S. Vecchiarelli, M. Macchini, A. Astolfi, V. Indio, E. Grassi, L. R. Martella, R. Casadei, C. Serra, D. Santini, R. Pezzilli, F. Minni, G. Biasco, M. Marco
Context We merged clinical history of a locally advanced pancreatic cancer (LAPC) patient with data obtained from a whole transcriptome massively parallel sequencing (RNASeq). Case report A 56-year-old man with histological diagnosis of LAPC. After obtained informed consent, we collected a fragment of pancreatic lesion. Patient received 6 induction cycles treatment with gemcitabine and oxaliplatin (GEMOX) from November 2011, followed by chemoradiotherapy with bi-weekly gemcitabine 50 mg/m 2 for 6 weeks. CT-scan demonstrated partial response, so patient received additional 12 cycles of GEMOX, with further response, which currently persist since 17 months (to 3.8 cm vs . 2.5 cm). At the same time, the RNASeq was performed at 75x2 bp on a HiScanSQ (Illumina Inc., San Diego, CA, USA) platform. Single nucleotide variants (SNVs) were detected with SNVMix2 and filtered on dbSNP, 1000 Genomes Project, and Cosmic databases. Non-synonymous SNVs were analyzed with SNPsG ATXN10-TMEM49; chromosome 22 and 17) and 2 out-of-frame fusions [ t (15;3) and t (19;22)] leading to SMAD3-KIAA1143 and LTBP4-SPATS2L, both disrupting genes of the TGFbeta pathway. Conclusion We found a novel somatic alteration involving HMGCR in LAPC. Due to the key role of HMGCR in cellular transformation, we hypothesize a strong potential in the development and outcome of LAPC, whose the optimal treatment remains to be elucidated. Trials that integrate RNASeq data with clinical options are needed.
我们将一位局部晚期胰腺癌(LAPC)患者的临床病史与全转录组大规模平行测序(RNASeq)获得的数据合并。病例报告1例56岁男性,组织学诊断为LAPC。在获得知情同意后,我们收集了胰腺病变的碎片。患者从2011年11月开始接受6个诱导周期的吉西他滨和奥沙利铂(GEMOX)治疗,随后进行双周吉西他滨50 mg/ m2的放化疗,持续6周。ct扫描显示部分反应,因此患者接受了额外的12个周期的GEMOX,进一步的反应,目前持续了17个月(至3.8 cm)。2.5厘米)。同时,在HiScanSQ (Illumina Inc., San Diego, CA, USA)平台上进行75x2 bp的RNASeq。用SNVMix2检测单核苷酸变异(snv),并用dbSNP、1000 Genomes Project和Cosmic数据库进行筛选。用SNPsG ATXN10-TMEM49分析非同义snv;染色体22和17)和2个框外融合[t(15;3)和t(19;22)]导致SMAD3-KIAA1143和LTBP4-SPATS2L,两者都破坏tgf β途径的基因。结论在LAPC中发现了一种新的与HMGCR有关的体细胞改变。由于HMGCR在细胞转化中的关键作用,我们假设LAPC的发展和结局具有强大的潜力,其最佳治疗方法仍有待阐明。需要将RNASeq数据与临床选择相结合的试验。
{"title":"Whole Transcriptome Sequencing Reveals Somatic HMGCR Mutation in a Case of Pancreatic Adenocarcinoma with Long-Term Therapy Response","authors":"S. Vecchiarelli, M. Macchini, A. Astolfi, V. Indio, E. Grassi, L. R. Martella, R. Casadei, C. Serra, D. Santini, R. Pezzilli, F. Minni, G. Biasco, M. Marco","doi":"10.6092/1590-8577/1746","DOIUrl":"https://doi.org/10.6092/1590-8577/1746","url":null,"abstract":"Context We merged clinical history of a locally advanced pancreatic cancer (LAPC) patient with data obtained from a whole transcriptome massively parallel sequencing (RNASeq). Case report A 56-year-old man with histological diagnosis of LAPC. After obtained informed consent, we collected a fragment of pancreatic lesion. Patient received 6 induction cycles treatment with gemcitabine and oxaliplatin (GEMOX) from November 2011, followed by chemoradiotherapy with bi-weekly gemcitabine 50 mg/m 2 for 6 weeks. CT-scan demonstrated partial response, so patient received additional 12 cycles of GEMOX, with further response, which currently persist since 17 months (to 3.8 cm vs . 2.5 cm). At the same time, the RNASeq was performed at 75x2 bp on a HiScanSQ (Illumina Inc., San Diego, CA, USA) platform. Single nucleotide variants (SNVs) were detected with SNVMix2 and filtered on dbSNP, 1000 Genomes Project, and Cosmic databases. Non-synonymous SNVs were analyzed with SNPsG ATXN10-TMEM49; chromosome 22 and 17) and 2 out-of-frame fusions [ t (15;3) and t (19;22)] leading to SMAD3-KIAA1143 and LTBP4-SPATS2L, both disrupting genes of the TGFbeta pathway. Conclusion We found a novel somatic alteration involving HMGCR in LAPC. Due to the key role of HMGCR in cellular transformation, we hypothesize a strong potential in the development and outcome of LAPC, whose the optimal treatment remains to be elucidated. Trials that integrate RNASeq data with clinical options are needed.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"601-601"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. C. Milanetto, V. Liço, L. Iaria, R. Alaggio, C. Sperti, S. Pedrazzoli, C. Pasquali
Context Primary pancreatic carcinoid tumors (foregut) are very rare. A typical carcinoid syndrome with diarrhea and flushing may be present. The diagnosis is based on the high urinary 5-HIAA (5-hydroxyndole acetic acid) levels (or high serum serotonin levels) or the immunostaining of serotonin (5-HT) in the tumor cells. Objective We evaluated clinical presentation, endocrine tumor markers, histology, therapeutic approach and follow up. Methods From 1986 to 2011 in our department we observed 211 neuroendocrine (NE) pancreatic tumors and 8 of them (3.8%) were primary carcinoid tumors (5 males and 3 females; averaging 55.8 years, range: 38-69 years). Follow up was updated until December 2012. Results Among the eight patients enrolled, 3 were symptomatic. Seven had high serum 5-HT or high urinary 5-HIAA, and one was asymptomatic with immunostaining of 5-HT in tumor cells. Location: 6 body-tail. All were malignant tumors: 7 liver and 1 single nodal metastases. Markers: 4 high serum 5-HT (up to 176 µmol/L), 7 high urinary 5-HIAA (up to 522 µmol/L). Surgery: 1 left pancreatectomy, 7 biopsy. Histology: 7 NE tumor, 1 negative pancreatic biopsy (liver metastases). Other therapy: 3 treated with somatostatin analogues (SST-A) and chemotherapy (CT), 1 CT and radiometabolic therapy after hepatic artery embolization (HAE), 1 HAE and SST-A, 1 CT. Follow up: 6 dead for disease progression (mean survival 52 months), 2 alive (1 without disease 78 months after surgery; 1 asymptomatic with high 5-HIAA 33 months after SST-A and CT). Conclusion Most of primary pancreatic carcinoids are locally advanced tumors or have liver metastases at time of diagnosis, then patients are not amenable to surgery. Although most patients had high 5-HIAA urinary excretion, few patients had carcinoid syndrome. A long term survival may be achieved with multimodal approach, including chemotherapy, in foregut carcinoid tumors.
{"title":"Primary Carcinoid Tumors of the Pancreas: Report of Eight Cases","authors":"A. C. Milanetto, V. Liço, L. Iaria, R. Alaggio, C. Sperti, S. Pedrazzoli, C. Pasquali","doi":"10.6092/1590-8577/1694","DOIUrl":"https://doi.org/10.6092/1590-8577/1694","url":null,"abstract":"Context Primary pancreatic carcinoid tumors (foregut) are very rare. A typical carcinoid syndrome with diarrhea and flushing may be present. The diagnosis is based on the high urinary 5-HIAA (5-hydroxyndole acetic acid) levels (or high serum serotonin levels) or the immunostaining of serotonin (5-HT) in the tumor cells. Objective We evaluated clinical presentation, endocrine tumor markers, histology, therapeutic approach and follow up. Methods From 1986 to 2011 in our department we observed 211 neuroendocrine (NE) pancreatic tumors and 8 of them (3.8%) were primary carcinoid tumors (5 males and 3 females; averaging 55.8 years, range: 38-69 years). Follow up was updated until December 2012. Results Among the eight patients enrolled, 3 were symptomatic. Seven had high serum 5-HT or high urinary 5-HIAA, and one was asymptomatic with immunostaining of 5-HT in tumor cells. Location: 6 body-tail. All were malignant tumors: 7 liver and 1 single nodal metastases. Markers: 4 high serum 5-HT (up to 176 µmol/L), 7 high urinary 5-HIAA (up to 522 µmol/L). Surgery: 1 left pancreatectomy, 7 biopsy. Histology: 7 NE tumor, 1 negative pancreatic biopsy (liver metastases). Other therapy: 3 treated with somatostatin analogues (SST-A) and chemotherapy (CT), 1 CT and radiometabolic therapy after hepatic artery embolization (HAE), 1 HAE and SST-A, 1 CT. Follow up: 6 dead for disease progression (mean survival 52 months), 2 alive (1 without disease 78 months after surgery; 1 asymptomatic with high 5-HIAA 33 months after SST-A and CT). Conclusion Most of primary pancreatic carcinoids are locally advanced tumors or have liver metastases at time of diagnosis, then patients are not amenable to surgery. Although most patients had high 5-HIAA urinary excretion, few patients had carcinoid syndrome. A long term survival may be achieved with multimodal approach, including chemotherapy, in foregut carcinoid tumors.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"550"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71231365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
E. Bona, V. Beltrame, S. Blandamura, M. Pizzi, C. Pasquali, C. Sperti
Context Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic tumor defined as intraductal mucin-producing neoplasm with tall, columnar, mucin-producing epithelium. IPMNs have already been described in association with inherited genetic disorder including familial adenomatous polyposis and Peutz-Jeghers syndrome. However, description of familial history of IPMN is very rarely reported. We present two cases of malignant IPMN in identical twins. Case report A 54-year-old woman was admitted in August 2010 with epigastric pain and high serum levels of amylase and lipase. Abdominal CT revealed dilation of main pancreatic duct (5 mm) with multiple cysts in the head of the pancreas. Serum CA 19-9 was in the normal range, and positron emission tomography with CT acquisition (PET/CT) was negative. A diagnosis of mixed type IPMN was made, and the patient underwent pancreaticoduodenectomy. Pathologic examination showed a tubular, poorly differentiated adenocarcinoma, tubular type, in combined type IPMN (pancreatico-biliary type) of the head of the pancreas with high grade dysplasia (pT3N0M0 G3). Postoperative course was uneventful, and the patient underwent adjuvant chemo-radiotherapy. Three years after surgery, there was no evidence of tumor relapse. Her sister, a 57-year-old woman, was admitted in February 2013 for obstructive jaundice and weight loss. Serum CA 19-9 was 86.2 U/mL. Magnetic resonance of the abdomen showed a 4.8 cm, pluricystic mass of the head of the pancreas, with marked dilation (10 mm) of the main pancreatic duct. FNAC under EUS examination showed mucinous epithelial cells with low-moderate dysplasia. PET/CT revealed a pathologic uptake of the radiotracer in the pancreatic head and in the right colon. Colonoscopy did not show colonic lesions. In March 2013 the patient underwent pylorus-preserving pancreaticoduodenectomy. Pathologic examination showed a colloid, poorly differentiated adenocarcinoma in main duct IPMN (intestinal type) of the head of the pancreas (pT3N0M0G3). Adjuvant therapy with gemcitabine was started, and the patient is alive 3 months after operation, without tumor relapse. Conclusion Although rare, the coexistence of IPMN reported here in two identical twins, suggests that it is due to a genetic inherited factor that remains to be elucidated. Physicians should carefully study the familial history of patients with IPMN.
{"title":"Malignant Intraductal Papillary Mucinous Neoplasms of the Pancreas in Two Identical Twins","authors":"E. Bona, V. Beltrame, S. Blandamura, M. Pizzi, C. Pasquali, C. Sperti","doi":"10.6092/1590-8577/1659","DOIUrl":"https://doi.org/10.6092/1590-8577/1659","url":null,"abstract":"Context Intraductal papillary mucinous neoplasm (IPMN) is a rare pancreatic tumor defined as intraductal mucin-producing neoplasm with tall, columnar, mucin-producing epithelium. IPMNs have already been described in association with inherited genetic disorder including familial adenomatous polyposis and Peutz-Jeghers syndrome. However, description of familial history of IPMN is very rarely reported. We present two cases of malignant IPMN in identical twins. Case report A 54-year-old woman was admitted in August 2010 with epigastric pain and high serum levels of amylase and lipase. Abdominal CT revealed dilation of main pancreatic duct (5 mm) with multiple cysts in the head of the pancreas. Serum CA 19-9 was in the normal range, and positron emission tomography with CT acquisition (PET/CT) was negative. A diagnosis of mixed type IPMN was made, and the patient underwent pancreaticoduodenectomy. Pathologic examination showed a tubular, poorly differentiated adenocarcinoma, tubular type, in combined type IPMN (pancreatico-biliary type) of the head of the pancreas with high grade dysplasia (pT3N0M0 G3). Postoperative course was uneventful, and the patient underwent adjuvant chemo-radiotherapy. Three years after surgery, there was no evidence of tumor relapse. Her sister, a 57-year-old woman, was admitted in February 2013 for obstructive jaundice and weight loss. Serum CA 19-9 was 86.2 U/mL. Magnetic resonance of the abdomen showed a 4.8 cm, pluricystic mass of the head of the pancreas, with marked dilation (10 mm) of the main pancreatic duct. FNAC under EUS examination showed mucinous epithelial cells with low-moderate dysplasia. PET/CT revealed a pathologic uptake of the radiotracer in the pancreatic head and in the right colon. Colonoscopy did not show colonic lesions. In March 2013 the patient underwent pylorus-preserving pancreaticoduodenectomy. Pathologic examination showed a colloid, poorly differentiated adenocarcinoma in main duct IPMN (intestinal type) of the head of the pancreas (pT3N0M0G3). Adjuvant therapy with gemcitabine was started, and the patient is alive 3 months after operation, without tumor relapse. Conclusion Although rare, the coexistence of IPMN reported here in two identical twins, suggests that it is due to a genetic inherited factor that remains to be elucidated. Physicians should carefully study the familial history of patients with IPMN.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"567-567"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71231408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Lapolla, Immacolata Forlano, A. D. Lascia, M. Gorgoglione, Vincenzo Neri
Context Diabetes may increase the risk of acute pancreatitis and may also adversely affects the evolution of the acute pancreatitis (AP). Objective The aim of the study was to evaluate if diabetes is associated with higher incidence of severe acute pancreatitis and also of critical forms (early severe acute pancreatitis; ESAP) and, moreover, how diabetes may modify the evolution of acute pancreatitis. Methods Since 2001 to 2012 we treated 276 acute biliary pancreatitis. All severe acute forms of pancreatitis were 21.7% (n=60); 13 (21.7%) critical forms were identified among SAP. Clinical features, organ failure, therapeutic choices and results between SAP (n=47) and ESAP (n=13) were compared. We evaluated the prevalence of patients with diabetes in each group (AP, SAP, and ESAP). Furthermore, we evaluated the prevalence of diabetes by the criteria usually used to define the different severity grades of pancreatitis. Results The comparison between SAP and ESAP has shown the following results: impairment degree of pancreas (Balthazar CT score): SAP 2.3 vs . ESAP 3.85; abdominal compartment syndrome (ACS): ESAP 7.6% (1/13); multiorgan dysfunction syndrome (MODS): ESAP 46.1% (6/13); simple organ dysfunction: SAP 51% (24/47) vs . ESAP 53.8% (7/13); hypoxemia: SAP 65.9 % (31/47) vs . ESAP 76.9% (10/13); pancreatic infections: SAP 6.3% (3/47) vs . ESAP 23% (3/13); mortality: SAP 4.2% (2/47) vs . ESAP 15.4% (2/13). The prevalence of diabetes in AP patients was 19.5% (54/276), 31.7% (19/60) in all severe acute forms of pancreatitis group and 38.4% (5/13) in ESAP group (P<0.05 chi-square test). Regarding the severity criteria, diabetes had a prevalence of 23.3% (14/60) in single organ dysfunction and 23.1% (3/13) in MODS and 6.6% (4/60) in septic complications of fluid necrotic collections. Conclusion The association of AP with the diabetes is in evidence: the risk of acute pancreatitis is raised by diabetes, but also of critical forms. In our experience diabetes may worsen acute pancreatitis in the first phase of systemic inflammation, otherwise it seems to be not strongly connected to the evolution of possible late septic complications.
{"title":"Severe Acute Biliary Pancreatitis and Type 2 Diabetes: Which Kind of Connection?","authors":"F. Lapolla, Immacolata Forlano, A. D. Lascia, M. Gorgoglione, Vincenzo Neri","doi":"10.6092/1590-8577/1673","DOIUrl":"https://doi.org/10.6092/1590-8577/1673","url":null,"abstract":"Context Diabetes may increase the risk of acute pancreatitis and may also adversely affects the evolution of the acute pancreatitis (AP). Objective The aim of the study was to evaluate if diabetes is associated with higher incidence of severe acute pancreatitis and also of critical forms (early severe acute pancreatitis; ESAP) and, moreover, how diabetes may modify the evolution of acute pancreatitis. Methods Since 2001 to 2012 we treated 276 acute biliary pancreatitis. All severe acute forms of pancreatitis were 21.7% (n=60); 13 (21.7%) critical forms were identified among SAP. Clinical features, organ failure, therapeutic choices and results between SAP (n=47) and ESAP (n=13) were compared. We evaluated the prevalence of patients with diabetes in each group (AP, SAP, and ESAP). Furthermore, we evaluated the prevalence of diabetes by the criteria usually used to define the different severity grades of pancreatitis. Results The comparison between SAP and ESAP has shown the following results: impairment degree of pancreas (Balthazar CT score): SAP 2.3 vs . ESAP 3.85; abdominal compartment syndrome (ACS): ESAP 7.6% (1/13); multiorgan dysfunction syndrome (MODS): ESAP 46.1% (6/13); simple organ dysfunction: SAP 51% (24/47) vs . ESAP 53.8% (7/13); hypoxemia: SAP 65.9 % (31/47) vs . ESAP 76.9% (10/13); pancreatic infections: SAP 6.3% (3/47) vs . ESAP 23% (3/13); mortality: SAP 4.2% (2/47) vs . ESAP 15.4% (2/13). The prevalence of diabetes in AP patients was 19.5% (54/276), 31.7% (19/60) in all severe acute forms of pancreatitis group and 38.4% (5/13) in ESAP group (P<0.05 chi-square test). Regarding the severity criteria, diabetes had a prevalence of 23.3% (14/60) in single organ dysfunction and 23.1% (3/13) in MODS and 6.6% (4/60) in septic complications of fluid necrotic collections. Conclusion The association of AP with the diabetes is in evidence: the risk of acute pancreatitis is raised by diabetes, but also of critical forms. In our experience diabetes may worsen acute pancreatitis in the first phase of systemic inflammation, otherwise it seems to be not strongly connected to the evolution of possible late septic complications.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"547"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71231518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. C. Milanetto, E. Orvieto, C. Sperti, C. Pasquali
Context First described by Luchtrath and Schriefers in 1985 [1], lymphoepithelial cysts (LECs) of the pancreas are rare true benign cystic tumors of uncertain etiology (0.5% of all pancreatic cysts). They are found mainly in middle-aged males in the tail of the pancreas (size range: 2-10 cm). The challenging preoperative differential diagnosis of pancreatic LECs is among pseudocysts, cystic neoplasms and intraductal carcinomas. Case report During follow up for prostatic cancer, a 66-year-old man presented as an incidental finding at abdomen CT scan, a multiloculated cystic lesion (8x6 cm), located between duodenum and pancreatic head, with a solid component in its lower side, without contrast enhancement. MRI confirmed the lesion, suspected to be a mucinous tumor non communicating with the Wirsung duct. A pancreatic EUS showed a inhomogeneous cystic mass of the head of the pancreas, which had internal septa and a solid component. The amylase level in the cystic fluid content was 84 U/L, and CEA and CA 19-9 levels were 301 μg/L and 76,579 kU/L, respectively. Histology of the solid component was inconclusive. A 18 FDG-PET was negative for pancreatic malignancy. Blood tests showed a severe increase of creatinine and urea levels, because the patient had an acute renal failure due to the prostatic cancer, and serum CEA and CA 19-9 levels were 2.7 μg/L and 81 kU/L, respectively. After renal function normalization, with the suspicion of a mucinous cystic neoplasm (MCN), the patient underwent surgery. The mass had a tight-elastic thickness and seemed not to involve the pancreatic parenchyma, so a resection of the lesion was performed. The post-operative course was uneventful. Histology revealed a cystic lesion (8x4 cm) containing yellowish fluid, lined by a stratified squamous epithelium with focal sebaceous differentiation, and surrounded by lymphoid tissue. The patient is well and asymptomatic three months after surgery. Conclusion LECs should be considered in the differential diagnosis of cystic pancreatic tumors, whenever a large, well-defined solid or cystic peripheral pancreatic lesion is found. Imaging findings of LECs are non-specific, so surgical resection with pathological examination of the cyst is the gold standard for diagnosis. Cytology from EUS-FNA can help to distinguish LECs from cystic neoplasms.
{"title":"Lymphoepithelial Cyst of the Pancreas: A Challenging Differential Diagnosis among Cystic Pancreatic Tumors","authors":"A. C. Milanetto, E. Orvieto, C. Sperti, C. Pasquali","doi":"10.6092/1590-8577/1696","DOIUrl":"https://doi.org/10.6092/1590-8577/1696","url":null,"abstract":"Context First described by Luchtrath and Schriefers in 1985 [1], lymphoepithelial cysts (LECs) of the pancreas are rare true benign cystic tumors of uncertain etiology (0.5% of all pancreatic cysts). They are found mainly in middle-aged males in the tail of the pancreas (size range: 2-10 cm). The challenging preoperative differential diagnosis of pancreatic LECs is among pseudocysts, cystic neoplasms and intraductal carcinomas. Case report During follow up for prostatic cancer, a 66-year-old man presented as an incidental finding at abdomen CT scan, a multiloculated cystic lesion (8x6 cm), located between duodenum and pancreatic head, with a solid component in its lower side, without contrast enhancement. MRI confirmed the lesion, suspected to be a mucinous tumor non communicating with the Wirsung duct. A pancreatic EUS showed a inhomogeneous cystic mass of the head of the pancreas, which had internal septa and a solid component. The amylase level in the cystic fluid content was 84 U/L, and CEA and CA 19-9 levels were 301 μg/L and 76,579 kU/L, respectively. Histology of the solid component was inconclusive. A 18 FDG-PET was negative for pancreatic malignancy. Blood tests showed a severe increase of creatinine and urea levels, because the patient had an acute renal failure due to the prostatic cancer, and serum CEA and CA 19-9 levels were 2.7 μg/L and 81 kU/L, respectively. After renal function normalization, with the suspicion of a mucinous cystic neoplasm (MCN), the patient underwent surgery. The mass had a tight-elastic thickness and seemed not to involve the pancreatic parenchyma, so a resection of the lesion was performed. The post-operative course was uneventful. Histology revealed a cystic lesion (8x4 cm) containing yellowish fluid, lined by a stratified squamous epithelium with focal sebaceous differentiation, and surrounded by lymphoid tissue. The patient is well and asymptomatic three months after surgery. Conclusion LECs should be considered in the differential diagnosis of cystic pancreatic tumors, whenever a large, well-defined solid or cystic peripheral pancreatic lesion is found. Imaging findings of LECs are non-specific, so surgical resection with pathological examination of the cyst is the gold standard for diagnosis. Cytology from EUS-FNA can help to distinguish LECs from cystic neoplasms.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"581-581"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71231531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefania Moz, Dania Bozzato, C. Zambon, P. Fogar, M. Pelloso, A. C. Milanetto, A. Padoan, F. Navaglia, E. Greco, C. Pasquali, M. Plebani, D. Basso
Context Tumor-stroma-endocrine interactions favour pancreatic adenocarcinoma (PDAC) growth/ progression and PDAC-associated diabetes mellitus (DM). S100A8/A9 and the matrix methalloproteinases (MMPs) 8 and 9 are overexpressed in PDAC stroma. Objective To verify whether S100A8, S100A9, MMP8 and MMP9 mRNA in peripheral blood mononuclear cells (PBMC) is useful for diagnosing and staging PDAC and/or for detecting PDAC-associated DM. To study the impact of S100A8/A9 and of PDAC-associated growth factors and cytokines on MMPs expression. Methods S100A8, S100A9, MMP8 e MMP9 mRNA were quantified by qRT-PCR in 62 PDAC, 37 chronic pancreatitis, 23 pancreatobiliary tract tumors (PBT) and 30 healthy controls (HC). PBMC (blood donors) were treated with insulin, EGF, TGFb1, S100A8/A9 before MMP8 and MMP9 mRNA analysis. Results : MMP8 and MMP9 were higher in PDAC and in PBT than in HC (Kruskal-Wallis test: P<0.0001). S100A8 (P=0.902) and S100A9 (P=0.303) did not vary. PDAC stage was not correlated with any molecule. At binary logistic regression analysis (PDAC presence or absence as dependent; S100A8, S100A9, MMP8, MMP9, age, gender, CA 19-9, bilirubin, glucose, C-peptide, CRP, and ALT as predictors), only MMP9 (OR=0.69; 95% CI: 0.48-0.99; P=0.047) and CA 19-9 (OR=1.74; 95% CI: 1.31-2.33; P=0.0002) were independently correlated with PDAC. In PDAC, DM was independently correlated only with S100A9 (OR=8.16; 95% CI: 2.31-28.78; P=0.001) and age (OR=1.10; 95% CI: 1.01-1.21; P=0.028). Insulin, EGF and TGFb1 did not affect MMP8 or MMP9 expression. S100A8/A9 significantly induced MMP8 (F=23.68; P=0.002) and MMP9 (F=93.84; P<0.0001) mRNA in PBMC. Conclusion PDAC is associated with an increased MMP9, while PDAC-associated DM is associated with an increased S100A9 expression in PBMC. S100A8/A9 effects on MMPs support the hypothesis of an intriguing relationship between inflammation, diabetes and PDAC.
{"title":"MMP9 and S100A9 Expression in Peripheral Blood Mononuclear Cells (PBMC) Are Correlated with Pancreatic Adenocarcinoma (PDAC) and with PDAC-Associated Diabetes Mellitus","authors":"Stefania Moz, Dania Bozzato, C. Zambon, P. Fogar, M. Pelloso, A. C. Milanetto, A. Padoan, F. Navaglia, E. Greco, C. Pasquali, M. Plebani, D. Basso","doi":"10.6092/1590-8577/1698","DOIUrl":"https://doi.org/10.6092/1590-8577/1698","url":null,"abstract":"Context Tumor-stroma-endocrine interactions favour pancreatic adenocarcinoma (PDAC) growth/ progression and PDAC-associated diabetes mellitus (DM). S100A8/A9 and the matrix methalloproteinases (MMPs) 8 and 9 are overexpressed in PDAC stroma. Objective To verify whether S100A8, S100A9, MMP8 and MMP9 mRNA in peripheral blood mononuclear cells (PBMC) is useful for diagnosing and staging PDAC and/or for detecting PDAC-associated DM. To study the impact of S100A8/A9 and of PDAC-associated growth factors and cytokines on MMPs expression. Methods S100A8, S100A9, MMP8 e MMP9 mRNA were quantified by qRT-PCR in 62 PDAC, 37 chronic pancreatitis, 23 pancreatobiliary tract tumors (PBT) and 30 healthy controls (HC). PBMC (blood donors) were treated with insulin, EGF, TGFb1, S100A8/A9 before MMP8 and MMP9 mRNA analysis. Results : MMP8 and MMP9 were higher in PDAC and in PBT than in HC (Kruskal-Wallis test: P<0.0001). S100A8 (P=0.902) and S100A9 (P=0.303) did not vary. PDAC stage was not correlated with any molecule. At binary logistic regression analysis (PDAC presence or absence as dependent; S100A8, S100A9, MMP8, MMP9, age, gender, CA 19-9, bilirubin, glucose, C-peptide, CRP, and ALT as predictors), only MMP9 (OR=0.69; 95% CI: 0.48-0.99; P=0.047) and CA 19-9 (OR=1.74; 95% CI: 1.31-2.33; P=0.0002) were independently correlated with PDAC. In PDAC, DM was independently correlated only with S100A9 (OR=8.16; 95% CI: 2.31-28.78; P=0.001) and age (OR=1.10; 95% CI: 1.01-1.21; P=0.028). Insulin, EGF and TGFb1 did not affect MMP8 or MMP9 expression. S100A8/A9 significantly induced MMP8 (F=23.68; P=0.002) and MMP9 (F=93.84; P<0.0001) mRNA in PBMC. Conclusion PDAC is associated with an increased MMP9, while PDAC-associated DM is associated with an increased S100A9 expression in PBMC. S100A8/A9 effects on MMPs support the hypothesis of an intriguing relationship between inflammation, diabetes and PDAC.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"551-551"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71231627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Ricci, G. Taffurelli, C. Zingaretti, E. Peri, M. D'ambra, S. Buscemi, A. Cucchetti, G. Ercolani, R. Casadei, A. Pinna, F. Minni
Context Safety and cost-effectiveness of venous resection (VR) in resectable/borderline resectable ductal adenocarcinoma of the pancreatic head is still debate. Objectives Primary end point was to compare post-operative mortality between patients treated with a standard resection and patients treated with a VR. Secondary end points were postoperative morbidity, type of discharge, costs of hospitalization, R1 rate, and overall (OS) and disease free (DFS) survivals. Methods From 2001 to 2013, data of 291 pancreatic resections were collected. All patients (n=91) affected by head ductal adenocarcinoma were divided in two groups: with (group B; n=15) or without vascular resection (group A; n=76). The two groups were compared for postoperative course, OS and DFS. Multivariate analysis was carried out in order to evaluate the role of demographic, clinical, surgical (including VR) and pathological factors on mortality, morbidity, type of discharge, costs, R1 rate, OS and DFS. Results Postoperative mortality, morbidity and type of discharge were similar in the two groups. The total costs of hospitalization was similar, while the costs of ICU stay were higher in group B (P=0.012). No differences between two groups about R1 rate, DFS and OS were detected. Age >80 years was the only factor related to postoperative mortality (OR=3.9, P=0.048). ASA score increased the risk of postoperative complications (OR=2.9, P=0.029). Discharge to health care facility was more frequent in patients with age >80 years (OR=405.3, P=0.001) and with an higher preoperative total bilirubin (OR=1.2, P=0.042). ASA score increase by 34% the total hospital stay (P=0.004), by 48% the total hospital costs (P G1 at imaging were all predictive of a worse DFS (HR=3.2, P=0.050; HR=2.6, P=0.027; and HR=1.6, P=0.043, respectively). Conclusions VR is safe and useful to reach an R0 resection. VR affects the costs of postoperative management. OS and DFS were similar in patients with or without VR.
{"title":"Safety and Cost-Effectiveness of Venous Resection in Pancreatic Cancer","authors":"C. Ricci, G. Taffurelli, C. Zingaretti, E. Peri, M. D'ambra, S. Buscemi, A. Cucchetti, G. Ercolani, R. Casadei, A. Pinna, F. Minni","doi":"10.6092/1590-8577/1713","DOIUrl":"https://doi.org/10.6092/1590-8577/1713","url":null,"abstract":"Context Safety and cost-effectiveness of venous resection (VR) in resectable/borderline resectable ductal adenocarcinoma of the pancreatic head is still debate. Objectives Primary end point was to compare post-operative mortality between patients treated with a standard resection and patients treated with a VR. Secondary end points were postoperative morbidity, type of discharge, costs of hospitalization, R1 rate, and overall (OS) and disease free (DFS) survivals. Methods From 2001 to 2013, data of 291 pancreatic resections were collected. All patients (n=91) affected by head ductal adenocarcinoma were divided in two groups: with (group B; n=15) or without vascular resection (group A; n=76). The two groups were compared for postoperative course, OS and DFS. Multivariate analysis was carried out in order to evaluate the role of demographic, clinical, surgical (including VR) and pathological factors on mortality, morbidity, type of discharge, costs, R1 rate, OS and DFS. Results Postoperative mortality, morbidity and type of discharge were similar in the two groups. The total costs of hospitalization was similar, while the costs of ICU stay were higher in group B (P=0.012). No differences between two groups about R1 rate, DFS and OS were detected. Age >80 years was the only factor related to postoperative mortality (OR=3.9, P=0.048). ASA score increased the risk of postoperative complications (OR=2.9, P=0.029). Discharge to health care facility was more frequent in patients with age >80 years (OR=405.3, P=0.001) and with an higher preoperative total bilirubin (OR=1.2, P=0.042). ASA score increase by 34% the total hospital stay (P=0.004), by 48% the total hospital costs (P G1 at imaging were all predictive of a worse DFS (HR=3.2, P=0.050; HR=2.6, P=0.027; and HR=1.6, P=0.043, respectively). Conclusions VR is safe and useful to reach an R0 resection. VR affects the costs of postoperative management. OS and DFS were similar in patients with or without VR.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"591"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71232327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Archibugi, Ilaria Passacantilli, Sara Calabretta, G. Capurso, G. Fave, C. Sette
Context Pancreatic neuroendocrine tumors (pNETs) are becoming high in prevalence and have started showing a more aggressive behavior. Current therapies for advanced pNETs are inadequate as many patients develop primary or secondary resistance to mTOR (mammalian target of rapamicin) inhibitors, in part due to the activation of escape routes such as the PI3K/AKT pathway. SFKs (Src Family of Kinases) are overexpressed in pNETs and have a central role in controlling cell growth, adhesion and migration, also by regulating the mTOR pathway and the activation of the epithelial growth factor receptor in pNETs. SFK inhibitors are already safely used in patients with other tumors but have never been tested on pNETs. Objective To evaluate the use of SFK inhibitors on pNETs both alone and in combination with mTOR inhibitors. Methods Different dosages of dasatinib and bosutinib were tested in two human pNET cell lines, a pancreatic carcinoid (BON-1) and a somatostatinoma (QGP-1), either alone or in combination with the mTOR inhibitor RAD001 (everolimus). Src activation was assessed by monitoring Y416 phosphorylation. mTOR activation was assessed by testing rp-S6 and 4E-BP1 phosphorylation. Escape pathways were investigated through Akt and eIF4E phosphorylation. MTT and colony formation assays were used to evaluate cell proliferation. Results Dasatinib and bosutinib are effective at inhibiting Src activation and, when administrated together with RAD001, escape pathways are not activated. Extremely low dosages of RAD001 reduce cell proliferation when administered in combination with dasatinib or bosutinib. Colony formation assays show a strong reduction in colony number. BON-1 cells respond better than QGP-1 cells to treatments. Conclusions SFK inhibitors are promising new drug options for pNETs, as they reduce tumor cell proliferation when used in combination with RAD001. They allow to reduce RAD001 dosage, which may lower the risk of developing adverse effects in patients. Additional studies on animal models should be pursued to better assess their potential use in clinical therapies.
{"title":"Src Inhibitors: a Synergic Help for Pancreatic Neuroendocrine Tumors Treatment","authors":"L. Archibugi, Ilaria Passacantilli, Sara Calabretta, G. Capurso, G. Fave, C. Sette","doi":"10.6092/1590-8577/1735","DOIUrl":"https://doi.org/10.6092/1590-8577/1735","url":null,"abstract":"Context Pancreatic neuroendocrine tumors (pNETs) are becoming high in prevalence and have started showing a more aggressive behavior. Current therapies for advanced pNETs are inadequate as many patients develop primary or secondary resistance to mTOR (mammalian target of rapamicin) inhibitors, in part due to the activation of escape routes such as the PI3K/AKT pathway. SFKs (Src Family of Kinases) are overexpressed in pNETs and have a central role in controlling cell growth, adhesion and migration, also by regulating the mTOR pathway and the activation of the epithelial growth factor receptor in pNETs. SFK inhibitors are already safely used in patients with other tumors but have never been tested on pNETs. Objective To evaluate the use of SFK inhibitors on pNETs both alone and in combination with mTOR inhibitors. Methods Different dosages of dasatinib and bosutinib were tested in two human pNET cell lines, a pancreatic carcinoid (BON-1) and a somatostatinoma (QGP-1), either alone or in combination with the mTOR inhibitor RAD001 (everolimus). Src activation was assessed by monitoring Y416 phosphorylation. mTOR activation was assessed by testing rp-S6 and 4E-BP1 phosphorylation. Escape pathways were investigated through Akt and eIF4E phosphorylation. MTT and colony formation assays were used to evaluate cell proliferation. Results Dasatinib and bosutinib are effective at inhibiting Src activation and, when administrated together with RAD001, escape pathways are not activated. Extremely low dosages of RAD001 reduce cell proliferation when administered in combination with dasatinib or bosutinib. Colony formation assays show a strong reduction in colony number. BON-1 cells respond better than QGP-1 cells to treatments. Conclusions SFK inhibitors are promising new drug options for pNETs, as they reduce tumor cell proliferation when used in combination with RAD001. They allow to reduce RAD001 dosage, which may lower the risk of developing adverse effects in patients. Additional studies on animal models should be pursued to better assess their potential use in clinical therapies.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"529-529"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71232589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Taffurelli, C. Ricci, E. Lazzarini, M. D'ambra, S. Buscemi, R. Pezzilli, C. A. Pacilio, F. Monari, N. Antonacci, R. Casadei, F. Minni
Context The impact on heath care service of pancreatic resections in elderly patients is unknown. Objective To evaluate the costs of postoperative stay in elderly patients undergone pancreatic resections for malignancy. Methods From 2004 to 2013, 213 patients underwent pancreatic resections and were recorded in a prospective data base. They were divided in three groups (<70 years, 70-80 years and ≥80 years) and analyzed regarding the costs and overall long-term survival (OS). Multivariate analysis was carried out to verify the impact of age, on postoperative costs and long-term results. Results The total costs of postoperative stay of pancreatic resections was higher in patients aged 70-80 years (11,461±9,352€; P=0.050) and in those ≥80 years (13,130±10,000€; P=0.032) in comparison to patients <70 years (8,855±8,479€). The cost of ordinary stay was higher in patients aged ≥80 yrs (9,325±8,855€) when compared with both patients <70 years (5,726±3,866€; P=0.002) and 70-80 years (5,856±4,769€; P=0.016). ICU stay costs were increased in patients aged 70-80 years (5,605±7,352€; P=0.020) respect on those <70 years (3,129±6,895€). Age, presence of comorbidities, jaundice and chronic renal failure increased the total costs by 15% (P=0.031), 25% (P=0.011), 29% (P=0.004), and 80% (P=0.001), respectively, at multivariate analysis. Total pancreatectomy reduced total costs by 12% (P=0.033). Age did not influence ordinary costs while cardiac disease, chronic renal failure, and jaundice increased them by 12% (P=0.044), 78% (P=0.002) and 17% (P=0.049), respectively. Total pancreatectomy and presence of hard pancreatic stump reduced ordinary costs by 18% (P=0.001) and 79% (P=0.048), respectively. Comorbidities and ductal adenocarcinoma increased ICU costs by 40% (P=0.033) and 18% (P=0.018), respectively. Age ≥80 years (HR=3.2; P=0.003), ASA score=3 (HR=2.2; P=0.011), comorbidities (HR=1.7; P=0.015), jaundice (HR=2.6; P=0.004), tumor-related pain (HR=1.8; P=0.001) and reoperation (HR=2.9; P=0.015) reduced the OS. Malignant cystic and endocrine tumors were related to a longer OS (HR=0.17; P=0.019 and HR=0.18; P=0.001, respectively). Conclusions Pancreatic resections in elderly patients with comorbidities affected by ductal adenocarcinoma were not cost-effective.
{"title":"Are Pancreatic Resections Cost-Effective in Elderly Patients?","authors":"G. Taffurelli, C. Ricci, E. Lazzarini, M. D'ambra, S. Buscemi, R. Pezzilli, C. A. Pacilio, F. Monari, N. Antonacci, R. Casadei, F. Minni","doi":"10.6092/1590-8577/1722","DOIUrl":"https://doi.org/10.6092/1590-8577/1722","url":null,"abstract":"Context The impact on heath care service of pancreatic resections in elderly patients is unknown. Objective To evaluate the costs of postoperative stay in elderly patients undergone pancreatic resections for malignancy. Methods From 2004 to 2013, 213 patients underwent pancreatic resections and were recorded in a prospective data base. They were divided in three groups (<70 years, 70-80 years and ≥80 years) and analyzed regarding the costs and overall long-term survival (OS). Multivariate analysis was carried out to verify the impact of age, on postoperative costs and long-term results. Results The total costs of postoperative stay of pancreatic resections was higher in patients aged 70-80 years (11,461±9,352€; P=0.050) and in those ≥80 years (13,130±10,000€; P=0.032) in comparison to patients <70 years (8,855±8,479€). The cost of ordinary stay was higher in patients aged ≥80 yrs (9,325±8,855€) when compared with both patients <70 years (5,726±3,866€; P=0.002) and 70-80 years (5,856±4,769€; P=0.016). ICU stay costs were increased in patients aged 70-80 years (5,605±7,352€; P=0.020) respect on those <70 years (3,129±6,895€). Age, presence of comorbidities, jaundice and chronic renal failure increased the total costs by 15% (P=0.031), 25% (P=0.011), 29% (P=0.004), and 80% (P=0.001), respectively, at multivariate analysis. Total pancreatectomy reduced total costs by 12% (P=0.033). Age did not influence ordinary costs while cardiac disease, chronic renal failure, and jaundice increased them by 12% (P=0.044), 78% (P=0.002) and 17% (P=0.049), respectively. Total pancreatectomy and presence of hard pancreatic stump reduced ordinary costs by 18% (P=0.001) and 79% (P=0.048), respectively. Comorbidities and ductal adenocarcinoma increased ICU costs by 40% (P=0.033) and 18% (P=0.018), respectively. Age ≥80 years (HR=3.2; P=0.003), ASA score=3 (HR=2.2; P=0.011), comorbidities (HR=1.7; P=0.015), jaundice (HR=2.6; P=0.004), tumor-related pain (HR=1.8; P=0.001) and reoperation (HR=2.9; P=0.015) reduced the OS. Malignant cystic and endocrine tumors were related to a longer OS (HR=0.17; P=0.019 and HR=0.18; P=0.001, respectively). Conclusions Pancreatic resections in elderly patients with comorbidities affected by ductal adenocarcinoma were not cost-effective.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"557-557"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71232680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Taffurelli, C. Ricci, E. Lazzarini, A. Labate, R. Pezzilli, M. D'ambra, S. Buscemi, C. A. Pacilio, R. Casadei, F. Minni
Context The incidence of pancreatic and peri-ampullary cancer is expected to increase significantly among the elderly population. Recently, several authors have published data on peri-operative outcomes of pancreatic resections among the elderly. Objective Primary endpoint was to assess the difference in term of post-operative mortality after pancreatic resections between patients <80 years old and patients ≥80 years old. Secondary end-points were: post-operative morbidity, incidence of postoperative pancreatic fistula, delayed gastric empty, bile leak, infections or sepsis, pulmonary and cardiac complications, reoperation rate and length of hospital stay. Methods Articles were extracted from MEDLINE, Cochrane Library, Scopus and ISI-Web of Science until April 24 th , 2013. Articles were excluded when they were not in English; when the study population was divided in group of ages by using a cut-off different from 80 years; if they were case-reports, review, guidelines, abstracts and letters to editor. The quality of selected studies was assessed with the Newcastle-Ottawa scale. Odds ratios (ORs) were compared with Mantel-Haenzel method by using the statistical software Review Manager Version 5.2 (The Cochrane Collaboration, Software Update, Oxford, London). Results Initial search identified 1,518 reference articles, of these 19 relevant articles were selected and reviewed. Data were extracted from 9 studies (no. of cases 12,930) which met the inclusion criteria. Patients aged ≥80 years had a significantly higher postoperative mortality (OR=2.16, 95% CI: 1.61-2.89; P<0.001), postoperative morbidity (OR=1.66, 95% CI: 1.38-1.99; P<0.001), cardiac complications (OR=2.54, 95% CI: 1.66-3.88; P<0.001) and a longer hospital stay (OR=2.00; 95% CI: 1.86-2.14; P<0.001) than patients <80 years of age. No significant difference were demonstrated between younger and older patients in terms of postoperative pancreatic fistula, delayed gastric empty, bile leak, pulmonary complications, infection or sepsis and reoperation rate. Conclusions According to the results of this meta-analysis, pancreatic resections in patients aged ≥80 should be carefully planned because of an increased risk of morbidity, cardiac complications, longer hospital stay and, most of all, an increased risk of postoperative mortality.
胰腺癌和壶腹周围癌的发病率预计将在老年人群中显著增加。最近,几位作者发表了关于老年人胰腺切除术围手术期结果的数据。目的主要终点是评估年龄<80岁和年龄≥80岁胰腺切除术患者术后死亡率的差异。次要终点为:术后发病率、术后胰瘘发生率、胃延迟排空、胆漏、感染或败血症、肺部和心脏并发症、再手术率和住院时间。方法检索截至2013年4月24日的MEDLINE、Cochrane Library、Scopus和ISI-Web of Science。非英文文章被排除在外;当研究人群按年龄分组时使用不同于80岁的临界值;如果是病例报告、综述、指南、摘要和给编辑的信。所选研究的质量用纽卡斯尔-渥太华量表进行评估。使用统计软件Review Manager Version 5.2 (the Cochrane Collaboration, software Update, Oxford, London)比较优势比(ORs)与Mantel-Haenzel方法。结果初步检索到1518篇文献,从中选取19篇相关文献进行综述。数据来自9项研究(no. 6)。12930例病例符合纳入标准。年龄≥80岁的患者术后死亡率明显较高(OR=2.16, 95% CI: 1.61-2.89;P<0.001),术后发病率(OR=1.66, 95% CI: 1.38-1.99;P<0.001),心脏并发症(OR=2.54, 95% CI: 1.66-3.88;P<0.001)和更长的住院时间(OR=2.00;95% ci: 1.86-2.14;P<0.001)高于<80岁的患者。术后胰瘘、胃空延迟、胆漏、肺部并发症、感染或脓毒症、再手术率等方面,青年与老年患者无显著差异。根据本荟萃分析的结果,年龄≥80岁患者的胰腺切除术应仔细计划,因为发病率、心脏并发症、住院时间更长,最重要的是,术后死亡率增加。
{"title":"Pancreatic Resections in Patients Aged 80 and Over: A Meta-Analysis and Systematic Review","authors":"G. Taffurelli, C. Ricci, E. Lazzarini, A. Labate, R. Pezzilli, M. D'ambra, S. Buscemi, C. A. Pacilio, R. Casadei, F. Minni","doi":"10.6092/1590-8577/1723","DOIUrl":"https://doi.org/10.6092/1590-8577/1723","url":null,"abstract":"Context The incidence of pancreatic and peri-ampullary cancer is expected to increase significantly among the elderly population. Recently, several authors have published data on peri-operative outcomes of pancreatic resections among the elderly. Objective Primary endpoint was to assess the difference in term of post-operative mortality after pancreatic resections between patients <80 years old and patients ≥80 years old. Secondary end-points were: post-operative morbidity, incidence of postoperative pancreatic fistula, delayed gastric empty, bile leak, infections or sepsis, pulmonary and cardiac complications, reoperation rate and length of hospital stay. Methods Articles were extracted from MEDLINE, Cochrane Library, Scopus and ISI-Web of Science until April 24 th , 2013. Articles were excluded when they were not in English; when the study population was divided in group of ages by using a cut-off different from 80 years; if they were case-reports, review, guidelines, abstracts and letters to editor. The quality of selected studies was assessed with the Newcastle-Ottawa scale. Odds ratios (ORs) were compared with Mantel-Haenzel method by using the statistical software Review Manager Version 5.2 (The Cochrane Collaboration, Software Update, Oxford, London). Results Initial search identified 1,518 reference articles, of these 19 relevant articles were selected and reviewed. Data were extracted from 9 studies (no. of cases 12,930) which met the inclusion criteria. Patients aged ≥80 years had a significantly higher postoperative mortality (OR=2.16, 95% CI: 1.61-2.89; P<0.001), postoperative morbidity (OR=1.66, 95% CI: 1.38-1.99; P<0.001), cardiac complications (OR=2.54, 95% CI: 1.66-3.88; P<0.001) and a longer hospital stay (OR=2.00; 95% CI: 1.86-2.14; P<0.001) than patients <80 years of age. No significant difference were demonstrated between younger and older patients in terms of postoperative pancreatic fistula, delayed gastric empty, bile leak, pulmonary complications, infection or sepsis and reoperation rate. Conclusions According to the results of this meta-analysis, pancreatic resections in patients aged ≥80 should be carefully planned because of an increased risk of morbidity, cardiac complications, longer hospital stay and, most of all, an increased risk of postoperative mortality.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"598-598"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71232698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}