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The American Journal of Surgical... Jun 2024The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from...
The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3 cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an "ampullary-duodenal tumor," with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2 cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in ≤1 cm IAPNs). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41 months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P=0.047). Unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the "ampullary-ductal" carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma).
PubMed: 38938087
DOI: 10.1097/PAS.0000000000002275 -
International Journal of Molecular... Jun 2024A family of bifunctional dihetarylmethanes and dibenzoxanthenes is assembled via a reaction of acetals containing a 2-chloroacetamide moiety with phenols and related...
A family of bifunctional dihetarylmethanes and dibenzoxanthenes is assembled via a reaction of acetals containing a 2-chloroacetamide moiety with phenols and related oxygen-containing heterocycles. These compounds demonstrated selective antitumor activity associated with the induction of cell apoptosis and inhibition of the process of glycolysis. In particular, bis(heteroaryl)methane containing two 4-hydroxy-6-methyl-2-pyran-2-one moieties combine excellent in vitro antitumor efficacy with an IC of 1.7 µM in HuTu-80 human duodenal adenocarcinoma models with a high selectivity index of 73. Overall, this work highlights the therapeutic potential of dimeric compounds assembled from functionalized acetals and builds a starting point for the development of a new family of anticancer agents.
Topics: Humans; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Methane; Cell Proliferation; Xanthenes
PubMed: 38928428
DOI: 10.3390/ijms25126724 -
Pathology Jun 2024Hepatocyte nuclear factors (HNF) 6 and 4α are master transcriptional regulators of development and maintenance of the liver and pancreaticobiliary tract in mice and...
HNF6 and HNF4α expression in adenocarcinomas of the liver, pancreaticobiliary tract, and gastrointestinal tract: an immunohistochemical study of 480 adenocarcinomas of the digestive system.
Hepatocyte nuclear factors (HNF) 6 and 4α are master transcriptional regulators of development and maintenance of the liver and pancreaticobiliary tract in mice and humans. However, little is known about the prevalence of HNF6 and HNF4α expression in carcinomas of the hepatobiliary tract and pancreas. We aimed to reveal the diagnostic utility of HNF6 and HNF4α immunolabelling in adenocarcinomas of these organs. We investigated HNF6 and HNF4α expression by immunohistochemistry using a total of 480 adenocarcinomas of the digestive system, including 282 of the hepatobiliary tract and pancreas and 198 of the gastrointestinal tract. HNF6 expression was primarily restricted to intrahepatic cholangiocarcinomas (CCs) (63%, n=80) and gallbladder adenocarcinomas (43%, n=88), among others. Notably, small duct intrahepatic CCs almost invariably expressed HNF6 (90%, n=42), showing stark contrast to a low prevalence in large duct intrahepatic CCs (10%, n=21; p<0.0001). HNF6 expression was infrequent in extrahepatic CCs (9%, n=55) and pancreatic ductal adenocarcinomas (7%, n=58), and it was rare in adenocarcinomas of the gastrointestinal tract [oesophagus/oesophagogastric junction (EGJ) (2%, n=45), stomach (2%, n=86), duodenum (0%, n=25), and colorectum (0%, n=42)]. In contrast, HNF4α was widely expressed among adenocarcinomas of the digestive system, including intrahepatic CCs (88%), extrahepatic CCs (94%), adenocarcinomas of the gallbladder (98%), pancreas (98%), oesophagus/EGJ (96%), stomach (98%), duodenum (80%), and colorectum (100%). HNF6 was frequently expressed in and almost restricted to intrahepatic CCs of small duct type and gallbladder adenocarcinomas, while HNF4α was expressed throughout adenocarcinomas of the digestive system. HNF6 immunolabelling may be useful in distinguishing small duct intrahepatic CCs from other types of CC as well as metastatic gastrointestinal adenocarcinomas.
PubMed: 38926048
DOI: 10.1016/j.pathol.2024.03.010 -
Cureus May 2024Periampullary cancers, which include pancreatic adenocarcinoma, ampullary cancer, distal cholangiocarcinoma, and duodenal cancer, present diagnostic and management...
Periampullary cancers, which include pancreatic adenocarcinoma, ampullary cancer, distal cholangiocarcinoma, and duodenal cancer, present diagnostic and management challenges due to their aggressive nature and nonspecific symptoms. We describe a case of a female patient, age 20, who had obstructive jaundice brought on by a periampullary tumor. Despite difficulties in diagnosis and treatment, including failed endoscopic retrograde cholangiopancreatography (ERCP), the patient underwent a successful pancreaticoduodenectomy (Whipple's resection), and subsequent immunohistochemistry revealed adenocarcinoma with a mixed immunophenotype expressing duodenal and pancreatic markers. This example emphasizes the significance of taking young patients' periampullary tumors into account, the difficulties in diagnosing them, and the possibility of effective surgical surgery throughout this age range.
PubMed: 38915985
DOI: 10.7759/cureus.61013 -
Cureus May 2024Background Gastric adenocarcinoma (GCA) poses a significant global health burden due to its prevalence and high morbidity and mortality rates. GCA is classified into...
Background Gastric adenocarcinoma (GCA) poses a significant global health burden due to its prevalence and high morbidity and mortality rates. GCA is classified into three main histological types: well-differentiated (intestinal type), poorly differentiated (diffuse type), and mixed or indeterminate forms. These types vary in causes, epidemiology, and genetics, with the diffuse type often associated with the worst prognosis. Endoscopic biopsy is the primary method for characterization, but it has its limitations. There is potential in using contrast-enhanced computed tomography (CT) to differentiate between histological subtypes of gastric adenocarcinoma, which could aid subtype differentiation. Building on this, our study aims to assess CT's effectiveness in distinguishing between broad histological groups of gastric adenocarcinoma based on enhancement patterns, contributing to improved diagnostic accuracy Objective Our research focuses on evaluating the effectiveness of multiphasic contrast-enhanced computed tomography (CECT) in distinguishing between the three broad histopathological subtypes of gastrointestinal cancers. Methods This study was a prospective, analytical observational study that was approved and carried out in our institutional tertiary care hospital. Consecutive individuals who had undergone endoscopic-guided biopsy and demonstrated histological evidence of GCA were taken into consideration for participation in the study. In order to complete the clinical staging process, further multiphasic CT scans were carried out on each of the fifty patients and were categorised accordingly based on the findings of histopathology. Results In the differentiated type, segmental distribution was: 5.5% upper segment, 16.7% middle segment, 66.7% lower segment, and 11.1% diffuse type. Esophageal involvement was 5.6%, duodenal involvement was similar, and lymph node involvement was approximately 38.8%. TNM staging: 38.8% IIIB, 22.2% III, 27.8% IVA, and 11.1% IVB. In the undifferentiated type, segmental distribution: 6.2% upper segment, 31.2% middle segment, 50.0% lower segment, and 12.5% diffuse type. Esophageal involvement was around 6.25%, duodenal involvement was 18.75%, and lymph node involvement was about 71.8%. TNM staging: 34.4% IIIB, 21.8% III, 28.1% IVA, and 15.6% IVB. Conclusion Multiphasic CT evaluations provide valuable insights into the prognostic aspects of gastric carcinomas by assessing peak enhancement. Differentiated tumors typically exhibit arterial phase enhancement, while undifferentiated tumors show venous phase enhancement, reflecting their microvascular architecture. Recent studies emphasize the importance of understanding gastric carcinoma characteristics for diagnosis and prognosis. Our research aligns with this, revealing distinct contrast enhancement patterns between differentiated and undifferentiated types. However, discrepancies in histological classifications and contrast enhancement patterns across studies warrant further investigation. Integrating histopathological and radiological insights is essential for accurate diagnosis and treatment planning.
PubMed: 38910671
DOI: 10.7759/cureus.60841 -
European Radiology Jun 2024To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the...
OBJECTIVES
To assess 3-Tesla (3-T) ultra-small superparamagnetic iron oxide (USPIO)-enhanced MRI in detecting lymph node (LN) metastases for resectable adenocarcinomas of the pancreas, duodenum, or periampullary region in a node-to-node validation against histopathology.
METHODS
Twenty-seven consecutive patients with a resectable pancreatic, duodenal, or periampullary adenocarcinoma were enrolled in this prospective single expert centre study. Ferumoxtran-10-enhanced 3-T MRI was performed pre-surgery. LNs found on MRI were scored for suspicion of metastasis by two expert radiologists using a dedicated scoring system. Node-to-node matching from in vivo MRI to histopathology was performed using a post-operative ex vivo 7-T MRI of the resection specimen. Sensitivity and specificity were calculated using crosstabs.
RESULTS
Eighteen out of 27 patients (median age 65 years, 11 men) were included in the final analysis (pre-surgery withdrawal n = 4, not resected because of unexpected metastases peroperatively n = 2, and excluded because of inadequate contrast-agent uptake n = 3). On MRI 453 LNs with a median size of 4.0 mm were detected, of which 58 (13%) were classified as suspicious. At histopathology 385 LNs with a median size of 5.0 mm were found, of which 45 (12%) were metastatic. For 55 LNs node-to-node matching was possible. Analysis of these 55 matched LNs, resulted in a sensitivity and specificity of 83% (95% CI: 36-100%) and 92% (95% CI: 80-98%), respectively.
CONCLUSION
USPIO-enhanced MRI is a promising technique to preoperatively detect and localise LN metastases in patients with pancreatic, duodenal, or periampullary adenocarcinoma.
CLINICAL RELEVANCE STATEMENT
Detection of (distant) LN metastases with USPIO-enhanced MRI could be used to determine a personalised treatment strategy that could involve neoadjuvant or palliative chemotherapy, guided resection of distant LNs, or targeted radiotherapy.
REGISTRATION
The study was registered on clinicaltrials.gov NCT04311047. https://clinicaltrials.gov/ct2/show/NCT04311047?term=lymph+node&cond=Pancreatic+Cancer&cntry=NL&draw=2&rank=1 .
KEY POINTS
LN metastases of pancreatic, duodenal, or periampullary adenocarcinoma cannot be reliably detected with current imaging. This technique detected LN metastases with a sensitivity and specificity of 83% and 92%, respectively. MRI with ferumoxtran-10 is a promising technique to improve preoperative staging in these cancers.
PubMed: 38907886
DOI: 10.1007/s00330-024-10838-w -
Annals of Surgical Oncology Jun 2024Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal...
BACKGROUND
Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior.
METHODS
This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC.
RESULTS
Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size.
CONCLUSIONS
Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.
PubMed: 38888860
DOI: 10.1245/s10434-024-15555-8 -
Langenbeck's Archives of Surgery Jun 2024Middle segment-preserving pancreatectomy (MSPP) is a relatively new parenchymal-sparing surgery that has been introduced as an alternative to total pancreatectomy (TP)... (Review)
Review
PURPOSE
Middle segment-preserving pancreatectomy (MSPP) is a relatively new parenchymal-sparing surgery that has been introduced as an alternative to total pancreatectomy (TP) for multicentric benign and borderline pancreatic diseases. To date, only 36 cases have been reported in English.
METHODS
We reviewed 22 published articles on MSPP and reported an additional case.
RESULTS
Our patient was a 49-year-old Japanese man diagnosed with Zollinger-Elison syndrome (ZES) caused by duodenal and pancreatic gastrinoma associated with multiple endocrine neoplasia syndrome type 1. We avoided TP and chose MSPP as the operative technique due to his relatively young age. The patient developed a grade B postoperative pancreatic fistula (POPF), which improved with conservative treatment. He was discharged without further treatment. To date, no tumor has recurred, and pancreatic function seems to be maintained. According to a literature review, the morbidity rate of MSPP is as high as 54%, mainly due to the high incidence of POPF (32%). In contrast, there was no perioperative mortality, and postoperative pancreatic function was comparable to that after conventional pancreatectomy.
CONCLUSIONS
Despite the high incidence of POPF, MSPP appears to be safe, with low perioperative mortality and good postoperative pancreatic sufficiency.
Topics: Humans; Pancreatectomy; Male; Middle Aged; Pancreatic Neoplasms; Zollinger-Ellison Syndrome; Gastrinoma; Postoperative Complications; Organ Sparing Treatments; Multiple Endocrine Neoplasia Type 1
PubMed: 38847851
DOI: 10.1007/s00423-024-03370-4 -
South African Journal of Surgery.... May 2024The value of the textbook outcome in pancreatic surgery (TOPS) score, a composite measure of surgical performance for quality assurance, was evaluated in a South African...
BACKGROUND
The value of the textbook outcome in pancreatic surgery (TOPS) score, a composite measure of surgical performance for quality assurance, was evaluated in a South African tertiary hospital cohort of pancreaticoduodenectomies (PD) performed for adenocarcinoma of the ampulla of Vater (AAV).
METHODS
A review of all patients undergoing a PD for AAV at a single centre between January 1999 and December 2023 was performed. Demographic, operative, pathological and postoperative variables were recorded. Ten clinical and histological variables were used to construct a TOPS score. These included an R0 resection, no postoperative pancreatic fistula (POPF), no bile leak, no post-pancreatectomy haemorrhage, no delayed gastric emptying, no major postoperative complications (< Gr 3 Clavien-Dindo), no readmission to ICU, length of stay ≤ 10 days, no 30-day readmission or intervention and no 30-day mortality. A textbook outcome (TO) was defined as the fulfilment of all 10 variables. In patients in whom TO was not achieved, the reasons for failure were identified. In addition, the number of patients who had major complications and died were categorised as failure to rescue (FTR).
RESULTS
A positive TOPS score was achieved in 27 of 79 (34.2%) patients undergoing a PD. Overall five-year survival after PD was 33.9%. TOPS conferred a significant 1-year survival benefit, 88.9% vs 66.7% (OR 4.12, 95% CI 1.08-15.67, = 0.038). There was no significant difference in 5-year survival between TOPS and non-TOPS patients, 40.0% vs 32.4% (OR 1.39, 95% CI 0.48-3.99, = 0.54). A POPF occurred in 31.6% patients, resulting in a significantly longer hospital admission, 17 vs 10 days (95% CI 2.66-11.34, = 0.0019). Twenty-one (26.6%) patients developed a major complication, five of whom died (FTR = 6.3%).
CONCLUSION
This study confirmed the value of TOPS as a useful measurement to assess hospital quality metrics and short-term survival after PD for AAV. One quarter of patients developed a major complication with a 6.3% FTR.
Topics: Humans; Pancreaticoduodenectomy; Ampulla of Vater; Male; Female; Common Bile Duct Neoplasms; Middle Aged; Adenocarcinoma; Aged; Retrospective Studies; Prognosis; Postoperative Complications; South Africa; Adult; Treatment Outcome
PubMed: 38838117
DOI: No ID Found -
Journal of Surgical Case Reports Jun 2024Ampulla of Vater (AOV) is typically located in the second part of the duodenum. There are few reported cases of ectopic AOV over the line extending from the pylorus of...
Ampulla of Vater (AOV) is typically located in the second part of the duodenum. There are few reported cases of ectopic AOV over the line extending from the pylorus of the stomach down to the distal part of the duodenum. However, to the best of our knowledge, there are only five cases reported in the English literature of an ectopic AOV in the fourth part of the duodenum, with only one of them having adenocarcinoma of the ampulla. Hereby, we report the first case of ectopic AOV in the fourth part of the duodenum, presenting with obstructive due to adenocarcinoma with focal squamous differentiation. This is the case a 42-year-old lady who had a sleeve gastrectomy for morbid obesity in the past. She presented with right upper quadrant pain for one month associated with subjective fever, unintentional weight loss, pale stool, and dark urine. The physical examination revealed a deeply jaundiced lady with an unremarkable abdominal exam. A computed tomography scan of the abdomen revealed intrahepatic and extrahepatic biliary dilation with ectopic insertion of the distal CBD into the fourth part of the duodenum with no evidence of biliary stones. She underwent pancreaticoduodenectomy after difficult biliary decompression. Histopathological diagnosis was moderately differentiated adenocarcinoma, pancreaticobiliary type with focal squamous differentiation. Ectopic AOV is a very rare entity, especially when it is associated with adenosquamous carcinoma changes.
PubMed: 38832061
DOI: 10.1093/jscr/rjae377