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Pediatric Reports May 2024Complete surgical resection in the context of a multimodal approach has been associated with excellent long-term survival in children diagnosed with pancreatoblastoma... (Review)
Review
Complete surgical resection in the context of a multimodal approach has been associated with excellent long-term survival in children diagnosed with pancreatoblastoma (PB). Traditionally, curative intent surgery for PB implies standard pancreatic resections such as pancreaticoduodenectomies and distal pancreatectomies with splenectomies, surgical procedures that may lead to significant long-term pancreatic functional deficiencies. Postoperative pancreatic functional deficiencies are particularly interesting to children because they may interfere with their development, considering their long life expectancy and the significant role of pancreatic functions in their nutritional status and growth. Thus, organ-sparing pancreatectomies, such as spleen-preserving distal pancreatectomies and central pancreatectomies, are emerging in specific tumoral pathologies in children. However, data about organ-sparing pancreatectomies' potential role in curative-intent PB surgery in children are scarce. Based on the literature data, the current review aims to present the early and late outcomes of pancreatectomies in children (including long-term deficiencies and their potential impact on the development and quality of life), particularly for PB, and further explore the potential role of organ-sparing pancreatectomies for PB. Organ-sparing pancreatectomies are associated with better long-term pancreatic functional outcomes, particularly central pancreatectomies, and have a reduced impact on children's development and quality of life without jeopardizing their oncological safety. The long-term preservation of pancreatic functions should not be disregarded when performing pancreatectomies for PB in children. A subset of patients with PB might benefit from organ-sparing pancreatectomies, particularly from central pancreatectomies, with the same oncological results as standard pancreatectomies but with significantly less impact on long-term functional outcomes.
PubMed: 38804376
DOI: 10.3390/pediatric16020033 -
Modern Pathology : An Official Journal... Sep 2020There is now evidence that gene fusions activating the MAPK pathway are relatively common in pancreatic acinar cell carcinoma with potentially actionable BRAF or RET...
There is now evidence that gene fusions activating the MAPK pathway are relatively common in pancreatic acinar cell carcinoma with potentially actionable BRAF or RET fusions being found in ~30%. We sought to investigate the incidence of RAF1 fusions in pancreatic malignancies with acinar cell differentiation. FISH testing for RAF1 was undertaken on 30 tumors comprising 25 'pure' acinar cell carcinomas, 2 mixed pancreatic acinar-neuroendocrine carcinomas, 1 mixed acinar cell-low grade neuroendocrine tumor and 2 pancreatoblastomas. RAF1 rearrangements were identified in 5 cases and confirmed by DNA and RNA sequencing to represent oncogenic fusions (GATM-RAF1, GOLGA4-RAF1, PDZRN3-RAF1, HERPUD1-RAF1 and TRIM33-RAF1) and to be mutually exclusive with BRAF and RET fusions, as well as KRAS mutations. Large genome-wide copy number changes were common and included 1q gain and/or 1p loss in all five RAF1 FISH-positive acinar cell carcinomas. RAF1 expression by immunohistochemistry was found in 3 of 5 (60%) of fusion-positive cases and no FISH-negative cases. Phospho-ERK1/2 expression was found in 4 of 5 RAF1-fusion-positive cases. Expression of both RAF1 and phospho-ERK1/2 was heterogeneous and often only detected at the tumor-stroma interface, thus limiting their clinical utility. We conclude that RAF1 gene rearrangements are relatively common in pancreatic acinar cell carcinomas (14.3% to 18.5% of cases) and can be effectively identified by FISH with follow up molecular testing. The combined results of several studies now indicate that BRAF, RET or RAF1 fusions occur in between one third and one-half of these tumors but are extremely rare in other pancreatic malignancies. As these fusions are potentially actionable with currently available therapies, a strong argument can be made to perform FISH or molecular testing on all pancreatic acinar cell carcinomas.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Carcinoma, Acinar Cell; Databases, Factual; Female; Gene Fusion; Gene Rearrangement; Humans; Male; Middle Aged; Pancreatic Neoplasms; Proto-Oncogene Proteins c-raf; Young Adult
PubMed: 32358589
DOI: 10.1038/s41379-020-0545-9 -
BMC Gastroenterology Mar 2024Pancreatic tumors in children are uncommon, and data is scarce. The purpose of this study is to examine the prognostic factors of pediatric pancreatic tumors in a...
PURPOSE
Pancreatic tumors in children are uncommon, and data is scarce. The purpose of this study is to examine the prognostic factors of pediatric pancreatic tumors in a population-based cohort.
METHODS
The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all pediatric patients with pancreatic tumors diagnosed between 1975 and 2018. The overall survival (OS) rates were determined using a Kaplan-Meier analysis. The log-rank test was used for univariate survival analysis. Cox proportional-hazards regression was used to determine the variables related to OS.
RESULTS
We identified 195 children with pancreatic tumors, with a median age at diagnosis of 16 years. Tumors were classified as neuroendocrine tumors (33.8%), solid pseudopapillary tumors (SPTs) (32.3%), pancreatoblastoma (11.3%), and others (22.6%). Of the patients, 30.3% had distant metastases, and 69.7% had surgery. Pancreatoblastomas were more common in younger children, whereas solid pseudopapillary tumors were more common in female patients. Overall 1-year, 3-year, and 5-year survival rates for all patients were 90.3%, 79.2%, and 77.7%, respectively. The Cox proportional hazard regression revealed that SEER stage and surgery were significant independent predictors of overall survival.
CONCLUSIONS
Pancreatic tumors are rare in children, and overall survival is grim except for SPTs. SEER stage and surgery were determined to be the most relevant determinants of OS in our study.
Topics: Humans; Child; Female; Adolescent; Prognosis; Survival Analysis; Kaplan-Meier Estimate; Pancreatic Neoplasms
PubMed: 38486208
DOI: 10.1186/s12876-024-03194-y -
Pediatric Surgery International Mar 2020Pancreatic tumors are rare in children and limited data are available regarding incidence, treatment, and outcomes. We aim to describe patient and tumor characteristics...
PURPOSE
Pancreatic tumors are rare in children and limited data are available regarding incidence, treatment, and outcomes. We aim to describe patient and tumor characteristics and to report on survival of these diseases.
METHODS
Children with pancreatic tumors were queried from the National Cancer Database (2004-2014). The association between treatment and hazard of death was assessed using Kaplan-Meier method and Cox regression model.
RESULTS
We identified 109 children with pancreatic tumors; 52% were male and median age at diagnosis was 14 years. Tumors were distributed as follows: pseudopapillary neoplasm (30%), endocrine tumors (27%), pancreatoblastoma (16%), pancreatic adenocarcinoma (16%), sarcoma (6%) and neuroblastoma (5%). Seventy-nine patients underwent surgery, of which 76% achieved R0 resection. Most patients (85%) had lymph nodes examined, of which 22% had positive nodes. Five-year overall survival by tumor histology was 95% (pseudopapillary neoplasm), 75% (neuroblastoma), 70% (pancreatoblastoma), 51% (endocrine tumors), 43% (sarcoma), and 34% (adenocarcinoma). On multivariable analysis, surgical resection was the strongest predictor of survival (HR 0.26, 95% CI 0.10-0.68, p < 0.01).
CONCLUSION
Overall survival of children with pancreatic tumors is grim, with varying survival rates among different tumors. Surgical resection is associated with improved long-term survival.
Topics: Adenocarcinoma; Adolescent; Aged; Child; Child, Preschool; Combined Modality Therapy; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Neoplasm Staging; Pancreatectomy; Pancreatic Neoplasms; Survival Rate; United States
PubMed: 31989243
DOI: 10.1007/s00383-020-04617-z -
Modern Pathology : An Official Journal... Jul 2022Pancreatic neoplasms are heterogenous and have traditionally been classified by assessing their lines of cellular differentiation using histopathologic methods,...
Pancreatic neoplasms are heterogenous and have traditionally been classified by assessing their lines of cellular differentiation using histopathologic methods, particularly morphologic and immunohistochemical evaluation. These methods frequently identify overlapping differentiation along ductal, acinar, and neuroendocrine lines, raising diagnostic challenges as well as questions regarding the relationship of these neoplasms. Neoplasms with acinar differentiation, in particular, frequently show more than one line of differentiation based on immunolabeling. Genome methylation signatures, in contrast, are better conserved within cellular lineages, and are increasingly used to support the classification of neoplasms. We characterized the epigenetic relationships between pancreatoblastomas, acinar cell carcinomas (including mixed variants), pancreatic neuroendocrine tumors, solid pseudopapillary neoplasms, and pancreatic ductal adenocarcinomas using a genome-wide array platform. Using unsupervised learning approaches, pancreatic neuroendocrine tumors, solid pseudopapillary neoplasms, ductal adenocarcinomas, and normal pancreatic tissue samples all localized to distinct clusters based on their methylation profiles, whereas all neoplasms with acinar differentiation occupied a broad overlapping region located between the predominantly acinar normal pancreatic tissue and ductal adenocarcinoma clusters. Our data provide evidence to suggest that acinar cell carcinomas and pancreatoblastomas are similar at the epigenetic level. These findings are consistent with genomic and clinical observations that mixed acinar neoplasms are closely related to pure acinar cell carcinomas rather than to neuroendocrine tumors or ductal adenocarcinomas.
Topics: Carcinoma, Acinar Cell; Epigenesis, Genetic; Humans; Pancreas; Pancreatic Neoplasms
PubMed: 34969956
DOI: 10.1038/s41379-021-00989-2 -
World Neurosurgery Oct 2020Pancreatoblastoma is an extremely rare neoplasm that accounts for 0.5% of all pancreatic exocrine tumors. These rare entities typically manifest in the pediatric...
BACKGROUND
Pancreatoblastoma is an extremely rare neoplasm that accounts for 0.5% of all pancreatic exocrine tumors. These rare entities typically manifest in the pediatric population but can rarely occur in adults. Systemic seeding has been described before but intracranial metastasis in adults has yet to be described.
CASE DESCRIPTION
A 28-year-old woman with a history of pancreatoblastoma that had been in remission for 51 months after treatment with cisplatin, doxorubicin (Adriamycin), and etoposide had presented to the emergency room with chronic recurrent headaches. Conservative management of the headaches failed, which led to a diagnostic workup with magnetic resonance imaging of the brain. Magnetic resonance imaging demonstrated a well-circumscribed solitary cerebellar lesion. Metastatic disease was suspected, and the patient underwent suboccipital craniotomy for tumor resection with adjuvant gamma knife radiosurgery.
CONCLUSIONS
Central nervous system seeding of pancreatoblastoma is rare, and the available evidence suggests that the strategy we used could be adequate for treating such occurrences.
Topics: Adult; Cerebellar Neoplasms; Craniotomy; Female; Humans; Neoplasm Seeding; Pancreatic Neoplasms; Radiosurgery
PubMed: 32622062
DOI: 10.1016/j.wneu.2020.06.210 -
World Journal of Clinical Cases Sep 2021Pancreatic neoplasms are uncommon in children and in most cases they are benign or have low malignant potential. Pancreatoblastoma and solid pseudopapillary tumor are...
BACKGROUND
Pancreatic neoplasms are uncommon in children and in most cases they are benign or have low malignant potential. Pancreatoblastoma and solid pseudopapillary tumor are the most frequent types in early and late childhood, respectively. Complete resection, although burdened by severe complications, is the only curative treatment for these diseases. Pancreatic surgery may result in impaired exocrine and endocrine pancreatic function. However, limited data are available on the long-term pediatric pancreatic function following surgical resection.
AIM
To investigate endocrine and exocrine pancreatic function and growth after oncological pancreatic surgery in a pediatric series.
METHODS
A retrospective analysis of all pediatric patients who underwent surgery for pancreatic neoplasm in our Institution from January 31, 2002 to the present was performed. Endocrine and exocrine insufficiency, auxological and fat-soluble vitamin status (A, D, E and clotting tests) were assessed at diagnosis and at every follow-up visit. Exocrine insufficiency was defined as steatorrhea with fecal elastase-1 < 200 µg/g stool, while endocrine insufficiency was identified as onset of Diabetes or Impaired Glucose Tolerance. Growth was evaluated based on body mass index (BMI) -score trend.
RESULTS
Sixteen patients (12 girls and 4 boys, mean age 10.7 ± 5.3 years), were included. Nine patients (56%) had a neoplasm in the pancreatic head, 4 in the body/tail, 2 in the tail and 1 in the body. Histological findings were as follows: Solid pseudopapillary tumor in 10 patients (62.5%), insulinoma in 2 patients, neuroendocrine tumor in 2 patients and acinar cell carcinoma in 2 patients. The most frequent surgery was pancreaticoduodenectomy (50%). Exocrine failure occurred in 4 patients (25%) and endocrine failure in 2 patients (12.5%). Exocrine insufficiency occurred early (within 6 mo after surgery) and endocrine insufficiency later (8 and 10 years after surgery). Mean BMI -score was 0.36 ± 1.1 at diagnosis and 0.27 ± 0.95 at the last assessment. Vitamin D was insufficient (< 30 ng/mL) in 8 of the 16 patients during the follow-up period. Vitamins A, E and clotting test were into the normal ranges in all patients.
CONCLUSION
Careful and long-term monitoring should follow any pancreatic surgery, to recognize and promptly treat exocrine and endocrine pancreatic insufficiency, which can occur after surgery.
PubMed: 34616800
DOI: 10.12998/wjcc.v9.i25.7340 -
Pediatric Blood & Cancer Oct 2018Primary pancreatic carcinoma and pancreatic metastases are rare in the pediatric population. Pancreatoblastoma is the most common pancreatic malignant tumor in young...
PURPOSE
Primary pancreatic carcinoma and pancreatic metastases are rare in the pediatric population. Pancreatoblastoma is the most common pancreatic malignant tumor in young children and solid-pseudopapillary tumor in teenagers. Pancreatic adenocarcinoma is extremely rare under the age of 40 and is usually associated with underlying genetic abnormalities. Secondary malignancies of the pancreas occur more frequently than primary pancreatic malignancies in children and are most commonly seen with non-Hodgkin lymphomas (NHL) and mesenchymal sarcomas. The purpose of this study was to characterize the metabolism of primary and secondary tumors of the pancreas in pediatric patients.
MATERIALS AND METHODS
A retrospective analysis of all primary and secondary pancreatic malignancies imaged with 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) computed tomography (CT) was conducted.
RESULTS
Three patients with primary pancreatic cancers were identified, one each with pancreatoblastoma, solid-pseudopapillary tumor, and adenocarcinoma. Each tumor showed elevated uptake of FDG. Metastatic disease in the pancreas was identified in 12 patients-five NHL (including three Burkitt lymphomas), six sarcomas (three osteosarcomas, two rhabdomyosarcomas, and one Ewing sarcoma family tumor), and one malignant rhabdoid tumor. Elevated but variable uptake of FDG was found in each of the tumors of patients with metastatic disease within the pancreas.
CONCLUSION
Both primary malignancies and metastatic disease within the pancreas, though very rare in children, adolescents, and young adults, are metabolically active and can be functionally characterized using FDG-PET CT.
Topics: Adolescent; Child; Female; Fluorodeoxyglucose F18; Humans; Infant; Male; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Retrospective Studies; Young Adult
PubMed: 29750397
DOI: 10.1002/pbc.27115 -
Oncology Letters May 2015The present study describes the case of a 24-year-old patient who presented with obstructive jaundice and weight loss, and was diagnosed with pancreatoblastoma (PB)....
The present study describes the case of a 24-year-old patient who presented with obstructive jaundice and weight loss, and was diagnosed with pancreatoblastoma (PB). Abdominal imaging studies revealed a heterogenous lesion of the pancreatic head with dilatation of the common bile duct. The patient underwent pancreaticoduodenectomy, however, three months after surgery multiple liver and bone metastases were identified on follow-up computed tomography scans. Despite treatment with four cycles of systemic chemotherapy and five courses of radiofrequency ablation, the patient succumbed due to tumour dissemination 13 months after initial diagnosis. PB is a malignant tumour of the pancreas that typically occurs in the pediatric population. The aim of the present study was to highlight the aggressive behavior of this rare clinical entity, focusing on the pitfalls of pre-operative diagnosis and the lack of management strategy guidelines in adults. Preoperative diagnosis of PB based on radiographic features may be difficult, as the imaging characteristics are non-specific. Furthermore, cytology may also be misleading, as the neoplasm consists of multiple cell lines (acinar, ductal and neuroendocrine cells) and diagnosis depends largely on the identification of the distinctive histological characteristic of squamoid corpuscles, which present as nests of flattened cells with a squamous appearance. Despite the use of surgical resection and adjuvant chemoradiotherapy for the treatment of this malignancy, its aggressive nature means that PB is associated with a poor prognosis in adult patients.
PubMed: 26137059
DOI: 10.3892/ol.2015.3001 -
World Journal of Gastrointestinal... Aug 2020Exocrine pancreatic neoplasms represent up to 95% of pancreatic cancers (PCs) and are widely recognized among the most lethal solid cancers, with a very poor 5-year... (Review)
Review
Exocrine pancreatic neoplasms represent up to 95% of pancreatic cancers (PCs) and are widely recognized among the most lethal solid cancers, with a very poor 5-year survival rate of 5%-10%. The remaining < 5% of PCs are neuroendocrine tumors that are usually characterized by a better prognosis, with a median overall survival of 3.6 years. The most common type of PC is pancreatic ductal adenocarcinoma (PDAC), which accounts for roughly 85% of all exocrine PCs. However up to 10% of exocrine PCs have rare histotypes, which are still poorly understood. These subtypes can be distinguished from PDAC in terms of pathology, imaging, clinical presentation and prognosis. Additionally, due to their rarity, any knowledge regarding these specific histotypes is mostly based on case reports and a small series of retrospective analyses. Therefore, treatment strategies are generally deduced from those used for PDAC, even if these patients are often excluded or not clearly represented in clinical trials for PDAC. For these reasons, it is essential to collect as much information as possible on the management of PC, as assimilating it with PDAC may lead to the potential mistreatment of these patients. Here, we report the most significant literature regarding the epidemiology, typical presentation, possible treatment strategies, and prognosis of the most relevant histotypes among rare PCs.
PubMed: 32879662
DOI: 10.4251/wjgo.v12.i8.833