RESUMO
BACKGROUND: Visceral peritoneal colorectal metastases (VPCMs) may further metastasize to lymph nodes that drain those organs. The rate of lymph node metastases (LNMs) from VPCMs and their clinical and prognostic significance are unknown. METHODS: This study retrospectively analyzed the authors' institutional databases of 160 patients with peritoneal colorectal metastases who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Patients with LNM-VPCM (n = 12) were identified by pathologic reports, and both their short- and long-term outcomes were compared with those of patients without LNM-VPCM. RESULTS: The clinical presentation and primary tumor pathologic characteristics did not differ between the two groups. The patients with LNM-VPCM had a higher tumor burden (measured by the peritoneal carcinomatosis index [PCI]) and visible remnant disease compared with those who had no LNM-VPI (10 vs 5.5 [p = 0.03] vs 33.3% vs 6.8% [p = 0.007], respectively). The postoperative outcomes also were comparable. The patients with LNM-VPCM had a shorter overall survival (OS) than those without LNM-VPCM (median OS, 22.5 months; 95% confidence interval [CI], 15.1-29.9 months vs 40.1 months; 95% CI, 38.1-42 months; p = 0.02). However, only tumor grade and PCI were predictors of OS in the multivariate analysis (hazard ratio [HR], 2.33 [p = 0.001]; 1.77 [p = 0.03], respectively). The study showed that LNM-VPCM was associated with systemic but not peritoneal recurrence compared with non-LNM-VPCM (81.8% vs 51.6% for systemic recurrence, respectively; p = 0.05). CONCLUSION: The small distinct group of patients defined by LNM-VPCM were prone to systemic recurrence. Given its correlation with systemic recurrence, LNM-VPCM may indicate the need for adjuvant treatment.
Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Metástase Linfática , Neoplasias Peritoneais/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Retroperitoneal sarcoma (RPS) surgery entails multivisceral resection, which may cause postoperative complications. We assessed the effects of complications on survival to identify their predisposing factors in primary (PRPS) and recurrent (RRPS) RPS. METHODS: We retrospectively analyzed our institutional database. Severe postoperative complications (SC) were defined as Clavien-Dindo classification ≥ 3. Predisposing factors for complications were investigated, as was their effect on long-term outcomes. RESULTS: In total, 154 RPS resections (78 PRPS and 76 RRPS) performed between January 2008 and December 2018 were included. Neoadjuvant chemotherapy and multifocal tumors were more common in RRPS than PRPS (34.2% vs. 11.3%, P = 0.001 and 42.1% vs. 10.3%, P < 0.001, respectively). Although surgical extent in RRPS was limited compared with PRPS (weighted organ score 1 vs. 2, P = 0.01; transfusion requirement 23.6% vs. 35.8%, P = 0.04), SC and mortality rates were comparable. SC rates were 30.1% and 35.5% for PRPS and RRPS, respectively. NACT rate tended to be higher in PRPS patients with SC (20.8% vs. 7.4%, P = 0.09), whereas weighted organ score and transfusion requirement were increased in RRPS patients with SC (2 vs. 1, P = 0.01; 40.7% vs. 14.3%, P = 0.009, respectively). PRPS patients with SC had decreased overall survival (35 months, 95% confidence interval [CI] 12.2-57.7) compared with those without SC (90 months, 95% CI 71.4-108.5, P = 0.01). CONCLUSIONS: Postoperative complications are associated with impaired outcomes in PRPS but not in RRPS. The negative effects of complications on outcomes should be factored to perioperative management.
Assuntos
Neoplasias Retroperitoneais , Sarcoma , Humanos , Recidiva Local de Neoplasia/cirurgia , Complicações Pós-Operatórias/etiologia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Sarcoma/cirurgia , Taxa de SobrevidaRESUMO
BACKGROUND: Carriers of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) who receive cephalosporin-based prophylaxis have twice the risk of surgical site infection (SSI) following colorectal surgery as noncarriers. We tested whether ESBL-PE screening and personalized prophylaxis with ertapenem reduces SSI risk among carriers. METHODS: We conducted a prospective nonrandomized, nonblinded, interventional study in 3 hospitals in Israel, Switzerland, and Serbia. Patients were screened for ESBL-PE carriage before elective colorectal surgery. During the baseline phase, departmental guidelines advised prophylaxis with a cephalosporin plus metronidazole. In the intervention phase, guidelines were changed for ESBL-PE carriers to receive ertapenem. The primary outcome was any type of SSI within 30 days. We calculated adjusted risk differences (ARDs) following logistic regression. RESULTS: The intention-to-treat analysis compared 209 ESBL-PE carriers in the baseline phase to 269 in the intervention phase. SSI rates were 21.5% and 17.5%, respectively (ARD, -4.7% [95% confidence interval {CI}, -11.8% to 2.4%]). Unplanned crossover was high (15%), so to assess efficacy we performed an as-treated analysis comparing 247 patients who received cephalosporin-based prophylaxis with 221 who received ertapenem. SSI rates were 22.7% and 15.8%, respectively (ARD, -7.7% [95% CI, -14.6% to -.8%]), and rates of SSI caused by ESBL-PE were 6.5% and 0.9%, respectively (ARD, -5.6% [95% CI, -8.9% to -2.3%]). There was no significant difference in the rate of deep SSI. The number needed to treat to prevent 1 SSI in ESBL-PE carriers was 13. CONCLUSIONS: Screening for ESBL-PE carriage before colorectal surgery and personalizing prophylaxis for carriers is efficacious in reducing SSI.
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Cirurgia Colorretal , Infecções por Enterobacteriaceae , Antibacterianos/uso terapêutico , Cirurgia Colorretal/efeitos adversos , Enterobacteriaceae , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/prevenção & controle , Ertapenem , Humanos , Israel , Estudos Prospectivos , Suíça , beta-LactamasesRESUMO
BACKGROUND: Neoadjuvant FOLFIRINOX is a standard-of-care treatment for BRPC patients. Patients with gBRCAm who have demonstrated improved response to platinum-based chemotherapy may have impaired homologous repair deficiency. This study aimed to describe the pathologic complete response rate and long-term survival for patients with germline BRCA1 or BRCA2 mutation (gBRCAm) and borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX. METHODS: A dual-center retrospective analysis was performed. Patients who had BRPC treated with neoadjuvant FOLFIRINOX followed by curative resection were identified from clinical databases. Pathologic complete response was defined as no viable tumor cells present in the specimen. Common founder Jewish germline BRCA1 or BRCA2 mutation was determined for available patients. RESULTS: The 61 BRPC patients in this study underwent resection after neoadjuvant FOLFIRINOX. Analysis of BRCA mutation was performed for 39 patients, and 9 patients were found to be BRCA2 germline mutation carriers. The pathologic complete response rate was 44.4% for the gBRCAm patients and 10% for the BRCA non-carriers (p = 0.009). The median disease-free survival was not reached for the gBRCAm patients and was 7 months for the BRCA non-carriers (p = 0.03). The median overall survival was not reached for the gBRCAm patients and was 32 months for the BRCA non-carriers (p = 0.2). After a mean follow-up period of 33.7 months, all eight patients with pathologic complete response were disease-free. CONCLUSIONS: The study showed that gBRCAm patients with BRPC have an increased chance for pathologic complete response and prolonged survival after neoadjuvant FOLFIRINOX. The results support the benefit of exposing gBRCAm patients to platinum-based chemotherapy early in the course of the disease. Neoadjuvant FOLFIRINOX should be considered for BRCA carriers who have resectable pancreatic cancer.
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Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fluoruracila , Humanos , Irinotecano , Leucovorina , Mutação , Terapia Neoadjuvante , Oxaliplatina , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Estudos RetrospectivosRESUMO
Liver regeneration depends on sequential activation of pathways and cells involving the remaining organ in recovery of mass. Proliferation of parenchyma is dependent on angiogenesis. Understanding liver regeneration-associated neovascularization may be useful for development of clinical interventions. Myeloid-derived suppressor cells (MDSCs) promote tumor angiogenesis and play a role in developmental processes that necessitate rapid vascularization. We therefore hypothesized that the MDSCs could play a role in liver regeneration. Following partial hepatectomy, MDSCs were enriched within regenerating livers, and their depletion led to increased liver injury and postoperative mortality, reduced liver weights, decreased hepatic vascularization, reduced hepatocyte hypertrophy and proliferation, and aberrant liver function. Gene expression profiling of regenerating liver-derived MDSCs demonstrated a large-scale transcriptional response involving key pathways related to angiogenesis. Functionally, enhanced reactive oxygen species production and angiogenic capacities of regenerating liver-derived MDSCs were confirmed. A comparative analysis revealed that the transcriptional response of MDSCs during liver regeneration resembled that of peripheral blood MDSCs during progression of abdominal tumors, suggesting a common MDSC gene expression profile promoting angiogenesis. In summary, our study shows that MDSCs contribute to early stages of liver regeneration possibly by exerting proangiogenic functions using a unique transcriptional program.-Nachmany, I., Bogoch, Y., Sivan, A., Amar, O., Bondar, E., Zohar, N., Yakubovsky, O., Fainaru, O., Klausner, J. M., Pencovich, N. CD11b+Ly6G+ myeloid-derived suppressor cells promote liver regeneration in a murine model of major hepatectomy.
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Hepatectomia , Regeneração Hepática , Células Supressoras Mieloides/citologia , Animais , Antígenos Ly/metabolismo , Antígeno CD11b/metabolismo , Linhagem Celular Tumoral , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Fígado/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Mieloides/citologia , Neovascularização Patológica , Espécies Reativas de Oxigênio/metabolismoRESUMO
INTRODUCTION: Existing prognostic tools for retroperitoneal sarcomas (RPS) utilize parameters that can be accurately determined only postoperatively. This study evaluated the application of the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels for predicting prognosis in primary RPS. MATERIALS AND METHODS: We retrospectively analyzed our database of patients with primary RPS operated between 2008 and 2018. The NLR was calculated from preoperative blood tests and its association with outcomes was determined. RESULTS: The NLR values of 78 suitable patients were analyzed. Patients were classified in the NLR-high group if the NLR was ≥2.1. High-grade tumors were more common in the NLR-high group (71.6% vs 48%, P = .02). NLR-high patients had impaired overall survival (OS) and progression-free survival (PFS) compared to NLR-low patients (median OS not reached vs 74 months 95% confidence interval [CI]: 21.6-126.4, P = .03; median PFS not reached vs 48 months 95% CI: 6.5-98.6, P = .06, respectively). Multivariate analysis showed statistical significance only for PFS but not for OS (hazard ratio [HR] = 4.1, P = .03; HR = 2.3, P = .3). Patients with low CRP levels had improved OS and PFS. CONCLUSIONS: The NLR may serve as a preoperative, easily derived marker for prognosis in RPS. Serum biomarkers may prove useful in these large and spatially heterogeneous tumors.
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Biomarcadores Tumorais/análise , Plaquetas/patologia , Inflamação/diagnóstico , Linfócitos/patologia , Neutrófilos/patologia , Neoplasias Retroperitoneais/mortalidade , Sarcoma/mortalidade , Idoso , Feminino , Seguimentos , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/cirurgia , Estudos Retrospectivos , Sarcoma/patologia , Sarcoma/cirurgia , Taxa de SobrevidaRESUMO
BACKGROUND: The influence of postoperative complications, specifically, pancreatic fistula (PF), on long-term oncologic outcome in patients with pancreatic ductal adenocarcinoma (PDAC) is unclear. METHODS: Prospectively collected data of patients who underwent pancreaticoduodenectomy (PD) for PDAC between 2008 and 2016 were retrospectively reviewed and analyzed. Deaths within 90 days were excluded. Median follow-up time was 22 months for the entire cohort (range 2-102 months). PF was graded as biochemical leak, grade B, or grade C according to the criteria of the International Study Group on Pancreatic Fistula. Postoperative complications were graded according to the Clavien-Dindo classification (CDC). Data on clinical and pathological characteristics as well as on recurrence and survival were collected. RESULTS: Twenty-nine of the 148 identified patients (19%) developed PF, of whom 17 (11.4%) had a PF grade B or C. 29 patients developed a postoperative complication CDC grade 3 or 4. The respective 3-year disease-free survival was 15.5% and 19.2% (P = 0.725), and the 5-year overall survival was 20% and 16% (P = 0.914) in patients with and without PF. On multivariate analysis, the use of adjuvant chemotherapy, lymph node involvement, surgical margin involvement, and tumor grade were associated with patient survival. PF and postoperative complications CDC grade 3 or 4 were not associated with decreased long-term survival, disease-free survival or local recurrence rate. CONCLUSIONS: While acknowledging the limited sample size, no association was seen between PF or postoperative complications and overall or disease-free survival in patients undergoing PD for PDAC.
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Carcinoma Ductal Pancreático/cirurgia , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Incidência , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: Abdominal tumors invading the inferior vena cava (IVC) present significant challenges to surgeons and oncologists. OBJECTIVES: To describe a surgical approach and patient outcomes. METHODS: The authors conducted a retrospective analysis of surgically resected tumors with IVC involvement by direct tumor encasement or intravascular tumor growth. Patients were classified according to level of IVC involvement, presence of intravascular tumor thrombus, and presence of hepatic parenchymal involvement. RESULTS: Study patients presented with leiomyosarcomas (n=5), renal cell carcinoma (n=7), hepatocellular carcinoma (n=1), cholangiocarcinoma (n=2), Wilms tumor (n=1), neuroblastoma (n=1), endometrial leiomyomatosis (n=1), adrenocortical carcinoma (n=1), and paraganglioma (n=1). The surgeries were conducted between 2010 and 2019. Extension of tumor thrombus above the hepatic veins required a venovenous bypass (n=3) or a full cardiac bypass (n=1). Hepatic parenchymal involvement required total hepatic vascular isolation with in situ hepatic perfusion and cooling (n=3). Circular resection of IVC was performed in five cases. Six patients had early postoperative complications, and the 90-day mortality rate was 10%. Twelve patients were alive, and six were disease-free after a mean follow-up of 1.6 years. CONCLUSIONS: Surgical resection of abdominal tumors with IVC involvement can be performed in selected patients with acceptable morbidity and mortality. Careful patient selection, and multidisciplinary involvement in preoperative planning are key for optimal outcome.
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Neoplasias Abdominais/patologia , Neoplasias Abdominais/cirurgia , Neoplasias Vasculares/patologia , Neoplasias Vasculares/cirurgia , Veia Cava Inferior , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Células Neoplásicas Circulantes , Estudos Retrospectivos , Adulto JovemRESUMO
Myeloid derived suppressor cells (MDSCs) play key roles in cancer development. Accumulation of peripheral-blood MDSCs (PB-MDSCs) corresponds to the progression of various cancers, but provides only a crude indicator. We aimed toward identifying changes in the transcriptional profile of PB-MDSCs in response to tumor growth. CT26 colon cancer cells and B16 melanoma cells (106) were inoculated into peritoneal cavities of BALB/c mice and subcutaneously to C57-black mice, respectively. The circulating levels and global transcriptional patterns of PB CD11b+Ly6g+ MDSCs were assessed in control mice, and 4, 8, and 11 days following tumor cell inoculation. Although a significant accumulation of PB-MDSCs was demonstrated only 11 days following tumor induction, a pronounced transcriptional response was identified already on day 4 while the tumor was ~1 mm in size. Further transcriptional changes correlated with different stages of tumor growth. Key MDSC genes and canonical signaling pathways were activated along tumor progression. This phenomenon was demonstrated in both cancer models, and a consensus set of 817 genes, involved in myeloid cell recruitment and angiogenesis, was identified. The data suggest that the transcriptional signatures of PB-MDSC may serve as markers for tumor progression, as well as providing potential targets for future therapies.
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Antígeno CD11b/genética , Células Supressoras Mieloides/metabolismo , Animais , Antígeno CD11b/análise , Progressão da Doença , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Células Supressoras Mieloides/fisiologia , Neoplasias/imunologia , Transcriptoma/genéticaRESUMO
BACKGROUND: Antibiotic prophylaxis that covers enteric pathogens is essential in preventing surgical site infections (SSIs) after colorectal surgery. Current prophylaxis regimens do not cover extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). We aimed to determine whether the risk of SSI following colorectal surgery is higher in ESBL-PE carriers than in noncarriers. METHODS: We conducted a prospective cohort study of patients who underwent elective colorectal surgery in 3 hospitals in Israel, Switzerland, and Serbia between 2012 and 2017. We included patients who were aged ≥18 years, were screened for ESBL-PE carriage before surgery, received routine prophylaxis with a cephalosporin plus metronidazole, and did not have an infection at the time of surgery. The exposed group was composed of ESBL-PE-positive patients. The unexposed group was a random sample of ESBL-PE-negative patients. We collected data on patient and surgery characteristics and SSI outcomes. We fit logistic mixed effects models with study site as a random effect. RESULTS: A total of 3600 patients were screened for ESBL-PE; 13.8% were carriers SSIs occurred in 55/220 carriers (24.8%) and 49/440 noncarriers (11.1%, P < .001). In multivariable analysis, ESBL-PE carriage more than doubled the risk of SSI (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.50-3.71). Carriers had higher risk of deep SSI (OR, 2.25; 95% CI, 1.27-3.99). SSI caused by ESBL-PE occurred in 7.2% of carriers and 1.6% of noncarriers (OR, 4.23; 95% CI, 1.70-10.56). CONCLUSIONS: ESBL-PE carriers who receive cephalosporin-based prophylaxis are at increased risk of SSI following colorectal surgery.
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Antibioticoprofilaxia , Portador Sadio/microbiologia , Cirurgia Colorretal/efeitos adversos , Infecções por Enterobacteriaceae/etiologia , Infecção da Ferida Cirúrgica/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Portador Sadio/prevenção & controle , Cefalosporinas/administração & dosagem , Cefalosporinas/efeitos adversos , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Infecções por Enterobacteriaceae/prevenção & controle , Fezes/microbiologia , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Sérvia , Infecção da Ferida Cirúrgica/prevenção & controle , Suíça , beta-LactamasesRESUMO
BACKGROUND AND OBJECTIVES: The impact of resection margins on the outcome of patients with colorectal liver metastasis (CRLM) remains controversial. We evaluated the short and long-term results of R1 resection. METHODS: Between 2006 and 2016, 202 patients underwent liver resection for CRLM. R1 resection was defined as a distance of less than 1 mm between tumor cells and the transection plain. Patient and tumor characteristics, perioperative, and long-term outcomes were assessed. RESULTS: In 161 (79.7%) and 41 (20.3%) patients, an R0 and R1 resections were achieved, respectively. Patients that underwent an R1 resection had higher rates of disease progression while on chemotherapy (12.1% vs 5.5%, P = 0.001), need for second-line chemotherapy (17% vs 6.2%, P < 0.001), increased use of preoperative volume manipulation (14.6% vs 5.5%, P = 0.001), and inferior vena-cava involvement (21.9% vs 8.7%, P < 0.001). These patients had higher rates of major postoperative complications (19.5% vs 6.8%, P < 0.001) and reoperations (7.3% vs 2.4%, P < 0.001). Multivariate analysis demonstrated that R1 resections were not associated with decreased recurrence-free survival or overall survival. CONCLUSIONS: Although R1 resection is associated with worse disease behavior and postoperative complications, the long-term outcome of patients following an R1 resection is non-inferior to those who underwent an R0 resection.
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Neoplasias Colorretais/mortalidade , Hepatectomia/mortalidade , Neoplasias Hepáticas/mortalidade , Margens de Excisão , Complicações Pós-Operatórias/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Reoperation following PD is a surrogate marker for a complex post-operative course and may lead to devastating consequences. We evaluate the indications for early reoperation following PD and analyze its effect on short- and long-term outcome. METHODS: Four hundred and thirty-three patients that underwent PD between August 2006 and June 2016 were retrospectively analyzed. RESULTS: Forty-eight patients (11%; ROp group) underwent 60 reoperations within 60 days from PD. Forty-two patients underwent 1 reoperation, and 6 had up to 6 reoperations. The average time to first reoperation was 10.1 ± 13.4 days. The most common indications were anastomotic leaks (22 operations in 18 patients; 37.5% of ROp), followed by post-pancreatectomy hemorrhage (PPH) (14 reoperations in 12 patients; 25%), and wound complications in 10 (20.8%). Patients with cholangiocarcinoma had the highest reoperation rate (25%) followed by ductal adenocarcinoma (12.3%). Reoperation was associated with increased length of hospital stay and a high post-operative mortality of 18.7%, compared to 2.6% for the non-reoperated group. For those who survived the post-operative period, the overall and disease-free survival were not affected by reoperation. CONCLUSIONS: Early reoperations following PD carries a dramatically increased mortality rate, but has no impact on long-term survival.
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Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/cirurgia , Reoperação/estatística & dados numéricos , Idoso , Fístula Anastomótica/cirurgia , Neoplasias dos Ductos Biliares/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Colangiocarcinoma/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/mortalidade , Estudos RetrospectivosRESUMO
BACKGROUND: Although lymph node (LN) metastases is considered a grave prognostic sign in pancreatic ductal adenocarcinoma (PDAC), patients with positive lymph nodes (PLN) constitute a heterogeneous group. Our purpose was to identify morphological and immune parameters in the primary tumor and in PLN of resected PDAC patients, which could further stratify these patients to different subgroups. METHODS: We retrospectively evaluated histological and immunohistochemical characteristics of 66 patients with PDAC who were operated at our institution. These were subsequently correlated to clinical outcome. RESULTS: Mean patient age and number of LN harvested was 65.5 ± 10.3 and 12.3 ± 6.5 years, respectively. Tumor size (T stage) and perineural invasion had no effect on clinical outcome. High-grade tumor was associated with decreased survival [overall survival (OS) = 19.6 ± 2.7 months for poorly differentiated PDAC vs. 31.2 ± 4 for well and moderately differentiated, p = 0.03]. Patients with ≥ 8 PLN had significantly worse outcome (OS = 7.3 ± 0.8 months for PLN ≥ 8 vs. OS = 30.1 ± 3.2 months for PLN < 8, p < 0.0001). T helper (Th) 1 immune response was measured both by its effector cells (CD8+) and expression of its main transcription factor, T-bet. CD8+ high patients had significantly increased OS compared with CD8+ low (OS = 36.8 ± 5.3 months for CD8 + high vs. OS = 24.3 ± 3.5 for CD8 + low, p = 0.03) Similarly, Th1 predominant immune response measured by T-bet expression was associated with improved OS compared with non-Th1 (OS = 32.8 ± 3.2 vs. OS = 19.5 ± 2.9, p < 0.0001). CONCLUSIONS: Our data indicate an association between Th1-type immune response and increased survival. Future research is needed to exploit Th1 immune response as a biological marker for immunotherapy.
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Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/mortalidade , Linfonodos/imunologia , Recidiva Local de Neoplasia/mortalidade , Neoplasias Pancreáticas/mortalidade , Células Th1/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/imunologia , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/secundário , Carcinoma Ductal Pancreático/cirurgia , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/mortalidade , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Iatrogenic ureteral injury is an increasing concern in the laparoscopic era, affecting both patient morbidity and costs. Current techniques enabling intraoperative ureteral identification require invasive procedures or radiations. Our aim was to develop a real-time, non-invasive, radiation-free method to visualize ureters, based on near-infrared (NIR) imaging. For this purpose, we interfered with the biliary excretion pathway of the indocyanine green (ICG) fluorophore by loading it into liposomes, enabling renal excretion. In this work, we studied various parameters influencing ureteral imaging. METHODS: Fluorescence intensity (FI) of various liposomal ICG sizes and doses were characterized in vitro and subsequently tested in vivo in mice and pigs. Quantification was performed by measuring FI in multiple points and applying the ureteral/retroperitoneum ratio (U/R). RESULTS: The optimal liposomal ICG loading dose was 20%, for the different liposomes' sizes tested (30, 60, 100 nm). Higher concentration of ICG decreased FI. In vivo, the optimal liposome size for ureteral imaging was 60 nm, which yielded a U/R of 5.2 ± 1.7 (p < 0.001 vs. free ICG). The optimal ICG dose was 8 mg/kg (U/R = 2.1 ± 0.4, p < 0.05 vs. 4 mg/kg). Only urine after liposomal ICG injection had a measurable FI, and not after free ICG injection. Using a NIR-optimized laparoscopic camera, ureters could be effectively imaged in pigs, from 10 min after injection and persisting for at least 90 min. Ureteral peristaltic waves could be clearly identified only after liposomal ICG injection. CONCLUSIONS: Optimization of liposomal ICG allowed to visualize enhanced ureters in animal models and seems a promising fluorophore engineering, which calls for further developments.
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Corantes Fluorescentes/administração & dosagem , Verde de Indocianina/administração & dosagem , Imagem Óptica/métodos , Ureter/diagnóstico por imagem , Animais , Feminino , Lipossomos , Masculino , Camundongos , Espectroscopia de Luz Próxima ao Infravermelho , SuínosRESUMO
BACKGROUND: Hartmann's reversal is a challenging surgical procedure with significant postoperative morbidity rates. Various surgical methods have been suggested to lower the risk of postoperative complications. In this study, we aimed to compare the postoperative results between open and laparoscopic techniques for Hartmann's reversal. METHODS: A retrospective study of all patients who underwent Hartmann's reversal in five centers in central Israel between January 2004 and June 2015 was conducted. Medical charts were reviewed, analyzing preoperative and operative parameters and short-term postoperative outcomes. RESULTS: 260 patients were included in the study. 76 patients were operated laparoscopically with a conversion rate of 26.3% (20 patients). No differences were found between patients operated laparoscopically and those operated in an open technique regarding gender (p = 0.785), age (61.34 vs. 62.64, p = 0.521), body mass index (26.6 vs. 26.2, p = 0.948), Charlson index score (1.79 vs. 1.95, p = 0.667), and cause for Hartmann's procedure (neoplastic vs. non-neoplastic, p = 0.644). No differences were seen in average time from the Hartmann's procedure to reversal (204.89 vs. 213.60 days, p = 0.688) and in overall complication rate (46.4 vs. 46.5%, p = 1). The Clavien-Dindo score for distinguishing between minor (0-2 score, p = 1) and major complications (3-5 score, p = 0.675) failed to demonstrate an advantage to laparoscopy, as well as to average length of stay (10.91 days in the laparoscopic group vs. 11.72 days in the open group, p = 0.529). An analysis based on the intention-to-treat with laparoscopy, including converted cases in the laparoscopic group, showed similar results, including overall complication rate (48.6 vs. 45.6%, p = 0.68) and Clavien-Dindo score in both minor (p = 0.24) and major complications (p = 0.44). Length of stay (10.92 vs. 11.81 days, p = 0.45) was also similar between the two groups. CONCLUSION: In this series, a laparoscopic approach to Hartmann's reversal did not offer any short-term advantage when compared to an open surgical approach.
Assuntos
Colectomia , Colostomia , Obstrução Intestinal/cirurgia , Perfuração Intestinal/cirurgia , Laparoscopia , Complicações Pós-Operatórias , Anastomose Cirúrgica/métodos , Colectomia/efeitos adversos , Colectomia/métodos , Colo/cirurgia , Colostomia/efeitos adversos , Colostomia/métodos , Feminino , Humanos , Israel , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos RetrospectivosRESUMO
Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme cells in correspondence to its mediated transcriptome and genome-wide occupancy pattern. Overexpression of RUNX1 led to diminished tumor growth in nude and severe combined immunodeficiency mouse xenograft tumor model. At the molecular level, RUNX1 occupied thousands of genomic regions and regulated the expression of hundreds of target genes, both directly and indirectly. RUNX1 occupied genomic regions that corresponded to genes that were shown to play a role in brain tumor progression and angiogenesis and upon overexpression led to a substantial down-regulation of their expression level. When overexpressed in U87 glioblastoma multiforme cells, RUNX1 down-regulated key pathways in glioblastoma multiforme progression including epithelial to mesenchymal transition, MTORC1 signaling, hypoxia-induced signaling, and TNFa signaling via NFkB. Moreover, master regulators of the glioblastoma multiforme mesenchymal phenotype including CEBPb, ZNF238, and FOSL2 were directly regulated by RUNX1. The data suggest a central role for RUNX1 as master regulator of gene expression in the U87 glioblastoma multiforme cell line and mark RUNX1 as a potential target for novel future therapies for glioblastoma multiforme.
Assuntos
Proliferação de Células/genética , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Transição Epitelial-Mesenquimal/genética , Glioblastoma/genética , Animais , Proteína beta Intensificadora de Ligação a CCAAT/genética , Linhagem Celular Tumoral , Subunidade alfa 2 de Fator de Ligação ao Core/biossíntese , Antígeno 2 Relacionado a Fos/genética , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Humanos , Camundongos , Proteínas Repressoras/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: Hartmann's procedure is commonly practiced in emergent cases with the restoration of bowel continuity planned at a second stage. This study assessed the rate of restorations following Hartmann's procedure and evaluated factors affecting decision-making. METHODS: Data on patient demographics, comorbidities, causes for Hartmann's procedure, reversal rate, and complications were collected in a multicenter retrospective cohort study of patients who underwent Hartmann's procedure in five medical centers. RESULTS: Six hundred forty patients underwent Hartmann's procedure for diverticular disease (36.1%), obstructing malignancy (31.8%), benign obstruction (5%), and other reasons (23.1%). Overall, 260 (40.6%) patients underwent subsequent restoration of bowel continuity. One hundred twenty-one (46.5%) patients had post-reversal complications, with an average Clavien-Dindo score of 1.4 and a mortality rate of 0.77%. Decision to avoid reversal was mostly related to comorbidities (49.7%) and metastatic disease (21.6%). Factors associated with the decision to restore bowel continuity included male gender (P = 0.02), patient age (62.3 years in Hartmann's reversal patients vs 73.5 years in non-reversal patients; P < 0.0001), number of comorbidities (1.1 vs 1.58; P < 0.001), average Charlson score (1.93 vs 3.44; P < 0.001), and a neoplastic etiology (P < 0.0001). A sub-analysis excluding all patients who died in the 30 days following Hartmann's procedure showed similar factors associated with ostomy closure. CONCLUSION: Many patients do not have restoration of bowel continuity after undergoing Hartmann's procedure. Hartmann's reversal is associated with a significant postoperative morbidity. Surgeons and patients should be aware of the possibility that the colostomy might become permanent.
Assuntos
Anastomose Cirúrgica , Colo Sigmoide/cirurgia , Doenças do Colo/cirurgia , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias , Reto/cirurgia , Reoperação , Adulto , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Estudos de Coortes , Colectomia/efeitos adversos , Colectomia/métodos , Colo Sigmoide/patologia , Colo Sigmoide/fisiopatologia , Colostomia/efeitos adversos , Colostomia/métodos , Feminino , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/estatística & dados numéricos , Reoperação/efeitos adversos , Reoperação/métodos , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Tumor localization may pose a significant challenge during minimally invasive rectal resection. Near-infrared (NIR) imaging can penetrate biological tissue and afford tumor localization from the external surface of the rectum. Our aim was to develop an NIR-based tool for rectal tumor imaging that can be administered intravenously. METHODS: We prepared indocyanine-green (ICG)-loaded liposomes by sonication. Liposomes were evaluated for their size and morphology. We then used an endoscopically induced rectal cancer in mice as a model for rectal cancer. After intravenous administration, tumors were evaluated for their fluorescence intensity. Tumor intensity was expressed in relation to the background signal, that is, tumor to background ratio (TBR). RESULTS: Liposomes in various sizes could be prepared by adjusting sonication time. We selected 100-nm-sized liposomes for further experiments. Transmission electron microscopy showed spherical particles and confirmed the size measurements. The liposomes could be lyophilized and then rehydrated again before use without compromising their structure or signal. Fluorescence intensity was kept for 24 hours after solubilization. Testing the optimal time course for rectal tumor imaging revealed that early time course (up to 3 hours) yielded nonspecific imaging, whereas after long time course (24 hours), a very weak signal remained in the tissue. The optimal time window for imaging was after 12 hours from injection, with TBR = 8.1 ± 3.6 ( P = .002). Free ICG could not achieve similar results. CONCLUSIONS: The liposomal ICG can be reproducibly prepared and kept in lyophilized form. Liposomal ICG could serve as a tool for intraoperative tumor localization.
Assuntos
Verde de Indocianina/uso terapêutico , Laparoscopia/métodos , Lipossomos/uso terapêutico , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/cirurgia , Cirurgia Assistida por Computador/métodos , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
BACKGROUND AND OBJECTIVES: Liver resection of colorectal liver metastasis (CRLM) may necessitate large metabolic and physiologic reserve. As the population ages, resection of CRLM is increasingly required in the elderly. We assessed the safety and efficacy of these operations. METHODS: Between February 2010 and 2015, 174 patients underwent liver resection of CRLM. Fifty-four and 120 patients were over and under the age of 70 at the time of surgery, respectively (mean ages: 76 ± 4 and 56.5 ± 9 years). Patient and tumor characteristics, perioperative, and long-term outcomes were compared. RESULTS: Elderly patients had increased rates of IHD (18.5% versus 6.6%, P = 0.0002), COPD (9.2% versus 4.1%, P = 0.01), and DM (30% versus 14%, P = 0.02). Operative time was shorter in elderly patients (222 ± 109 versus 261 ± 110 min; P = 0.04). Intraoperative blood loss was comparable. The rate of minor postoperative complications was similar between groups, but elderly patients had higher rate of major complications (11.1% versus 2.5%, P < 0.0001). One elderly patient died following surgery (1.8%). Length of hospital stay was similar between groups. No difference in 3-year survival was demonstrated. CONCLUSIONS: Although associated with a small increase in postoperative morbidity and mortality, liver resection may be performed safely and effectively in carefully selected elderly patients. J. Surg. Oncol. 2016;113:485-488. © 2016 Wiley Periodicals, Inc.
Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To improve the preoperative assessment of pancreatic incidentalomas (PIs) by analysis of 1 index case and characterization of the published features of intrapancreatic accessory spleen (IPAS) compared to pancreatic neuroendocrine tumor (PNET). METHODS: A search of the literature using the online database MEDLINE. RESULTS: In all, 46 cases of IPAS have been described to date: 17 were "presumed" as IPAS based on technetium-99m (Tc-99m) scanning, fine-needle aspiration (FNA) stain for CD8, or contrast-enhanced sonography; 29 were misdiagnosed as PNET and underwent surgery. The pancreatic lesions were 1) mostly solitary; 2) solid on imaging; 3) well defined; 4) located predominantly at the pancreatic tail; 5) not exceeding 3 cm in the largest diameter; 5) all detected in adults (22-81 years); 6) not related to sex. In subjects referred for surgery, standard imaging studies/imaging protocols did not differentiate between IPAS and PNET. FNA was performed in 5/46 cases, all of which were false-positive for PNET. Immunohistochemical staining for T-cells on FNA material and specific imaging features (characteristic arciform splenic enhancement pattern on dynamic computed tomography [CT]; nuclear scintigraphies with radioisotope specifically trapped by splenic tissue [Tc-99m]) or contrast-enhanced sonography offered valuable clues. Still, distal pancreatectomy and splenectomy was carried out in 72%, and the rest had distal pancreatectomies. CONCLUSION: IPAS should be considered before surgery in patients with PIs. A new practical algorithm is presented for better preoperative evaluation of such lesions; it combines the recognition of early indicators and sequential consideration of cytologic and imaging features to decrease the hazards of unnecessary major surgery. ABBREVIATIONS: CT = computed tomography EUS = endoscopic ultrasound FNA = fine-needle aspiration HDRBC = heat-damaged red blood cells IPAS = intrapancreatic accessory spleen MRI = magnetic resonance tomography NF-PNET = nonfunctioning pancreatic neuroendocrine tumor PET = positron emission tomography PNET = pancreatic neuroendocrine tumor PI = pancreatic incidentalomas SPIO = superparamagnetic iron oxide Tc-99m = technetium-99m.