg Endosc ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107480

RESUMEN

BACKGROUND: It has been reported that higher surgeon experience leads to better patient outcomes. In this study, we look at surgeon experience and its association with postoperative outcomes and variation among the practice of surgeons performing paraesophageal hernia repairs (PEH). METHOD: This was a retrospective study of 1155 patients who underwent PEH repair at a single institution (2010-2023). Surgeon experience was defined as the number of surgeries performed per surgeon and was split using the median surgeries (n = 100), with surgeons performing at or above the median categorized as high-experience and below the median as low-experience surgeons. A multivariable logistic regression model was used to test correlation between surgeon experience and variables, including demographics and intra- and post-operative outcomes. RESULTS: High-experience surgeons performed more elective cases (93.4% vs 85.5%), but low-experience surgeons operated more on emergent (2.7% vs 0.9%), semi-elective (2.3% vs 1.4%), and urgent cases (9.5% vs 4.3%). Low-experience surgeons operated more on patients who were older (67.5 vs 63.2 years, p < 0.001) and had an increased risk of CVD (72.9% vs 61.5%, p < 0.001). Intraoperative OR time was considerably less for high-experience surgeons (115.8 vs 172.9 min, p < 0.001). Low-experience surgeons had increased risk of intra-operative complications (4.5% vs 1.8%, p = 0.021) and post-op pneumonia within 30 days (1.8% vs 0.3%). However, long-term outcomes such as hernia recurrence (OR: 1.10, CI: 0.78-1.54) and redo-operations for hiatal hernia (OR: 1.10, CI: 0.65-1.75) were similar for both groups. CONCLUSION: High-experience surgeons perform more complex revisional surgeries in less time with fewer complications. Low-experience surgeons operated more on patients with higher comorbidities but had significantly higher OR times. Long-term results of recurrence and redo-operations were comparable. These variations suggest that high-experience surgeons are more efficient while operating on more complex cases. These findings have pivotal implications to facilitate mentorship and education among less-experienced surgeons.

3.
Surg Endosc ; 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160310

RESUMEN

BACKGROUND: Gastroparesis can be a debilitating disease process for which durable treatment options are lacking. While dietary changes and pharmacotherapy have some efficacy, symptoms frequently recur and some patients progress to needing supplemental enteral feeding access. Per oral pyloromyotomy (POP) has been shown to be a durable minimally invasive treatment option for refractory gastroparesis with a low side effect profile, and therefore has been performed at this institution for the past 6 years. METHODS: This was a retrospective case series of all patients who underwent a POP at a single institution over a 6-year period (2018-2023). Patient demographics, preoperative symptomatology and subsequent workup, postoperative complications, and symptom recurrence were collected and analyzed. RESULTS: There were 56 patients included in the study. There was a 1.8:1 female:male ratio. The average patient age was 56 years old (range 23-85). The average duration of symptoms was 1-3 years. Thirty-eight percent of patients had undergone previous endoscopic therapy for gastroparesis (pyloric botox injection or pyloric dilation) and 16% of patients underwent multiple endoscopic therapies. Twenty-nine percent of patients were on a medication for gastroparesis. Past surgery was the most common gastroparesis etiology for POP (50% of patients). Diabetes (23%) and idiopathic (19%) were the other most common gastroparesis etiologies for POP. Nausea was the most common symptom at first follow-up (30%) but these patients continued to improve with 14% of patients continuing to endorse nausea at 6 months. Twenty-seven percent of patients developed symptom recurrence. Forty percent of patients with symptom recurrence underwent a repeat endoscopic or surgical therapy. CONCLUSIONS: In this present study, POP leads to durable results in approximately 75% of patients with minimal complications. Furthermore, the majority of patients who do develop symptom recurrence do not require additional gastroparesis interventions.

4.
Surg Endosc ; 38(9): 5253-5258, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38997454

RESUMEN

BACKGROUND: Per oral endoscopic myotomy (POEM) is a safe therapy for the treatment of achalasia. Long-term effects of untreated achalasia include worsening dysmotility and disruptions in esophageal anatomy, i.e., tortuosity and dilation. We hypothesize that long-standing achalasia prior to intervention will have worse outcomes following POEM than in patients with symptoms for shorter duration. METHODS: We retrospectively analyzed achalasia patients who underwent POEM at our institution from 2011 to 2023, categorizing them into symptom duration cohorts (< 1 year, 1-3 years, 4-10 years, > 10 years). Inclusion criteria comprised patients with documented achalasia diagnosis who received POEM treatment at our facility. Exclusion criteria encompassed individuals lacking data pertaining to achalasia diagnosis, the time frame before intervention, or those missing pre and postoperative Eckardt scores. POEM failure was defined as symptom recurrence, necessity for repeat intervention, or high postoperative Eckardt score. We compared demographic, preoperative, and postoperative outcomes across these cohorts, and employed multivariable logistic regression to explore the link between symptom duration and POEM response. RESULTS: During the study period, in our increased cohort 234 patients met inclusion criteria. 75 patients had symptoms for < 1 year, 78 patients had symptoms from 1 to 3 years, 47 patients had symptoms from 4 to 10 years, and 34 patients had symptoms > 10 years. Patient demographics such as age, sex, BMI, Charleson-Deyo-Comorbidity-Index, and diabetes did not differ amongst cohorts. High-resolution manometry data, including achalasia type, Median IRP, LES residual pressure, and Basal LES pressure did not differ between groups. Preoperative Eckardt scores ranged from 4 to 5 across groups (p 0.24). Patients endorsed an average of three total preoperative symptoms across groups (p 0.13). Patients with symptoms greater than 4 years had significantly more endoscopic interventions prior to POEM (37% vs, 68% p .001). There was no significant difference in post-procedure mean Eckardt scores between cohorts. All cohorts experienced the same number of post-POEM symptoms. Post-POEM manometric measurements remained consistent across cohorts. Similarly, there were no significant differences in terms of symptom recurrence, requirement for repeat interventions, or repeat POEM among the cohorts. Multivariable logistic regression analysis determined achalasia symptoms greater than a decade did not result in increased odds of having a higher postoperative Eckardt score, worse dysphagia, regurgitation, or weight loss. CONCLUSIONS: In this increased cohort, this data once again suggests that longer symptom duration is not associated with increased rates of POEM failure.


Asunto(s)
Acalasia del Esófago , Humanos , Acalasia del Esófago/cirugía , Acalasia del Esófago/fisiopatología , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Resultado del Tratamiento , Factores de Tiempo , Adulto , Miotomía/métodos , Anciano , Cirugía Endoscópica por Orificios Naturales/métodos , Recurrencia , Manometría , Esofagoscopía/métodos
5.
Surg Endosc ; 38(9): 5148-5152, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39039293

RESUMEN

INTRODUCTION: The routine use of post-operative esophogram has come under evaluation for multiple upper GI surgeries such as with bariatric surgery and gastric resections. A major complication following Per Oral Endoscopic Myotomy (POEM) is a leak from the myotomy site. A post-operative contrast esophogram is often utilized to evaluate the presence of a leak, however it is not a standardized care practice for all patients. Presently it is selectively performed depending on physician assessment intra-operatively. This project will evaluate the necessity of post-operative contrast esophogram following POEM. MATERIALS AND METHODS: We retrospectively reviewed 277 patients diagnosed with achalasia who underwent POEM by two surgeons from 2011 to 2022. 173 patients met the inclusion criteria. A post-operative esophogram was used for the evaluation of a leak. Post-operative esophagram were selectively performed on day 1 following surgery using a water-soluble material. Data was evaluated using Stata. RESULTS: There were 3 detected leaks in the group that underwent esophagrams compared to the non-esophagram group in the early post-operative period. The overall complication rate was 5.5% in the non-esophagram versus 7.9% in the esophagram group. Length of stay was 1.48 days in the non-UGI vs 1.76 days in the esophagram group. Readmission rate was 10.9% in non-esophagram versus 8.7% in esophagram group. CONCLUSION: There was no statistically significant difference in outcomes in patients undergoing POEM who received post-operative esophagram verses patients who did not receive post-operative esophagram. The routine use of a contrast esophogram to detect a leak following POEM may not be justified. This study suggests that esophagrams should be performed depending on the clinical signs/symptoms post-operatively that would warrant imaging and intervention.


Asunto(s)
Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Humanos , Estudios Retrospectivos , Femenino , Masculino , Acalasia del Esófago/cirugía , Persona de Mediana Edad , Adulto , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Cirugía Endoscópica por Orificios Naturales/métodos , Miotomía/métodos , Miotomía/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Anciano , Medios de Contraste , Tiempo de Internación/estadística & datos numéricos , Fuga Anastomótica/etiología
7.
Surg Endosc ; 37(10): 8000-8005, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37460816

RESUMEN

INTRODUCTION: Per oral endoscopic myotomy (POEM) is a relatively novel technique to address achalasia; however, little is known about the efficacy of POEM for patients with long-standing achalasia. We hypothesize that patients with long-standing achalasia prior to intervention will be more recalcitrant to POEM than patients with symptoms for a short duration. METHODS: We performed a retrospective analysis of patients with achalasia who received a POEM at a single institution from 2012 to 2022. Patients were grouped into cohorts based on the time of symptom duration: < 1 year, 1-3 years, 4-10 years, > 10 years. POEM failure was defined as need for repeat intervention, symptom recurrence, and a high postoperative Eckart score. Demographic and clinical data were compared between cohorts. Measures of failure multivariable logistic regression analyzed the association between symptom duration and response to POEM. RESULTS: During the study period, 132 patients met inclusion criteria. Patient age at surgery, sex, BMI, Charleston-Deyo Comorbidity Index, and patients with diabetes with and without end organ complications, connective tissue diseases, and patients with ulcer diseases did not differ among cohorts. Patients who have had symptoms for greater than 10 years had significantly more endoscopic interventions prior to their POEM (30% vs, 60% p = 0.002). Patients in all cohorts experienced the same number of symptoms post-POEM. Manometric measurements did not vary across cohorts after POEM. Symptom recurrence, need for repeat endoscopic intervention, repeat surgical intervention, or repeat POEM also did not vary across cohorts. Having symptoms of achalasia > 10 years did not increase the odds POEM failure on multivariable logistical regression. CONCLUSIONS: These data suggest that longer symptom duration is not associated with increased rates of POEM failure. This is promising as clinicians should not exclude patients for POEM eligibility based on duration of symptoms alone.


Asunto(s)
Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Humanos , Acalasia del Esófago/cirugía , Acalasia del Esófago/diagnóstico , Estudios Retrospectivos , Cirugía Endoscópica por Orificios Naturales/métodos , Manometría/métodos , Miotomía/métodos , Resultado del Tratamiento , Esfínter Esofágico Inferior/cirugía
8.
J Immunother Cancer ; 11(6)2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37399354

RESUMEN

BACKGROUND: Efforts to modulate the function of tumor-associated myeloid cell are underway to overcome the challenges in immunotherapy and find a cure. One potential therapeutic target is integrin CD11b, which can be used to modulate the myeloid-derived cells and induce tumor-reactive T-cell responses. However, CD11b can bind to multiple different ligands, leading to various myeloid cell functions such as adhesion, migration, phagocytosis, and proliferation. This has created a major challenge in understanding how CD11b converts the differences in the receptor-ligand binding into subsequent signaling responses and using this information for therapeutic development. METHODS: This study aimed to investigate the antitumor effect of a carbohydrate ligand, named BG34-200, which modulates the CD11b+ cells. We have applied peptide microarrays, multiparameter FACS (fluorescence-activated cell analysis) analysis, cellular/molecular immunological technology, advanced microscopic imaging, and transgenic mouse models of solid cancers, to study the interaction between BG34-200 carbohydrate ligand and CD11b protein and the resulting immunological changes in the context of solid cancers, including osteosarcoma, advanced melanoma, and pancreatic ductal adenocarcinoma (PDAC). RESULTS: Our results show that BG34-200 can bind directly to the activated CD11b on its I (or A) domain, at previously unreported peptide residues, in a multisite and multivalent manner. This engagement significantly impacts the biological function of tumor-associated inflammatory monocytes (TAIMs) in osteosarcoma, advanced melanoma, and PDAC backgrounds. Importantly, we observed that the BG34-200-CD11b engagement triggered endocytosis of the binding complexes in TAIMs, which induced intracellular F-actin cytoskeletal rearrangement, effective phagocytosis, and intrinsic ICAM-1 (intercellular adhesion molecule I) clustering. These structural biological changes resulted in the differentiation in TAIMs into monocyte-derived dendritic cells, which play a crucial role in T-cell activation in the tumor microenvironment. CONCLUSIONS: Our research has advanced the current understanding of the molecular basis of CD11b activation in solid cancers, revealing how it converts the differences in BG34 carbohydrate ligands into immune signaling responses. These findings could pave the way for the development of safe and novel BG34-200-based therapies that modulate myeloid-derived cell functions, thereby enhancing immunotherapy for solid cancers.


Asunto(s)
Melanoma , Osteosarcoma , Neoplasias Pancreáticas , Ratones , Animales , Ligandos , Células Mieloides , Inmunoterapia , Diferenciación Celular , Microambiente Tumoral , Neoplasias Pancreáticas
9.
Surg Endosc ; 37(9): 7226-7229, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37389740

RESUMEN

BACKGROUND: While per oral endoscopic myotomy (POEM) has been shown to be efficacious in the treatment of achalasia, it can be difficult to predict who will have a robust and durable response. Historically, high lower esophageal sphincter pressures have been shown to predict a worse response to endoscopic therapies such as botox therapy. This study was designed to evaluate if modern preoperative manometric data could predict a response to therapy after POEM. METHODS: This was a retrospective study of 144 patients who underwent a POEM at a single institution by a single surgeon over an 8-year period (2014-2022) who had high-resolution manometry performed preoperatively and had an Eckardt symptom score performed both preoperatively and postoperatively. The achalasia type and integrated relaxation pressures (IRP) were then tested for potential correlation with need for any further achalasia interventions postoperatively as well as the degree of Eckardt score reduction using univariate analysis. RESULTS: The achalasia type on preoperatively manometry was not predictive of need for further interventions or degree of Eckardt score reduction (p = 0.74 and 0.44, respectively). A higher IRP was not predictive of need for further interventions however it was predictive of a greater reduction in postoperative Eckardt scores (p = 0.03) as shown by a nonzero regression slope. CONCLUSION: In this study, achalasia type was not a predictive factor in need for further interventions or degree of symptom relief. While IRP was not predictive of need for further interventions, a higher IRP did predict better symptomatic relief postoperatively. This result is opposite that of other endoscopic treatment modalities. Therefore, patients with higher IRP on high-resolution manometry would likely benefit from myotomy which provides significant symptomatic relief postoperatively.


Asunto(s)
Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Humanos , Acalasia del Esófago/diagnóstico , Esfínter Esofágico Inferior/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Esofagoscopía
10.
Surg Endosc ; 37(9): 7153-7158, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37328594

RESUMEN

BACKGROUND: Studies assessing outcomes of patients undergoing peroral endoscopic myotomy (POEM) after botulinum injection or dilation have had various results with respect to failure, although this has not been differentiated between lack of clinical response and recurrence. We hypothesize that patients with previous endoscopic intervention(s) are more likely to recur than treatment-naïve patients. METHODS: This is a retrospective cohort study of patients that underwent POEM for achalasia at a single tertiary care center between 2011 and 2022. Patients were excluded if they had previous myotomy (POEM or Heller). The remaining patients were stratified into treatment-naïve patients (TN), those with previous botulinum injection (BTX), those with previous dilatation (BD), and those with both previous endoscopic interventions (BOTH). Primary outcome was recurrence indicated by clinical symptoms or need for repeat endoscopic intervention or surgery after originally having clinical resolution (Eckardt ≤ 3). Multivariate logistic regression using preoperative and intraoperative factors was completed to assess odds of recurrence. RESULTS: A total of 164 patients were included in the analysis, 90 TN, 34 BD, 28 BTX, and 12 BOTH. There were no other significant differences in demographics or in preoperative Eckardt score (p = 0.53). There was no difference in the proportion of patients that had postoperative manometry (p = 0.74), symptom recurrence (p = 0.59), surgical intervention (p = 0.16). BTX (14.3%) and BOTH (16.7%) patients had a higher rate of repeat endoscopic intervention than BD and TN patients (5.9% and 1.1%). In the logistic regression analysis, there was no association among the BTX, BD, or BOTH groups compared to the TN group. No odds ratios achieved statistical significance. CONCLUSIONS: There were no increased likelihood of recurrence with botulinum injection or dilatation prior to POEM, implying that they are similarly good candidates compared to treatment-naïve patients.


Asunto(s)
Acalasia del Esófago , Miotomía , Cirugía Endoscópica por Orificios Naturales , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Endoscopía , Acalasia del Esófago/cirugía , Acalasia del Esófago/diagnóstico , Miotomía/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Esfínter Esofágico Inferior/cirugía
11.
Surg Endosc ; 37(9): 7178-7182, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37344752

RESUMEN

BACKGROUND: Per oral endoscopic myotomy (POEM) has been shown to be an efficacious and safe therapy for the treatment of achalasia. Compared to laparoscopic Heller myotomy however, no antireflux procedure is routinely combined with POEM and therefore the development of symptomatic or silent reflux is of concern. This study was designed to determine if various patient factors and anatomy would predict the development of gastroesophageal reflux disease post-operatively. METHODS: This was a retrospective cohort study of all patients who underwent a POEM at a single institution by a single surgeon over an eight-year period (2014-2022). It has been our practice to obtain a postoperative ambulatory pH test on all patients 6 months after POEM off all acid reducing medications. Patients without a postoperative ambulatory esophageal pH monitoring test were excluded. Age, sex, obesity (BMI > 30), achalasia type, presence of a hiatal hernia, history of prior endoscopic achalasia treatments or myotomy were analyzed using univariate analysis as predictive factors for the development of postoperative GERD (DeMeester score > 14.7 on ambulatory pH monitoring). RESULTS: There were 179 total patients included in the study with 42 patients (23.5%) having undergone postoperative ambulatory pH testing. The majority of patients (137 or 76.5%) were lost to follow up and did not undergo ambulatory pH testing. Twenty-three out of those 42 patients (55%) had evidence of GERD on ambulatory pH testing. Multiple preoperative patient characteristics including demographics, manometric results, EGD findings, and history of prior achalasia interventions did not correlate with the development of post-operative GERD. CONCLUSIONS: Despite the high rate of reflux after POEM, there does not appear to be any reliable preoperative indicators of which patients have a higher risk of developing post-operative GERD after POEM.


Asunto(s)
Acalasia del Esófago , Reflujo Gastroesofágico , Miotomía , Cirugía Endoscópica por Orificios Naturales , Humanos , Acalasia del Esófago/cirugía , Estudios Retrospectivos , Reflujo Gastroesofágico/etiología , Fundoplicación/métodos , Miotomía/métodos , Esofagoscopía/métodos , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Cirugía Endoscópica por Orificios Naturales/métodos , Resultado del Tratamiento , Esfínter Esofágico Inferior/cirugía
12.
Surg Endosc ; 37(9): 6791-6797, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37253871

RESUMEN

BACKGROUND: Although obesity is an established risk factor for adverse outcomes after paraesophageal hernia repair (PEHR), many obese patients nonetheless receive PEHR. The purpose of this study was to explore risk factors for adverse outcomes of PEHR among this high-risk cohort. We hypothesized that obese patients may have other risk factors for adverse outcomes following PEHR. METHODS: A retrospective study of adult obese patients who underwent minimally invasive PEHR from 2017 to 2019 was performed. Patients were excluded for BMI < 30 or if they had concomitant bariatric surgery at time of PEHR. The primary outcome of interest was a composite adverse outcome (CAO) defined as having any of the four following outcomes after PEHR: persistent GERD > 30 d, persistent dysphagia > 30 d, recurrence, or reoperation. Chi-square and t-test analysis was used to compare demographic and clinical characteristics. Multivariable logistic regression analysis was used to evaluate independent predictors of CAO. RESULTS: In total, 139 patients met inclusion criteria with a median follow-up of 19.7 months (IQR 8.8-81). Among them, 51/139 (36.7%) patients had a CAO: 31/139 (22.4%) had persistent GERD, 20/139 (14.4%) had persistent dysphagia, 24/139 (17.3%) had recurrence, and 6/139 (4.3%) required reoperation. On unadjusted analysis, patients with a CAO were more likely to have a history of prior abdominal surgery (86.3% vs 70.5%, p = 0.04) and were less likely to have undergone a preoperative CT scan (27.5% vs 45.5%, p = 0.04). On multivariable analysis, previous abdominal surgery was independently associated with an increased likelihood of CAO whereas age and preoperative CT scan had a decreased likelihood of CAO. CONCLUSIONS: Although there were adverse outcomes among obese patients, minimally invasive PEHR may be feasible in a subset of patients at specialized centers. These findings may help guide the appropriate selection of obese patients for PEHR.


Asunto(s)
Trastornos de Deglución , Reflujo Gastroesofágico , Hernia Hiatal , Laparoscopía , Adulto , Humanos , Hernia Hiatal/complicaciones , Hernia Hiatal/cirugía , Estudios Retrospectivos , Trastornos de Deglución/etiología , Laparoscopía/efectos adversos , Obesidad/cirugía , Factores de Riesgo , Herniorrafia/efectos adversos , Recurrencia , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/cirugía , Resultado del Tratamiento
13.
Cancers (Basel) ; 14(23)2022 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-36497393

RESUMEN

High levels of myeloid-derived cells are characteristic of the tumor microenvironment (TME) of advanced melanoma. These cells interact with tumor cells to suppress the development of antitumor immune responses, regulate tumor metastasis, and drive cancer's resistance to virtually all types of therapy. Therefore, methods to disrupt tumor-associated myeloid cell function are actively being sought to find a cure. Our team has recently developed a plant-derived carbohydrate molecule, BG34-200, that modulates tumor-associated myeloid cells by targeting the cell surface receptor CD11b. In this study, we found that BG34-200 IV administration could significantly inhibit tumor growth and improve survival in B16F10 mice with advanced melanoma. Our data supported a model that the entry of BG34-200 into circulating melanoma tumor-associated inflammatory monocytes (TAIMs) could trigger a sequential immune activation: the BG34-200+ TAIM subsets migrated to tumor and differentiated into monocyte-derived dendritic cells (mo-DCs); then, the BG34-200+ mo-DCs migrated to tumor draining lymph nodes, where they triggered the generation of tumor-antigen-specific T cells. Based upon these results, we combined BG34-200 treatment with adoptive transfer of TdLN-derived T cells to treat advanced melanoma, which significantly improved animal survival and helped tumor-free survivors be resistant to a second tumor-cell challenge. The scientific findings from this study will allow us to develop new technology and apply BG34-200-based immunotherapy to patients with advanced melanoma who have not responded to current standard of care therapies with and without immunotherapy.

14.
Ann Surg Oncol ; 28(11): 6283-6292, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33835301

RESUMEN

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival of common cancers, partly because there are no reliable early detection tests. Unintentional weight loss (≥ 5% decrease from baseline) has been linked to PDAC, but the frequency and severity of weight loss using objective measures, and its relationship to prognosis, have not been well characterized. METHODS: We identified 390 patients with PDAC (all stages) and two or more prediagnosis weights in the electronic medical record. Percentage weight loss in the 365 and 180 days preceding diagnosis was calculated. Results were compared with raw weights of age- and sex-matched non-cancer controls (n = 780). Odds ratios for PDAC were calculated using conditional logistic regression. Cox proportional hazards models were used for survival. RESULTS: Within 1 year of diagnosis, more PDAC patients lost ≥ 5% weight relative to controls (74.9% vs. 11.2%; p < 0.001), with a median weight loss of 14.2 versus 2.9 lbs. The odds ratio for PDAC comparing weight loss within 1 year of 5 to < 10% was 10.30 (p < 0.001) and 77.82 for ≥ 10% (p < 0.001), compared with stable weight. Weight loss prior to diagnosis was also associated with early-stage PDAC. PDAC cases with ≥ 10% prediagnosis weight loss had worse survival compared with stable weights (hazard ratio [HR] 1.60; p = 0.01). Greater prediagnosis weight loss was associated with poor survival after pancreatectomy (5 to < 10% vs. < 5%, HR 2.40, p = 0.03; ≥ 10% vs. < 5%, HR 2.59, p = 0.03). CONCLUSIONS: Diagnosis of PDAC is preceded by unintentional weight loss in the majority of patients, even at an early stage. Greater prediagnosis weight loss severity is also associated with poor postoperative survival.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico , Detección Precoz del Cáncer , Humanos , Neoplasias Pancreáticas/diagnóstico , Pronóstico , Pérdida de Peso
15.
J Surg Educ ; 76(6): e110-e117, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31668694

RESUMEN

BACKGROUND: There are almost twice as many applicants as there are general surgery internships, each utilizing a common application with standard components. These elements are frequently not useful in determining affinity for a program or overall ability, and resultant poor fit may be partially responsible for program attrition. Alternative evaluation instruments would be beneficial to both programs and applicants. METHODS: An application review committee comprised of resident representatives, faculty representing all program-affiliated institutions, and program leadership completed a written evaluation developed by a third party (SurgWise Consulting) that specializes in industrial and organizational psychology. The responses were compiled to create a standardized assessment tool. This assessment was sent to applicants who were subsequently ranked according to fit with our program. The pool of applicants was separately evaluated using our traditional application review. Two residents independently graded each applicant on a 5-point Likert scale to evaluate common application elements; applicants were subsequently assigned an overall score. RESULTS: The assessment was completed by 507 (99%) of 512 qualifying applicants. Separately, 378 applications were reviewed by the traditional method for a total of 756 reviews. Of the 96 applicants identified by the assessment tool to invite for interviews, 22 (23%) qualified for interview invitations according to the traditional review method. The assessment produced 74 applicants that otherwise would not have been interviewed. CONCLUSION: Traditional application review strategies have many shortcomings. A competency-based assessment tool in the residency application selection process identifies a pool of applicants not identified by traditional review methods.


Asunto(s)
Cirugía General/educación , Internado y Residencia , Entrevistas como Asunto , Solicitud de Empleo , Selección de Personal/métodos , Femenino , Humanos , Masculino , Estudios Retrospectivos
16.
Am J Surg ; 217(3): 419-422, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30190077

RESUMEN

BACKGROUND: The timing of inpatient discharges can impact hospital throughput with later discharges leading to decreased patient satisfaction, increased length of stay (LOS), and longer boarding times. METHODS: A 12-month targeted intervention that included both pre-operative and inpatient components was implemented across all surgical inpatient services to increase the proportion of patients discharged by noon. RESULTS: Discharge by noon rates increased from 14.3% to 21.5% during the 12-month initiative (p < 0.01). The case mix index adjusted LOS (aLOS) decreased from 2.17 to 2.02 days (p < 0.01). ED, PACU, and ICU boarding times were all significantly lower during the initiative (p < 0.01, p < 0.01, p = 0.03 respectively). CONCLUSIONS: A targeted initiative to discharge surgical patients earlier resulted in a 50% increase in the proportion of patients discharged by noon. Associated with this finding were improvements in hospital throughput as measured by aLOS and boarding times in the ED, ICUs, and PACU.


Asunto(s)
Tiempo de Internación/estadística & datos numéricos , Alta del Paciente/estadística & datos numéricos , Servicio de Cirugía en Hospital/organización & administración , Eficiencia Organizacional , Femenino , Humanos , Masculino , Ohio , Satisfacción del Paciente , Evaluación de Procesos, Atención de Salud , Factores de Tiempo
17.
J Burn Care Res ; 35(3): 257-60, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24126474

RESUMEN

Skin meshing is frequently used in the coverage of extensive burn injuries as well as other skin and soft tissue wounds. This technique allows coverage of more extensive areas with smaller donor sites and prevents fluid from collecting beneath the skin grafts. The devices used to achieve this expansion differ in their technology and the use of skin carriers. In addition, many of the devices permit meshing at single or multiple ratios depending upon the device chosen. Although commonly used, there have been few definitive studies analyzing the actual expansion ratios achieved by many of these devices. The purpose of this study was to measure the actual meshing ratios achieved using some of the most commonly used skin meshers. The authors used split-thickness cadaveric skin samples provided by the regional tissue bank to compare the area of skin both before and after meshing to determine the actual expansion ratio and compared that with the ratio claimed by the device manufacturer. For all ratios greater than 1:1, the extent of actual expansion was significantly less than that expected for each device (P < .001). In addition, using devices that claimed to yield increasingly greater expansion ratios resulted in increasingly greater discrepancies between the area predicted by the device manufacturer and the actual surface area of skin (P < .01). These findings suggest that there is great variability in the expected and observed expansion ratios achieved by skin graft meshing devices. This has significant applicability to practice as it is likely to affect surgical decisions related to estimating the extent of donor area needed to cover skin and soft tissue defects.


Asunto(s)
Quemaduras/cirugía , Fuerza Compresiva/fisiología , Trasplante de Piel/instrumentación , Mallas Quirúrgicas , Cadáver , Diseño de Equipo , Humanos , Trasplante de Piel/métodos , Bancos de Tejidos
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