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1.
Surgery ; 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32183994

RESUMO

BACKGROUND: The International Study Group for Pancreatic Surgery provides globally accepted definitions for reporting of complications after pancreatic surgery. This International Study Group for Pancreatic Surgery project aims to provide a standardized framework for reporting of the results of operative treatment for chronic pancreatitis. METHODS: An International Study Group for Pancreatic Surgery project circulation list was created with pre-existing and new members and including gastroenterologists in addition to surgeons. A computerized search of the literature was undertaken for articles reporting the operative treatment of chronic pancreatitis. The results of the literature search were presented at the first face-to-face meeting of this International Study Group for Pancreatic Surgery project group. A document outlining proposed reporting standards was produced by discussion during an initial meeting of the International Study Group for Pancreatic Surgery. An electronic questionnaire was then sent to all current members of the International Study Group for Pancreatic Surgery. Responses were collated and further discussed at international meetings in North America, Europe, and at the International Association of Pancreatology World Congress in 2019. A final consensus document was produced by integration of multiple iterations. RESULTS: The International Study Group for Pancreatic Surgery consensus standards for reporting of surgery in chronic pancreatitis recommends 4 core domains and the necessary variables needed for reporting of results: clinical baseline before operation; the morphology of the diseased gland; a new, standardized, operative terminology; and a minimum outcome dataset. The 4 domains combine to give a comprehensive framework for reports. CONCLUSION: Adoption of the 4 domains of the International Study Group for Pancreatic Surgery reporting standards for surgery for chronic pancreatitis will facilitate comparison of results between centers and help to improve the care for patients with this debilitating disease.

2.
Pancreatology ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32222341

RESUMO

BACKGROUND/OBJECTIVES: We sought to identify the reliability of AJCC clinical staging was in comparison to pathologic staging in surgically resected patients with pancreatic cancer. METHODS: We used the National Cancer Database Pancreas from 2004 to 2016 and evaluated patients who underwent resection for PDAC with all documented components of clinical and pathologic stage. We first evaluated the distribution of overall clinical stage and pathologic stage and then evaluated for stage migration by assessing the number of patients who shifted from a clinical stage group to a respective pathologic stage group. To further characterize the migratory pattern, we assessed the distribution of clinical and pathologic T-stage and N-stage. RESULTS: In our cohort of 28,338 patients who underwent resection for PDAC, AJCC clinical staging did not reliably predict pathologic stage. Stage migration after resection was responsible for discrepancies between the distribution of overall clinical stage and pathologic stage. The predominant migration was from patients with clinical stage I disease to pathologic stage II disease. Most patients with clinical T1 and T2 disease were upstaged to pathologic T3 disease and over half of patients with clinical N0 disease were upstaged to pathologic N1 disease after resection. DISCUSSION: Clinical staging appears to overrepresent early T1, T2, and N0 disease, and underrepresent T3 and N1 disease.

3.
Surg Infect (Larchmt) ; 21(1): 54-61, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31429662

RESUMO

Background: More than 145,500 abdominal abscesses occur annually in the U.S. Percutaneous catheter drainage (PCD) is the primary treatment for clinically significant intra-abdominal collections (IACs), but only approximately 90% of all IACs are treatable with PCD. This leaves a significant number of patients facing long courses of management, including multiple interventions. Minimally invasive debridement techniques are now employed regularly for the treatment of infected necrosis caused by acute pancreatitis. We describe the use of minimally invasive videoscopic debridement techniques employed as part of a "step-up" approach to resolve IACs of other etiologies that are unresponsive to PCD. Methods: Data of all patients undergoing this procedure at a tertiary referral academic center from 2015 to 2017 after failure of different PCD techniques were analyzed retrospectively. Results: Four men and two women, mean age 54.6 years (range 26-70 years), with refractory IACs (mean drainage time 91.3 days; mean number of drainage procedures 4.6) following a variety of surgical interventions and inflammatory conditions underwent either video-assisted retroperitoneal debridement or sinus tract endoscopic debridement with a rigid or flexible endoscope. Technical success was achieved in all cases, and clinical success was observed in five cases. No immediate procedural complications were detected. The mean hospital stay and post-procedure drainage times were 5.5 and 25.2 days, respectively. There were no recurrent IACs. Conclusion: Minimally invasive debridement techniques can safely resolve IACs refractory to standard PCD techniques. Employment of these techniques as part of a step-up approach may reduce the morbidity and duration of drainage for the thousands of patients treated annually who have refractory IACs, whatever their etiology.

4.
Ann Surg ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804389

RESUMO

OBJECTIVE: To evaluate the influence of consensus guidelines on the management of intraductal papillary mucinous neoplasms (IPMN) and the subsequent changes in pathologic outcomes. BACKGROUND: Over time, multiple guidelines have been developed to identify high-risk IPMN. We hypothesized that the development and implementation of guidelines should have increased the percentage of resected IPMN with high-risk disease. METHODS: Memorial Sloan-Kettering (MSK), Johns Hopkins (JH), and Massachusetts General Hospital (MGH) databases were queried for resected IPMN (2000-2015). Patients were categorized into main-duct (MD-IPMN) versus branch-duct (BD-IPMN). Guideline-specific radiographic/endoscopic features were recorded. High-risk disease was defined as high-grade dysplasia/carcinoma. Fisher's exact test was used to detect differences between institutions. Logistic regression evaluated differences between time-points [preguidelines (pre-GL, before 2006), Sendai (SCG, 2006-2012), Fukuoka (FCG, after 2012)]. RESULTS: The study included 1210 patients. The percentage of BD-IPMN with ≥1 high-risk radiographic feature differed between centers (MSK 69%, JH 60%, MGH 45%; P < 0.001). In MD-IPMN cohort, the presence of radiographic features such as solid component and main pancreatic duct diameter ≥10 mm also differed (solid component: MSK 38%, JH 30%, MGH 18%; P < 0.001; duct ≥10 mm: MSK 49%, JH 32%, MGH 44%; P < 0.001). The percentage of high-risk disease on pathology, however, was similar between institutions (BD-IPMN: P = 0.36, MD-IPMN: P = 0.48). During the study period, the percentage of BD-IPMN resected with ≥1 high-risk feature increased (52% pre-GL vs 67% FCG; P = 0.005), whereas the percentage of high-risk disease decreased (pre-GL vs FCG: 30% vs 20%). For MD-IPMN, there was not a clear trend towards guideline adherence, and the rate of high-risk disease was similar over the time (pre-GL vs FCG: 69% vs 67%; P = 0.63). CONCLUSION: Surgical management of IPMN based on radiographic criteria is variable between institutions, with similar percentages of high-risk disease. Over the 15-year study period, the rate of BD-IPMN resected with high-risk radiographic features increased; however, the rate of high-risk disease decreased. Better predictors are needed.

5.
Ann Surg ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31851002

RESUMO

OBJECTIVE: To test the hypothesis that complete, tumor-free resection at the pancreatic neck, achieved either en-bloc or non-en-bloc (ie, revision based on intraoperative frozen section [FS] analysis), is associated with improved survival as compared with incomplete resection (IR) in pancreatic ductal adenocarcinoma. SUMMARY BACKGROUND DATA: Given the likely systemic nature of pancreatic ductal adenocarcinoma, the oncologic benefit of achieving a histologically complete local resection, particularly through revision of a positive intraoperative FS at the pancreatic neck, remains controversial. METHODS: Clinicopathologic and treatment data were reviewed for 986 consecutive patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas who underwent open pancreatectomy as well as intraoperative FS analysis between 1998 and 2012 at Massachusetts General Hospital and between 1998 and 2013 at the University of Verona. Overall survival (OS) and perioperative morbidity and mortality were compared across 3 groups: complete resection achieved en-bloc (CR-EB), complete resection achieved non-en-bloc (CR-NEB), and IR. RESULTS: The CR-EB cohort comprised 749 (76%) patients, CR-NEB 159 patients (16%), and IR 78 patients (8%). Other than a higher incidence of vascular resection among CR-NEB and IR patients, no demographic, pathologic (eg, tumor grade, lymph node positivity, superior mesenteric artery involvement), or treatment factors (eg, neoadjuvant and adjuvant therapy use) differed between the groups. Median OS was significantly higher in patients with CR-EB (28 mo, P = 0.01) and CR-NEB resections (24 mo, P = 0.02) as compared with patients with IR resections (19 mo). After adjusting for clinicopathologic and treatment characteristics, CR-EB and CR-NEB margin status were found to be independent predictors of improved OS (relative to IR, CR-EB hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.49-0.86; CR-NEB HR 0.69, 95% CI 0.50-0.96). There were no intergroup differences in perioperative morbidity and mortality, including rates of pancreatic fistula. CONCLUSIONS: For patients with ductal adenocarcinoma at the head, neck, or uncinate process of the pancreas undergoing pancreatectomy, complete tumor extirpation via either en-bloc or non-en-bloc complete resection based on FS analysis is associated with improved OS, without an associated increased perioperative morbidity or mortality.

6.
Ann Surg Oncol ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758284

RESUMO

OBJECTIVE: To define short-term and long-term outcomes of IORT for the management of BR/LA PDAC in the era of modern neoadjuvant therapy (NAT). BACKGROUND: In the era of neoadjuvant FOLFIRINOX, many patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC) become candidates for surgical exploration with curative intent. IORT may be used to consolidate treatment for successfully resected patients with close or positive margins or administered in unresectable patients without distant metastases. METHODS: A retrospective review of 158 patients who received IORT in the setting of biopsy-proven BR/LA PDAC following NAT between 2008 and 2017 was performed. The Kaplan-Meier method was used to analyze progression-free survival (PFS) and overall survival (OS) of FOLFIRINOX treated patients. RESULTS: Most patients (83%) received FOLFIRINOX, and 95% underwent consolidative chemoradiation therapy (50.4-58.8 Gy). Among FOLFIRINOX-treated patients, 86 underwent combined surgical resection with IORT (10 Gy) while 46 received IORT alone (15-20 Gy). The median PFS and OS were 21.5 and 46.7 months for patients who underwent resection with IORT and 14.7 and 23 months in the IORT alone group. Local progression occurred in 12.7% of patients after resection with IORT, and in 15% of patients who received IORT alone. Major complications occurred in 13% of patients following resection, and 5% of patients after IORT alone, including one death. CONCLUSION: IORT combined with surgical resection appears to be associated with improved survival and minimal morbidity in patients with positive or close margins. IORT is also associated with improved survival in patients with unresectable, non-metastatic disease.

7.
Ann Surg Oncol ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31722071

RESUMO

BACKGROUND: Pancreatic cancer induces parenchymal atrophy and duct dilation. The aim of this study was to evaluate whether these radiologic modifications are associated with outcomes. METHODS: Upfront pancreaticoduodenectomy patients with available preoperative contrast enhanced CT scan imaging were retrospectively analyzed. Thickness of the pancreas, size of the main pancreatic duct (MPD), and distance of the tumor from the ampulla were assessed. A training cohort was selected, including short- (3-12 months following surgery) and long-term (≥ 36 months) survivors. Identified survival determinants were validated in the overall cohort. RESULTS: Two-hundred-sixteen patients were analyzed. In the training cohort (N = 118), 68 patients (57.6%) were in the short-term and 50 (42.4%) in the long-term survival group. The short-term survival group had significantly higher CA 19-9 levels (p = 0.027), larger tumors (32.6 ± 12.1 mm vs. 26.5 ± 11.6 mm, p = 0.007), poorer differentiation (p = 0.003), higher rate of R < 1 mm resections (54% vs. 32%, p = 0.008), and reduced receipt of adjuvant chemotherapy (p = 0.020). The MPD-to-pancreatic thickness ratio was significantly lower in the short-term survivors (3.6 ± 6.2 vs. 8.2 ± 12.0, p = 0.016). In the entire cohort, an MPD-to-pancreatic thickness ratio ≥ 3.5 was associated with improved OS [median 33.0 months IQR (19.7-48.1) versus 17 months IQR (14.8-19.2), p = 0.004], and confirmed by a Cox-proportional hazards model independently associated with OS (HR = 0.58; p = 0.009), together with tumor size (HR = 1.02; p =0.012), R1/R2 status (HR = 1.53; p = 0.029), and receipt of adjuvant treatment (HR = 0.61; p = 0.021). CONCLUSIONS: High MPD-to-pancreatic thickness ratio was associated with improved long-term survival in pancreaticoduodenectomy for cancer. Whether these features are related to tumor chronicity, indolent biology, or local growth over metastasis remains to be determined.

9.
Nat Med ; 25(8): 1260-1265, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31263286

RESUMO

Most pancreatic neuroendocrine tumors (PNETs) do not produce excess hormones and are therefore considered 'non-functional'1-3. As clinical behaviors vary widely and distant metastases are eventually lethal2,4, biological classifications might guide treatment. Using enhancer maps to infer gene regulatory programs, we find that non-functional PNETs fall into two major subtypes, with epigenomes and transcriptomes that partially resemble islet α- and ß-cells. Transcription factors ARX and PDX1 specify these normal cells, respectively5,6, and 84% of 142 non-functional PNETs expressed one or the other factor, occasionally both. Among 103 cases, distant relapses occurred almost exclusively in patients with ARX+PDX1- tumors and, within this subtype, in cases with alternative lengthening of telomeres. These markedly different outcomes belied similar clinical presentations and histology and, in one cohort, occurred irrespective of MEN1 mutation. This robust molecular stratification provides insight into cell lineage correlates of non-functional PNETs, accurately predicts disease course and can inform postoperative clinical decisions.


Assuntos
Elementos Facilitadores Genéticos , Neoplasias Pancreáticas/genética , Linhagem da Célula , Proteínas de Homeodomínio/análise , Humanos , Mutação , Neoplasias Pancreáticas/química , Proteínas Proto-Oncogênicas/genética , Telômero , Transativadores/análise , Fatores de Transcrição/análise
10.
Gastroenterology ; 157(3): 720-730.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31175863

RESUMO

BACKGROUND & AIMS: Although pancreatic cystic lesions (PCLs) are frequently and incidentally detected, it is a challenge to determine their risk of malignancy. In immunohistochemical and enzyme-linked immunosorbent assay (ELISA) analyses of tissue and cyst fluid from pancreatic intraductal papillary mucinous neoplasms, the monoclonal antibody Das-1 identifies those at risk for malignancy with high levels of specificity and sensitivity. We aimed to validate the ability of Das-1 to identify high-risk PCLs in comparison to clinical guidelines and clinical features, using samples from a multicenter cohort. METHODS: We obtained cyst fluid samples of 169 PCLs (90 intraductal papillary mucinous neoplasms, 43 mucinous cystic neoplasms, and 36 non-mucinous cysts) from patients undergoing surgery at 4 tertiary referral centers (January 2010 through June 2017). Histology findings from surgical samples, analyzed independently and centrally re-reviewed in a blinded manner, were used as the reference standard. High-risk PCLs were those with invasive carcinomas, high-grade dysplasia, or intestinal-type intraductal papillary mucinous neoplasms with intermediate-grade dysplasia. An ELISA with Das-1 was performed in parallel using banked cyst fluid samples. We evaluated the biomarker's performance, generated area under the curve values, and conducted multivariate logistic regression using clinical and pathology features. RESULTS: The ELISA for Das-1 identified high-risk PCLs with 88% sensitivity, 99% specificity, and 95% accuracy, at a cutoff optical density value of 0.104. In 10-fold cross-validation analysis with 100 replications, Das-1 identified high-risk PCLs with 88% sensitivity and 98% specificity. The Sendai, Fukuoka, and American Gastroenterological Association guideline criteria identified high-risk PCLs with 46%, 52%, and 74% accuracy (P for comparison to Das-1 ELISA <.001). When we controlled for Das-1 in multivariate regression, main pancreatic duct dilation >5 mm (odds ratio, 14.98; 95% confidence interval, 2.63-108; P < .0012), main pancreatic duct dilation ≥1 cm (odds ratio, 47.9; 95% confidence interval, 6.39-490; P < .0001), and jaundice (odds ratio, 6.16; 95% confidence interval, 1.08-36.7; P = .0397) were significantly associated with high-risk PCLs. CONCLUSIONS: We validated the ability of an ELISA with the monoclonal antibody Das-1 to detect PCLs at risk for malignancy with high levels of sensitivity and specificity. This biomarker might be used in conjunction with clinical guidelines to identify patients at risk for malignancy.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos/análise , Biomarcadores Tumorais/análise , Ensaio de Imunoadsorção Enzimática , Neoplasias Císticas, Mucinosas e Serosas/química , Cisto Pancreático/química , Neoplasias Intraductais Pancreáticas/química , Neoplasias Pancreáticas/química , Adulto , Idoso , Anticorpos/imunologia , Especificidade de Anticorpos , Biomarcadores Tumorais/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Císticas, Mucinosas e Serosas/imunologia , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Cisto Pancreático/imunologia , Cisto Pancreático/patologia , Cisto Pancreático/cirurgia , Neoplasias Intraductais Pancreáticas/imunologia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Medição de Risco , Estados Unidos
11.
Am J Surg Pathol ; 43(7): 898-906, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31135488

RESUMO

BACKGROUND: Autoimmune pancreatitis (AIP) encompasses a heterogenous disease group that includes IgG4-related type 1 AIP and non-IgG4-related type 2 AIP. Clinically and on imaging, type 2 AIP mimics type 1 AIP, other forms of chronic pancreatitis and pancreatic ductal adenocarcinoma (PDAC); therefore, discriminatory markers may aid proper diagnosis. Herein, we examine the expression of PD-L1 and indoleamine 2,3-dioxygenase (IDO1) as a diagnostic tool to distinguish type 2 AIP from other forms of pancreatitis and PDAC. DESIGN: We evaluated 35 pancreatectomy specimens diagnosed with type 2 AIP and potential mimics of this disease including type 1 AIP (n=14), chronic pancreatitis-not otherwise specified (n=10), groove pancreatitis (n=14), and PDAC (n=278). We scored inflammatory infiltrates, fibrosis and atrophy and performed immunohistochemical staining for PD-L1 and IDO1. We validated our findings on a series of endoscopic ultrasound-guided biopsies from patients with suspected type 2 AIP and inflammatory and neoplastic mimics of this disease (n=37). RESULTS: The mean age of patients with type 2 AIP was 50 years with a F:M ratio of 1.2:1. Patients with type 2 AIP showed pancreatic ductal staining for PD-L1 and IDO1 in 69% (24/35) and 60% (15/25) of cases, respectively. PD-L1 reactivity was noted in 3% of patients with other forms of chronic pancreatitis and 3% of PDACs; notably, peritumoral ducts and acini were negative. Eight of 9 endoscopic ultrasound-guided biopsies with pancreatic ductal epithelium from patients with type 2 AIP were positive for PD-L1, while the inflammatory and neoplastic mimics were negative. Collectively, the sensitivity and specificity of PD-L1 as a marker of type 2 AIP was 70% and 99%, respectively. CONCLUSIONS: Ductal PD-L1 reactivity has the potential to distinguish type 2 AIP from other forms of pancreatitis and PDAC.

12.
Ann Surg ; 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30672796

RESUMO

MINI: Our study explores patterns of recurrence after potentially curative resection in lymph node-positive and lymph node-negative pancreatic cancer, including both timing and site of recurrence. Although the time to recurrence and median survival were significantly longer for pN0 as compared with pN1 cancer, there was no corresponding difference in site of first recurrence or metastasis in upfront resected patients, nor in neoadjuvant-treated patients. OBJECTIVE: Our aim was to evaluate recurrence patterns of surgically resected PDAC patients with negative (pN0) or positive (pN1) lymph nodes. SUMMARY BACKGROUND DATA: Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer death by 2030. This is mostly due to early local and distant metastasis, even after surgical resection. Knowledge about patterns of recurrence in different patient populations could offer new therapeutic avenues. METHODS: Clinicopathologic data were collected for 546 patients who underwent resection of their PDAC between 2005 and 2016 from 2 tertiary university centers. Patients were divided into an upfront resection group (n = 394) and a neoadjuvant group (n = 152). RESULTS: Tumor recurrence was significantly less common in pN0 patients as compared with pN1 patients, (upfront surgery: 55% vs. 77%, P < 0.001 and 64% vs. 78%, P = 0.040 in the neoadjuvant group). In addition, time to recurrence was significantly longer in pN0 versus pN1 patients in the upfront resected patients (median 16 mo pN0 vs. 10 mo pN1 P < 0.001), and the neoadjuvant group (pN0 21 mo vs. 11 mo pN1, P < 0.001). Of the patients who recurred, 62% presented with distant metastases (63% of pN0 and 62% of pN1, P = 0.553), 24% with local disease (27% of pN0 and 23% of pN1, P = 0.672) and 14% with synchronous local and distant disease (10% of pN0 and 15% of pN1, P = 0.292). Similarly, there was no difference in recurrence patterns between pN0 and pN1 in the neoadjuvant group, in which 68% recurred with distant metastases (76% of pN0 and 64% of pN1, P = 0.326) and 18% recurred with local disease (pN0: 22% and pN1: 15%, P = 0.435). CONCLUSION: Time to recurrence was significantly longer for pN0 patients. However, patterns of recurrence for pN0 vs. pN1 patients were identical. Lymph node status was predictive of time to recurrence, but not location of recurrence.

13.
Clin Cancer Res ; 25(8): 2644-2655, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30670493

RESUMO

PURPOSE: This study evaluated the potential role of immune cells and molecules in the pathogenesis and clinical course of pancreatic neuroendocrine tumors (PanNET). EXPERIMENTAL DESIGN: Surgically resected PanNETs (N = 104) were immunohistochemically analyzed for Ki67 index, mitotic rate, macrophage, CD4+ cells, and CD8+ T-cell infiltration, as well as HLA class I, PD-L1, and B7-H3 expression. Results were correlated with clinicopathologic characteristics as well as with disease-free (DFS) and disease-specific (DSS) survival. RESULTS: The median age of the 57 WHO grade 1 and 47 WHO grade 2 patients was 55 years. High intratumoral CD8+ T-cell infiltration correlated with prolonged DFS (P = 0.05), especially when the number of tumor-associated macrophages (TAM) was low. In contrast, high peritumoral CD4+ cell and TAM infiltration was associated with a worse DFS and DSS. PD-L1 and B7-H3 were expressed in 53% and 78% PanNETs, respectively. HLA class I expression was defective in about 70% PanNETs. HLA-A expression correlated with favorable DSS in PD-L1-negative tumors (P = 0.02). TAM infiltration (P = 0.02), WHO grade (P = 0.04), T stage (P = 0.01), and lymph node positivity (P = 0.04) were independent predictors of DFS. TAM infiltration (P = 0.026) and T stage (P = 0.012) continued to be predictors of DFS in WHO grade 1 PanNET patients. TAM infiltration was the sole independent predictor of DSS for WHO grade 1 and 2 patients (P = 0.02). Therefore, this biomarker may contribute to identifying WHO grade 1 patients with poor prognosis. CONCLUSIONS: TAM infiltration appears to be the most informative prognostic biomarker in PanNET. It may represent a useful immunotherapeutic target in patients with PanNET.

14.
J Gastrointest Surg ; 23(10): 1984-1990, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30225794

RESUMO

BACKGROUND: Postoperative major morbidity has been associated with worse survival gastrointestinal tumors. This association remains controversial in pancreatic cancer (PC). We analyzed whether major complications after surgical resection affect long-term survival. METHODS: Records of all PC patients resected from 2007 to 2015 were reviewed. Major morbidity was defined as any grade-3 or higher 30-day complications, per the Clavien-Dindo Classification. Patients who died within 90 days after surgery were excluded from survival analysis. RESULTS: Of 616 patients, 81.7% underwent pancreatoduodenectomy (PD) and 18.3% distal pancreatectomy (DP). Major complications occurred in 19.1% after PD and 15.9% after DP. In patients who survived > 90 days, the likelihood of receiving adjuvant treatment was 43.9% if major complications had occurred, vs. 68.5% if not (p < 0.001), and those who received it started the treatment median 10 days later compared with uncomplicated patients (median 60 days (50-72) vs. 50 days (41-61), p = 0.001). By univariate analysis, in addition to the conventional pathology-related prognostic determinants and the receipt of adjuvant treatment, major complications worsened long-term survival after PD (median OS 26 months vs. 15, p = 0.008). A difference was also seen after DP, but it did not reach statistical significance, likely related to the small sample size (median OS 33 months vs. 18, p = 0.189). At multivariate analysis for PD, major postoperative complications remained independently associated with worse survival [HR 1.37, 95%CI (1.01-1.86)]. CONCLUSIONS: Major surgical complications after pancreaticoduodenectomy are associated with worse long-term survival in pancreatic cancer. This effect is independent of the receipt of adjuvant treatment.

15.
Ann Surg ; 269(4): 733-740, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29227344

RESUMO

OBJECTIVE: The aim of this study was to determine (1) whether preoperative factors can predict resectability of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant FOLFIRINOX, (2) which patients might benefit from adjuvant therapy, and (3) survival differences between resected BR/LA patients who received neoadjuvant FOLFIRINOX and upfront resected patients. BACKGROUND: Patients with BR/LA PDAC are often treated with FOLFIRINOX to obtain a margin-negative resection, yet selection of patients for resection remains challenging. METHODS: Clinicopathologic data of PDAC patients surgically explored between 04/2011-11/2016 in a single institution were retrospectively collected. RESULTS: Following neoadjuvant FOLFIRINOX, 141 patients were surgically explored (BR: 49%, LA: 51%) and 110 (78%) were resected. Resected patients had lower preoperative CA 19-9 levels (21 vs 40 U/mL, P = 0.03) and smaller tumors on preoperative computed tomography (CT) scan (2.3 vs 3.0 cm, P = 0.03), but no predictors of resectability were identified. Median overall survival (OS) was 34.2 months from diagnosis for all FOLFIRINOX patients and 37.7 months for resected patients. Among resected patients, preoperative CA 19-9 >100 U/mL and >8 months between diagnosis and surgery predicted a shorter postoperative disease-free survival (DFS); Charlson comorbidity index >1, preoperative CA 19-9 >100 U/mL and tumor size (>3.0 cm on CT or >2.5 cm on pathology) predicted decreased OS. DFS and OS were significantly better for BR/LA PDAC patients treated with neoadjuvant FOLFIRINOX compared with upfront resected patients (DFS: 29.1 vs 13.7, P < 0.001; OS: 37.7 vs 25.1 months from diagnosis, P = 0.01). CONCLUSION: BR/LA PDAC patients with no progression on neoadjuvant FOLFIRINOX should be offered surgical exploration. Except size, traditional pathological parameters fail to predict survival among resected FOLFIRINOX patients. Resected FOLFIRINOX patients have survival that appears to be superior than that of resectable patients who go directly to surgery.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Idoso , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Feminino , Fluoruracila/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
16.
Pancreas ; 47(10): 1256-1261, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30286013

RESUMO

OBJECTIVES: The aim of this study was to evaluate the impact of Animated Pancreas Patient (APP) educational modules (APP website and YouTube) on pancreas education, awareness, and health outcomes. METHODS: This was a retrospective study of APP metrics data from September 2013 to October 2017. We evaluated audience reach (number of visit sessions, unique visitors, page views) and calculated top views by media type (animation, expert video, patient video, and slide show) and top retention videos from the modules. We also assessed the educational impact through learner feedback survey. RESULTS: The APP had 1,475,252 views (547,693 unique visitors, 63.1% in United States) during the study period. Most popular topic viewed among the animations was "Role and Anatomy of the Pancreas" (n = 361,116), and most common expert video viewed was "Chronic Pancreatitis: What Foods and Beverages Should I Avoid?" (n = 31,667). Participants who completed the online feedback survey reported knowledge gains and commitments to change. CONCLUSIONS: Pancreas education in visual formats of learning provided by APP demonstrated wide reach and has substantial potential to inform and impact behaviors of patients and caregivers. Continued efforts should be made to provide patient resources that address health literacy and patient education and respond to patient needs for better quality of life and improved health outcomes in pancreatic diseases.


Assuntos
/métodos , Pancreatopatias/diagnóstico , Pancreatopatias/terapia , Educação de Pacientes como Assunto/métodos , Gravação em Vídeo/métodos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estudos Retrospectivos , Inquéritos e Questionários
17.
Ann Surg ; 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30339622

RESUMO

OBJECTIVE: To reappraise the concept of conditional survival (CS) following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC), accounting for the patient's present disease status relative to recurrence. BACKGROUND: CS, defined as the probability of surviving an additional time frame based on accrued lifespan, offers dynamic survival projections as compared with baseline overall survival. METHODS: Patients undergoing pancreatectomy for PDAC at 2 institutions from 2000 to 2013 were retrospectively analyzed. The 12-month CS was estimated separately for patients who were disease-free or with recurrence at the given time points. Next, the conditional probability of reaching 60-months of survival was examined in each conditioning set across strata of prognostic covariates, including American Joint Committee on Cancer stage, tumor grade, R-status, and adjuvant treatment. RESULTS: The study population consisted of 1005 patients. In disease-free patients, the 12-month CS increased as a function of time already survived, showing an opposite trend compared with overall survival. In patients who recurred, the 12-month CS was lower than the disease-free counterpart, especially within 24 months postoperatively. When stratifying by the levels of prognostic covariates, the 60-months CS estimates for disease-free patients tended to level off progressively, indicating that factors independently associated with survival at the time of pancreatectomy lost power over time. This concept did not apply to the conditioning set of patients with recurrence, where CS estimates across variables strata diverged with accrued lifespan. CONCLUSION: This paper provides new information on how prognosis following pancreatectomy for PDAC evolves over time, adjusting for the time the patient already survived, and for the patient's present disease status relative to recurrence.

18.
Curr Opin Gastroenterol ; 34(5): 343-348, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29912020

RESUMO

PURPOSE OF REVIEW: With recent advances in radiographic testing, there have been increases in the incidental identification of pancreatic cysts. Determining management, specifically, which cysts can be watched versus intervened upon has significant impact on at the patient-physician level as well as globally on resource allocation and healthcare expenditures. This review focuses on the three main guidelines (Fukuoka guidelines, European consensus, and American Gastroenterological Association recommendations) for management of pancreatic cystic disease after incidental identification. RECENT FINDINGS: There are iterant revisions to each set of recommendations every few years as new data is published on the subject. This review encompasses the most up-to-date recommendations for management while also providing a framework for conceptualizing work-up for varying types of pancreatic cystic disease before and after incidental identification. SUMMARY: Pancreatic cystic disease should be approached in thoughtful clinical manner, and each cyst should be evaluated in the context of patient's health and healthcare goals. All cysts, however, should be considered malignant until proven otherwise. Applications of different diagnostic modalities like MRI and EUS with FNA can better characterize cystic lesions and assess malignant potential. Resection should always be considered in cysts with concerning features. If deferred, surveillance should be continued indefinitely. Early termination of surveillance risks future malignant progression.


Assuntos
Cisto Pancreático/diagnóstico , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Cisto Pancreático/terapia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia
19.
Nat Cell Biol ; 20(7): 811-822, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29941929

RESUMO

G protein αs (GNAS) mediates receptor-stimulated cAMP signalling, which integrates diverse environmental cues with intracellular responses. GNAS is mutationally activated in multiple tumour types, although its oncogenic mechanisms remain elusive. We explored this question in pancreatic tumourigenesis where concurrent GNAS and KRAS mutations characterize pancreatic ductal adenocarcinomas (PDAs) arising from intraductal papillary mucinous neoplasms (IPMNs). By developing genetically engineered mouse models, we show that GnasR201C cooperates with KrasG12D to promote initiation of IPMN, which progress to invasive PDA following Tp53 loss. Mutant Gnas remains critical for tumour maintenance in vivo. This is driven by protein-kinase-A-mediated suppression of salt-inducible kinases (Sik1-3), associated with induction of lipid remodelling and fatty acid oxidation. Comparison of Kras-mutant pancreatic cancer cells with and without Gnas mutations reveals striking differences in the functions of this network. Thus, we uncover Gnas-driven oncogenic mechanisms, identify Siks as potent tumour suppressors, and demonstrate unanticipated metabolic heterogeneity among Kras-mutant pancreatic neoplasms.


Assuntos
Carcinoma Ductal Pancreático/enzimologia , Carcinoma Ductal Pancreático/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Reprogramação Celular/genética , Cromograninas/genética , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Metabolismo dos Lipídeos/genética , Mutação , Neoplasias Pancreáticas/enzimologia , Neoplasias Pancreáticas/genética , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Transformação Celular Neoplásica/patologia , Cromograninas/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/genética , Repressão Enzimática , Ácidos Graxos/metabolismo , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/metabolismo , Regulação Neoplásica da Expressão Gênica , Genes ras , Predisposição Genética para Doença , Humanos , Masculino , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Mutantes , Camundongos Transgênicos , Oxirredução , Neoplasias Pancreáticas/patologia , Fenótipo , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais , Fatores de Tempo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
20.
Ann Surg ; 267(4): 608-616, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28594741

RESUMO

OBJECTIVE: The aim of this study was to identify the optimal fistula mitigation strategy following pancreaticoduodenectomy. BACKGROUND: The utility of technical strategies to prevent clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreatoduodenectomy (PD) may vary by the circumstances of the anastomosis. The Fistula Risk Score (FRS) identifies a distinct high-risk cohort (FRS 7 to 10) that demonstrates substantially worse clinical outcomes. The value of various fistula mitigation strategies in these particular high-stakes cases has not been previously explored. METHODS: This multinational study included 5323 PDs performed by 62 surgeons at 17 institutions. Mitigation strategies, including both technique related (ie, pancreatogastrostomy reconstruction; dunking; tissue patches) and the use of adjuvant strategies (ie, intraperitoneal drains; anastomotic stents; prophylactic octreotide; tissue sealants), were evaluated using multivariable regression analysis and propensity score matching. RESULTS: A total of 522 (9.8%) PDs met high-risk FRS criteria, with an observed CR-POPF rate of 29.1%. Pancreatogastrostomy, prophylactic octreotide, and omission of externalized stents were each associated with an increased rate of CR-POPF (all P < 0.001). In a multivariable model accounting for patient, surgeon, and institutional characteristics, the use of external stents [odds ratio (OR) 0.45, 95% confidence interval (95% CI) 0.25-0.81] and the omission of prophylactic octreotide (OR 0.49, 95% CI 0.30-0.78) were independently associated with decreased CR-POPF occurrence. In the propensity score matched cohort, an "optimal" mitigation strategy (ie, externalized stent and no prophylactic octreotide) was associated with a reduced rate of CR-POPF (13.2% vs 33.5%, P < 0.001). CONCLUSIONS: The scenarios identified by the high-risk FRS zone represent challenging anastomoses associated with markedly elevated rates of fistula. Externalized stents and omission of prophylactic octreotide, in the setting of intraperitoneal drainage and pancreaticojejunostomy reconstruction, provides optimal outcomes.


Assuntos
Fístula Pancreática/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Anastomose Cirúrgica/efeitos adversos , Drenagem , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Stents
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