RESUMO
This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new "evidence-based guidelines" is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, "stop surveillance" or "continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma", for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Neoplasias Intraductais Pancreáticas/diagnóstico , Neoplasias Intraductais Pancreáticas/cirurgia , Pâncreas , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Endossonografia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgiaRESUMO
BACKGROUND: Only two clinical trials have shown the effects of neoadjuvant treatment for borderline resectable pancreatic cancer with arterial involvement (BRPC-A). Here, we aimed to analyze the efficacy and safety of neoadjuvant gemcitabine plus nab-paclitaxel (GnP) for BRPC-A. PATIENTS AND METHODS: A prospective, single-arm, multicenter phase II trial was conducted. Patients who were radiologically and histologically diagnosed with BRPC-A were enrolled. A central review was conducted to confirm the presence of BRPC-A. Patients received two to four cycles of GnP before surgery. The primary endpoint of the study was the R0 resection rate. Overall survival (OS) was evaluated in an ancillary study. RESULTS: Thirty-five patients were enrolled, of whom 33 were subjected to central review and 28 were confirmed to have BRPC-A. All eligible patients with BRPC-A received neoadjuvant GnP. Nineteen patients underwent pancreatic resections. Postoperative complications of Clavien-Dindo IIIa or lower were observed in 11 patients. No treatment-related mortalities were observed. R0 resection was achieved in 17 patients (89%); the R0 resection rate was 61% in eligible patients. One patient underwent curative resection after termination of the treatment protocol, resulting in an overall R0 resection rate of 64%. The median overall survival (OS) and 2-year OS rate were 24.9 months [95% confidence interval (CI) 19.0 months to not estimatable] and 53.6%, respectively. OS in patients with BRPC-A who achieved overall R0 resection was significantly longer than that in the other patients (p = 0.0255). CONCLUSIONS: Neoadjuvant GnP is a safe and effective strategy for BRPC-A, providing a chance for curative resection and improved survival.
Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas , Humanos , Gencitabina , Estudos Prospectivos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgiaRESUMO
BACKGROUND: The ideal surveillance strategy after partial pancreatectomy for non-invasive IPMN remains undefined and existing guidelines provide conflicting recommendations. The present study was developed in anticipation of the joint meeting of the International Association of Pancreatology (IAP) and the Japan Pancreas Society (JPS) held in Kyoto in July 2022. METHODS: An international team of experts developed the four clinical questions (CQ) to operationalize issues pertaining to surveillance of patients in this context. A systematic review was designed following the PRISMA guidelines and registered in PROSPERO. The search strategy was executed in PubMed/Medline (Ovid), Embase, the Cochrane Library and Web of Science databases. Four investigators individually extracted data from the selected studies and drafted recommendations for each CQ. These were subsequently discussed and agreed upon that the IAP/JPS meeting. RESULTS: From a total of 1098 studies identified through the initial search, 41 studies were included in the review and informed the recommendations. No studies providing level one data were identified in this systematic review, all studies included were cohort or case-control studies. CONCLUSIONS: There is a lack of level 1 data addressing the issue of surveillance of patients following partial pancreatectomy for non-invasive IPMN. The definition of remnant pancreatic lesion in this setting is largely heterogeneous across all studies evaluated. Herein we propose an inclusive definition of remnant pancreatic lesions to guide future prospective efforts for reporting the natural history and long-term outcomes of these patients.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Císticas, Mucinosas e Serosas , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patologia , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/patologia , Pancreatectomia/efeitos adversos , Estudos Retrospectivos , Neoplasias Císticas, Mucinosas e Serosas/cirurgiaRESUMO
PURPOSE: The current study summarized the clinical course and treatment outcomes of intestinal cancer in CD seen in our department and explored the steps to take in the future. METHODS: Subjects were patients who had been diagnosed with CD at our hospital and who underwent surgery in our department from 1985 to 2020. RESULTS: Thirty-one patients had CD and intestinal cancer, including 6 with cancer of the small intestine and 25 with cancer of the large intestine. In all six patients with cancer of the small intestine, the site where cancer or a tumor developed was at or near the site of the anastomosis made at a previous surgery. Of the 25 patients with cancer of the large intestine, 22 developed cancer in the rectum or anal region. CONCLUSION: Many of the patients with cancer of the small intestine had previously undergone surgery, and the cancer developed at or near the site of the anastomosis. In patients who have previously undergone resection of the small intestine, the small intestine needs to be examined regularly. Cancer of the large intestine often developed in the rectum or anal region of our patients, so a detailed examination of the same site needs to be performed.
Assuntos
Neoplasias do Colo , Neoplasias Colorretais , Doença de Crohn , Cirurgiões , Humanos , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Recidiva Local de Neoplasia , Reto/cirurgia , Neoplasias Colorretais/cirurgiaRESUMO
AIM: Isolating the root of the splenic artery (SPA) is a challenging procedure in laparoscopic distal pancreatectomy (LDP). We investigated the usefulness of evaluation of the relationship between the SPA and pancreatic parenchyma using three-dimensional computed tomography (3D-CT). METHODS: In total, 104 patients were evaluated. The relationship between the SPA and pancreatic parenchyma was classified into two types: buried and non-buried. Video clips of 50 patients who underwent LDP requiring isolation of the SPA root were reviewed to determine whether the classification is related to difficulty of LDP. RESULTS: Of the 50 assessed patients who underwent LDP, the relationship between the SPA and pancreatic parenchyma was the buried type in 30 (60.0%) and non-buried type in 20 (40.0%). The buried type was associated with a significantly longer median operative time than the non-buried type (285.0 vs. 235.5 min, respectively; P < 0.01). The median time required to isolate the SPA in the buried type (25.8 min; range, 4.0-101 min) was significantly longer than that in the non-buried type (7.0 min; range, 1.0-27.0 min) (P < 0.001). CONCLUSION: Preoperative 3D-CT around the pancreas is practical for predicting the difficulty of SPA isolation and determining the safety of the procedure.
Assuntos
Laparoscopia , Neoplasias Pancreáticas , Humanos , Tempo de Internação , Pâncreas/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Artéria Esplênica/diagnóstico por imagem , Artéria Esplênica/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Pancreatic cancer is the most lethal malignancy of the digestive organs. Although pancreatic resection is essential to radically cure this refractory disease, the multi-organ resection involved, as well as sequelae such as glucose tolerance insufficiency and severe complications impose a heavy burden on these patients. Since the late twentieth century, minimally invasive surgery has become more popular for the surgical management of digestive disease and pancreatic cancer. Minimally invasive pancreatic resection (MIPR), including pancreaticoduodenectomy and distal pancreatectomy, is now a treatment option for pancreatic cancer. Some evidence suggests that MIPR for pancreatic cancer provides comparable oncological outcomes to open surgery, with some advantages in perioperative outcomes. However, as this evidence is retrospective, prospective investigations, including randomized controlled trials, are necessary. Because neoadjuvant therapy for resectable or borderline-resectable pancreatic cancer and conversion surgery for initially unresectable pancreatic cancer has become more common, the feasibility of MIPR after neoadjuvant therapy or as conversion surgery requires further assessment. It is expected that progress in surgical techniques and devices, as well as the standardization of surgical procedures and widespread educational programs will improve the outcomes of MIPR.
Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Humanos , Laparoscopia , Procedimentos Cirúrgicos Minimamente Invasivos/educação , Procedimentos Cirúrgicos Minimamente Invasivos/tendências , Terapia Neoadjuvante , Pancreaticoduodenectomia/métodos , Procedimentos Cirúrgicos Robóticos , Resultado do TratamentoRESUMO
An 83-year-old woman underwent laparoscopic distal gastrectomy and Billroth â ¡ reconstruction for gastric cancer. Since histopathological examination revealed that the lesion was Stage â ¢A, she had started taking S-1 as an adjuvant chemotherapy 7 weeks after gastrectomy. Seventeen days later after taking S-1 administration, she felt nauseous and self-interrupted. Nineteen days later, she was urgently hospitalized. Esophagogastroduodenoscopy(EGD)showed anastomotic lumen was open, but reconstructed small intestine mucosal damage was found, and reconstructed small intestine muscle layer was fused to anastomotic region. On 50th day of hospitalization, mucosa was regenerated and endoscopic balloon dilatation (EBD)was performed from 78th day. She was discharged on 151th day of hospitalization after 7 times of EBD. One year later, she does not need EBD and can be taken orally and has no recurrence.
Assuntos
Laparoscopia , Neoplasias Gástricas , Idoso de 80 Anos ou mais , Constrição Patológica , Feminino , Gastrectomia/efeitos adversos , Gastroenterostomia , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgiaRESUMO
OBJECTIVE: To determine the factors predicting the subsequent development of pancreatic ductal adenocarcinoma in remnant pancreas (PDAC-RP) after partial pancreatectomy for PDAC. SUMMARY BACKGROUND DATA: PDAC-RP after partial pancreatectomy for PDAC is currently not so rare because of improved prognosis of PDAC patients due to recent advances in surgical techniques and adjuvant therapy. However, the predictive factors related to PDAC-RP remain unknown. METHODS: We retrospectively reviewed the clinicopathological data of a consecutive series of 379 patients with PDAC treated by partial pancreatectomy between 1992 and 2015; 14 patients (3.69%) had PDAC-RP. Clinicopathological variables were compared between PDAC-RP and non-PDAC-RP. RESULTS: In univariate analysis, concomitant intraductal papillary mucinous neoplasm (IPMN) (P = 0.0005), cancer location (body/tail) (P = 0.0060), and lower T factor in UICC (P = 0.0039) were correlated with PDAC-RP development. Multivariate analysis revealed concomitant IPMN (P = 0.0135) to be an independent predictive factor for PDAC-RP. PDAC concomitant with IPMN had higher cumulative incidence of PDAC-RP (47.5%/10 yrs) than PDAC without IPMN (9.96%/10 yrs) (P = 0.0071). Moreover, the density of pancreatic intraepithelial neoplasia lesions in the background pancreas of cases of PDAC concomitant with IPMN (1.86/cm) was higher than that of cases of PDAC without IPMN (0.91/cm) (P = 0.0007). CONCLUSIONS: Concomitant IPMN in PDAC is an independent predictive factor for the development of new PDAC in remnant pancreas. Cancer susceptibility of remnant pancreas after resection for PDAC concomitant with IPMN is probably due to an increased density of pancreatic intraepithelial neoplasia lesions.
Assuntos
Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Segunda Neoplasia Primária/patologia , Pancreatectomia/métodos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
Progress in diagnostic modalities, surgical procedures, and multidisciplinary treatment for pancreatic diseases has increased the number of long-term survivors after pancreatic resection. Several reports have focused on high-risk lesions (HRLs), including high-grade pancreatic intraepithelial neoplasia (PanIN), pancreatic ductal adenocarcinoma, high-grade intraductal papillary mucinous neoplasm (IPMN), and IPMN with an associated invasive carcinoma, in the remnant pancreas after partial pancreatic resection for pancreatic cancer or IPMN. The etiology of HRLs in the remnant pancreas is thought to be either isolated local recurrence of the initial lesion in the remnant pancreas or a newly developed primary lesion. Although it is difficult to distinguish between local recurrence and a new primary lesion, comparison of genetic alterations between two lesions may help with this distinction. Early detection of HRLs in the remnant pancreas may improve the prognosis of patients, and several investigators have proposed predictive factors for HRLs in the remnant pancreas after partial pancreatic resection for pancreatic cancer or IPMN. The reported short- and long-term outcomes of surgical resection of HRLs in the remnant pancreas are relatively favorable. Life-long surveillance of the remnant pancreas is recommended after partial pancreatic resection for pancreatic cancer or IPMN.
Assuntos
Adenocarcinoma Mucinoso/cirurgia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Papilar/cirurgia , Neoplasia Residual , Pancreatectomia/métodos , Neoplasias Pancreáticas/terapia , Humanos , Recidiva Local de Neoplasia , Prognóstico , Risco , Fatores de TempoRESUMO
Although recent studies revealed that adipose tissue accelerates pancreatic tumor progression with excessive extracellular matrix, key players for desmoplasia in the adipose microenvironment remains unknown. Here, we investigated the roles of adipose tissue-derived stromal cells (ASCs) in desmoplastic lesions and tumor progression by in vitro and in vivo experiments. In a three-dimensional (3-D) organotypic fat invasion model using visceral fat from CAG-EGFP mice, GFP-positive fibroblastic cells infiltrated toward cancer cells. When tumor cells were inoculated into transplanted visceral fat pads in vivo, tumor weights and stromal components were enhanced compared to subcutaneous and orthotopic tumor cells inoculated without fat pads. Expression of αSMA in established human ASCs was lower compared to cancer associated fibroblasts, and the 3-D collagen matrices produced by ASCs cultured in cancer cell-conditioned medium changed from loose to dense structures that affected the motility of cancer cells. Microarray analyses revealed upregulation of S100A4 in ASCs, while S100A4-positive stromal cells were observed at extrapancreatic invasion sites of human pancreatic cancer. The present findings indicate that ASCs are recruited to extrapancreatic invasion sites and produce dense collagen matrices that lead to enhanced tumor progression. Both inhibition of ASCs recruitment and activation could lead to a novel antistromal therapy.
Assuntos
Fibroblastos Associados a Câncer/patologia , Carcinoma Ductal Pancreático/patologia , Colágeno/metabolismo , Neoplasias Pancreáticas/patologia , Células Estromais/patologia , Actinas/metabolismo , Idoso , Animais , Carcinoma Ductal Pancreático/cirurgia , Diferenciação Celular , Meios de Cultivo Condicionados/metabolismo , Progressão da Doença , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Humanos , Gordura Intra-Abdominal/citologia , Gordura Intra-Abdominal/transplante , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Camundongos Transgênicos , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Cultura Primária de Células , Proteína A4 de Ligação a Cálcio da Família S100/metabolismo , Células Tumorais Cultivadas , Microambiente TumoralRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal neoplasm because of difficulties in early detection. Several studies have recently suggested that exosomes may have potential as novel biomarkers. This study aimed to isolate exosomes from pancreatic juice and to investigate whether exosomal microRNAs (ex-miRs) could be used as biomarkers for PDAC. METHODS: Pancreatic juice was collected from patients with PDAC and chronic pancreatitis (CP) by endoscopic retrograde pancreatography. Exosomes were extracted by ultracentrifugation. The presence of exosomes was confirmed by electron microscopy and Western blotting using anti-CD63, -CD81, and -TSG101 antibodies. Relative levels of ex-miR-21 and ex-miR-155 were quantified and compared between PDAC and CP patients. RESULTS: A total of 35 pancreatic juice samples (27 PDAC and 8 CP) were collected. Relative levels of both ex-miR-21 and ex-miR-155 were significantly higher in PDAC patients compared with CP patients (p < 0.001 and p = 0.008, respectively). By contrast, no significant difference was apparent in relative levels of miR-21 and miR-155 in whole pancreatic juice from PDAC patients compared with CP patients (p = 0.08 and p = 0.61, respectively). Ex-miR-21 and ex-miR-155 levels discriminated PDAC patients from CP patients with area under the curve values of 0.90 and 0.89, respectively. The accuracies of ex-miR-21 levels, ex-miR-155 levels, and pancreatic juice cytology were 83%, 89%, and 74%, respectively. When combining the results of ex-miR profiling with pancreatic juice cytology, the accuracy was improved to 91%. CONCLUSIONS: We successfully extracted exosomes from pancreatic juice. Ex-miRs, including ex-miR-21 and ex-miR-155, in pancreatic juice may be developed as biomarkers for PDAC.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/diagnóstico , Exossomos/genética , MicroRNAs/genética , Suco Pancreático/metabolismo , Neoplasias Pancreáticas/diagnóstico , Pancreatite Crônica/diagnóstico , Adulto , Idoso , Carcinoma Ductal Pancreático/genética , Diagnóstico Diferencial , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Pancreatite Crônica/genética , Prognóstico , Taxa de Sobrevida , Neoplasias PancreáticasRESUMO
BACKGROUND: Accumulation of evidence suggests that neoadjuvant chemotherapy improves the outcomes of borderline resectable pancreatic cancer (BRPC). Gemcitabine plus nab-paclitaxel (GnP) has been widely accepted as systemic chemotherapy for unresectable pancreatic cancer and reportedly results in remarkable tumor shrinkage. This study was performed to evaluate the safety and efficacy of neoadjuvant chemotherapy using neoadjuvant GnP for BRPC. METHODS: The medical records of 57 patients who underwent treatment of BRPC from 2010 to 2017 were retrospectively reviewed. The patient characteristics and short- and intermediate-term outcomes were compared between the GnP and upfront surgery (UFS) groups. RESULTS: The GnP group comprised 31 patients and the UFS group comprised 26 patients. The patient characteristics were comparable with the exception of a higher prevalence of arterial involvement in the GnP group. Twenty-seven of the 31 patients (87%) in the GnP group and all 26 patients in the UFS group underwent resection. The GnP group showed a significantly shorter operation time (429 vs. 509.5 min, p = 0.0068), less blood loss (760 vs. 1324 ml, p = 0.0115), and a higher R0 resection rate (100% vs. 77%, p = 0.0100) than the UFS group. Postoperative complications and hospital stay were comparable between the two groups, and no treatment-related mortality occurred in either group. Both the disease-free survival and overall survival times were significantly longer in the GnP group (p = 0.0018 and p = 0.0024, respectively). CONCLUSIONS: Neoadjuvant GnP is a safe and effective treatment strategy for BRPC. It potentially improves patients' prognosis and facilitates surgical procedures.
Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/mortalidade , Neoplasias Pancreáticas/mortalidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Pancreatectomia/estatística & dados numéricos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , GencitabinaRESUMO
BACKGROUND/OBJECTIVES: The biological features of cystic pancreatic neuroendocrine tumors (PNETs) remain unclear. The aim of this study was to clarify the clinicopathological characteristics of non-functioning PNETs (NF-PNETs) with a cystic component. METHODS: The medical records of 75 patients with NF-PNETs who had undergone resection in our institution were retrospectively reviewed. Clinicopathological factors were compared between PNETs with and without a cystic component. Expression of somatostatin 2 receptor (SSTR-2) was also analyzed. RESULTS: Cystic PNETs were diagnosed in 14 patients (19%). The proportion of men was significantly higher for cystic than solid PNETs (79% vs. 44%, Pâ¯<â¯0.05) and cystic PNETs were significantly larger than solid PNETs (25â¯mm vs. 17â¯mm, Pâ¯<â¯0.01). However, there were no significant differences in the prevalence of lymph node metastases (14% vs. 10%, Pâ¯=â¯0.64), hepatic metastasis (7% vs. 3%, Pâ¯=â¯0.54), or disease-free survival rate (both 86%, Pâ¯=â¯0.29) between PNETs with and without a cystic component. SSTR-2 expression was more frequently observed in PNETs with a cystic component than in those without (100% vs. 70%, Pâ¯<â¯0.01). CONCLUSIONS: Although cystic PNETs were larger upon diagnosis than solid PNETs in this study, prognosis after surgical resection did not differ significantly between these types of PNET. Somatostatin receptor scintigraphy and somatostatin analogues may be more useful for diagnosing and treating cystic PNETs, respectively.
Assuntos
Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: Neoadjuvant therapy (NAT) is increasingly used to improve the prognosis of patients with borderline resectable pancreatic cancer (BRPC) albeit with little evidence of its advantage over upfront surgical resection. We analyzed the prognostic impact of NAT on patients with BRPC in a multicenter retrospective study. METHODS: Medical data of 165 consecutive patients who underwent treatment for BRPC between January 2010 and December 2014 were collected from ten institutions. We defined BRPC according to the National Comprehensive Cancer Network guidelines, and subclassified patients according to venous invasion alone (BR-PV) and arterial invasion (BR-A). RESULTS: The rates of NAT administration and resection were 35% and 79%, respectively. There were no significant differences in resection rates and prognoses between patients in the BR-PV and BR-A subgroups. NAT did not have a significant impact on prognosis according to intention-to-treat analysis. However, in patients who underwent surgical resection, NAT was independently associated with longer overall survival (OS). The median OS of patients who underwent resection after NAT (53.7 months) was significantly longer than that of patients who underwent upfront (17.8 months) or no resection (14.9 months). The rates of superior mesenteric or portal vein invasion, lymphatic invasion, venous invasion, and lymph node metastasis were significantly lower in patients who underwent resection after NAT than in those who underwent upfront resection despite similar baseline clinical profiles. CONCLUSIONS: Resection after NAT in patients with BRPC is associated with longer OS and lower rates of both invasion to the surrounding tissues and lymph node metastasis.
Assuntos
Adenocarcinoma/terapia , Terapia Neoadjuvante , Neoplasias Pancreáticas/terapia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Terapia Combinada , Humanos , Metástase Linfática , Invasividade Neoplásica , Pancreatectomia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is characterized by cystic dilation of the pancreatic duct, caused by mucin hypersecretion, with slow progression via the adenoma-carcinoma sequence mechanism. Mutation of GNAS at codon 201 is found exclusively in IPMNs, occurring at a rate of 41-75%. Recent advances in molecular biological techniques have demonstrated that GNAS mutation might play a role in the transformation of IPMNs after the appearance of neoplastic cells, rather than in the tumorigenesis of IPMNs. GNAS mutation is observed frequently in the intestinal subtype of IPMNs with MUC2 expression, and less frequently in IPMNs with concomitant pancreatic ductal adenocarcinoma (PDAC). Research has focused on assessing GNAS mutation status in clinical practice using various samples. In this review, we discuss the clinical application of GNAS mutation assessment to differentiate invasive IPMNs from concomitant PDAC, examine the clonality of recurrent IPMNs in the remnant pancreas using resected specimens, and differentiate pancreatic cystic lesions using cystic fluid collected by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), duodenal fluid, and serum liquid biopsy samples.
Assuntos
Cromograninas/genética , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Mutação , Neoplasias Primárias Múltiplas , Neoplasias Intraductais Pancreáticas/genética , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Transformação Celular Neoplásica/genética , Códon/genética , Diagnóstico Diferencial , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Expressão Gênica , Humanos , Mucina-2/genética , Mucina-2/metabolismo , Neoplasias Intraductais Pancreáticas/diagnóstico , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)RESUMO
BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor environment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated to produce these factors, or whether this process can be inhibited. PSCs have morphologic and functional similarities to hepatic stellate cells, which undergo autophagy to promote fibrosis and tumor growth. We investigated whether autophagy activates PSCs, which promotes development of the tumor stroma and growth of pancreatic tumors in mice. METHODS: We used immunofluorescence microscopy and immunohistochemistry to analyze pancreatic tumor specimens from 133 patients who underwent pancreatectomy in Japan from 2000 to 2009. PSCs were cultured from pancreatic tumor tissues or tissues of patients with chronic pancreatitis; these were analyzed by immunofluorescence microscopy, immunoblots, quantitative reverse transcription polymerase chain reaction, and in assays for invasiveness, proliferation, and lipid droplets. Autophagy was inhibited in PSCs by administration of chloroquine or transfection with small interfering RNAs. Proteins were knocked down in immortalized PSCs by expression of small hairpin RNAs. Cells were transplanted into pancreatic tails of nude mice, and tumor growth and metastasis were quantified. RESULTS: Based on immunohistochemical analyses, autophagy was significantly associated with tumor T category (P = .018), histologic grade (P = .001), lymph node metastases (P < .001), stage (P = .009), perilymphatic invasion (P = .001), and perivascular invasion (P = .003). Autophagy of PSCs was associated with shorter survival times of patients with pancreatic cancer. PSC expression of microtubule-associated protein 1 light chain 3, a marker of autophagosomes, was associated with poor outcomes (shorter survival time, disease recurrence) for patients with pancreatic cancer (relative risk of shorter survival time, 1.56). Immunoblots showed that PSCs from pancreatic tumor samples expressed higher levels of markers of autophagy than PSCs from chronic pancreatitis samples. Inhibitors of autophagy increased the number of lipid droplets of PSCs, indicating a quiescent state of PSCs, and reduced their production of ECM molecules and interleukin 6, as well as their proliferation and invasiveness in culture. PSCs exposed to autophagy inhibitors formed smaller tumors in nude mice (P = .001) and fewer liver metastases (P = .018) with less peritoneal dissemination (P = .018) compared to PSCs not exposed to autophagy inhibitors. CONCLUSIONS: Autophagic PSCs produce ECM molecules and interleukin 6 and are associated with shorter survival times and disease recurrence in patients with pancreatic cancer. Inhibitors of PSC autophagy might reduce pancreatic tumor invasiveness by altering the tumor stroma.
Assuntos
Autofagia , Matriz Extracelular/metabolismo , Interleucina-6/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/fisiopatologia , Células Estreladas do Pâncreas/fisiologia , Animais , Autofagia/efeitos dos fármacos , Autofagia/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cloroquina/farmacologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Gotículas Lipídicas , Metástase Linfática , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/metabolismo , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Transplante de Neoplasias , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/diagnóstico por imagem , Células Estreladas do Pâncreas/metabolismo , Pancreatite Crônica/diagnóstico por imagem , Pancreatite Crônica/metabolismo , RNA Interferente Pequeno/genética , Taxa de Sobrevida , TransfecçãoRESUMO
BACKGROUND: Preoperative nutritional and immunological patient factors have been found to be associated with prognostic outcomes of malignant tumors; however, the clinical significance of these factors in pancreatic ductal adenocarcinoma (PDAC) remains controversial. OBJECTIVE: The aim of this study was to evaluate the prognostic value of nutritional and immunological factors in predicting survival of patients with PDAC. METHODS: Retrospective studies of 329 patients who underwent surgical resection for PDAC and 95 patients who underwent palliative surgery were separately conducted to investigate the prognostic impact of tumor-related factors and patient-related factors, including Glasgow Prognostic Score (GPS), modified GPS, Prognostic Nutritional Index (PNI), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, and lymphocyte/monocyte ratio. RESULTS: In multivariate analysis for patients with surgical resection for PDAC, PNI was an independent factor for overall survival (OS) and disease-free survival. The median OS of patients with PNI ≤ 45 was significantly shorter than that of patients with PNI > 45 (17.5 and 36.2 months, respectively; p < 0.001). In multivariate analysis for patients undergoing palliative surgery for PDAC, only NLR was an independent prognosis factor. The median OS of patients with NLR > 5 was significantly shorter than that of patients with NLR ≤ 5 (2.7 and 8.9 months, respectively; p < 0.001). CONCLUSIONS: PNI in patients with surgical resection and NLR in patients with palliative surgery for PDAC may be useful prognostic factors.
Assuntos
Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/patologia , Neutrófilos , Estado Nutricional , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/cirurgia , Idoso , Antígeno Carcinoembrionário/sangue , Intervalo Livre de Doença , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos , Gradação de Tumores , Estadiamento de Neoplasias , Avaliação Nutricional , Cuidados Paliativos , Contagem de Plaquetas , Período Pré-Operatório , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND/OBJECTIVES: It is often difficult to determine an adequate resection line during pancreatectomy for intraductal papillary mucinous neoplasm involving the main pancreatic duct during partial pancreatectomy. The aim of this study was to evaluate the usefulness of improved peroral pancreatoscopy using SpyGlass-DStm in the preoperative assessment of intraductal papillary mucinous neoplasm involving the main pancreatic duct. METHODS: We collected and retrospectively analyzed clinicopathological data from seven consecutive patients who underwent preoperative assessment of intraductal papillary mucinous neoplasm involving the main duct using SpyGlass-DStm. RESULTS: Good imaging quality of the intraductal protruding lesion was obtained in all seven patients, and only one adverse event was noted wherein a patient had mild pancreatitis. Six patients underwent pancreatectomy. In one patient, masked-type concomitant pancreatic ductal adenocarcinoma and low-length dysplastic lesion was found near the surgical margin, which was not detected by preoperative imaging modalities including SpyGlass-DStm. The sensitivity of targeting biopsy during SpyGlass-DStm to diagnose high-grade dysplasia was 0%. CONCLUSIONS: SpyGlass-DStm can be safely performed in patients with intraductal papillary mucinous neoplasm involving the main duct, and has excellent visualization of the target lesion. However, challenges include poor diagnostic ability of targeting biopsy, and, therefore, intraoperative frozen section is still needed to obtain negative surgical margins.