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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 -
The British Journal of Surgery Jun 2017Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periampullary cancers are uncommon malignancies, often amenable to surgery. Several studies have suggested a role for adjuvant chemotherapy and chemoradiotherapy in improving survival of patients with periampullary cancers, with variable results. The aim of this meta-analysis was to determine the survival benefit of adjuvant therapy for periampullary cancers.
METHODS
A systematic review was undertaken of literature published between 1 January 2000 and 31 December 2015 to elicit and analyse the pooled overall survival associated with the use of either adjuvant chemotherapy or chemoradiotherapy versus observation in the treatment of surgically resected periampullary cancer. Included articles were also screened for information regarding stage, prognostic factors and toxicity-related events.
RESULTS
A total of 704 titles were screened, of which 93 full-text articles were retrieved. Fourteen full-text articles were included in the study, six of which were RCTs. A total of 1671 patients (904 in the control group and 767 who received adjuvant therapy) were included. The median 5-year overall survival rate was 37·5 per cent in the control group, compared with 40·0 per cent in the adjuvant group (hazard ratio 1·08, 95 per cent c.i. 0·91 to 1·28; P = 0·067). In 32·2 per cent of patients who had adjuvant therapy, one or more WHO grade 3 or 4 toxicity-related events were noted. Advanced T category was associated worse survival (regression coefficient -0·14, P = 0·040), whereas nodal status and grade of differentiation were not.
CONCLUSION
This systematic review found no associated survival benefit for adjuvant chemotherapy or chemoradiotherapy in the treatment of periampullary cancer.
Topics: Adenocarcinoma; Ampulla of Vater; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Common Bile Duct Neoplasms; Duodenal Neoplasms; Humans; Survival Rate
PubMed: 28518410
DOI: 10.1002/bjs.10563 -
Journal of Comparative Pathology Nov 2021An 11-year-old male common marmoset (Callithrix jacchus) presented with chronic, progressive weight loss and diarrhoea. Response to treatment with nutritional...
An 11-year-old male common marmoset (Callithrix jacchus) presented with chronic, progressive weight loss and diarrhoea. Response to treatment with nutritional supplementation, antibiotics and immunosuppressants was modest and transient, and the animal was humanely euthanized. At necropsy, the proximal 8 cm of small intestine was diffusely pale with transmural thickening. The lungs contained coalescing tan, firm nodules measuring up to 4 mm in diameter. Histological examination revealed infiltrative mucinous adenocarcinoma of the duodenum with extensive metastases to the lungs, liver and left parapatellar adipose tissue. The mucinous matrix secreted by the primary and metastatic lesions was strongly periodic acid-Schiff positive. Warthin Starry staining for spirochaetes was negative. Pancytokeratin expression was attenuated in the primary tumour as well as in the metastases, which correlated to a poorly differentiated phenotype. To the authors' knowledge, this is the first report of a proximal duodenal adenocarcinoma with extensive metastatic disease in a common marmoset.
Topics: Adenocarcinoma; Animals; Callithrix; Duodenal Neoplasms; Liver; Lung; Male
PubMed: 34886977
DOI: 10.1016/j.jcpa.2021.09.002 -
MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma.Modern Pathology : An Official Journal... Dec 2012MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue...
MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P=2.06 × 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from non-neoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic and ampullary adenocarcinomas from chronic pancreatitis and normal pancreas with high sensitivity and accuracy. Ongoing prospective studies will evaluate if these microRNA profiles are useful on fine-needle biopsies for early diagnosis of pancreatic cancer.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Chronic Disease; Common Bile Duct Neoplasms; Female; Formaldehyde; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Middle Aged; Neoplasm Staging; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis; Paraffin Embedding; Reproducibility of Results
PubMed: 22878649
DOI: 10.1038/modpathol.2012.122 -
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 -
Annals of Surgical Oncology Dec 2017The prognostic impact of pathologic response to preoperative therapy on patients with duodenal adenocarcinoma (DA) and ampullary adenocarcinoma (AMPA) has not been...
BACKGROUND
The prognostic impact of pathologic response to preoperative therapy on patients with duodenal adenocarcinoma (DA) and ampullary adenocarcinoma (AMPA) has not been established.
METHODS
A retrospective review of 266 patients who underwent curative resection for DA (n = 97) or AMPA (n = 169) during 1993-2015 was performed. For patients who underwent preoperative therapy, the pathologic response was systematically evaluated and classified as major (0-49% of viable residual tumor cells) or minor (≥ 50% of viable residual tumor cells). Uni- and multivariable analyses were performed to identify predictors of pathologic response and disease-specific survival (DSS).
RESULTS
For the 79 patients treated with preoperative therapy (DA: n = 34; AMPA: n = 45), concomitant use of radiation (80%, 67/79) was the sole independent predictor of major pathologic response (odds ratio [OR] 8.17; 95% confidence interval [CI] 1.85-58.2; P = 0.005). The patients with major pathologic response had a better 5-year DSS rate than the patients with minor pathologic response (DA: 65 vs 25%; P = 0.028; AMPA: 85 vs 43%; P = 0.016). In the multivariable analysis of DSS for the 79 patients who underwent preoperative therapy, major pathologic response was the sole predictor of improved DSS (hazard ratio [HR] 2.88; 95% CI 1.41-5.98; P = 0.004). In the multivariable analysis of DSS for the entire cohort, pathologic stage 2 or lower was the sole predictor of better DSS.
CONCLUSION
The major pathologic response to preoperative therapy predicted improved DSS after resection of DA and AMPA and might represent a new prognosticator after resection of DA and AMPA.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Common Bile Duct Neoplasms; Duodenal Neoplasms; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Preoperative Care; Prognosis; Retrospective Studies; Survival Rate
PubMed: 28980211
DOI: 10.1245/s10434-017-6098-6 -
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 -
International Journal of Clinical and... 2013We investigated a series of pancreaticoduodenectomy and duodenal biopsies with a panel of immunohistochemical markers to identify duodenal mucosal invasion by pancreatic...
BACKGROUND
We investigated a series of pancreaticoduodenectomy and duodenal biopsies with a panel of immunohistochemical markers to identify duodenal mucosal invasion by pancreatic ductal adenocarcinoma (PDAC), including markers of poor prognosis and targets of promising novel immunotherapies.
MATERIALS AND METHODS
Eighteen consecutive pancreaticoduodenectomy specimens with duodenal mucosal invasion by PDAC were examined for expression of MUC1, MUC4, MUC5AC, MUC6, mesothelin, MUC2, CDX2, and DPC4 on formalin-fixed, paraffin-embedded sections of duodenal-ampullary-pancreatic junctions. Expression of all but MUC6 was also assessed in duodenal biopsies from 12 patients with duodenal mucosal invasion by PDAC.
RESULTS
The duodenal mucosa expressed MUC1 (crypts), MUC2 (goblet cells), MUC6 (Brunner glands), CDX2, and DPC4. PDACs in the duodenal mucosa from the resection (n=16-18) and biopsy (n=12) specimens were marked as follows: MUC1 100% (30/30), MUC4 83% (24/29), MUC5AC 83% (25/30), mesothelin 82% (23/28), MUC2 7% (2/30), and CDX2 36% (10/28). Loss of DPC4 expression was seen in 16 of 29 (55%) cases. Reactive mucosa adjacent to PDAC expressed MUC4, MUC5AC and mesothelin in 65% (17/26), 19% (5/27), and 19% (5/26) of cases, respectively. While MUC5AC and mesothelin had high diagnostic accuracy for detection of PDAC, MUC2, CDX2 and DPC4 expression demonstrated negative correlation with PDAC, with absent expression being highly specific for PDAC.
CONCLUSION
Immunohistochemical labeling for PDAC biomarkers may aid the diagnosis of PDAC in duodenal biopsy, especially in situations where diagnosis of a pancreatic mass is challenging.
Topics: Biomarkers, Tumor; Biopsy; Carcinoma, Pancreatic Ductal; Duodenum; Humans; Immunohistochemistry; Intestinal Mucosa; Neoplasm Invasiveness; Pancreatic Neoplasms; Pancreaticoduodenectomy; Predictive Value of Tests; Prognosis
PubMed: 24228110
DOI: No ID Found -
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 -
BJS Open Sep 2023The prevalence of different periampullary cancers (pancreatic ductal adenocarcinoma, distal cholangiocarcinoma, ampullary cancer and duodenal cancer) is heterogeneous in...
BACKGROUND
The prevalence of different periampullary cancers (pancreatic ductal adenocarcinoma, distal cholangiocarcinoma, ampullary cancer and duodenal cancer) is heterogeneous in the literature. During the 2010s, a standardized histopathological protocol for pancreatoduodenectomy specimens based on axial slicing was adopted in Sweden. The present study sought to provide information about periampullary cancers with regard to tumour types in curative and noncurative settings, preoperative diagnostic accuracy and the impact of a standardized evaluation of the surgical specimen on diagnosis, R status and lymph node assessment.
METHODS
Data from patients diagnosed with periampullary cancer from 2010 to 2019 were retrieved from the Swedish National Registry for Pancreatic and Periampullary Cancer.
RESULTS
Among non-curative patients, 3704 (83.6 per cent) were diagnosed with pancreatic ductal adenocarcinoma. Among patients treated with pancreatoduodenectomy, diagnosis was pancreatic ductal adenocarcinoma in 1380 (50.0 per cent), distal cholangiocarcinoma in 284 (10.3 per cent), ampullary cancer in 376 (13.6 per cent), duodenal cancer in 160 (5.8 per cent) and other diagnoses in 560 (20.3 per cent) patients. The preoperative diagnosis corresponded to the postoperative in 1177 (67.5 per cent) patients for pancreatic ductal adenocarcinoma, 162 (37.4 per cent) patients for distal cholangiocarcinoma, 220 (61.3 per cent) patients for ampullary cancer and 120 (53.6 per cent) patients for duodenal cancer. A higher rate of pancreatic ductal adenocarcinoma was seen in surgical specimens who underwent standardized evaluation, from 56.8 per cent to 64.3 per cent (P = 0.003). After standardization, higher rates of R1 resection (31.7 per cent versus 44.6 per cent, P < 0.001) and N1 stage (62.1 per cent versus 77.0 per cent, P < 0.001) were found.
CONCLUSION
The proportion of pancreatic ductal adenocarcinoma was higher in patients in a non-curative setting compared with patients who underwent surgery. The rate of misdiagnosis for periampullary cancers was confirmed to be high. Thus, it should be taken into account when preoperative oncological treatment is considered. Standardized evaluation of the surgical specimen has increased pancreatic ductal adenocarcinoma, R1 and N1 rates.
Topics: Humans; Ampulla of Vater; Duodenal Neoplasms; Cohort Studies; Adenocarcinoma; Common Bile Duct Neoplasms; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Cholangiocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 37864577
DOI: 10.1093/bjsopen/zrad104