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2.
Ann Surg Oncol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717544

RESUMO

BACKGROUND: Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries. METHODS: The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions. RESULTS: The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were larger than SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups. CONCLUSION: The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.

3.
Ann Surg ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771952

RESUMO

OBJECTIVE: The aim of this study is to determine perioperative outcomes and the patency of interposition conduits for visceral arterial reconstruction in this setting. SUMMARY BACKGROUND DATA: Visceral arterial encasement in locally advanced pancreatic cancer was historically a contraindication for surgery. With modern effective neoadjuvant strategies, our recent experience has made advanced vascular resection and reconstruction feasible in selected patients. METHODS: A retrospective review was performed of patients undergoing pancreatic tumor resection with en bloc arterial resection and interposition revascularization between 6/2002-10/2022. Endpoints included graft patency, vascular-related complications, reinterventions, morbidity, and mortality. RESULTS: Visceral arterial reconstruction with interposition grafting was performed in 111 patients undergoing en bloc arterial resections for pancreatic cancer. Graft types included autologous arterial conduits (n=66, 58 superficial femoral artery (SFA) and 8 splenic artery), cryopreserved arterial allografts (n=24), autologous saphenous veins (n=12), synthetic conduits (n=8), and composite autologous artery and synthetic (n=1). Perioperative 90-day mortality decreased significantly over time to 5% in the last six years. Vascular complications related to arterial reconstruction occurred in 11% (n=12) and included pseudoaneurysm (n=6), graft thrombus (n=2), stenosis requiring reintervention (n=2), hepatic failure (n=1), and hepatic and intestinal ischemia (n=1). Nine (8%) patients underwent vascular-related reinterventions. After median follow-up of 17-months, primary patency was 81% for the entire cohort and was highest in the SFA group (95%). The donor limb/harvest site complication rate was 8% with 100% primary patency. CONCLUSION: Visceral arterial resection with interposition reconstruction for locally advanced pancreatic cancer can be performed with acceptable vascular morbidity and durable patency. Autologous SFA was the most suitable conduit for reconstructions in our experience, with highest primary patency.

4.
Surgery ; 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38777657

RESUMO

BACKGROUND: The absence of surgical complications has traditionally been used to define successful recovery after pancreas surgery. However, patient-reported outcome measures as metrics of a challenging recovery may be superior to objective morbidity. This study aims to evaluate the use of patient-reported outcomes in assessing recovery after pancreas surgery. METHODS: Patients scheduled for pancreatoduodenectomy were prospectively enrolled between 2016 to 2018. Patient-reported outcomes were collected using the linear analog self-assessment questionnaire preoperatively and on postoperative days 2, 7, 14, 30, and monthly until 6 months. Patients were also asked if they felt fully recovered at 30 days and 6 months. Thirty-day surgical morbidity was prospectively assessed, and the comprehensive complication index at 30 days was used to categorize morbidity as major or multiple minor complications (comprehensive complication index ≥26.2) vs uncomplicated (comprehensive complication index <26.2). Clinically significant International Study Group Pancreas Surgery Grade B and C pancreatic fistulas and delayed gastric emptying were reported. χ2 and Kruskal-Wallis tests were used to assess associations with recovery by 6 months and quality of life throughout the postoperative period. RESULTS: Of 116 patients who met inclusion criteria and were enrolled, 32 (28%) had major or multiple minor complications (comprehensive complication index ≥26.2). Overall, fewer than 1 in 10 patients (7%) reported feeling fully recovered at 30 days postoperatively, whereas 55% reported feeling fully recovered at 6 months. Of patients suffering major morbidity, 62% did not recover by 6 months, whereas 38% of those in the uncomplicated group reported not being recovered at 6 months (P = .03). Patients who experienced delayed gastric emptying reported low quality-of-life scores at 1 month (P = .04) compared to those with no delayed gastric emptying, but this did not persist at 6 months (P = .80). Postoperative pancreatic fistula was not associated with quality of life at 1 or 6 months (both P > .05). In the uncomplicated patients, age, sex, surgical approach, and cancer status were not associated with failed recovery at 6 months (all P > .05), and healthier patients (American Society of Anesthesiologists 1-2) were less likely to report complete recovery (42% vs 69% American Society of Anesthesiologists 3-4, P = .04). With the exception of higher preoperative pain scores (mean 2.3 [standard deviation 2.4] among patients not fully recovered at 6 months vs 1.6 [2.2] among those fully recovered, P = .04), preoperative patient-reported outcomes were not associated with failed recovery at 6 months (all P > .05). However, lower 30-day quality of life, social activity, pain, and fatigue scores were associated with incomplete recovery at 6 months. CONCLUSION: More than 1 in 3 patients with an uncomplicated course do not feel fully recovered from pancreas surgery at 6 months; the presence of surgical complications did not universally correspond with recovery failure. In patients with complications, delayed gastric emptying appears to drive quality of life more significantly than postoperative pancreatic fistula. In patients with uncomplicated recovery, healthier patients were less likely to report full recovery at 6 months. Thirty-day patient-reported outcomes may be able to identify patients who are at risk of incomplete long-term recovery.

6.
Pancreatology ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38702207

RESUMO

BACKGROUND: Mucinous cystic neoplasms (MCN) of the pancreas express estrogen and progesterone receptors. Several case reports describe MCN increasing in size during gestation. The aim of this study is to assess if pregnancy is a risk factor for malignant degeneration of MCN. METHODS: All female patients who underwent pancreatic resection of a MCN between 2011 and 2021 were included. MCN resected or diagnosed within 12 months of gestation were defined perigestational. MCN with high grade dysplasia or an invasive component were classified in the high grade (HG) group. The primary outcome was defined as the correlation between exposure to gestation and peri-gestational MCN to development of HG-MCN. RESULTS: The study includes 176 patients, 25 (14 %) forming the HG group, and 151 (86 %) forming the low grade (LG) group. LG and HG groups had a similar distribution of systemic contraceptives use (26 % vs. 16 %, p = 0.262), and perigestational MCN (7 % vs 16 %, p = 0.108). At univariate analysis cyst size ≥10 cm (OR 5.3, p < 0.001) was associated to HG degeneration. Peri gestational MCN positively correlated with cyst size (R = 0.18, p = 0.020). In the subgroup of 14 perigestational MCN patients 29 % had HG-MCN and 71 % experienced cyst growth during gestation with an average growth of 55.1 ± 18 mm. CONCLUSIONS: Perigestational MCN are associated to increased cyst diameter, and in the subset of patients affected by MCN during gestation a high rate of growth was observed. Patients with a MCN and pregnancy desire should undergo multidisciplinary counselling.

7.
Ann Surg Oncol ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689169

RESUMO

BACKGROUND: Cytoreductive hepatectomy can improve survival and symptoms of hormonal excess in patients with small intestinal neuroendocrine tumor (siNET) liver metastases, but whether to proceed when peritoneal metastases are encountered at the time of planned cytoreductive hepatectomy is controversial. METHODS: This was a retrospective review of patients who underwent surgical management of metastatic siNETs at Mayo Clinic between 2000 and 2020. Patients who underwent cytoreductive operation for isolated liver metastases or both liver and peritoneal metastases were compared. RESULTS: Of 261 patients who underwent cytoreductive operation for siNETs, 211 had isolated liver metastases and 50 had liver and peritoneal metastases. Complete cytoreduction was achieved in 78% of patients with isolated liver metastases and 56% of those with liver and peritoneal metastases (p = 0.002). After complete cytoreduction, median overall survival (OS) was 11.5 years for isolated liver metastases and 11.2 years for liver and peritoneal metastases (p = 0.10), and relief of carcinoid syndrome was ≥ 97% in both groups. After incomplete cytoreduction with debulking of > 90% of hepatic disease and/or closing Lyon score of 1-2, median OS was 6.4 years for isolated liver metastases and 7.1 years for liver and peritoneal metastases (p = 0.12). CONCLUSIONS: Patients with siNETs metastatic to both the liver and peritoneum have favorable outcomes after aggressive surgical cytoreduction, with the best outcomes observed after complete cytoreduction. Therefore, the presence of peritoneal metastases should not by itself preclude surgical cytoreduction in this population.

8.
Updates Surg ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38684573

RESUMO

The REDISCOVER guidelines present 34 recommendations for the selection and perioperative care of borderline-resectable (BR-PDAC) and locally advanced ductal adenocarcinoma of the pancreas (LA-PDAC). These guidelines represent a significant shift from previous approaches, prioritizing tumor biology over anatomical features as the primary indication for resection. Condensed herein, they provide a practical management algorithm for clinical practice. However, the guidelines also highlight the need to redefine LA-PDAC to align with modern treatment strategies and to solve some contradictions within the current definition, such as grouping "difficult" and "impossible" to resect tumors together. Furthermore, the REDISCOVER guidelines highlight several areas requiring urgent research. These include the resection of the superior mesenteric artery, the management strategies for patients with LA-PDAC who are fit for surgery but unable to receive multi-agent neoadjuvant chemotherapy, the approach to patients with LA-PDAC who are fit for surgery but demonstrate high serum Ca 19.9 levels even after neoadjuvant treatment, and the optimal timing and number of chemotherapy cycles prior to surgery. Additionally, the role of primary chemoradiotherapy versus chemotherapy alone in LA-PDAC, the timing of surgical resection post-neoadjuvant/primary chemoradiotherapy, the efficacy of ablation therapies, and the management of oligometastasis in patients with LA-PDAC warrant investigation. Given the limited evidence for many issues, refining existing management strategies is imperative. The establishment of the REDISCOVER registry ( https://rediscover.unipi.it/ ) offers promise of a unified research platform to advance understanding and improve the management of BR-PDAC and LA-PDAC.

11.
J Am Coll Surg ; 239(1): 9-17, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38445645

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy. Surgical resection is the only curative modality combined with neoadjuvant chemotherapy to improve survival. Given the limitations of traditional responses such as cross-sectional imaging (CT/MRI) or tumor markers, carbohydrate antigen 19-9 (CA19-9), the 2023 National Comprehensive Cancer Network guidelines included 18 F-fluorodeoxyglucose (FDG)-PET as an adjunct to assess response to neoadjuvant chemotherapy. There are common misconceptions on the metabolic activity (tumor avidity) in PDAC so we aimed to describe the baseline characteristics and use of FDG-PET in a cohort of treatment-naive patients with PDAC. STUDY DESIGN: A single-center retrospective study was conducted capturing all biopsy-proven, treatment-naive patients with PDAC who underwent either baseline FDG-PET/CT or FDG-PET/MRI imaging between 2008 and 2023. Baseline FDG-PET characteristics were collected, including primary tumors' maximum standardized uptake value defined as metabolic activity (FDG uptake) of tumor compared with surrounding pancreatic parenchymal background, and the identification of extrapancreatic metastatic disease. RESULTS: We identified 1,095 treatment-naive patients with PDAC who underwent baseline FDG-PET imaging at diagnosis. CA19-9 was elevated in 76% of patients. Overall, 96.3% (1,054) of patients had FDG-avid tumors with a median maximum standardized uptake value of 6.4. FDG-PET also identified suspicious extrapancreatic metastatic lesions in 50% of patients, with a higher proportion (p < 0.001) in PET/MRI (59.9%) vs PET/CT (44.3%). After controlling for CA19-9 elevation, PET/MRI was superior in detection of extrapancreatic lesions compared with PET/CT. CONCLUSIONS: FDG-PET has significant use in PDAC as a baseline imaging modality earlier neoadjuvant therapy given the majority of tumors are FDG-avid. FDG-PET can identify additional extrapancreatic suspicious lesions allowing for optimal initial staging, with PET/MRI having increased sensitivity over PET/CT.


Assuntos
Carcinoma Ductal Pancreático , Fluordesoxiglucose F18 , Neoplasias Pancreáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Imageamento por Ressonância Magnética , Adulto , Tomografia por Emissão de Pósitrons/métodos , Idoso de 80 Anos ou mais
13.
Cancers (Basel) ; 16(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38473407

RESUMO

Upamostat is an orally available small-molecule serine protease inhibitor that is a highly potent inhibitor of trypsin 1, trypsin 2, trypsin 3 (PRSS1/2/3), and the urokinase-type plasminogen activator (uPA). These enzymes are expressed in many cancers, especially during tissue remodeling and subsequent tumor cell invasion. Opaganib (ABC294640), a novel, orally available small molecule is a selective inhibitor of the phosphorylation of sphingosine to sphingosine-1-phosphate (S-1-P) by sphingosine kinase 2 (SPHK2). Both sphingosine kinase 1 (SPHK1) and SPHK2 are known to regulate the proliferation-inducing compound S-1-P. However, SPHK2 is more critical in cancer pathogenesis. The goal of this project was to investigate the potential antitumor effects of upamostat and opaganib, individually and in combination, on cholangiocarcinoma (CCA) xenografts in nude mice. PAX165, a patient-derived xenograft (PDX) from a surgically resected CCA, expresses substantial levels of SPHK2, PRSS1, PRSS2, and PRSS3. Four groups of 18 mice each were treated with upamostat, opaganib, both, or vehicle. Mouse weights and PAX165 tumor volumes were measured. Tumor volumes in the upamostat, opaganib, and upamostat plus opaganib groups were significantly decreased compared to the control group.

14.
Ann Surg ; 280(1): 56-65, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38407228

RESUMO

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.


Assuntos
Carcinoma Ductal Pancreático , Pancreatectomia , Neoplasias Pancreáticas , Assistência Perioperatória , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Assistência Perioperatória/normas , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Técnica Delphi , Guias de Prática Clínica como Assunto , Estadiamento de Neoplasias , Seleção de Pacientes
15.
Ann Surg Oncol ; 31(4): 2632-2639, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38319513

RESUMO

BACKGROUND: The management of invasive intraductal papillary mucinous cystic neoplasm (I-IPMN) does not differ from de novo pancreatic ductal adenocarcinoma (PDAC); however, I-IPMNs are debated to have better prognosis. Despite being managed similarly to PDAC, no data are available on the response of I-IPMN to neoadjuvant chemotherapy. METHODS: All patients undergoing pancreatic resection for a pancreatic adenocarcinoma from 2011 to 2022 were included. The PDAC and I-IPMN cohorts were compared to evaluate response to neoadjuvant therapy (NAT) and overall survival (OS). RESULTS: This study included 1052 PDAC patients and 105 I-IPMN patients. NAT was performed in 25% of I-IPMN patients and 65% of PDAC patients. I-IPMN showed a similar pattern of pathological response to NAT compared with PDAC (p = 0.231). Furthermore, positron emission tomography (PET) response (71% vs. 61%; p = 0.447), CA19.9 normalization (85% vs. 76%, p = 0.290), and radiological response (32% vs. 37%, p = 0.628) were comparable between I-IPMN and PDAC. A significantly higher OS and disease-free survival (DFS) of I-IPMN was denoted by Kaplan-Meier analysis, with a p-value of < 0.001 in both plots. In a multivariate analysis, I-IPMN histology was independently associated with lower risk of recurrence and death. CONCLUSIONS: I-IPMN patients have a longer OS and DFS after surgical treatment when compared with PDAC patients. The more favorable oncologic outcome of I-IPMNs does not seem to be related to early detection, as I-IPMN histological subclass is independently associated with a lower risk of disease recurrence. Moreover, neoadjuvant effect on I-IPMN was non-inferior to PDAC in terms of pathological, CA19.9, PET, and radiological response and thus can be considered in selected patients.


Assuntos
Adenocarcinoma Mucinoso , Adenocarcinoma Papilar , Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/patologia , Terapia Neoadjuvante , Adenocarcinoma Mucinoso/tratamento farmacológico , Adenocarcinoma Mucinoso/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/cirurgia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Adenocarcinoma Papilar/patologia , Estudos Retrospectivos
16.
Ann Gastroenterol ; 37(1): 95-103, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38223247

RESUMO

Background: Cholangiocarcinoma is an epithelial malignancy of the intrahepatic or extrahepatic biliary tree, primarily driven by chronic inflammation and fibrosis. Fibrosis has been shown to correlate with malignancy, and the aminotransferase-platelet ratio index (APRI) score, a marker for hepatic fibrosis, has proved useful in prognosticating hepatocellular carcinoma. This study aimed to assess the utility of APRI score in predicting post-surgical outcomes in cholangiocarcinoma patients. Methods: Clinical data from a total of 152 cholangiocarcinoma patients who underwent surgical resection at the Mayo Clinic were collected. The data were subsequently analyzed to determine if there was a relationship between APRI score and the demographic, laboratory, pathologic and outcome data, including overall survival. To determine the relationship between quantitative and qualitative data and the APRI score, a P-value <0.05 was considered as statistically significant. Results: No relationship between APRI score and demographic factors was identified. There were correlations between APRI score and alanine transaminase, albumin and bilirubin, but the remaining laboratory parameters showed no correlation. APRI score did not prove to be useful as a prognostic tool, as it did not correlate with tumor pathology features (tumor grade t-test P=0.86, N stage ANOVA P=0.94, vascular invasion t-test P=0.59, and perineural invasion t-test P=0.14), or with post-surgical recurrence (t-test P=0.22) and mortality (t-test P=0.39). Conclusion: APRI score is not a prognostic tool for post-surgical outcomes in patients with cholangiocarcinoma.

17.
Ann Surg ; 279(5): 842-849, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37497660

RESUMO

OBJECTIVE: To describe long-term quality of life (QOL) and gastrointestinal (GI) symptoms in patients who underwent pancreatoduodenectomy for pancreatic cancer in the modern era. BACKGROUND: As advances in pancreatic cancer management improve outcomes, it is essential to assess long-term patient-reported outcomes after surgery. METHODS: Patients who underwent curative intent pancreatoduodenectomy for pancreatic cancer between January 2011 and June 2019 from a single center were identified. Patients alive ≥3 years after surgery were considered long-term survivors (LTS). LTS who were alive in June 2022 received a 55-question survey to assess their QOL (EORTC-QLQ-C30) and GI symptoms (EORTC-PAN26 and Problem Areas in Diabetes Questionnaire). Responses were compared against population norms. Clinicodemographic characteristics in LTS versus non-LTS and survey completion were compared. RESULTS: Six hundred seventy-two patients underwent pancreatoduodenectomy for pancreatic cancer; 340 were LTS. One hundred thirty-seven patients of the 238 eligible to complete the survey responded (response rate: 58%). Compared to the US general population, LTS reported significantly higher QOL (75 vs 64; P <0.001), less nausea/vomiting, pain, dyspnea, insomnia, appetite loss, and constipation, but more diarrhea (all P <0.001). Most patients (n=136/137, 99%) reported experiencing postoperative GI symptoms related to pancreatic insufficiency (n=71/135, 53%), reflux (n=61/135, 45%), and delayed gastric emptying (n=31/136, 23%). Most patients (n=113/136, 83%) reported that digestive symptoms overall had little to no impact on QOL, and 91% (n=124/136) would undergo surgery again. CONCLUSIONS: Despite known long-term complications following pancreatoduodenectomy, cancer survivors appear to have excellent QOL. Specific long-term gastrointestinal symptoms data should be utilized for preoperative education and follow-up planning.


Assuntos
Sobreviventes de Câncer , Refluxo Gastroesofágico , Neoplasias Pancreáticas , Humanos , Qualidade de Vida , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Refluxo Gastroesofágico/cirurgia , Inquéritos e Questionários
18.
HPB (Oxford) ; 26(1): 145-153, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37752029

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) impacts patients in their 60s, but its incidence in younger patients is increasing. We hypothesize that younger patients may have worse oncologic outcomes. METHODS: Patients who underwent curative pancreatic resection for PDAC between January 2011 and December 2021 at a single institution were analyzed. Early-onset pancreatic cancer (EOPC) was defined as pancreatic cancer diagnosed in patients ≤50 years. Clinical and survival outcomes were compared between EOPC and Conventional Onset Pancreas Cancer (COPC). RESULTS: A total of 1133 patients were identified, 65 (5.7%) were EOPC. Preoperative patient characteristics including sex, smoking status, alcohol habitus, diabetes mellitus, CA 19-9, and neoadjuvant therapy were similar between EOPC and COPC (p > 0.05). EOPC patients were more likely non-white (p = 0.03), had lower ASA scores (p = 0.02) and larger median tumor size (33 vs 28 mm, p = 0.04), but had similar pathological stages and rate of R0 resections (p > 0.05). Postoperative outcomes were similar (p > 0.05). There was no statistically significant difference in overall (HR 0.93, CI 0.64, 1.33; p = 0.68) or recurrence free (HR 1.05, CI 0.75, 1.48; p = 0.77) survival between the EOPC and COPC after adjusting for significant factors. CONCLUSION: Patients with EOPC who underwent surgical resection had similar oncological outcomes compared to patients with COPC.


Assuntos
Carcinoma Ductal Pancreático , Diabetes Mellitus , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Diabetes Mellitus/epidemiologia , Fumar , Estudos Retrospectivos
19.
PLoS One ; 18(11): e0294564, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38011131

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease prone to widespread metastatic dissemination and characterized by a desmoplastic stroma that contributes to poor outcomes. Fibroblast activation protein (FAP)-expressing Cancer-Associated Fibroblasts (CAFs) are crucial components of the tumor stroma, influencing carcinogenesis, fibrosis, tumor growth, metastases, and treatment resistance. Non-invasive tools to profile CAF identity and function are essential for overcoming CAF-mediated therapy resistance, developing innovative targeted therapies, and improved patient outcomes. We present the design of a multicenter phase 2 study (clinicaltrials.gov identifier NCT05262855) of [68Ga]FAPI-46 PET to image FAP-expressing CAFs in resectable or borderline resectable PDAC. METHODS: We will enroll up to 60 adult treatment-naïve patients with confirmed PDAC. These patients will be eligible for curative surgical resection, either without prior treatment (Cohort 1) or after neoadjuvant therapy (NAT) (Cohort 2). A baseline PET scan will be conducted from the vertex to mid-thighs approximately 15 minutes after administering 5 mCi (±2) of [68Ga]FAPI-46 intravenously. Cohort 2 patients will undergo an additional PET after completing NAT but before surgery. Histopathology and FAP immunohistochemistry (IHC) of initial diagnostic biopsy and resected tumor samples will serve as the truth standards. Primary objective is to assess the sensitivity, specificity, and accuracy of [68Ga]FAPI-46 PET for detecting FAP-expressing CAFs. Secondary objectives will assess predictive values and safety profile validation. Exploratory objectives are comparison of diagnostic performance of [68Ga]FAPI-46 PET to standard-of-care imaging, and comparison of pre- versus post-NAT [68Ga]FAPI-46 PET in Cohort 2. CONCLUSION: To facilitate the clinical translation of [68Ga]FAPI-46 in PDAC, the current study seeks to implement a coherent strategy to mitigate risks and increase the probability of meeting FDA requirements and stakeholder expectations. The findings from this study could potentially serve as a foundation for a New Drug Application to the FDA. TRIAL REGISTRATION: @ClinicalTrials.gov identifier NCT05262855.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adulto , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Radioisótopos de Gálio , Adenocarcinoma/tratamento farmacológico , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Fibroblastos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18/uso terapêutico , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase II como Assunto , Neoplasias Pancreáticas
20.
Ann Surg ; 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37860868

RESUMO

OBJECTIVE AND BACKGROUND: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). METHODS: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). RESULTS: A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. CONCLUSION: Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.

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