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1.
J Surg Res ; 251: 78-84, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32113041

RESUMO

BACKGROUND: There is limited information on the oncological outcomes of immediate autologous breast reconstruction in the Asian population. This study aimed to evaluate the oncological outcomes of immediate one-stage autologous breast reconstruction using a free perforator flap for breast cancer patients at a single institution in Japan. METHODS: We retrospectively reviewed 239 patients who underwent immediate one-stage autologous breast reconstruction using a free perforator flap after skin- or nipple-sparing mastectomy. The whole breast was pathologically analyzed in 5-mm sections. Clinical and pathological data were collected from medical records. RESULTS: For tumor stage among the 239 patients, 101 (42.3%) had stage 0, 127 (53.1%) had stage I and II, and 11 (4.6%) had stage III. Twenty-three patients (9.6%) had margin involvement in the surgical specimen. Adjuvant chemotherapy was performed in 75 patients (30%), and endocrine therapy was administered in 153 patients (64%). Radiation therapy was performed in 15 patients (6.3%) because of multiple lymph node metastases or margin involvement. With a median follow-up time of 73 mo, local recurrence was found in 3.3%, distant metastases in 2.5%, and contralateral breast cancer in 3.7%. All patients with local recurrence did not receive radiation therapy as adjuvant treatment. CONCLUSIONS: Among the patients who underwent immediate one-stage autologous reconstruction after breast surgery, 3.3% had local recurrence. For patients with margin involvement, radiation therapy is a promising option.

2.
Ann Surg Oncol ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198569

RESUMO

BACKGROUND: The objective of the current study was to assess the impact of serum CA19-9 and CEA and their combination on survival among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC). METHODS: Patients who underwent curative-intent resection of ICC between 1990 and 2016 were identified using a multi-institutional database. Patients were categorized into four groups based on combinations of serum CA19-9 and CEA (low vs. high). Factors associated with 1-year mortality after hepatectomy were examined. RESULTS: Among 588 patients, 5-year OS was considerably better among patients with low CA19-9/low CEA (54.5%) compared with low CA19-9/high CEA (14.6%), high CA19-9/low CEA (10.0%), or high CA19-9/high CEA (0%) (P < 0.001). No difference in 1-year OS existed between patients who had either high CA19-9 (high CA19-9/low CEA: 70.4%) or high CEA levels (low CA19-9/high CEA: 72.5%) (P = 0.92). Although patients with the most favorable tumor marker profile (low CA19-9/low CEA) had the best 1-year survival (87.9%), 15.1% (n = 39) still died within a year of surgery. Among patients with low CA19-9/low CEA, a high neutrophil-to-lymphocyte ratio (NLR) (odds ratio 1.09; 95% confidence interval 1.03-1.64) and large size tumor (odds ratio 3.34; 95% confidence interval 1.40-8.10) were associated with 1-year mortality (P < 0.05). CONCLUSIONS: Patients with either a high CA19-9 and/or high CEA had poor 1-year survival. High NLR and large tumor size were associated with a greater risk of 1-year mortality among patients with favorable tumor marker profile.

3.
In Vivo ; 34(2): 723-728, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32111776

RESUMO

BACKGROUND/AIM: The present study examined the utility of serum p53 antibody (Ab) for detecting colitis-associated cancer (CAC) in the era of immunosuppressive therapy. PATIENTS AND METHODS: Two hundred and fifty patients were analyzed, 219 had no carcinoma or dysplasia (Group non-CAC), and 31 had carcinoma or dysplasia (Group CAC). Serum p53 Abs were detected with an enzyme-linked immunosorbent assay. Immunohistochemical detection was performed in Group CAC. RESULTS: Immunosuppressive therapy was performed in 98.1% of Group non-CAC and 80.6% of Group CAC. There were no differences in serum p53 Abs positivity between Groups non-CAC and CAC (8.7% vs. 3.2%, p=0.30). p53 staining positivity was noted in 90.3% of Group CAC, and the rate of serum p53 positivity was significantly lower in patients with immunosuppressive therapy than in those without in Group CAC (0.0% vs. 16.7%, p=0.04). CONCLUSION: The utility of serum p53 Ab for detecting CAC is dubious in the era of immunosuppressive therapy.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32128955

RESUMO

BACKGROUND: Lymph node metastasis is an important prognostic factor for distal bile duct cancer. The number of lymph node metastases was adopted for nodal classification. However, different cutoff values have been proposed, ranging from two to five. METHODS: A total of 1,748 cases who underwent curative surgery with pancreatoduodenectomy for distal bile duct cancer registered in the nationwide biliary tract cancer registry in Japan from 2008 to 2013 were included. Univariate Cox regression was performed to assess the effect of prognostic lymph node metastasis counts on mortality and to determine cutoff values. RESULTS: The overall survival rate after resection was 47.4% at five years. Univariate and multivariate analysis found prognostic factors to include lymph node metastasis. The cutoff point was set to two lymph node metastases using the Cox model. There were significant differences in pairwise comparisons between three groups by the number of metastatic lymph node (P < 0.001 for 0 vs. 1-2 and P = 0.003 for 1-2 vs. ≥ 3). CONCLUSION: Our data suggest lymph node classification as N0 (patients without lymph node metastases), N1 (metastasis in 1-2 regional lymph nodes), and N2 (metastases in ≥ 3 regional lymph nodes).

5.
Anticancer Res ; 40(3): 1587-1595, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32132061

RESUMO

BACKGROUND/AIM: The purpose of this study was to evaluate the usefulness of minimally invasive esophagectomy (MIE) for stage II/III esophageal cancer (EC). PATIENTS AND METHODS: We compared surgical outcomes between MIE and open esohagectomy in EC patients with pStage II/III using the propensity scoring system. RESULTS: Fifty-seven patients were classified into the MIE group and 57 patients into the open esophagectomy (OE) group. The incidence of major complications was similar between the two groups. The 5-year OS was significantly better in the MIE group (69.0% vs. 35.5%; p=0.004) and no significant difference was observed in the 5-year recurrence-free survival (RFS, 52.2% vs. 29.2%; p=0.064). Multivariate analysis showed MIE was a prognostic factor of OS (p<0.001) and RFS (p=0.032). CONCLUSION: MIE was as safe and feasible as OE, and an independent prognostic factor for OS and RFS in patients with stage II/III EC.

6.
Transl Oncol ; 13(3): 100746, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32105991

RESUMO

Pancreatic intraepithelial neoplasia (PanIN), the most common premalignant lesion of the pancreas, is a histologically well-defined precursor to invasive pancreatic ductal adenocarcinoma (PDAC). However, the molecular mechanisms underlying the progression of PanINs have not been fully elucidated. Previously, we demonstrated that the expression of collapsin response mediator protein 4 (CRMP4) in PDAC was associated with poor prognosis. The expression of CRMP4 was also augmented in a pancreatitis mouse model. However, the role of CRMP4 in the progression of PanIN lesions remains uncertain. In the present study, we examined the relationship between CRMP4 expression and progression of PanIN lesions using genetically engineered mouse models. PanIN lesions were induced by peritoneal injection of the cholecystokinin analog caerulein in LSL-KRASG12D; Pdx1-Cre (KC-Crmp4 wild-type, WT) mice and LSL-KRASG12D; Pdx1-Cre; Crmp4-/- (KC-Crmp4 knockout, KO) mice. We analyzed pancreatic tissue sections from these mice and evaluated PanIN grade by hematoxylin and eosin staining. CRMP4 expression was examined and the cellular components assessed by immunohistochemistry using antibodies against CRMP4, CD3, and α-smooth muscle actin (SMA). The incidence of high-grade PanIN in KC-Crmp4 WT mice was higher than that in KC-Crmp4 KO animals. CRMP4 was expressed not only in epithelial cells but also in αSMA-positive cells in stromal areas of PanIN lesions. The CRMP4 expression in stromal areas correlated with PanIN grade in WT mice. These results suggested that the expression of CRMP4 in stromal cells may underlie the incidence or progression of PanIN.

7.
J Am Coll Surg ; 230(4): 381-391.e2, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32014569

RESUMO

BACKGROUND: Estimating prognosis in the preoperative setting is challenging, as most survival risk scores rely exclusively on postoperative factors. We sought to develop a composite score that incorporated preoperative liver, tumor, nutritional, and inflammatory markers to predict long-term outcomes after resection of intrahepatic cholangiocarcinoma (ICC). STUDY DESIGN: Patients who underwent curative-intent hepatectomy for ICC between 2000 and 2017 were identified using an international multi-institutional database. Clinicopathologic factors were assessed using bivariate and multivariable analysis and a prognostic model to estimate overall survival (OS) based only on preoperative laboratory values (LabScore) was developed and validated. RESULTS: Among 660 patients, median OS was 43.2 months and 5-year OS rate was 42.4%. On multivariable analysis, laboratory values associated with OS included carbohydrate antigen 19-9 (hazard ratio [HR] 1.16; 95% CI 1.05 to 1.27), neutrophil-to-lymphocyte ratio (HR 1.09; 95% CI, 1.05 to 1.13), platelet count (HR 1.01; 95% CI, 1.00 to 1.01), and albumin (HR 0.75; 95% CI, 0.62 to 0.92). A weighted LabScore was constructed based on the formula: (8.2 + 1.45 × natural logarithm of carbohydrate antigen 19-9 + 0.84 × neutrophil-to-lymphocyte ratio + 0.03 × platelets - 2.83 × albumin). Patients with a LabScore of 0 to 9 (n = 223), 10 to 19 (n = 353) and ≥20 (n = 88) had incrementally worse 5-year OS rates of 54.9%, 38.2% and 21.6%, respectively (p < 0.001). The model demonstrated good performance in both the test (c-index 0.70) and validation cohorts (c-index 0.67), as well as outperformed individual laboratory markers, the prognostic nutritional index (c-index 0.58), and American Joint Committee on Cancer staging system (c-index 0.60). CONCLUSIONS: A preoperative LabScore was able to predict long-term outcomes of patients after resection for ICC better than American Joint Committee on Cancer staging system. The LabScore can be used to preoperatively identify patients who will benefit the most from upfront operation or alternative treatment options, including neoadjuvant chemotherapy before resection.

8.
Neuroendocrinology ; 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32040951

RESUMO

BACKGROUND: The adoption of spleen-preserving distal pancreatectomy (SPDP) for malignant disease such as pancreatic neuroendocrine tumors (pNETs) has been controversial. The objective of the current study was to assess the impact of SPDP on outcomes of patients with pNETs. METHODS: Patients undergoing a distal pancreatectomy (DP) for pNET between 2002 and 2016 were identified in the U.S. Neuroendocrine Tumor Study Group database. Propensity score matching (PSM) was used to compare short- and long-term outcomes of patients undergoing SPDP versus distal pancreatectomy with splenectomy (DPS). RESULTS: Among 621 patients, 103 patients (16.6%) underwent an SPDP. Patients who underwent SPDP were more likely to have lower BMI (median, 27.5 [IQR 24.0-31.2] vs. 28.7 [IQR 25.7-33.6]; p=0.005), and have undergone minimally invasive surgery (n=56, 54.4% vs. n=185, 35.7%; p<0.001). After PSM, while the median total number of lymph nodes examined among patients who underwent an SPDP was lower compared with DPS (3 [IQR 1-8]) vs. 9 [5-13]; p<0.001), 5-year overall survival and recurrence-free survival were comparable (OS: 96.8% vs. 92.0%, log-rank p=0.21, RFS: 91.1% vs. 84.7%, log-rank p=0.93). In addition, patients undergoing SPDP had less intraoperative blood loss (median, 100 ml [IQR 10-250] vs. 150 ml [IQR 100-400]; p=0.001), lower incidence of serious complications (n=13, 12.8% vs. n=28, 27.5%; p=0.014) and shorter length-of-stay (median: 5 days [IQR 4-7] vs. 6 days [IQR 5-13]; p=0.049) compared with patients undergoing DPS. CONCLUSION: SPDP for pNET was associated with acceptable peri-operative and long-term outcomes that were comparable to DPS. SPDP should be considered for patients with pNET.

10.
J Surg Oncol ; 121(3): 503-510, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31907941

RESUMO

BACKGROUND: The survival benefit of lymphadenectomy among patients with gallbladder cancer (GBC) remains poorly understood. METHODS: Patients who underwent resection for GBC between 2000 and 2015 were identified from a US multi-institutional database. The therapeutic index (LNM rate multiplied by 3-year overall survival [OS]) was determined to assess the survival benefit of lymphadenectomy. RESULTS: Among 449 patients, less than half had LNM (N = 183, 40.8%). The median number of evaluated and metastatic lymph nodes (LNs) was 3 (interquartile range [IQR]: 1-6) and 1 (IQR: 0-1), respectively. 3-year OS among patients with LNM in the entire cohort was 26.8%. The therapeutic index was lower among patients with T4 (5.9) or T1 (6.0) tumors as well as carbohydrate antigen (CA19-9) ≥200 UI/mL (6.0). Of note, a therapeutic index difference ≥10 was noted relative to CA19-9 (<200: 18.7 vs ≥200: 6.0), American Joint Committee on Cancer T Stage (T1: 6.0 vs T2: 17.8 vs T4: 5.9) and number of LNs examined (1-2: 6.9 vs ≥6: 16.9). Concomitant common bile duct resection was not associated with a higher therapeutic index among patients with either T2 or T3 disease. CONCLUSION: Certain clinicopathological factors including T1 or T4 tumor and CA19-9 ≥200 UI/mL were associated with a low therapeutic index. Resection of six or more LNs was associated with a meaningful therapeutic index benefit among patients with LNM.


Assuntos
Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/cirurgia , Linfonodos/cirurgia , Idoso , Estudos de Coortes , Ducto Colédoco/cirurgia , Bases de Dados Factuais , Feminino , Neoplasias da Vesícula Biliar/patologia , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo/métodos , Excisão de Linfonodo/mortalidade , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Taxa de Sobrevida , Índice Terapêutico , Estados Unidos/epidemiologia
11.
Clin J Gastroenterol ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31970661

RESUMO

Regorafenib is an oral multikinase inhibitor affecting angiogenesis, oncogenesis, metastasis, and tumor immunity. As a systemic treatment, it has been shown to provide survival benefits in hepatocellular carcinoma (HCC) patients progressing on sorafenib treatment. We report herein a case of HCC with hepatic vein tumor thrombosis protruding into the inferior vena cava (IVC-HVTT) which was successfully treated by surgery following second-line chemotherapy with regorafenib. A 79-year-old man with chronic hepatitis was diagnosed with HCC. Computed tomography revealed a solitary tumor in segments 7 and 8 and an IVC-HVTT from the right hepatic vein. Since IVC-HVTT removal is a difficult procedure, the tumor was diagnosed as unresectable, and administration of sorafenib was started. Five weeks later, the lesion had increased in size by 15.3%; subsequently, regorafenib was given as second-line therapy for 12 months. After shrinkage of the IVC-HVTT, the patient was referred to our hospital for surgery. One month after the cessation of regorafenib, an extended resection of segment 8 and total removal of the IVC-HVTT was successfully performed without using total hepatic vascular exclusion. There were no serious postoperative complications. Additionally, there has been no recurrence for about 2 years since the initial therapy.

12.
Ann Surg Oncol ; 27(3): 866-874, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31696396

RESUMO

BACKGROUND: There is an ongoing debate about expanding the resection criteria for hepatocellular carcinoma (HCC) beyond the Barcelona Clinic Liver Cancer (BCLC) guidelines. We sought to determine the factors that held the most prognostic weight in the pre- and postoperative setting for each BCLC stage by applying a machine learning method. METHODS: Patients who underwent resection for BCLC-0, A and B HCC between 2000 and 2017 were identified from an international multi-institutional database. A Classification and Regression Tree (CART) model was used to generate homogeneous groups of patients relative to overall survival (OS) based on pre- and postoperative factors. RESULTS: Among 976 patients, 63 (6.5%) had BCLC-0, 745 (76.3%) had BCLC-A, and 168 (17.2%) had BCLC-B HCC. Five-year OS among BCLC-0/A and BCLC-B patients was 64.2% versus 50.2%, respectively (p = 0.011). The preoperative CART model selected α-fetoprotein (AFP) and Charlson comorbidity score (CCS) as the first and second most important preoperative factors of OS among BCLC-0/A patients, whereas radiologic tumor burden score (TBS) was the best predictor of OS among BCLC-B patients. The postoperative CART model revealed lymphovascular invasion as the best postoperative predictor of OS among BCLC-0/A patients, whereas TBS remained the best predictor of long-term outcomes among BCLC-B patients in the postoperative setting. On multivariable analysis, pathologic TBS independently predicted worse OS among BCLC-0/A (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.02-1.07) and BCLC-B patients (HR 1.13, 95% CI 1.06-1.19) undergoing resection. CONCLUSION: Prognostic stratification of patients undergoing resection for HCC within and beyond the BCLC resection criteria should include assessment of AFP and comorbidities for BCLC-0/A patients, as well as tumor burden for BCLC-B patients.

13.
Cancer Sci ; 111(2): 334-342, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31774932

RESUMO

Glypican-3 (GPC3) is a cancer antigen expressed in approximately 80% of hepatocellular carcinomas (HCC) and is secreted into the blood. To confirm the effectiveness of GPC3 as a biomarker in HCC, we analyzed the relationship between GPC3 expression levels in cancer cells and in blood in 56 patients with HCC. Preoperative plasma GPC3 levels were determined with an immunoassay, and expression of GPC3 in resected tumors was analyzed by immunohistochemical staining. Median plasma GPC3 level in all HCC cases was 4.6 pg/mL, and tended to be higher in patients with hepatitis C virus (HCV)-related HCC (HCV group) (9.9 pg/mL) than in patients with hepatitis B virus (HBV)-related HCC (HBV group) (2.6 pg/mL) or in those without virus infection (None group) (3.0 pg/mL), suggesting that the virus type most likely influences GPC3 secretion. Median percentage of GPC3+ cells in tumors was also higher in the HCV (26.2%) and HBV (11.1%) groups than in the None group (4.2%). In the HCV group, there was a positive correlation between the two parameters (r = 0.66, P < .01). Moreover, receiver operating characteristic analysis predicted >10% GPC3+ cells in a tumor if the cut-off value was 6.8 pg/mL (sensitivity 80%, specificity 100%; area under the curve 0.875, 95% confidence interval 0.726-1) in the HCV group. Plasma concentration of GPC3 could be a predictive marker of tumoral GPC3 expression in patients with HCV-related HCC, suggesting a useful biomarker for immunotherapies targeting GPC3, although larger-scale validations are needed.


Assuntos
Carcinoma Hepatocelular/virologia , Glipicanas/metabolismo , Hepatite C/sangue , Neoplasias Hepáticas/virologia , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirurgia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Glipicanas/sangue , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade
14.
Surg Today ; 50(1): 68-75, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31385041

RESUMO

PURPOSE: We conducted a prospective study to evaluate the efficacy and safety of postoperative enoxaparin for the prevention of venous thromboembolism (VTE) after laparoscopic surgery for colorectal cancer (LAC) in Japanese patients. METHODS: The subjects of this multicenter, open-label randomized-controlled trial were 121 patients who underwent LAC between September 2015 and May 2017. The patients were randomly allocated to receive intermittent pneumatic compression (IPC) with enoxaparin (20 mg, twice daily), started 24-36 h after surgery and continued until discharge (Enoxaparin group; n = 61), or IPC alone (IPC group; n = 60). The primary endpoint was the incidence of VTE on day 28 after surgery. The safety outcome was the incidence of any bleeding during treatment and follow-up. RESULTS: The incidence of VTE on day 28 after surgery was 12.3% (7/57 patients) in the enoxaparin group and 11.9% (7/59 patients) in the IPC group ((p = 1.00). One of the 57 patients (1.8%) in the enoxaparin group and none in the IPC group experienced a bleeding event. CONCLUSIONS: It may be unnecessary to give enoxaparin to all Japanese patients for the prevention of VTE after LAC. The UMIN Clinical Trials Registry number was UMIN000018633.

15.
Surg Endosc ; 34(1): 202-208, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30877565

RESUMO

BACKGROUND: Recent studies have shown the potential benefit of indocyanine green fluorescence imaging (ICG-FI) in lowering the anastomotic leakage (AL) rates by changing the surgical plan. The aim of this study was to evaluate the effect of ICG-FI on the AL rates in laparoscopic low anterior resection (LAR) for rectal cancer. METHODS: From September 2014 to December 2017, data from patients who underwent laparoscopic LAR for rectal cancer were collected and analyzed. The primary endpoint was the AL rate within 30 days after surgery. The incidence of AL in patients who underwent ICG (ICG-FI group) was compared with that in patients who did not undergo ICG (non-ICG-FI group) using propensity score matching. RESULTS: Data from 550 patients were collected from 3 institutions. A total of 211 patients were matched in both groups by the propensity score. ICG-FI shifted the point of the proximal colon transection line toward the oral side in 12 patients (5.7%). The AL rates of Clavien-Dindo (CD) grade ≥ II and ≥ III were 10.4% (22/211) and 9.5% (20/211) in the non-ICG-FI group and 4.7% (10/211) and 2.8% (6/211) in the ICG-FI group, respectively. ICG-FI significantly reduced the AL rate of CD grade ≥ II and ≥ III (odds ratio (OR) 0.427; 95% confidence interval (CI) 0.197-0.926; p = 0.042 and OR 0.280; CI 0.110-0.711; p = 0.007, respectively). The rate of reoperation was significantly lower (OR 0.192; CI 0.042-0.889; p = 0.036) and the postoperative hospital stay significantly shorter (mean difference 2.62 days; CI 0.96-4.28; p = 0.002) in the ICG-FI group than in the non-ICG-FI group. CONCLUSIONS: ICG-FI was associated with significantly lower odds of AL in laparoscopic LAR for rectal cancer. CLINICAL TRIAL: The study was registered with the Japanese Clinical Trials Registry as UMIN000032654.

17.
Cancer Lett ; 469: 217-227, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31669204

RESUMO

The pancreatic cancer microenvironment is crucial in cancer development, progression and drug resistance. Cancer-stromal interactions have been recognized as important targets for cancer therapy. However, identifying relevant and druggable cancer-stromal interactions is challenging due to the lack of quantitative methods to analyze the whole cancer-stromal interactome. Here we studied 14 resected pancreatic cancer specimens (8 pancreatic adenocarcinoma (PDAC) patients as a cancer group and 6 intraductal papillary-mucinous adenoma (IPMA) patients as a control). Shotgun proteomics of the stromal lesion dissected with laser captured microdissection (LCM) was performed, and identified 102 differentially expressed proteins in pancreatic cancer stroma. Next, we obtained gene expression data in human pancreatic cancer and normal pancreatic tissue from The Cancer Genome Atlas database (n = 169) and The Genotype-Tissue Expression database (n = 197), and identified 1435 genes, which were differentially expressed in pancreatic cancer cells. To identify relevant and druggable cancer-stromal-interaction targets, we applied these datasets to our in-house ligand-receptor database. Finally, we identified 9 key genes and 8 key cancer-stromal-interaction targets for PDAC patients. Furthermore, we examined FN1 and ITGA3 protein expression in pancreatic cancer tissues using tissue microarrays (TMAs) of 271 PDAC cases, and demonstrated that FN1-ITGA3 had unfavorable prognostic impact for PDAC patients.

18.
HPB (Oxford) ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31812552

RESUMO

BACKGROUND: Although most conventional risk prediction models have been based on preoperative information, intra- and post-operative events may be more relevant to mortality after surgery. We sought to develop a mortality risk calculator based on real time characteristics associated with hepatectomy. METHODS: Patients who underwent hepatectomy between 2014 and 2017 were identified in the ACS-NSQIP dataset. Three prediction models (pre-, intra-, post-operative) were developed and validated using perioperative data. RESULTS: Among 14,720 patients, 197 (1.3%) experienced 30-day mortality. The predictive ability of the real-time mortality risk calculator was very good based on only preoperative factors (AUC; training cohort: 0.813, validation cohort: 0.731). Incorporating intra-operative variables into the model increased the AUC (training: 0.838, validation: 0.777), while the post-operative model achieved an AUC of 0.922 in the training and 0.885 in the validation cohorts, respectively. While patients with low preoperative risk had only very small fluctuations in the estimated 30-day mortality risk during the intraoperative (Δ0.4%) and postoperative (Δ0.6%) phases, patients who were already deemed high risk preoperatively had additional increased mortality risk based on factors that occurred in the intraoperative (Δ5.4%) and postoperative (Δ9.3%) periods. CONCLUSION: A real-time mortality risk calculator may better help clinicians identify patients at risk of death at the different stages of the surgical episode.

19.
Ann Surg Oncol ; 2019 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-31838609

RESUMO

BACKGROUND: The role of routine lymphadenectomy in the surgical treatment of pancreatic neuroendocrine tumors (pNET) remains poorly defined. The objective of the current study was to investigate trends in the number of lymph nodes (LN) evaluated for pNET treatment at a nationwide level. METHODS: Patients undergoing surgery for pNET between 2000 and 2016 were identified in the U.S. Neuroendocrine Tumor Study Group (US-NETSG) database as well as the Surveillance, Epidemiology, and End Results (SEER) database. The number of LNs examined was evaluated over time. RESULTS: The median number of evaluated LNs increased roughly fourfold over the study period (US-NETSG, 2000: 3 LNs vs. 2016: 13 LNs; SEER, 2000: 3 LNs vs. 2016: 11 LNs, both p < 0.001). While no difference in 5-year OS and RFS was noted among patients who had 1-3 lymph node metastases (LNM) vs. ≥ 4 LNM between 2000-2007 (OS 73.5% vs. 69.9%, p = 0.12; RFS: 64.9% vs. 40.1%, p = 0.39), patients who underwent resection and LN evaluation during the period 2008-2016 had an incrementally worse survival if the patient had node negative disease, 1-3 LNM and ≥ 4 LNM (OS 86.8% vs. 82.7% vs. 74.9%, p < 0.001; RFS: 86.3% vs. 64.7% vs. 50.4%, p < 0.001). On multivariable analysis, a more recent year of diagnosis, pancreatic head tumor location, and tumor size > 2 cm were associated with 12 or more LNs evaluated in both US-NETSG and SEER databases. CONCLUSION: The number of LNs examined nearly quadrupled over the last decade. The increased number of LNs examined suggested a growing adoption of the AJCC staging manual recommendations regarding LN evaluation in the treatment of pNET.

20.
Clin Nutr ESPEN ; 34: 116-124, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31677701

RESUMO

BACKGROUNDS AND AIMS: This randomized clinical trial examined efficacy of prolonged elemental diet (ED) therapy after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC), which often causes postoperative malnutrition leading to worsened short- and long-term outcomes. METHODS: Thirty-nine patients with PDAC receiving PD was randomly assigned to prolonged ED group (PEDG) and control group (CG). Fat-free ED (Elental®, EA Pharma CO., Ltd., Tokyo, Japan) via tube jejunostomy was initiated on postoperative day 1 and increased to maintain with 600 kcal/day in addition to oral intake. ED was discontinued if sufficient oral intake was achieved in CG but continued during 3 postoperative months in PEDG. Primary outcome was complication necessitating readmission. Secondary outcomes were nutritional parameters, relative dose intensity (RDI) in cases of adjuvant chemotherapy, and survival outcomes. RESULTS: Twenty patients were assigned to CG and 19 to PEDG. Cumulative post-discharge readmission rate was significantly lower in PEDG than in CG (PEDG vs CG; 12.6% vs 43.7% at 12-post-discharge-month; p = 0.018). Total calorie and ED-derived protein intakes were significantly larger in PEDG than in CG up to 3-postoperative-month but thereafter similar among groups. Lymphocyte counts were significantly increased and neutrophil-to-lymphocyte-ratio (NLR) was significantly reduced in PEDG than in CG at 2-, 3-, and 6-postoperative-month. However, other outcome measures did not differ among groups. CONCLUSION: This trial failed to show survival benefit of prolonged ED therapy but demonstrated its favorable effect on increased lymphocyte counts, reduced NLR, and prevention of complications necessitating readmission, those which may lead to survival benefit with some modifications.

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