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Revista Espanola de Enfermedades... Sep 2021A 41-year-old caucasian female, with past medical history of pituitary adenoma medicated with cabergoline, presented with worsening dyspepsia and unintentional weight...
A 41-year-old caucasian female, with past medical history of pituitary adenoma medicated with cabergoline, presented with worsening dyspepsia and unintentional weight loss of 5%. Physical exam and laboratory results were unremarkable for pathological findings. Esophagogastroduodenoscopy revealed an oedematous and exuberant lymphangiectasia appearance in the duodenum, with no ulceration or suspected infiltration component. However, duodenal biopsies revealed infiltration by poorly differentiated carcinoma. In the meantime, infection and inflammatory/autoimmune causes were ruled out. A CT scan was performed revealing a thickened and enlarged pancreas with ill-defined limits and several intra-abdominal adenopathies, raising suspicion of pancreatic lymphoproliferative disease. EUS with FNB was performed with biopsy of the pancreas and one of the larger adenopathy. EUS also revealed an enlarged, non-nodular pancreas and a thickened duodenal wall. Mild ascites was detected. Both EUS-biopsies were concordant on the diagnosis of carcinoma with gastric or pancreatic-biliary origin, highly aggressive (Ki67 > 80 %). Therefore, the diagnosis of pancreatic adenocarcinoma was assumed (cT4N1Mx). The patient is currently on palliative chemotherapy and remains paucisymptomatic.
Topics: Adenocarcinoma; Adult; Duodenum; Female; Humans; Pancreas; Pancreatic Diseases; Pancreatic Neoplasms
PubMed: 33569966
DOI: 10.17235/reed.2021.7823/2021 -
American Journal of Physiology.... Dec 2019Pancreatic ductal adenocarcinoma (PDAC)'s growing incidence has been linked to the rise in obesity and type 2 diabetes mellitus. In previous work, we have shown that...
Pancreatic ductal adenocarcinoma (PDAC)'s growing incidence has been linked to the rise in obesity and type 2 diabetes mellitus. In previous work, we have shown that metformin can prevent the increased incidence of PDAC in a Kras mouse model subjected to a diet high in fat and calories (HFCD). One potential way that metformin can affect the host is through alterations in the gut microbiome. Therefore, we investigated microbial associations with PDAC development and metformin use in the same mouse model. Lox-Stop-Lox Kras G12D/+ (LSL-Kras G12D/+); p48-Cre (KC) mice were given control diet, HFCD, or HFCD with 5 mg/mL metformin in drinking water for 3 mo. At the end of the 3 mo, 16S rRNA sequencing was performed to characterize microbiome composition of duodenal mucosal, duodenal luminal, and cecal luminal samples. KC mice on an HFCD demonstrated depletion of intact acini and formation of advanced pancreatic intraepithelial neoplasia. This effect was completely abrogated by metformin treatment. HFCD was associated with significant changes in microbial composition and diversity in the duodenal mucosa and lumen, much of which was prevented by metformin. In particular, was negatively correlated with percent intact acini and seemed to be inhibited by the addition of metformin while on an HFCD. Administration of metformin eliminated PDAC formation in KC mice. This change was associated with significant microbial changes in both the mucosal and luminal microbiome of the duodenum. This suggests that the microbiome may be a potential mediator of the chemopreventive effects of metformin. Pancreatic ductal adenocarcinoma (PDAC)'s growing incidence has been linked to the rise in obesity and type 2 diabetes mellitus. Administration of metformin eliminated PDAC formation in KC mice with diet-induced obesity. This change was associated with significant microbial changes in both the mucosal and luminal microbiome of the duodenum. This suggests that the microbiome may be a potential mediator of the chemopreventive effects of metformin.
Topics: Animals; Carcinoma, Pancreatic Ductal; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Duodenum; Gastrointestinal Microbiome; Hypoglycemic Agents; Metformin; Mice; Obesity; Treatment Outcome
PubMed: 31545922
DOI: 10.1152/ajpgi.00170.2019 -
Journal of Translational Medicine Jun 2022Ampullary adenocarcinoma (AAC) arises from the ampulla of Vater where the pancreatic duct and bile duct join and empty into the duodenum. It can be classified into...
BACKGROUND
Ampullary adenocarcinoma (AAC) arises from the ampulla of Vater where the pancreatic duct and bile duct join and empty into the duodenum. It can be classified into intestinal and pancreatobiliary types based on histopathology or immunohistochemistry. However, there are no biomarkers for further classification of pancreatobiliary-type AAC which has important implications for its treatment. We aimed to identify the tumor origin of pancreatobiliary-type AAC by systematically analyzing whole-slide images (WSIs), survival data, and genome sequencing data collected from multiple centers.
METHODS
This study involved three experiments. First, we extracted quantitative and highly interpretable features from the tumor region in WSIs and constructed a histologic classifier to differentiate between pancreatic adenocarcinoma (PAC) and cholangiocarcinoma. The histologic classifier was then applied to patients with pancreatobiliary-type AAC to infer the tumor origin. Secondly, we compared the overall survival of patients with pancreatobiliary-type AAC stratified by the adjuvant chemotherapy regimens designed for PAC or cholangiocarcinoma. Finally, we compared the mutation landscape of pancreatobiliary-type AAC with those of PAC and cholangiocarcinoma.
RESULTS
The histologic classifier accurately classified PAC and cholangiocarcinoma in both the internal and external validation sets (AUC > 0.99). All pancreatobiliary-type AACs (n = 45) were classified as PAC. The patients with pancreatobiliary-type AAC receiving regimens designed for PAC showed more favorable overall survival than those receiving regimens designed for cholangiocarcinoma in a multivariable Cox regression (hazard ratio = 7.24, 95% confidence interval: 1.28-40.78, P = 0.025). The results of mutation analysis showed that the mutation landscape of AAC was very similar to that of PAC but distinct from that of cholangiocarcinoma.
CONCLUSIONS
This multi-center study provides compelling evidence that pancreatobiliary-type AAC resembles PAC instead of cholangiocarcinoma in different aspects, which can guide the treatment selection and clinical trials planning for pancreatobiliary-type AAC.
Topics: Adenocarcinoma; Ampulla of Vater; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Common Bile Duct Neoplasms; Data Analysis; Humans; Pancreatic Neoplasms; Prognosis
PubMed: 35705951
DOI: 10.1186/s12967-022-03473-w -
Der Chirurg; Zeitschrift Fur Alle... Sep 2021Periampullary neoplasms are a heterogeneous group of different tumor entities arising from the periampullary region, of which pancreatic ductal adenocarcinoma (PDAC) is... (Review)
Review
Periampullary neoplasms are a heterogeneous group of different tumor entities arising from the periampullary region, of which pancreatic ductal adenocarcinoma (PDAC) is the most common subgroup with 60-70%. As typical for pancreatic adenocarcinomas, periampullary pancreatic cancer is characterized by an aggressive growth and early systemic progression. Due to the anatomical location in close relationship to the papilla of Vater symptoms occur at an earlier stage of the disease, so that treatment options and prognosis are overall more favorable compared to pancreatic carcinomas at other locations. Nevertheless, the principles of treatment for periampullary pancreatic cancer are not substantially different from the standards for pancreatic cancer at other locations. A potentially curative approach for non-metastatic periampullary pancreatic cancer is a multimodal therapy concept, which includes partial pancreatoduodenectomy as a radical oncological resection in combination with a systemic adjuvant chemotherapy. As a result, long-term survival can be achieved in patients with favorable prognostic factors. In addition, with the continous development of surgery and systemic treatment potentially curative treatment concepts for advanced initially nonresectable tumors were also established, after completion of neoadjuvant treatment. This article presents the current surgical principles of a radical oncological resection for periampullary pancreatic cancer in the context of a multimodal treatment concept with an outlook for future developments of treatment.
Topics: Adenocarcinoma; Ampulla of Vater; Common Bile Duct Neoplasms; Duodenal Neoplasms; Humans; Pancreatic Neoplasms
PubMed: 34259884
DOI: 10.1007/s00104-021-01462-1 -
HPB : the Official Journal of the... Nov 2013Ampullary adenocarcinoma is considered to have a better prognosis than either pancreatic or bile duct adenocarcinoma. Pancreaticoduodenectomy is associated with... (Review)
Review
BACKGROUND
Ampullary adenocarcinoma is considered to have a better prognosis than either pancreatic or bile duct adenocarcinoma. Pancreaticoduodenectomy is associated with significant mortality and morbidity. Some recent publications have advocated the use of endoscopic papillectomy for the treatment of early ampullary adenocarcinoma. This article reviews investigations and surgical treatment options of ampullary tumours.
METHODS
A systematic review of English-language articles was carried out using an electronic search of the Ovid MEDLINE (from 1996 onwards), PubMed and Cochrane Database of Systematic Reviews databases to identify studies related to the investigation and management of ampullary tumours.
RESULTS
Distinguishing between ampullary adenoma and adenocarcinoma is challenging given the inaccuracy of endoscopic biopsy, for which high false negative rates of 25-50% have been reported. Endoscopic ultrasound is the most accurate method for local staging of ampullary lesions, but distinguishing between T1 and T2 adenocarcinomas is difficult. Lymph node metastasis occurs early in the disease process; it is lowest for T1 tumours, but the risk is still high at 8-45%. Case reports of successful endoscopic resection and transduodenal ampullectomy of T1 adenocarcinomas have been published, but their duration of follow-up is limited.
CONCLUSIONS
Optimal staging should be used to distinguish between ampullary adenoma and adenocarcinoma. Pancreaticoduodenectomy remains the treatment of choice for all ampullary adenocarcinomas.
Topics: Adenocarcinoma; Ampulla of Vater; Biopsy; Cholangiopancreatography, Endoscopic Retrograde; Common Bile Duct Neoplasms; Endosonography; Humans; Image-Guided Biopsy
PubMed: 23458317
DOI: 10.1111/hpb.12038 -
Annals of Surgery Oct 1970
Topics: Adenocarcinoma; Adenoma, Islet Cell; Adult; Aged; Carcinoma; Cholecystectomy; Duodenum; Female; Follow-Up Studies; Gastrostomy; Humans; Jejunum; Lymphatic Metastasis; Male; Middle Aged; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis; Prognosis; Splenectomy; Zollinger-Ellison Syndrome
PubMed: 4318798
DOI: 10.1097/00000658-197010000-00006 -
Human Pathology Dec 2013Because of the rarity of duodenal adenocarcinoma (DAC), the clinicopathologic features and prognostication data for DAC are limited. There are no published studies... (Comparative Study)
Comparative Study
Because of the rarity of duodenal adenocarcinoma (DAC), the clinicopathologic features and prognostication data for DAC are limited. There are no published studies directly comparing the prognosis of DAC to that of ampullary adenocarcinoma (AA) and of pancreatic ductal adenocarcinoma (PDA) after resection. In this study, we examined the clinicopathologic features of 68 patients with DAC, 92 patients with AA, and 126 patients with PDA who underwent resection. Patient clinicopathologic and survival information were extracted from medical records. Statistical analysis was performed using Statistical Package for the Social Sciences with 2-sided significance level of .05. Patients with DAC had higher American Joint Committee on Cancer (AJCC) stage than AA patients (P = .001). Lymph node metastasis (P = .013) and AJCC stage (P = .02) correlated with overall survival in DAC patients. Patients with DAC or AA had lower frequencies of lymph node metastasis and positive margin and better survival than those with PDA (P < .05). However, no differences in nodal metastasis, margin status, or survival were observed between DAC patients and those with AA. Our study showed that lymph node metastasis and AJCC stage are important prognostic factors for overall survival in DAC patients. Patients with DAC had less frequent nodal metastasis and better prognosis than those with PDA. There was no significant difference in prognosis between DAC and AA.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Carcinoma, Pancreatic Ductal; Common Bile Duct Neoplasms; Duodenal Neoplasms; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Pancreatic Neoplasms; Pancreaticoduodenectomy; Prognosis; Treatment Outcome
PubMed: 24139211
DOI: 10.1016/j.humpath.2013.07.030 -
BMC Surgery Aug 2022Local duodenectomy and primary closure is a simple option for some nonampullary duodenal neoplasms. Minimizing the resection area while ensuring curability is necessary... (Observational Study)
Observational Study
BACKGROUND
Local duodenectomy and primary closure is a simple option for some nonampullary duodenal neoplasms. Minimizing the resection area while ensuring curability is necessary for safe primary duodenal closure. However, it is often difficult to determine the appropriate resection line from the serosal side. We developed clip-guided local duodenectomy to easily determine the resection range and perform local duodenectomy safely, then performed a retrospective observational study to confirm the safety of clip-guided local duodenectomy.
METHODS
The procedure is as follows: placing endoscopic metal clips at four points on the margin around the tumor within 3 days before surgery, identifying the tumor extent with the clips under X-ray imaging during surgery, making an incision to the duodenum just outside of the clips visualized by X-ray imaging, full-thickness resection of the duodenum with the clips as guides of tumor demarcation, and transversely closure by Gambee suture. We evaluated clinicopathological data and surgical outcomes of patients who underwent clip-guided local duodenectomy at two surgical centers between January 2010 and May 2020.
RESULTS
Eighteen patients were included. The pathological diagnosis was adenoma (11 cases), adenocarcinoma (6 cases), and GIST (1 case). The mean ± SD tumor size was 18 ± 6 mm, and the tumor was mainly located in the second portion of the duodenum (66%). In all cases, the duodenal defect was closed with primary sutures. The mean operation time and blood loss were 191 min and 79 mL, respectively. The morbidity was 22%, and all complications were Clavien-Dindo grade II. No anastomotic leakage or stenosis was observed. In the 6 adenocarcinoma patients, all were diagnosed with pT1a, and postoperative recurrence was not observed. The 1-year overall and recurrence free survival rate was 100%.
CONCLUSIONS
Clip-guided local duodenectomy is a safe and useful surgical option for minimally local resection of nonampullary duodenal neoplasms such as duodenal adenoma, GIST, and early adenocarcinoma.
Topics: Adenocarcinoma; Adenoma; Duodenal Neoplasms; Duodenum; Gastrointestinal Stromal Tumors; Humans; Retrospective Studies; Surgical Instruments; Treatment Outcome
PubMed: 36038851
DOI: 10.1186/s12893-022-01771-0 -
Oncology (Williston Park, N.Y.) Oct 2002Small bowel adenocarcinoma is a relatively rare malignancy. Only limited information is available on the incidence, prognosis, and role of chemotherapy in the treatment... (Review)
Review
Small bowel adenocarcinoma is a relatively rare malignancy. Only limited information is available on the incidence, prognosis, and role of chemotherapy in the treatment of this disease. We present a review of currently available clinical data to assist the practicing oncologist in the treatment of these patients. Approximately 5,300 new cases and 1,100 deaths from small bowel adenocarcinoma are reported annually in the United States. Increased incidence is seen in patients with Crohn's disease, hereditary nonpolyposis colorectal cancer, and familial adenomatouspolyposis. Factors associated with poor prognosis are age > 75 years, lack of surgical resection, advanced stage, and tumor arising in the duodenum. The median survival of patients with localized, locally advanced, and metastatic disease is 50.1, 22.2, and 8.6 months, respectively. Few data exist on the use of (neo)adjuvant or palliative chemo(radio)therapy in this setting. Fluorouracil (5-FU)based chemotherapy, as a single agent or in combination with others, has been used in most case series. Duodenal adenocarcinoma accounts for more than 50% of all cases of small bowel adenocarcinoma. Resectability is the key prognostic factor, along with age, performance status, tumor location, and presence of distant metastasis. Although the activity of 5-FU-based regimens has been documented, the assessment of clinical benefit is hindered by the lack of prospective, randomized data.
Topics: Adenocarcinoma; Clinical Trials as Topic; Humans; Intestinal Neoplasms; Intestine, Small
PubMed: 12435206
DOI: No ID Found -
The Journal of Pathology Nov 2020The molecular and clinical characteristics of non-ampullary duodenal adenomas and intramucosal adenocarcinomas are not fully understood because they are rare. To clarify...
The molecular and clinical characteristics of non-ampullary duodenal adenomas and intramucosal adenocarcinomas are not fully understood because they are rare. To clarify these characteristics, we performed genetic and epigenetic analysis of cancer-related genes in these lesions. One hundred and seven non-ampullary duodenal adenomas and intramucosal adenocarcinomas, including 100 small intestinal-type tumors (90 adenomas and 10 intramucosal adenocarcinomas) and 7 gastric-type tumors (2 pyloric gland adenomas and 5 intramucosal adenocarcinomas), were investigated. Using bisulfite pyrosequencing, we assessed the methylation status of CpG island methylator phenotype (CIMP) markers and MLH1. Then using next-generation sequencing, we performed targeted exome sequence analysis within 75 cancer-related genes in 102 lesions. There were significant differences in the clinicopathological and molecular variables between small intestinal- and gastric-type tumors, which suggests the presence of at least two separate carcinogenic pathways in non-ampullary duodenal adenocarcinomas. The prevalence of CIMP-positive lesions was higher in intramucosal adenocarcinomas than in adenomas. Thus, concurrent hypermethylation of multiple CpG islands is likely associated with development of non-ampullary duodenal intramucosal adenocarcinomas. Mutation analysis showed that APC was the most frequently mutated gene in these lesions (56/102; 55%), followed by KRAS (13/102; 13%), LRP1B (10/102; 10%), GNAS (8/102; 8%), ERBB3 (7/102; 7%), and RNF43 (6/102; 6%). Additionally, the high prevalence of diffuse or focal nuclear β-catenin accumulation (87/102; 85%) as well as mutations of WNT pathway components (60/102; 59%) indicates the importance of WNT signaling to the initiation of duodenal adenomas. The higher than previously reported frequency of APC gene mutations in small bowel adenocarcinomas as well as the difference in the APC mutation distributions between small intestinal-type adenomas and intramucosal adenocarcinomas may indicate that the adenoma-carcinoma sequence has only limited involvement in duodenal carcinogenesis. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Adenocarcinoma; Adenoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinogenesis; DNA Copy Number Variations; DNA Methylation; Duodenal Neoplasms; Duodenum; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; High-Throughput Nucleotide Sequencing; Humans; Intestinal Mucosa; Male; Middle Aged; Mutation
PubMed: 32770675
DOI: 10.1002/path.5529