Materiały źródłowe

• #1 Ampullary Cancer: An Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4966534/

  Ampullary cancers are rare, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. […] In patients with true ampullary cancer, there is very limited data to guide physicians on the choice of therapy, largely because of the rarity of the disease and the paucity of related research. […] Evidence suggests that histologic sub-types also differ in biologic behavior, bearing implications on prognosis and outcome. […] Notably, ampullary adenocarcinomas with pancreaticobiliary histology have a much worse outcome than those with intestinal histology (median overall survival of 16 vs. 115.5 months; p 0.001 respectively). […] When controlled for other risk factors, in resectable periampullary cancers, biologic behavior appears to be the most important prognostic indicator for patient outcome.

• #2 Ampullary Carcinoma: An Overview of a Rare Entity and Discussion of Current and Future Therapeutic Challenges

  https://www.mdpi.com/1718-7729/28/5/293

  Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). […] From a histological point of view, intestinal-type AC is usually characterized by the presence of a non-invasive component of duodenal adenoma, and the morphology of this subtype has been suggested to be similar to that of colorectal cancer, with central necrosis and cribriform or tubular glands. […] Several studies suggested that ACs could present the adenoma–carcinoma sequence, as observed in other gastrointestinal malignancies such as colorectal cancer. […] Although most ACs occur sporadically and in absence of a clearly identifiable etiology, the presence of FAP has been associated with a 200-fold higher risk of AC compared with the general population.

• #3 Ampulla of Vater carcinoma: Molecular landscape and clinical implications

  https://www.wjgnet.com/1948-5204/full/v10/i11/370.htm

  Ampullary neoplasms represent a wide array of tumors arising in the ampulla of Vater, the most common of which is represented by ampulla of Vater carcinoma (AVC), although other rare malignancies, such as neuroendocrine tumors, may be encountered in this location. […] The etiology of ampullary carcinoma has not been clearly defined and an association with a noninvasive component displaying the adenoma-to-carcinoma sequence similar to colorectal carcinoma may be present. […] In recent years, much progress has been made in characterizing the molecular alterations underlying AVC tumorigenesis, showing a complex mutational spectrum that supports only in part the distinction in different histological subtypes. […] Molecular analysis showed alterations in overlapping pathways that may serve as foundation for developing new therapeutic approaches and may improve early prognostication models.

• #4 Periampullary Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK555958/

  Ampullary cancer arises from ampulla of Vater terminal to the confluence of the distal common bile duct (CBD) and the pancreatic duct. […] Recent studies further evaluated histological variation depending on the epithelium of origin. Ampullary carcinoma is commonly intestinal epithelial (about 47 percent) or pancreato-biliary (about 24 percent) epithelial subtypes. […] The histology of ampullary cancers commonly resembles that of adenocarcinomas of intestinal origin rather than pancreaticobiliary origin. […] The histology is differentiated by the expression of cyclooxygenase-2 (COX-2) by ampullary cancers that points towards intestinal origin than pancreato-biliary origin. […] These cancers are thought to arise from premalignant precursor lesions-ampullary adenomas. These tumors commonly associated with K-ras mutations.

• #5 Ampullary Carcinoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/276413-overview

  Ampullary adenocarcinomas have two principal histologic forms: intestinal and pancreaticobiliary. The intestinal form is thought to originate from the intestinal epithelium above the ampulla, while the pancreaticobiliary form is thought to originate from the epithelium of the distal pancreatic duct and the common bile duct. The clinical behavior of these tumors reflects this classification; the course of intestinal ampullary adenocarcinomas is similar to that of their duodenal counterparts, whereas pancreaticobiliary tumors follow a more aggressive course, similar to that of pancreatic adenocarcinomas. […] However, 20-40% of ampullary adenocarcinomas are mixed types, showing both pancreaticobiliary and intestinal features. Proposed definitions for mixed-type ampullary carcinoma vary, with different authors suggesting that at least 10% or at least 25% of both histologic subtypes must be present, or that hematoxylin and eosin (HE) staining results should be used to guide diagnosis.

• #6 Ampullary carcinoma is often of mixed or hybrid histologic type: an analysis of reproducibility and clinical relevance of classification as pancreatobiliary versus intestinal in 232 cases | Modern Pathology

  https://www.nature.com/articles/modpathol2016124

  More importantly, 40% of the ampullary carcinomas are designated as mixed. […] This heterogeneity is also amply demonstrated by immunohistochemical studies. […] Regardless of mechanism, this heterogeneity impedes the ability of pathologists to accurately classify these tumors in some cases, even on full-face tissue sections, a problem that is naturally compounded in small biopsies. […] This study also demonstrates the importance of classifying ampullary cancers separately from pancreatic carcinomas. […] Thus, histologic typing and primary site of the tumor ought to be evaluated and reported separately. […] In conclusion, as a transitional region, carcinomas of the ampulla often show hybrid phenotypes between pancreatobiliary and intestinal epithelium, which cause substantial subjectivity in their histologic designation. Mixed carcinomas with intratumoral heterogeneity are a frequent finding.

• #7 Management of ampullary neoplasms: A tailored approach between endoscopy and surgery

  https://www.wjgnet.com/1007-9327/full/v21/i26/7970.htm

  Ampullary neoplasms, although rare, present distinctive clinical and pathological features from other neoplastic lesions of the periampullary region. […] One of the possible causes of developing neoplasms in this area is that the ampullary region contains a transition from pancreatobiliary to intestinal epithelium, and such areas of transition are inherently unstable. […] The appropriate diagnosis of ampullary neoplasms can be challenging and nowadays different diagnostic modalities can be considered including high-resolution imaging techniques, endoscopy and endoscopic ultrasound (EUS). […] As a matter of fact, there are no specific guidelines for the diagnosis of these neoplasms. […] The first local resection of an ampullary lesion was reported in 1898 and the first radical resection (pancreaticoduodenectomy – PD) in 1912.

• #8 Molecular Pathology of Carcinomas of the Ampullary/Periampullary Region | SpringerLink

  https://link.springer.com/10.1007/978-1-4939-6631-8_75-1

  The ampullary/periampullary region is a complex anatomical environment giving rise to a number of heterogeneous malignancies. […] In recent times, crucial advances have been made in characterizing carcinomas of the ampullary/periampullary region on a molecular level. Several molecular patterns seem to correlate with prognosis. Moreover, some molecular pathways, e.g., the WNT pathway, represent potential therapeutic targets to be used in the context of personalized medicine in the future. Gene panel analysis is a promising approach that could be used to translate these findings into clinical applications. […] Carcinogenesis of cancer of the papilla and ampulla: pathophysiological facts and molecular biological mechanisms. […] Ampullary cancers harbor ELF3 tumor suppressor gene mutations and exhibit frequent WNT dysregulation.

• #9 Carcinogenesis of cancer of the papilla and ampulla: pathophysiological facts and molecular biological mechanisms.

  https://folia.unifr.ch/global/documents/218511

  Ampullary cancer has one of the highest resectability rates and best prognoses among neoplasms arising in the periampullary region. […] In the past few years, the molecular mechanisms underlying this disease have been investigated and alterations of genes that regulate different cell functions have been described. Mutations of K-ras and of the tumor suppressor genes APC, p16 and p53 indicate a major disturbance in cell cycle regulation. […] If the molecular profile of ampullary cancer is examined in terms of rate and type of molecular changes, it seems to be more similar to intestinal than to pancreatic cancer. Furthermore, the fact that many ampullary carcinomas arise from adenomas and the frequent finding of ampullary tumors in patients affected by polyposis syndromes also suggest that ampullary and colon cancers share common molecular mechanisms of carcinogenesis.

• #10 Ampullary Carcinoma: An Overview of a Rare Entity and Discussion of Current and Future Therapeutic Challenges

  https://www.mdpi.com/1718-7729/28/5/293

  In terms of molecular features, several recent studies have provided an impressive amount of molecular information regarding hepatobiliopancreatic tumors, including ACs. […] These studies have also suggested an important role in the carcinogenesis process of AC played by inactivating mutations of ELF3, since these aberrations have been observed in approximately the 11% of cases of AC. […] In the last few years, clinicians and researchers have been “tempted” to base their therapeutic decisions on the basis of molecular profiling, since some features have been suggested to have a putative prognostic value.

• #11 Ampullary Adenocarcinoma: A Review of the Mutational Landscape and Implications for Treatment

  https://www.mdpi.com/2072-6694/15/24/5772

  Ampullary carcinomas represent less than 1% of all gastrointestinal malignancies with an incidence of approximately 6 cases per 1 million. […] Genomic classifiers hold the promise of greater reliability, while providing potential targets for precision oncology. […] Molecular diagnostics may have a role in improving prognostication and treatment. […] Several gene mutations in major cell-signaling pathways have been identified. Those pathways are the WNT pathway, the RTK/RAS/MAPK/PI3K pathway, activin/TGF beta (β) signaling pathway, p53 pathway, and chromatin remodeling. […] INT tumors had more frequent alterations in the WNT signaling pathway (76%) compared to PB tumors (38%) (p < 0.001). In contrast, PB tumors had more frequent alterations in RTK-RAS (81.8%) and P53-Rb (74.2%) pathways (versus 63.4%, p = 0.006 and 54.8%, p = 0.008; respectively). [...] The hidden genome classifier incorporates both common and rare variants to optimally determine the cancer subtype. [...] There is growing recognition of the heterogeneous genomic landscape of ampullary adenocarcinoma, which mirrors its variable clinical course.

• #12 Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing

  https://www.jpatholtm.org/journal/view.php?number=16957

  Cancers arising from the ampulla of Vater, though designated as one entity of ampullary cancer (AC), are heterogeneous at morphological and molecular levels as well as in clinical behavior. […] The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles. […] The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. […] The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas. […] The combined RAS-RAF-MAPK/PI3-AKT pathway was the major signaling pathway (70%) altered in AC, followed by TP53 (~38%), WNT signaling (~32%), TGF- (24%), and the chromatin remodeling complex pathways (16%).

• #13 Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing

  https://www.jpatholtm.org/journal/view.php?number=16957

  The PI3-AKT pathway was mutated predominantly in the INT type (63.6%), while the RAS-RAF-MAPK pathway was most frequently mutated in PB differentiation (59.1%). […] The results suggest that PI3-AKT, RAS-RAF-MAPK, and WNT cascades were more frequently mutated in INT type, while the chromatin remodeling complex was more frequently mutated in the PB type. […] The WES data suggest that INT type cancers are more unstable genetically than PB types, and that both involve mutations in tumor suppressor, transcription factor, and chromatin remodeling complex genes. […] The most frequent targetable mutations were found in KRAS, CTNNB1, TP53, APC, and SMAD4 genes. […] Our data suggest the PI3/AKT and RAS/MAPK kinase pathways to be predominantly mutated in AC, suggesting support of primary targeting of the PI3/AKT pathway in INT and the RAS/MAPK kinase pathway in PB type AC.

• #14 Can we classify ampullary tumours better? Clinical, pathological and molecular features. Results of an AGEO study | British Journal of Cancer

  https://www.nature.com/articles/s41416-019-0415-8

  Our findings suggest that although molecular profiling adds nothing to clinicopathological variables, IHC classification is an independent prognostic factor and should be used in daily practice to classify patients. […] Furthermore, KRAS mutation appears as an early event in AA pathogenesis, as it has been reported present in 20% of adenomas and 80% of AA in a series of endoscopic papillectomy samples.

• #15 Ampulla of Vater carcinoma: Molecular landscape and clinical implications

  https://www.wjgnet.com/1948-5204/full/v10/i11/370.htm

  The association between driver mutations and histological subtypes has been evaluated with conflicting results. […] The lack of a specific genetic signature for the histological types suggests the existence of common biological mechanisms in the development of ampullary carcinoma, highlighting the heterogeneity of AVCs from the morphological to the molecular levels. […] Current treatment approaches do not distinguish patients based on subtypes, while molecular alterations may select patients that respond to different chemotherapeutic regimens, regardless of a clear histological differentiation. […] The detection of molecular alterations typical of late-stages may in the future support the choice of radical surgery with lymphadenectomy, rather than more conservative approaches. […] The morphological heterogeneity that characterizes a significant proportion of AVCs and the lack of a prognostic reliability of the histological classification, either individually or within immunohistochemical panels, led to the integration of molecular alterations into clinical practice in order to better define AVCs prognosis and treatment.

• #16

  https://journals.lww.com/ijpm/fulltext/2021/64040/muc1,_ck20,_and_cdx2_immunohistochemical_markers.13.aspx

  Pancreaticobiliary subtype of Periampullary carcinoma (PAC) has a poor prognosis in comparison to the intestinal subtype. […] Only TNM Stage III (tumor staging as per American Joint Committee on Cancer classification) and perineural invasion have been associated with predicting poor survival in PAC patients. […] Our results suggest that the combined expression of MUC1, CK20 and CDX2 could serve as markers to diagnose histological inconclusive specimens as mixed subtype tumors. […] The two major findings of our study are, first, we propose that combined immuno-positivity of CK20, MUC1, and CDX2 can detect the mixed subtype of periampullary cancers. Second, we confirm the significant relationship between overall survival and clinicopathological prognostic markers, such as TNM staging and perineural invasion.

• #17

  https://journals.lww.com/ijpm/fulltext/2021/64040/muc1,_ck20,_and_cdx2_immunohistochemical_markers.13.aspx

  To our knowledge from the previous studies, the performance of individual markers has not yielded higher sensitivity and specificity to make them utilize as definite markers for subtyping in periampullary tumors. […] Our results suggest that the combined immunophenotype expression of MUC1, CK20, and CDX2 could be used as markers to identify mixed subtype tumors where histological verification remains inconclusive.

• #18 Prognosis of ampullary cancer based on immunohistochemical type and expression of osteopontin | Diagnostic Pathology | Full Text

  https://diagnosticpathology.biomedcentral.com/articles/10.1186/1746-1596-6-98

  Ampullary cancer (AC) was classified as pancreatobiliary, intestinal, or other subtype based on the expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20). […] Numerous studies have reported that intestinal AC is associated with a better prognosis than pancreatobiliary AC. […] OPN may also be a suitable biomarker for overall survival and renal outcome of patients who are critically ill with acute kidney injury. […] However, few studies have investigated the expression of OPN in patients with AC. […] Our results also suggest that OPN plays a role in the pathogenesis of AC, but its mechanisms and relationship with CK7 and CK20 warrant further studies.

• #19 Signet ring cell carcinoma of the ampulla of Vater: Immunophenotype and differentiation

  https://www.spandidos-publications.com/10.3892/ol.2014.2344

  Signet ring cell carcinoma (SRC) of the ampulla of Vater is extremely rare and the histogenesis remains unknown. […] The majority of studies have attempted to discuss the cellular origin and differentiation of ampullary SRC based on the immunohistochemical staining of CK and MUC. […] Due to its association with the gastric epithelium, Blundell et al (13) hypothesized the origin of ampullary SRC only in the presence of gastric mucosa/metaplasia. […] The carcinogenesis of ampullary SRC may differ from that of other gastrointestinal malignancies. […] In conclusion, the current study presents eight cases of SRC in the ampulla of Vater with regard to the detailed clinicopathological features and immunohistochemical phenotypes. […] There is a possible pathogenic correlation between gastric-type ampullary SRC, and MU5AC and MUC6 expression.

• #20 Ampullary cancer: 9 things to know about this rare gastrointestinal cancer | MD Anderson Cancer Center

  https://www.mdanderson.org/cancerwise/ampullary-cancer-9-insights-on-this-rare-gastrointestinal-cancer.h00-159542112.html

  Ampullary cancer occurs when cells in the ampulla of Vater begin to grow out of control and form a tumor. […] Its not clear what causes ampullary cancer. But we know that people with inherited conditions like familial adenomatous polyposis (FAP) or Lynch syndrome that cause polyps to grow in the digestive system are more likely to develop the disease.

• #21 Molecular Targets and Therapies for Ampullary Cancer in: Journal of the National Comprehensive Cancer Network Volume 22 Issue 2D (2024)

  https://jnccn.org/abstract/journals/jnccn/22/2D/article-e237051.xml

  Differentiating histologic subtypes has biologic and prognostic relevance for ampullary adenocarcinomas. Pancreaticobiliary-type ampullary cancers are associated with a more aggressive phenotype compared with intestinal-type tumors. […] Patients with mixed subtype histology tumors have improved prognosis closer to the intestinal subtype in most of the studies where it is reported. […] Recurrence is common in ampullary cancer, at 43.5% after curative intention surgery. […] Microscopic venous and lymphatic vessel invasion is correlated with an increase in distant metastases and lymphomatous metastases. […] Several genetic mutations are considered risk factors for ampullary cancer. Patients with ampullary cancer can harbor pathogenic germline alterations in BRCA2, ATM, RAD50, and MUTYH.

• #22 Molecular Targets and Therapies for Ampullary Cancer in: Journal of the National Comprehensive Cancer Network Volume 22 Issue 2D (2024)

  https://jnccn.org/abstract/journals/jnccn/22/2D/article-e237051.xml

  Pathogenic germline variations in BRCA have been described with rates of 7% to 14%. Even higher frequencies were reported in a study in which whole-exome sequencing of 37 patients with ampullary carcinoma revealed that 23 (62%) had mutations in BRCA1 and 19 (51%) had mutations in BRCA2. […] Given that treatment of the pancreaticobiliary subtype of ampullary cancers is largely extrapolated from treatment of pancreas cancer, this underscores the importance that patients with pathogenic mutations in BRCA1/2 or PALB2 are treated with platinum-based chemotherapy. […] In a cohort of patients with ampullary cancer, 7% (3/44) were found to have pathogenic germline mutations in ATM. Although guidelines currently suggest a first-line platinum-based regimen only for advanced pancreas cancer with either BRCA or PALB2 mutation, given that ATM-mutated cells are predicted to be sensitive to platinum drugs, platinum-based chemotherapy may be considered for patients with ampullary cancer and an ATM mutation.

• #23 Progression of Metastatic, PD-L1–Positive, Ampullary Carcinoma with a Treatment Holiday from Off-Label Use of Pembrolizumab Therapy

  https://jhoponline.com/issue-archive/2020-issues/august-2020-vol-10-no-4/progression-of-metastatic-pd-l1-positive-ampullary-carcinoma-with-a-treatment-holiday-from-off-label-use-of-pembrolizumab-therapy

  Ampullary carcinoma, a rare type of tumor that arises from the ampulla of Vater, represents only 0.2% of all gastrointestinal (GI) tract neoplasms to date. […] The use of pembrolizumab in the setting of ampullary carcinoma has not been explicitly studied. […] We present a case of using off-label pembrolizumab therapy that produced a durable response in a 75-year-old woman with microsatellite-stable, metastatic ampullary carcinoma and 35% PD-L1 expression. […] Our patients PD-L1 expression status may explain the durable response observed with the use of pembrolizumab therapy. […] This case report describes a patient with 35% PD-L1 expression, microsatellite-stable, metastatic ampullary carcinoma who had stable disease with pembrolizumab therapy in the third line. […] Although a PD-L1 expression of 35% may explain this patients positive response to pembrolizumab therapy, it is interesting that such a durable response was maintained in a patient with microsatellite-stable status.

• #24 Mutational signatures define immune and Wnt-associated subtypes of ampullary carcinoma | Gut

  https://gut.bmj.com/content/early/2024/12/26/gutjnl-2024-333368

  Ampullary carcinoma (AMPAC) taxonomy is based on morphology and immunohistochemistry. This classification lacks prognostic reliability and unique genetic associations. […] We define Wnt pathway suppressor RNF43 mutations and deletions, recurrent MYC amplification and SND1-BRAF fusion as novel candidate drivers potentially involved in AMPAC tumourigenesis. […] We demonstrate the association of Wnt pathway-activating mutations, mutational signatures and global DNA methylation loss as hallmarks of distinct tumourigenic trajectories in AMPAC. […] We use mutational signatures to classify AMPAC into two distinct patient groups. The first group (C1 and C2) is defined by immune exclusion and intermediate immune type tumours characterised by Wnt pathway alterations and suitable for putative Wnt pathway-targeted therapies (-catenin/TGF- inhibitors). The second group (C3) is more likely to respond to immune checkpoint inhibitors.

• #25 Mutational signatures define immune and Wnt-associated subtypes of ampullary carcinoma | Gut

  https://gut.bmj.com/content/early/2024/12/26/gutjnl-2024-333368

  We demonstrate that signature 1, specifically CT at CpG sites, causes a hypermutator phenotype that correlates with mutations in Cadherin signalling and WNT pathway genes as well as loss of methylation in a subset of AMPAC tumours. […] Integration of AMPAC genomes, transcriptomes and DNA methylomes demonstrates the potential of mutational signatures deconstructed from tumour exomes to define biological-relevant and clinically distinct patient groups with distinct molecular subtypes. This molecular-based taxonomy may be relevant in designing personalised therapies for patients with AMPAC including future studies testing the clinical utility of immunotherapy and/or targeting the Wnt pathway (for example, -catenin/TGF-beta inhibition).

• #26 NCCN Establishes Standards of Care in Ampullary Adenocarcinoma

  https://www.onclive.com/view/nccn-establishes-standards-of-care-in-ampullary-adenocarcinoma

  Physicians determine treatment for ampullary adenocarcinomas depending on whether the tumor histology is pancreatobiliary, intestinal, or mixed. […] Most ampullary adenocarcinomas are intestinal or pancreatobiliary. […] Survival analysis from that study showed a significantly worse 5-year overall survival (OS) rate for the pancreatobiliary subtype compared with intestinal at 27.5% vs 61%, respectively (P .001). […] Chiorean said that physicians use regimens for pancreatic cancer to treat patients with ampullary adenocarcinomas of pancreaticobiliary subtype. […] The current standard of care for localized ampullary cancer is pancreaticoduodenectomy, also known as the Whipple procedure, in which a surgeon removes the head of the pancreas, part of the duodenum, the common bile duct, and the gallbladder.

• #27 Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience – Zhong – Journal of Gastrointestinal Oncology

  https://jgo.amegroups.org/article/view/3314/3825

  Ampullary adenocarcinoma is a rare malignancy associated with a relatively favorable prognosis. […] The primary treatment modality for ampullary carcinomas is pancreaticoduodenectomy. […] Despite the relatively favorable prognosis for ampullary tumors, patients with high-risk features often develop locoregional and distant recurrence. […] Many authors recommend the use of adjuvant chemoradiotherapy (CRT) for patients with nodal involvement, involved margins and advanced tumor stage. […] However, contemporary population-based data from the National Cancer Data Base demonstrated poor outcomes with 5-year OS rates of 40-44% for T1-T2N0 tumors. […] We hypothesize that even early stage (T1-T2N0) ampullary tumors may have failure rates high enough to warrant adjuvant therapy. […] Our study demonstrated a surprisingly high locoregional failure rate (39%) for the surgery only cohort compared to patients receiving combined modality therapy (15%) for these early stage patients.

• #28 Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience – Zhong – Journal of Gastrointestinal Oncology

  https://jgo.amegroups.org/article/view/3314/3825

  Given that 39% of patients who received surgery alone experienced locoregional failure, we believe there is a clinically significant risk of residual subclinical disease following radical resection, even for early tumors. […] Our data suggest that LC and OS for stage I ampullary carcinomas may not be as favorable as previously described. […] Patients who receive adjuvant CRT may derive a benefit in LC and potentially other disease-related outcomes.

• #29 Primary Squamous Cell Carcinoma of the Ampulla of Vater

  https://www.primescholars.com/articles/primary-squamous-cell-carcinoma-of-the-ampulla-of-vater-97520.html

  Primary malignant tumors originating from the papilla of Vater are mostly adenocarcinomas accounting for about 1% of all adenocarcinomas and approximately for 5% of gastrointestinal tract carcinomas. […] The ampulla of Vater is devoid of squamous epithelium and, therefore, the pathogenesis of ampullary squamous cell carcinoma remains elusive. Pure primary squamous cell carcinoma may be the result of malignant transformation of ectopic squamous epithelium or may originate from undifferentiated primitive multipotent cells. […] Squamous metaplasia and malignant transformation of ampullary epithelium in cases of chronic inflammation due to pancreaticobiliary maljunction, bile and pancreatic juice reflux, Carolis disease, choledochal cyst, choledocholithiasis, primary sclerosing cholangitis, ascariasis or liver fluke infestation has been postulated as a possible mechanism for this type of carcinoma but none of these factors was present in our patient.

• #30 Primary Squamous Cell Carcinoma of the Ampulla of Vater

  https://www.primescholars.com/articles/primary-squamous-cell-carcinoma-of-the-ampulla-of-vater-97520.html

  Transformation of an adenocarcinoma into adenosquamous and eventually to squamous cell carcinoma could be another possible mechanism. […] The optimal treatment and the prognosis of squamous cell carcinoma of the ampulla of Vater are elusive because of the rarity of this condition. […] This case report suggests that primary surgical treatment with curative intent should be performed although this type of carcinoma associates with dismal prognosis. […] Further documentation of this rare tumor will provide a better understanding of its pathogenesis and management for optimal survival rates.

• #31 Primary squamous cell carcinoma of the ampulla of Vater: a case report | Surgical Case Reports | Full Text

  https://surgicalcasereports.springeropen.com/articles/10.1186/s40792-016-0130-0

  Primary squamous cell carcinoma of the ampulla of Vater is a very rare histological type with an unclear pathogenesis. […] The exact pathogenesis of primary squamous cell carcinoma in the ampulla of Vater is still unknown. […] A better understanding of pathogenesis might be helpful in optimizing the treatment for this specific rare type of tumor.

• #32 Ampullary Carcinoma: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/276413-overview

  Immunohistochemical stains for expressions of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, Ki-67, and p53 have been studied for prognostic power. In a series of 45 patients, expression of CA 19-9 labeling intensity and apical localization both were statistically significant predictors of poor prognosis. Although earlier studies suggested that CA 19-9 may be used as a prognostic marker, a study by Zhou et al did not demonstrate a difference in survival based on CA 19-9 level. CEA expression also might be a marker for prognosis, but it may also be elevated in other GI malignancies. Ki-67 and p53 have not been demonstrated to have an effect on outcome. Research along these avenues ultimately might provide the rationale for discriminative administration of adjuvant therapy.

• #33 Molecular Targets and Therapies for Ampullary Cancer in: Journal of the National Comprehensive Cancer Network Volume 22 Issue 2D (2024)

  https://jnccn.org/abstract/journals/jnccn/22/2D/article-e237051.xml

  Ampullary carcinomas are rare but increasing in incidence. Ampullary cancers have molecular alterations that guide choice of therapy, particularly in nonresectable cases. These alterations can be more common by subtype (intestinal, pancreaticobiliary, or mixed), and next-generation sequencing is recommended for all patients who cannot undergo surgery. […] Common molecular targets of interest in ampullary cancer are also discussed in this review, including HER2/ERBB2, HER3, tumor mutational burden, microsatellite instability, KRAS, and germline BRCA and ATM mutations, along with emerging and rarer alterations. […] Ampullary cancer arises from the ampulla of Vater at the confluence of the distal bile duct, pancreatic duct, and duodenum. There are emerging molecularly targeted treatments that can be considered. This is important as ampullary cancers vary by intestinal and pancreatobiliary subtypes, which confer selected alterations that can guide treatment.

• #34 Ampullary Cancer: An Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4966534/

  The management of locoregional disease is primarily a surgical intervention by a pancreaticoduodenectomy (or Whipples procedure) followed by the administration of adjuvant chemotherapy (preferably gemcitabine). […] The management of unresectable and metastatic disease is primarily through the administration of systemic therapy with an anti-metabolite (fluoropyrimidine and/or gemcitabine) combined with a platinum compound, (usually cisplatin or oxaliplatin). […] Given the rarity of this disease, there is absence of randomized clinical trials focused on ampullary carcinomas and treatment recommendations are mainly derived from results of adjuvant clinical trials conducted in pancreaticobiliary cancers where ampullary cancers may represent a sub-group of patients. […] Overall, most studies did not suggest the presence of a survival benefit from adjuvant chemoradiation, except perhaps for a subset of patients with adverse risk factors (T stage, lymph node involvement, histologic grade) that may potentially benefit from chemoradiation.

• #35 Ampullary carcinoma is often of mixed or hybrid histologic type: an analysis of reproducibility and clinical relevance of classification as pancreatobiliary versus intestinal in 232 cases | Modern Pathology

  https://www.nature.com/articles/modpathol2016124

  Histologic classification of ampullary carcinomas as intestinal versus pancreatobiliary is rapidly becoming a part of management algorithms, with immunohistochemical classification schemes also being devised using this classification scheme as their basis. […] Interestingly, when compared with 476 cases of pancreatic ductal adenocarcinomas, the pancreatobiliary-type ampullary carcinomas had better survival (16 versus 41 months, P=0.001), even when matched by size and node status. […] Caution is especially warranted when applying this histologic classification to biopsies and tissue microarrays. […] While ampullary carcinomas with more pancreatobiliary morphology have a worse prognosis than intestinal ones this does not appear to be an independent prognostic factor. […] This study reveals that the reproducibility of the histology-based pancreatobiliary versus intestinal classification system for invasive ampullary carcinomas in fact presents many challenges in daily practice, especially if intended to be applied for the stratification of individual patients to different (biologically defined) treatment protocols using a purist approach.

• #36 Periampullary Tumors – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK555958/

  The common presenting symptom at the time of diagnosis is obstructive jaundice due to distal biliary ductal blockage, which prompts further evaluation for diagnosis. […] Surgical resection is not feasible for advanced disease with distant metastasis, and these tumors are treated with systemic chemotherapy regimens that are used to treat pancreatic cancer or colorectal cancers. […] The only curative potential treatment modality for ampullary cancer is surgical resection with pancreaticoduodenectomy/Whipple with or without preserving the pylorus. […] The prognostic outcome is dependent upon the extent of local invitation, the status of surgical margins after the definitive surgery, and the presence of nodal metastasis. […] Recently the role of histology phenotype has emerged with some data indicating poor prognosis associated with pancreaticobiliary histopathology compared to intestinal type.

• #37 Management of ampullary neoplasms: A tailored approach between endoscopy and surgery

  https://www.wjgnet.com/1007-9327/full/v21/i26/7970.htm

  Compared to the previous one, the new stage classification has been modified according to new prognostic information; nodal positivity is included in stage IIB, while stage III comprises patients with extensive (T4) tumors, with or without nodal disease. […] Following surgical resection, recurrence may occur locally (involving the tumor bed or the para-aortic lymphatics) or at a distant site. […] After curative resection, nodal status is one of the strongest predictors of survival. […] In contrast to pancreatic cancers, in case of ampullary cancer a lymphatic pathway has been identified, extending from posterior pancreatico-duodenal nodes around the mesenteric artery up to para-aortic lymph nodes. […] The role of neo-adjuvant therapy for advanced ampullary cancer is not defined, as most studies have included ampullary neoplasms with other malignancies due to their rare occurrence.

• #38 Management of ampullary neoplasms: A tailored approach between endoscopy and surgery

  https://www.wjgnet.com/1007-9327/full/v21/i26/7970.htm

  Overall survival rate at 5 years is widely variable between different reports, ranging from 32% to 67.7%. […] In patients who undergo a potentially curative resection, the presence of nodal metastases, poorly differentiated histology, and tumor invasion into the pancreas are associated with a less favourable outcome.

• #39 Ampullary Cancer: An Overview

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4966534/

  The role of adjuvant chemotherapy in pancreatic cancer has been investigated in several randomized trials suggesting a consistent benefit for gemcitabine of 5FU. […] The majority of patients with resected ampullary carcinomas will eventually die from recurrent disease. […] For unresectable and metastatic disease, systemic therapy with an antimetabolite (fluoropyrimidine and/or gemcitabine) combined with a platinum compound, (usually cisplatin or oxaliplatin) should be considered. […] Findings suggest a distinct oncogenesis, which may be important in the therapeutic context for the development of targeted therapies, including PI3K inhibition. […] Additionally, studies investigating microRNA expression profiles confirm ampullary cancers are distinct compared to pancreatic adenocarcinoma.

• #40 NCCN Establishes Standards of Care in Ampullary Adenocarcinoma

  https://www.onclive.com/view/nccn-establishes-standards-of-care-in-ampullary-adenocarcinoma

  Neoadjuvant therapy is an option for patients with localized pancreatic cancer because those tumors are more commonly closed to the celiac arterial axis, but the guidelines say that there is limited evidence supporting such treatment for ampullary cancers and most such patients proceed straight to surgery. […] After surgical resection, we consider administering adjuvant therapy to reduce the odds of recurrence based, again, on the histology, Chiorean said. […] The guidelines suggest FOLFIRINOX or modified FOLFIRINOX with or without subsequent chemoradiation, or gemcitabine-based regimens with cisplatin, capecitabine, or nab-paclitaxel (Abraxane), all with or without subsequent chemoradiation for those with pancreatobiliary or mixed disease. […] In the adjuvant setting, the guidelines specifically cite the phase 3 ESPAC-3 trial (NCT00058201), which included patients with ampullary cancers, to support the use of postoperative gemcitabine or 5-fluorouracil (5-FU).

• #41 NCCN Establishes Standards of Care in Ampullary Adenocarcinoma

  https://www.onclive.com/view/nccn-establishes-standards-of-care-in-ampullary-adenocarcinoma

  Recurrence is common following surgery at 89.6% at 3 years in one study. […] The choice of second-line therapy depends on both disease subtype and the regimen used in up front. […] Similar to other solid tumor indications, the guidelines recommend genetic testing for hereditary cancer genes, as well as tumor genomic and molecular profiling, the latter for patients with advanced disease. […] Chiorean noted that there are no current clinical trials looking at ampullary cancers exclusively, and she sees these guidelines as a way to boost interest and attention to this malignancy.

• #42 Ampullary Cancer: Symptoms, Diagnosis & Outlook

  https://my.clevelandclinic.org/health/diseases/21905-ampullary-cancer

  Ampullary cancer is a rare and aggressive (fast-growing) cancer that forms inside the ampulla of Vater. […] Experts arent sure what causes ampullary cancer specifically. But they do know that cancer begins when cells develop mutations (changes) in their DNA. These abnormal cells start to multiply and grow out of control. […] Experts continue to learn more about the specific types of mutations associated with ampullary cancer. This information helps them develop treatments that target the abnormalities and kill cancer cells. But this research is still in its early stages.

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