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Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Reparo de Erro de Pareamento de DNA/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Junção EsofagogástricaRESUMO
BACKGROUND: Peritoneal metastases (PM) develop in approximately 20% of patients with gastric cancer (GC). For selected patients, treatment of PM with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results. This report aims to describe the safety and perioperative outcomes of laparoscopic HIPEC for GC/PM. METHODS: This retrospective cohort study evaluated patients who had GC and PM treated with laparoscopic HIPEC (2018-2022). The HIPEC involved cisplatin and mitomycin C (MMC) or MMC alone. The primary end point was perioperative safety. RESULTS: The 22 patients in this study underwent 27 procedures. The mean age was 58 ± 13 years. All the patients were Eastern Cooperative Oncology Group (ECOG) 0 or 1 (55 and 45%, respectively). Five patients underwent a second laparoscopic HIPEC, with a median of 126 days (interquartile range [IQR], 117-166 days) between procedures. The median peritoneal carcinomatosis index (PCI) was 4 (IQR, 2-9), and the median hospital stay was 2 days (IQR, 1-3 days). No 30-day readmissions or complications occurred. Eight patients (36%) underwent gastrectomy (CRS ± HIPEC). After an average follow-up period of 11 months, 7 (32%) of the 22 patients were alive. The median overall survival was 11 months (IQR, 195-739 days) from the initial procedure and 19.3 months (IQR, 431-1204 days) from the diagnosis. CONCLUSIONS: Laparoscopic HIPEC appears to be safe with minimal perioperative complications. Approximately one third of the patients undergoing initial laparoscopic HIPEC ultimately proceeded to cytoreduction and gastrectomy. Preliminary survival data from this highly selected cohort suggest that the addition of laparoscopic HIPEC to systemic chemotherapy does not compromise other treatment options. These initial results suggest that laparoscopic HIPEC may offer benefit to patients with GC and PM and aid in the selection of patients who may benefit from curative-intent resection.
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Protocolos de Quimioterapia Combinada Antineoplásica , Procedimentos Cirúrgicos de Citorredução , Quimioterapia Intraperitoneal Hipertérmica , Laparoscopia , Mitomicina , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Seguimentos , Taxa de Sobrevida , Mitomicina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Terapia Combinada , Prognóstico , Gastrectomia , Idoso , Quimioterapia do Câncer por Perfusão Regional/mortalidadeRESUMO
BACKGROUND: Mismatch repair deficient (dMMR) gastroesophageal cancers (GEC) are a distinct subgroup. Among patients with locally advanced disease, previous trial data suggest a good response to neoadjuvant immune checkpoint inhibitors (nICI). PATIENTS AND METHODS: Since 2019, our institution has routinely performed MMR testing for new GEC cases. Patients diagnosed with GEC (2019-2024) were included in the study. Quantitative data are described as the median and interquartile range (IQR); qualitative data are described as quantities and percentages. RESULTS: A total of 24 patients with dMMR GEC were identified following implementation of routine immunohistochemical testing; 14 were potentially resectable with a median follow-up of 14 months (IQR 8-27). All patients underwent pre-treatment positron emission tomography (PET; median SUV 20.9). Among the 14 potentially resectable patients, 4 underwent immediate surgery, 10 were treated with nICI, and 5 underwent surgical resection to date. All regimens included PD-1 inhibitors, with 70% receiving pembrolizumab. Re-staging PET was performed in five patients; the median post-nICI SUV was 5.1 (range 4.7-6.3). All resected specimens had gross ulceration after nICI, but 60% (N = 3) had a pathologic complete response (pCR) following nICI; one patient had a near-complete response (nCR) and one patient had a partial response (pPR). Reduction in SUV was 75% and 82% in the pCR patients, 25% in the nCR patient, and 43% in the pPR patient. CONCLUSIONS: dMMR GECs are responsive to nICI in this limited experience, mirroring early clinical trial data. Given persistent metabolic activity and visible ulceration despite pCR, studies should continue to optimize tools for estimating post-nICI pCR in these patients.
RESUMO
BACKGROUND: Delayed gastric emptying (DGE) is a common complication after esophagectomy. BOTOX injections and pyloric surgeries (PS), including pyloroplasty (PP) and pyloromyotomy (PM), are performed intraoperatively as prophylaxis against DGE. This study compares the effects of pyloric BOTOX injection and PS for preventing DGE post-esophagectomy. METHODS: We retrospectively reviewed Moffitt's IRB-approved database of 1364 esophagectomies, identifying 475 patients receiving BOTOX or PS during esophageal resection. PS was further divided into PP and PM. Demographics, clinical characteristics, and postoperative outcomes were compared using Chi-Square, Fisher's exact test, Wilcoxon rank-sum, and ANOVA. Propensity-score matching was performed between BOTOX and PP cohorts. RESULTS: 238 patients received BOTOX, 108 received PP, and 129 received PM. Most BOTOX patients underwent fully minimally invasive robotic Ivor-Lewis esophagectomy (81.1% vs 1.7%) while most PS patients underwent hybrid open/Robotic Ivor-Lewis esophagectomy (95.7% vs 13.0%). Anastomotic leak (p = 0.57) and pneumonia (p = 0.75) were comparable between groups. However, PS experienced lower DGE rates (15.9% vs 9.3%; p = 0.04) while BOTOX patients had less postoperative weight loss (9.7 vs 11.45 kg; p = 0.02). After separating PP from PM, leak (p = 0.72) and pneumonia (p = 0.07) rates remained similar. However, PP patients had the lowest DGE incidence (1.9% vs 15.7% vs 15.9%; p = < 0.001) and the highest bile reflux rates (2.8% vs 0% vs 0.4%; p = 0.04). Between matched cohorts of 91 patients, PP had lower DGE rates (18.7% vs 1.1%; p = < 0.001) and less weight loss (9.8 vs 11.4 kg; p = < 0.001). Other complications were comparable (all p > 0.05). BOTOX was consistently associated with shorter LOS compared to PS (all p = < 0.001). CONCLUSION: PP demonstrates lower rates of DGE in unmatched and matched analyses. Compared to BOTOX, PS is linked to reduced DGE rates. While BOTOX is associated with more favorable LOS, this may be attributable to difference in operative approach. PP improves DGE rates after esophagectomy without improving other postoperative complications.
Assuntos
Toxinas Botulínicas Tipo A , Esofagectomia , Complicações Pós-Operatórias , Piloro , Humanos , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Piloro/cirurgia , Toxinas Botulínicas Tipo A/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Gastroparesia/prevenção & controle , Gastroparesia/etiologia , Idoso , Cuidados Intraoperatórios/métodos , Piloromiotomia/métodos , Esvaziamento Gástrico/efeitos dos fármacos , Pontuação de Propensão , Injeções , Fístula Anastomótica/prevenção & controle , Fístula Anastomótica/etiologia , Fístula Anastomótica/epidemiologiaRESUMO
BACKGROUND: Pre-/perioperative chemotherapy is well-established for management of locoregional gastric cancer (LRGC). The American Joint Committee on Cancer advocates histopathologic assessment of tumor regression grade (TRG) but does not endorse a specific schema. We sought to examine the prognostic value of the recently revised National Comprehensive Cancer Network (NCCN) definition of TRG specifying TRG0 as no disease in primary tumor or lymph nodes. PATIENTS AND METHODS: Patients with clinical-stage T2+/N+/M0 LRGC receiving preoperative chemotherapy and curative-intent gastrectomy were identified (2000-2020). TRG using the current NCCN definition was retrospectively assigned. Factors associated with TRG were examined using ordinal logistic regression and overall survival (OS) was assessed using the Kaplan-Meier method and Cox regression. RESULTS: Among 117 patients, the most common chemotherapy regimen was epirubicin, cisplatin, plus fluorouracil or capecitabine (ECF/ECX) (n = 48, 41%), followed by folinic acid, fluorouracil, and oxaliplatin (FOLFOX) (n = 30, 26%), and fluorouracil, leucovorin, oxaliplatin, plus docetaxel (FLOT) (n = 13, 11%). TRG3 was the most common histopathologic response (n = 68, 58%), followed by TRG2 (n = 25, 21%), TRG1 (n = 18, 15%), and, lastly, TRG0 (n = 6, 5.1%). The only preoperative factor independently associated with lower TRG was gastroesophageal junction tumor location (OR 0.24, p = 0.012). Higher TRG was independently associated with worse OS in a stepwise fashion (HR 1.49, p = 0.026). Posttreatment pathologic lymph node status was the strongest prognostic factor (HR 1.93, p = 0.026). Independent prognostic value of TRG and ypT stage could not be shown due to substantial overlap. CONCLUSIONS: TRG using the contemporary NCCN definition is associated with OS in LRGC. TRG0 is uncommon but with excellent prognosis. ypN status is the strongest prognostic factor and the revised NCCN definition acknowledging this is appropriate.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Fluoruracila/uso terapêutico , Prognóstico , Terapia Neoadjuvante , Gastrectomia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.
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Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Segunda Neoplasia Primária , Humanos , Qualidade de Vida , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/terapia , Junção Esofagogástrica/patologia , Carcinoma de Células Escamosas/patologia , Segunda Neoplasia Primária/patologiaRESUMO
OBJECTIVE: To evaluate perioperative and oncologic outcomes in our RAMIE cohort and compare outcomes with contemporary OE controls. SUMMARY OF BACKGROUND DATA: RAMIE has emerged as an alternative to traditional open or laparoscopic approaches. Described in all esophagectomy techniques, rapid adoption has been attributed to both enhanced visualization and technical dexterity. METHODS: We retrospectively reviewed patients who underwent RAMIE for malignancy. Patient characteristics, perioperative outcomes, and survival were evaluated. For perioperative and oncologic outcome comparison, contemporary OE controls were propensity-score matched from NSQIP and NCDB databases. RESULTS: We identified 350 patients who underwent RAMIE between 2010 and 2019. Median body mass index was 27.4, 32% demonstrated a Charlson Comorbidity Index >4. Nodal disease was identified in 50% of patients and 74% received neoadjuvant chemoradiotherapy. Mean operative time and blood loss were 425 minutes and 232âmL, respectively. Anastomotic leak occurred in 16% of patients, 2% required reoperation. Median LOS was 9âdays, and 30-day mortality was 3%. A median of 21 nodes were dissected with 96% achieving an R0 resection. Median survival was 67.4âmonths. 222 RAMIE were matched 1:1 to the NSQIP OE control. RAMIE demonstrated decreased LOS (9 vs 10âdays, P = 0.010) and reoperative rates (2.3 vs 12.2%, P = 0.001), longer operative time (427 vs 311 minutes, P = 0.001), and increased rate of pulmonary embolism (5.4% vs 0.9%, P = 0.007) in comparison to NSQIP cohort. There was no difference in leak rate or mortality. Three hundred forty-three RAMIE were matched to OE cohort from NCDB with no difference in median overall survival (63 vs 53âmonths; P = 0.130). CONCLUSION: In this largest reported institutional series, we demonstrate that RAMIE can be performed safely with excellent oncologic outcomes and decreased hospital stay when compared to the open approach.
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Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Fístula Anastomótica/cirurgia , Esofagectomia/métodos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Gastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ) are molecularly diverse. TP53 is the most frequently altered gene with approximately 50% of patients harboring mutations. This qualitative study describes the distinct genomic alterations in GCs and GEJs stratified by TP53 mutation status. PATIENTS AND METHODS: Tumor DNA sequencing results of 324 genes from 3741 patients with GC and GEJ were obtained from Foundation Medicine. Association between gene mutation frequency and TP53 mutation status was examined using Fisher's exact test. Functional gene groupings representing molecular pathways suggested to be differentially mutated in TP53 wild-type (TP53WT) and TP53 mutant (TP53MUT) tumors were identified. The association of the frequency of tumors containing a gene mutation in the molecular pathways of interest and TP53 mutation status was assessed using Fisher's exact test with a P-value of <.01 deemed statistically significant for all analyses. RESULTS: TP53 mutations were noted in 61.6% of 2946 GCs and 81.4% of 795 GEJs (P < .001). Forty-nine genes had statistically different mutation frequencies in TP53WT vs. TP53MUT patients. TP53WT tumors more likely had mutations related to DNA mismatch repair, homologous recombination repair, DNA and histone methylation, Wnt/B-catenin, PI3K/Akt/mTOR, and chromatin remodeling complexes. TP53MUT tumors more likely had mutations related to fibroblast growth factor, epidermal growth factor receptor, other receptor tyrosine kinases, and cyclin and cyclin-dependent kinases. CONCLUSION: The mutational profiles of GCs and GEJs varied according to TP53 mutation status. These mutational differences can be used when designing future studies assessing the predictive ability of TP53 mutation status when targeting differentially affected molecular pathways.
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Adenocarcinoma , Fosfatidilinositol 3-Quinases , Adenocarcinoma/genética , Adenocarcinoma/patologia , DNA de Neoplasias , Junção Esofagogástrica/patologia , Humanos , Mutação , Fosfatidilinositol 3-Quinases/genética , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND/PURPOSE: Malignant small bowel obstruction (mSBO) is a common consequence of advanced malignancies. Surgical consultation is common, however data on the outcomes following an operation are lacking. We investigated a specific operative approach-intestinal bypass-to determine the outcomes associated with this intervention. METHODS: Patients with a preoperative diagnosis of mSBO who underwent intestinal bypass between 2015 and 2021 were included. Isolated colonic obstruction was excluded as was gastric outlet obstruction. Perioperative and postoperative outcomes were measured, including complications, overall survival, return to oral intake, and return to intended oncologic therapy. Patients were additionally grouped as to whether the operation was performed as elective or as inpatient. RESULTS: Overall, 55 patients were identified, with a mean age of 61.2 ± 14 years. The most common primary malignancy was colorectal cancer (65.5%) and 80% of patients had a preoperative diagnosis of metastatic disease. Small bowel to colon was the most common bypass procedure (51%). Severe complications occurred in 25.5% of patients with three in-hospital mortalities (5.5%). Survival rates at 30, 90, and 180 days were 91%, 80%, and 62%, respectively. The majority of patients were discharged to home (85.5%) and were tolerating an oral diet (74.6%). Twenty-seven patients (49.1%) returned to some form of oncologic treatment. CONCLUSIONS: Patients with mSBO face a potentially terminal condition. In this study, approximately 75% of patients who underwent intestinal bypass were able to regain the ability to eat, and 49% returned to oncologic therapy. Although retrospective, these data suggest the approach is efficacious for palliation of this difficult sequela of advanced cancer.
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Obstrução Intestinal , Derivação Jejunoileal , Idoso , Humanos , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Intestino Delgado/cirurgia , Pessoa de Meia-Idade , Cuidados Paliativos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIMS: Fundic gland polyps (FGPs) comprise 66% of all gastric polyps. Although they are usually non-syndromic, they may be associated with various syndromes, including familial adenomatous polyposis (FAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). We aimed to evaluate how histological features relate to distinct FGP subtypes. METHODS AND RESULTS: We performed a retrospective analysis of 118 FGPs from 109 patients for the architecture of fundic glands, microcyst lining, parietal cell hyperplasia and surface foveolar epithelial changes. Age, gender and history of FAP or GAPPS were collected. Based on combinations of histological features, three distinct patterns (A, B and C) of FGPs were delineated and correlated to the aetiologies. Non-syndromic FGPs were well-formed polyps composed of disordered fundic glands with intermediate-sized microcysts typically lined by a mixture of oxyntic and mucin-secreting cells (73%). Parietal cell hyperplasia (80%) and foveolar surface hyperplasia (78%) were common. FAP-associated cases demonstrated small microcysts that were predominantly lined by fundic epithelium (77%), with limited parietal cell hyperplasia (27%); foveolar hyperplasia was uncommon. GAPPS-related polyps were the largest, with prominent, mucin-secreting epithelium-lined microcysts (73%). Hyperproliferative aberrant pits were universally present, whereas parietal cell hyperplasia was uncommon. Pattern A was identified in most non-syndromic FGPs (74%) and in a minority of FAP-related FGPs (26%). The majority (82%) of FAP-related FGPs showed pattern B, but only 18% of non-syndromic FGPs did. Pattern C consisted exclusively of GAPPS-associated polyps. CONCLUSIONS: We conclude that, although FGPs share similar histomorphology, subtle differences exist between polyps of different aetiology. In the appropriate clinical setting, the recognition of these variations may help to consider syndromic aetiologies.
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Fundo Gástrico/patologia , Pólipos/etiologia , Pólipos/patologia , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Polipose Adenomatosa do Colo/classificação , Polipose Adenomatosa do Colo/etiologia , Polipose Adenomatosa do Colo/patologia , Pólipos Adenomatosos/classificação , Pólipos Adenomatosos/etiologia , Pólipos Adenomatosos/patologia , Feminino , Mucosa Gástrica/patologia , Humanos , Hiperplasia , Masculino , Células Parietais Gástricas/patologia , Pólipos/classificação , Estudos Retrospectivos , Neoplasias Gástricas/classificaçãoRESUMO
Gastric cancer is the third leading cause of cancer-related deaths worldwide. Over 95% of gastric cancers are adenocarcinomas, which are typically classified based on anatomic location and histologic type. Gastric cancer generally carries a poor prognosis because it is often diagnosed at an advanced stage. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability (MSI) status, and the expression of programmed death-ligand 1 (PD-L1), has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with localized gastric cancer. This selection from the NCCN Guidelines for Gastric Cancer focuses on the management of unresectable locally advanced, recurrent, or metastatic disease.
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Neoplasias Gástricas , Adenocarcinoma/patologia , Humanos , Oncologia , Instabilidade de Microssatélites , Qualidade de Vida , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapiaRESUMO
INTRODUCTION: We hypothesized that first-generation cephalosporins (G1CEP) provide adequate antimicrobial coverage for pancreaticoduodenectomy (PD) when no biliary stent is present but might be inferior to second-generation cephalosporins or broad-spectrum antibiotics (G2CEP/BS) in decreasing surgical-site infection (SSI) rates when a biliary stent is present. METHODS: The National Surgical Quality Improvement Program 2014-2019 was used to select patients who underwent elective open PD. We divided the population into no-stent versus stent groups based on the status of biliary drainage and then divided each group into G1CEP versus G2CEP/BS subgroups based on the choice of perioperative antibiotics. We matched the subgroups per a propensity score match and analyzed postoperative outcomes. RESULTS: Six thousand two hundred forty five cases of 39,779 were selected; 2821 in the no-stent (45.2%) versus 3424 (54.8%) in the stent group. G1CEP were the antibiotics of choice in 2653 (42.5%) versus G2CEP/BS in 3592 (57.5%) cases. In the no-stent group, we matched 1129 patients between G1CEP and G2CEP/BS. There was no difference in SSI-specific complications (20.3% versus 21.0%; P = 0.677), general infectious complications (25.7% versus 26.9%; P = 0.503), PD-specific complications, overall morbidity, length of stay, or mortality. In the stent group, we matched 1244 pairs. G2CEP/BS had fewer SSI-specific complications (19.9% versus 26.6%; P < 0.001), collections requiring drainage (9.6% versus 12.9%; P = 0.011), and general infectious complications (28.5% versus 34.1%; P = 0.002) but no difference in overall morbidity, mortality, length of stay, and readmission rates. CONCLUSIONS: G2CEP/BS are associated with reduced rates of SSI-specific and infectious complications in stented patients undergoing open elective PD. In patients without prior biliary drainage, G1CEP seems to provide adequate antimicrobial coverage.
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Neoplasias Pancreáticas , Pancreaticoduodenectomia , Antibacterianos/uso terapêutico , Cefalosporinas , Drenagem/efeitos adversos , Humanos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/efeitos adversos , Melhoria de Qualidade , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: The gold standard for locoregional esophageal cancer (LEC) treatment includes preoperative chemoradiation and surgical resection, with possible perioperative or adjuvant systemic therapy. With few data associating histologic grade and prognosis in LEC patients receiving neoadjuvant chemoradiation followed by resection, we seek to evaluate this association. METHODS: Our institutional esophagectomy database between 1999 and 2019 was queried, selecting esophageal adenocarcinoma patients who completed neoadjuvant therapy (NAT), followed by esophagectomy. Propensity-score matching of low- and high-histologic grade groups was performed to assess survival metrics using initial clinical grade (cG) and final pathologic grade (pG). We performed a multivariable logistic regression to study predictors of pathologic complete response as a secondary objective. RESULTS: A total of 518 patients met the inclusion criteria. Kaplan-Meier analysis of the matched dataset showed no difference in initial or 5-year recurrence-free survival or overall survival (OS) between cG1 and cG2 versus cG3 based on original grade. When matched according to pG, cG1-2 had improved median survival parameters compared to cG3, with 5-year OS for cG1-2 of 45% versus 27% (p = 0.001). Higher pG, pathologic N stage, and poor response to NAT are predictors of poor survival. CONCLUSION: Patients with post-NAT pG1-2 demonstrated improved survival. Integrating histologic grade into postneoadjuvant staging may be warranted.
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Adenocarcinoma , Neoplasias Esofágicas , Adenocarcinoma/patologia , Quimiorradioterapia , Neoplasias Esofágicas/patologia , Esofagectomia , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
BACKGROUND: Progression of Barrett esophagus (BE) to esophageal adenocarcinoma occurs among a minority of BE patients. To date, BE behavior cannot be predicted on the basis of histologic features. AIMS: We compared BE samples that did not develop dysplasia or carcinoma upon follow-up of ≥ 7 years (BE nonprogressed [BEN]) with BE samples that developed carcinoma upon follow-up of 3 to 4 years (BE progressed [BEP]). METHODS: The NanoString nCounter miRNA assay was used to profile 24 biopsy samples of BE, including 13 BENs and 11 BEPs. Fifteen samples were randomly selected for miRNA prediction model training; nine were randomly selected for miRNA validation. RESULTS: Unpaired t tests with Welch's correction were performed on 800 measured miRNAs to identify the most differentially expressed miRNAs for cases of BEN and BEP. The top 12 miRNAs (P < .003) were selected for principal component analyses: miR-1278, miR-1301, miR-1304-5p, miR-517b-3p, miR-584-5p, miR-599, miR-103a-3p, miR-1197, miR-1256, miR-509-3-5p, miR-544b, miR-802. The 12-miRNA signature was first self-validated on the training dataset, resulting in 7 out of the 7 BEP samples being classified as BEP (100% sensitivity) and 7 out of the 8 BEN samples being classified as BEN (87.5% specificity). Upon validation, 4 out of the 4 BEP samples were classified as BEP (100% sensitivity) and 4 out of the 5 BEN samples were classified as BEN (80% specificity). Twenty-four samples were evaluated, and 22 cases were correctly classified. Overall accuracy was 91.67%. CONCLUSION: Using miRNA profiling, we have identified a 12-miRNA signature able to reliably differentiate cases of BEN from BEP.
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Adenocarcinoma/genética , Esôfago de Barrett/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Transcriptoma , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Esôfago de Barrett/patologia , Progressão da Doença , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Pancreaticoduodenectomy (PD) remains the cornerstone of managing pancreatic ductal adenocarcinoma (PDAC) of the pancreas head/neck, but it is associated with high morbidity. We hypothesize that, in absence of pancreatectomy-specific morbidity (PSM), minimally invasive PD (MIPD) provides improved short-term outcomes compared to open PD (OPD). METHODS: NSQIP pancreatectomy-targeted database 2014-2019 was utilized. PSM was defined as the occurrence of delayed gastric emptying (DGE) and/or post-operative pancreatic fistula (POPF). The cohort was divided into No-PSM and PSM groups. Propensity score match was applied in each group to compare outcomes of MIPD vs. OPD. RESULTS: 8,121 patients were selected. Patients were divided into No-PSM (N = 6267) and PSM (N = 1854) groups. In No-PSM group, we matched 1656 OPD to 552 MIPD patients. MIPD had longer operations (423 vs. 359 min; p < 0.001) but less overall morbidity (22.1% vs. 29.1%; p = 0.001) mostly attributed to less bleeding and sepsis. MIPD patients also had a one-day shorter median LOS (6 vs. 7 days; p = 0.005) and higher rates of home discharge (92.8% vs. 89.6%; p = 0.027). No difference was noted in mortality and 30-day readmission. In PSM group, 441 OPD were matched to 147 MIPD peers. MIPD had longer operations but without short-term benefits. General morbidity (61.2% vs. 61.9%), median LOS (12 vs. 12 days), mortality (2.7% vs. 1.8%), and readmission rates (32.7% vs. 26.5%) were similar. Same conclusions were drawn in the per-protocol analysis. CONCLUSION: PSM is common following PD for PDAC. In the absence of PSM, MIPD is associated with less postoperative morbidity and shorter LOS.
Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Laparoscopia , Neoplasias Pancreáticas , Adenocarcinoma/complicações , Carcinoma Ductal Pancreático/cirurgia , Humanos , Laparoscopia/efeitos adversos , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
OBJECTIVE: We compare neoadjuvant chemotherapy (CT) to neoadjuvant chemotherapy plus chemoradiation (CRT) for patients with gastric adenocarcinoma (GA). SUMMARY OF BACKGROUND DATA: The optimal neoadjuvant therapy regimen for resectable GA is not defined. METHODS: Utilizing data from 2 high-volume cancer centers, we analyzed patients who underwent surgery for localized GA from 1/1/2000-12/31/2017. Standard CT regimens were used according to treatment period. We compared propensity matched cohorts based on age, sex, race, histology, and clinical stage. RESULTS: Four-hundred five patients (age 62 ± 12 year, 58% male, 56% White) were analyzed. 231 (57%) received CRT and 174 (43%) received CT. Groups differed based on histopathologic characteristics including preoperative stage (p = 0.013). To control for these differences, propensity matched cohorts of 113 CT and 113 CRT patients were compared. CRT had similar frequencies of microscopically negative resections to CT (93% vs 91%, p = 0.81), but higher rates of complete pathologic response (15% vs 4%, p = 0.003) and lower pathologic stage (p = 0.002). Completion of intended perioperative therapy occurred in 63% of CT and 91% of CRT patients (p < 0.001). Median DFS was 45mo (95%CI: 20-70) in the CT group and 113mo (95%CI: 75-151) in the CRT group (p = 0.018). Median OS was 53mo (95%CI: 30-77) versus 120mo (95%CI: 101-138); p = 0.015. CONCLUSIONS: In this multi-institutional comparison of neoadjuvant CT and CRT for resectable GA, CRT is associated with higher rates of completed perioperative therapy, higher rates of complete pathologic response, lower pathologic stage, and improved survival.Level of Evidence: Level III.
Assuntos
Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Quimiorradioterapia , Gastrectomia , Terapia Neoadjuvante , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Epirubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the impact of a granular measure of SED on pancreatic surgical and cancer-related outcomes at a high-volume cancer center that employs a standardized clinic pathway. SUMMARY OF BACKGROUND DATA: Prior research has shown that low socioeconomic status leads to less treatment and worse outcomes for PDAC. However, these studies employed inconsistent definitions and categorizations of socioeconomic status, aggregated individual socioeconomic data using large geographic areas, and lacked detailed clinicopathologic variables. METHODS: We conducted a retrospective cohort study of 1552 PDAC patients between 2008 and 2015. Patients were stratified using the area deprivation index, a validated dataset that ranks census block groups based on SED. Multivariable models were used in the curative surgery cohort to predict the impact of SED on (1) grade 3/4 Clavien-Dindo complications, (2) initiation of adjuvant therapy, (3) completion of adjuvant therapy, and (4) overall survival. RESULTS: Patients from high SED neighborhoods constituted 29.9% of the cohort. Median overall survival was 28 months. The rate of Clavien-Dindo grade 3/4 complications was 14.2% and completion of adjuvant therapy was 65.6%. There was no evidence that SED impacted surgical evaluation, receipt of curative-intent surgery, postoperative complications, receipt of adjuvant therapy or overall survival. CONCLUSIONS: Although nearly one-quarter of curative-intent surgery patients were from high SED neighborhoods, this factor was not associated with measures of treatment quality or survival. These observations suggest that treatment at a high-volume cancer center employing a standardized clinical pathway may in part address socioeconomic disparities in pancreatic cancer.
Assuntos
Adenocarcinoma/cirurgia , Procedimentos Clínicos , Neoplasias Pancreáticas/cirurgia , Fatores Socioeconômicos , Adenocarcinoma/mortalidade , Institutos de Câncer/estatística & dados numéricos , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Utilização de Instalações e Serviços , Feminino , Humanos , Masculino , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/mortalidade , Complicações Pós-Operatórias , Características de Residência , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
To date, there have been no studies comparing the molecular subtypes of Index gastric cancers (IGCs) and metachronous gastric cancers (MGCs). We evaluated a cohort of 42 patients with 43 IGCs and 45 MGCs. Molecular subtyping was performed by immunohistochemistry of mismatch repair (MMR) proteins, E-cadherin, p53, and Epstein-Barr virus- (EBV-) in situ hybridization (ISH). Gastric adenocarcinomas were classified into 5 subtypes: EBV-associated, MMR deficient (MMRD), E-cadherin aberrant, p53-aberrant [p53(+)], and p53 non-aberrant [p53(neg)]. All IGCs had been successfully treated by either surgery (19%) or endoscopic resection (81%). The mean interval between IGCs and MGCs was 85 months. Among the IGCs, EBV-associated, MMRD, E-cadherin-aberrant, p53(+), and p53(neg) molecular subtypes represented 2 (5%), 4 (9%), 2 (5%), 21 (49%), and 14 (32%) of the cases, respectively. Two cases had concomitant p53(+) and aberrant E-cadherin molecular subtypes. Among metachronous cancers, EBV-associated, MMRD, E-cadherin-aberrant, p53(+), and p53(neg) molecular subtypes represented 3 (7%), 11 (24%), 0 (0%), 22 (49%), and 9 (20%) cases. Concomitant p53(+) was observed in 1 EBV-associated and 2 MMRD MGCs. Although, there was no significant difference in the frequency of most molecular subtypes in IGCs and MGCs, the number of MMRD gastric cancers more than doubled in the MGC group. Half of the MGCs had a divergent molecular subtype compared to that of the IGCs. Notably, the interval between the development of IGCs and MGCs was significantly longer in patients with divergent molecular subtypes (P = 0.010). All 4 patients with MMRD IGC developed MMRD MGCs. Although the concept of mucosal field cancerization may explain the matching molecular subtypes in early-developing MGCs, the presence of divergent subtypes in late-occurring MGCs suggests a shift in the carcinogenic mechanism affecting the residual mucosa possibly related to Helicobacter pylori eradication.
Assuntos
Adenocarcinoma/genética , Segunda Neoplasia Primária/genética , Neoplasias Gástricas/genética , Adenocarcinoma/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/patologia , República da Coreia , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
Gastric cancer (GC) is a common cancer worldwide, with patients developing isolated peritoneal metastases (PM) in approximately 30% of cases. In patients with PM, prognosis is quite poor, and long-term survival is almost zero. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been demonstrated to be an effective treatment in many peritoneal malignancies, including appendiceal and ovarian cancers and in peritoneal mesothelioma. In this educational review, we summarize many of the seminal studies addressing the potential benefit of CRS/HIPEC for patients with gastric cancer and peritoneal metastases (GC/PM).
Assuntos
Hipertermia Induzida , Neoplasias Gástricas , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Peritônio , Estudos Retrospectivos , Neoplasias Gástricas/terapia , Taxa de SobrevidaRESUMO
INTRODUCTION: To implement a mastery-based robotic surgery curriculum using virtual reality (VR) and inanimate reality (IR) drills at multiple Complex General Surgical Oncology (CGSO) fellowships. PATIENTS AND METHODS: A prospective study of curriculum feasibility and efficacy was conducted at four CGSO fellowship sites. All sites had simulators, and kits were provided to perform 19 biotissue drills. Fellows from three non-UPMC sites (n = 15) in 2016-2018 were compared with fellows from University of Pittsburgh (UPMC; n = 15) where the curriculum was validated in 2014-2018. RESULTS: All fellows completed the pre- and post-test. There was no difference in pre-test scores between UPMC and non-UPMC sites. Only 7 of 15 non-UPMC fellows completed the VR curriculum (47% compliance) compared with all 15 UPMC fellows completing the VR curriculum (100% compliance). UPMC had higher curriculum times (217 versus 93 mins) and % mastery (86% versus 55%). Time spent on curriculum was associated with % mastery (p = 0.01). Both groups showed improvement between pre- and post-test. Post-test VR scores trended higher for UPMC (221 versus 180). Between the non-UPMC sites, there was a difference in compliance (p = 0.03) and % mastery (p = 0.03). Zero non-UPMC fellows performed the biotissue drills, while five contemporary UPMC fellows completed 253 biotissue drills. Approximately 140 UPMC faculty and 300 staff hours were spent on the pilot. CONCLUSIONS: A proficiency curriculum can result in improved robotic console skills. However, multiple barriers to implementation potentially exist, including availability of simulators, availability of a training robot, on-site support staff, and universal buy-in from fellows, faculty, and leadership.