Duodenal Adenocarcinoma Research Articles

Inverted nonampullary duodenal adenocarcinoma treated with underwater EMR

Inverted nonampullary duodenal adenocarcinoma treated with underwater EMR

Stage I duodenal adenocarcinoma cured by a short treatment cycle of pembrolizumab: a case report

Abstract Objectives The use of Immune checkpoint inhibitor (ICI) therapy (pembrolizumab) in duodenal cancer is rarely reported, and ICI therapy are mostly used in advanced-stage cancer according to its current indication. The case report aimed to demonstrate the special role of ICI therapy in early-stage duodenal cancer and discuss the possibility of modifying and broadening the indication of ICI therapy. Case presentation A female in her 70s were diagnosed early-stage tubular adenocarcinoma with immunohistochemistry showing deficiency in DNA mismatch repair (dMMR)/high microsatellite instability (MSI-H). Pembrolizumab was selected and the patient was treated regularly for 2 standard cycles. 5 months after the second cycle, the lesion showed no significant change, while 31 months after, the original lesion achieved almost complete remission. Conclusions ICI therapy may have unexpected effect on early-stage duodenal cancer and more specific indication of ICI treatment may be established.

S4059 Primary Duodenal Adenocarcinoma Manifesting as Gastric Outlet Obstruction

S4059 Primary Duodenal Adenocarcinoma Manifesting as Gastric Outlet Obstruction

S4063 Sometimes it's Not Cannabis Hyperemesis Syndrome: A Case of Duodenal Adenocarcinoma in a 48-Year-Old Female

S4063 Sometimes it's Not Cannabis Hyperemesis Syndrome: A Case of Duodenal Adenocarcinoma in a 48-Year-Old Female

Endoscopic Ultrasonography-Guided Biliary Drainage: Experience of a Moroccan Center

Background: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is a relatively new therapeutic modality in the arsenal of endoscopists for attaining satisfactory biliary drainage when traditional ERC fails. The aim of our study is to describe the first Moroccan experience with EUS-BD in patients with malignant biliary obstruction after a failed or inaccessible ERCP. Methods: This is a retrospective study conducted at Ibn Sina Hospital, from Mars 2018 to July 2022, which include 27 patients with an inoperable or metastatic malignant biliary obstruction who underwent endoscopic ultrasonography-guided biliary drainage (EUS-BD) in case of endoscopic retrograde cholangiopancreatography (ERCP) failure. Results: From a total of 288 patients with malignant biliary obstruction,27 underwent EUS-BD (9,3%), 15 EUS-guided hepaticogastrostomy (55,5%) and 12 EUS-guided choledocoduodenostomy (44,4%) were performed. The mean age was 62.5 years (age range: 23-74 years), a male predominance of 59% was noted, cholestatic jaundice was present in 100% of patients and associated with pruritus in 92.59% of cases. The mean level of Total Bilirubin was 190 mg/l. The causes of biliary obstruction were: an inoperable pancreatic head mass in 13 patients(48,1%), a cholangiocarcinoma in 7 patients (25.9%), an ampullary mass in 4 patients(14,8%), a gallbladder cancer with hepatic and duodenal invasion in one patient (3,7%), a gastric antropyloric adenocarcinoma with pancreatic head invasion in one patient (3,7%) and Duodenal adenocarcinoma in one patient (3,7%).The leading causes of failed ERCP were secondary to tumor infiltration of the duodenal wall and critical duodenal stenosis in 11 cases (40,7%), in 9 cases due to a difficult cannulation (33.3%) and in 7 cases due to a failure to pass the stricture by ERCP (25.9%). In EUS-HG The technical and the clinical success rates were 86.6% (13/15) and 84.6% (11/13), respectively, the complication rate was 13.3% (2/15) including one case of stent migration complicated with bile leak and one case of cholangitis. In EUS-CD The technical and the clinical success rates were 91.6% (11/12) and 81.8% (9/11)), respectively, the complication rate was 16.6% (2/12) including two cases of cholangitis. The technical and the clinical success rates in all EUS-BD were 85.1% (24/27) and 83.3% (20/24), respectively. The complication rate was 14.8% (4/27). Conclusion: EUS-BD appears to be an effective and safe therapeutic option for biliary decompression in cases where ERCP fails.

SP2.2 Time to Pancreaticoduodenectomy in a Regional Hepatobiliary Unit in the COVID recovery era

Abstract Aims To assess factors influencing time from multidisciplinary (MDT) discussion to surgery for patients undergoing Whipple’s resection for malignant disease in a regional HPB unit. Methods Patients who underwent Whipple’s resection for cholangiocarcinoma, ampullary, duodenal and pancreatic ductal adenocarcinoma between 01/02/2021–29/11/2022 were identified from a prospectively maintained operative database. The NI Electronic Care Record was used to collect data. Results 74 patients met the inclusion criteria. 83.8% (62/74) presented as an inpatient, compared to 74% in 2020. Patients presenting as an inpatient had a significantly shorter time to surgery than those presenting as outpatients (84.7vs152.8 days, p=0.03). The average time from MDT to surgery without neoadjuvant therapy was 57 days. 20.3% (15/74) had neoadjuvant treatment with an average time to surgery of 248 days. This has increased since 2020 from 38 and 212 days respectively, however this was not statistically significant (p=0.051). 54.1% (40/74) had staging PET-CT compared to 26% of patients in 2020. Time to surgery with a PET-CT was not significantly different to those who had no PET-CT (107vs81.9 days, p=0.18). 13 patients (17.6%) had both ERCP and EUS. 52 patients (70.2%) had either EUS or ERCP. There is a significant difference in time to surgery for patients undergoing both EUS and ERCP compared to those undergoing one endoscopic procedure (224vs65.9 days, p=0.001). Conclusions Use of staging PET-CT and overall time to surgery has increased since 2020 however, this was not statistically significant. Presenting as an outpatient and undergoing both ERCP and EUS were two factors identified that lead to significant delays to surgery.

An autopsy case of alpha-fetoprotein-producing large duodenal adenocarcinoma.

We report an autopsy case of a large duodenal adenocarcinoma that produced alpha-fetoprotein (AFP). The patient was a man in his 70s with diabetes mellitus. He presented with epigastralgia and was referred to our hospital. Upper gastrointestinal endoscopy and abdominal computed tomography revealed a large tumor of 11cm in diameter in the descending limb of the duodenum. A tumor biopsy showed poorly differentiated adenocarcinoma. Although his carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels were within the normal range, his AFP levels were significantly elevated (42,078.4ng/mL). Due to vascular invasion, curative resection was not feasible, and chemotherapy was chosen as the treatment option. After gastrojejunostomy was performed to enable oral intake, one cycle of modified leucovorin/5-fluorouracil/oxaliplatin (mFOLFOX6) therapy was administered. However, it proved ineffective, and the patient's anorexia gradually worsened. Ultimately, he succumbed to the progression of cancer cachexia. Autopsy findings revealed a 14-cm-long duodenal carcinoma primarily located in the duodenal bulb, with direct invasion into the stomach, pancreas, and liver. A pathological examination confirmed a diagnosis of poorly differentiated adenocarcinoma with AFP production. Duodenal cancer is rare, and AFP-producing duodenal cancer is even rarer, with only 21 reported cases, including our own. We present this autopsy case of AFP-producing duodenal adenocarcinoma and review the cases reported in the relevant literature.

Duodenal Adenocarcinoma: 4 Cases Report

Duodenal adenocarcinoma being the most common tumor of the small intestine: 33 to 48%, it remains very rare representing only 0.5% of malignant tumors of the digestive tract. Our retrospective study focused on four cases during the period 2017-2022 with an average age of 53.25 years and a sex ratio of 1M/3F. The clinical signs were varied with a predominance of cholestatic jaundice and a deterioration in general condition. The diagnosis was confirmed thanks to the endoscopy and the anatomopathological study of the biopsies carried out in all our patients. All our patients benefited from a surgical treatment, curative or palliative, which consisted of three cephalic pancreaticoduodenectomy and in one case a gastro-jejunal anastomosis. The post-operative follow-up was simple in two patients, one of our patients presented with gastroparesis which progressed well under medical treatment. In addition, we deplore a death which presented a hemoperitoneum related to a hemostasis disorder.

Antitumor Effect of Galectin-9 on Cell Proliferation and Tumor Growth of Human Duodenal Adenocarcinoma Cells.

Galectin-9 (Gal-9) induces tumor cell apoptosis in lymphoma and other malignant cell types. Duodenal adenocarcinoma is a rare malignancy, and there are insufficient data to determine a standard therapeutic approach. Here, we investigated the antitumor effect of Gal-9 in HuTu-80 duodenal adenocarcinoma cells. Cell proliferation was examined in HuTu-80 cells using a Cell Counting Kit-8 assay. Cell cycle analysis, apoptosis array, and microRNA expression analysis were performed to identify the effect of Gal-9 on HuTu-80 cells. The antitumor effect of Gal-9 was also examined using xenograft mouse models. Gal-9 suppressed the proliferation of HuTu-80 via blockade of the G0 to G1 cell cycle transition. This blockade was accompanied by a strong decrease in cyclin D1 and phosphorylated Rb, suggesting a G1 arrest. Additionally, Gal-9 induced apoptosis, and the expression of cleaved caspase-3 was increased in Gal-9-treated HuTu-80 cells according to the apoptosis array. MiRNA microarrays revealed that Gal-9 altered the expression of miRNAs in HuTu-80 cells. These data demonstrate the therapeutic potential of Gal-9 and provide molecular mechanistic insights into its antitumor effect in HuTu-80 cells.

A pathological complete response after immunotherapy with pembrolizumab for distal duodenal adenocarcinoma caused by Lynch syndrome: a case report.

Primary adenocarcinoma of the duodenum is a rare neoplasm that is often microsatellite instability-high (MSI-H). Pembrolizumab, a monoclonal antibody, has been recently approved in Japan for treatment of MSI-H solid tumors. Lynch syndrome is a frequent hereditary cancer predisposition syndrome. It is linked to an increased risk of various types of cancer, including colorectal and endometrial cancer, and is closely related to MSI-H. We present the case of a 55-year-old woman who was diagnosed with duodenal cancer. Biopsy findings revealed MSI-H, and pembrolizumab therapy was initiated because the tumor was in contact with the left renal vein and had metastasized to the mesenteric lymph nodes of the small intestine. Subsequently, after completing two courses of pembrolizumab therapy, the patient developed duodenal stenosis and underwent surgery. Pathological analysis of the resected specimen revealed no evidence of malignancy. Given the patient's previous cancer history and the occurrence of cancer in close relatives, genetic testing of peripheral blood was performed, which revealed the diagnosis of Lynch syndrome. Furthermore, the variant responsible for Lynch syndrome was found to be a mutation of NM_000251.3:c.211 + 1G > C in MSH2.

Computed Tomography Imaging Evaluation of Pancreatic Density and Muscular Mass as Predictive Risk Factors for Pancreatic Fistula Formation after Duodenocephalopancreasectomy

The aim of this study was to investigate the predictive role of preoperative pancreatic density and muscular mass, assessed via CT imaging, in patients undergoing duodenocephalopancreasectomy, specifically in relation to the occurrence of postoperative pancreatic fistula (POPF). A retrospective analysis was conducted on a cohort of 57 consecutive patients who had been diagnosed with cephalo-pancreatic disease and had undergone duodenocephalopancreasectomy in the last five years. The most prevalent pathologies observed were ductal adenocarcinoma (29.2%), biliary adenocarcinoma (12.9%), and duodenal and papillary adenocarcinoma (13.9%). We collected information about age, sex, histopathological findings, type of surgery, presence or absence of pancreatic fistula, pancreatic density on preoperative CT images, and muscular area, calculated at the level of the L3 vertebra using “3D Slicer” software. Our data show that 28% of patients developed a pancreatic fistula, with an average attenuation of pancreatic density of 27 HU, which was lower than that observed in the non-fistula group (33.31 HU). However, statistical analysis did not reveal a significant association between low pancreatic density and fistula development. Therefore, our findings do not establish a significant association between pancreatic fistula and pancreatic density, aligning with the existing literature on the subject.

EUS-guided gallbladder drainage using a lumen-apposing metal stent as rescue treatment for malignant distal biliary obstruction: a large multicenter experience

EUS-guided gallbladder drainage (EUS-GBD) with lumen-apposing metal stents (LAMSs) has been reported as a rescue treatment with encouraging results for the relief of jaundice in patients with distal malignant biliary obstruction (DMBO) and after failure of both ERCP and EUS-guided choledochoduodenostomy. This was a multicenter retrospective analysis of all cases of consecutive EUS-GBD with LAMSs used as a rescue treatment for patients with DMBO in 14 Italian centers from June 2015 to June 2020. Primary endpoints were technical and clinical success, whereas the secondary endpoint was the adverse event (AE) rate. Forty-eight patients (52.1% women) with a mean age of 74.3 ± 11.7 years were included in the study. Biliary stricture was related to pancreatic adenocarcinoma (85.4%), duodenal adenocarcinoma (2.1%), cholangiocarcinoma (4.2%), ampullary cancer (2.1%), colon cancer (4.2%), and metastatic breast cancer (2.1%). The mean diameter of the common bile duct was 13.3 ± 2.8mm. LAMSs were placed transgastrically in 58.3% of cases and transduodenally in 41.7%. Technical success was 100%, whereas clinical success was 81.3%, with a mean total bilirubin reduction after 2 weeks of 66.5%. The mean procedure time was 26.4 minutes, and the mean hospital stay was 9.2 ± 8.2 days. AEs occurred in 5 patients (10.4%): 3 were classified as intraprocedural and 2 were classified as delayed because they occurred after >15 days. When the American Society for Gastrointestinal Endoscopy lexicon was used, 2 AEs were mild and 3 were moderate (2 buried LAMSs). The mean follow-up was 122 days. Our study shows that EUS-GBD with LAMSs used as a rescue treatment for patients affected by DMBO represents a valuable option in terms of technical and clinical success rates, with an acceptable AE rate. To the best of our knowledge, this is the largest study concerning the use of this procedure. (Clinical trial registration number: NCT03903523.).

Clinical outcome of resected nonampullary duodenal adenocarcinoma: A single center experience

Soo Yeun LIM, Dong Il CHUNG, Hye Jeong JEONG, Hyun Jeong JEON, So Jeong YOON, Hongbeom KIM, In Woong HAN, Jin Seok HEO, Sang Hyun SHIN*. Ann Hepatobiliary Pancreat Surg 2023;27:S258. https://doi.org/10.14701/ahbps.2023S1.BP-PP-7-4

The five periampullary cancers: Not just different siblings but different families—An international multicenter cohort study.

4167 Background: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC) and ampullary adenocarcinoma (AAC). Based on histopathology, the AAC is currently subdivided in the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype. Despite close anatomical resemblance, it is unclear how the ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. Methods: This is an international multicenter cohort study, including patients after curative intent resection for periampullary cancer retrieved from 45 centers (from Europe, USA, Asia and Canada) between 2010 and 2021. Pre-operative CA19-9, differences in pathology and postoperative pancreatic fistula (POPF, grade B/C), 8-year overall survival (OS) and disease-free interval (DFI) were compared between DAC, AmpIT, AmpPB, dCCA and PDAC. Results: Overall, 3809 patients were included of which 348 DAC, 774 AmpIT, 848 AmpPB, 1036 dCCA and 803 PDAC. The best 8-years 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 last, PDAC (12.9%, P<0.001). The best 8-years DFI was measured for AmpIT (62.7%) and the worst for both dCCA and PDAC (24.9% and 21.8%). This pattern correlated with the height of the pre-operative CA19-9 but not with the pathology, in which the largest and most progressed tumors were found in DAC. The incidence of POPF was lower in the pancreas-related tumor types (AmpPB 18.5%, PDAC 8.3%) compared to the non-pancreas related types (DAC 27.3%, AmpIT 25.5%, dCCA 27.6%). Conclusions: Despite the close anatomic relation of the five periampullary cancers, this study shows that there are prognostic and clinically relevant differences in terms of preoperative blood markers, pathology, complications, long-term survival, and recurrence. More 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”, this study emphasizes the need for individual evaluation of each histopathological periampullary subtype with the ampullary subtypes as individual entities in future studies.

Importance of carbohydrate antigen (CA 19-9) and carcinoembrionic antigen (CEA) in the prognosis of patients with duodenal adenocarcinoma: a retrospective single-institution cohort study

Duodenal adenocarcinoma (DA) is a rare malignancy without validated tumor markers. In practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) are often used in the management of DA, though their prognostic value is unknown. A single-institution retrospective review included patients diagnosed with biopsy-confirmed adenocarcinoma of the duodenum between 2006 and 2021. Peri-ampullary tumors were excluded. Levels of CA 19-9 and CEA were collected as continuous variables and were analyzed as binary variables: normal vs. high, using the maximum normal value as a cut-off (normal Ca 19-9 <35 U/ml; CEA <3 ng/ml). Survival analysis was conducted using Kaplan Meier curves, log-rank test and Cox proportional hazards model. There were 68 patients included in the final analysis. Median age was 67 years old and median follow-up time was 22.2 months. CA 19-9 and CEA were elevated in 36.8% and 48.5% of patients, respectively. A concomitant elevation of both tumor markers was associated with worsened OS (HR 2.140, 95% CI: 1.114-4.112; p = 0.019). After controlling for age and sex on multivariate analysis, elevation in both CA 19-9 ≥35 and CEA ≥3.0 remained significantly associated with increased mortality (HR 2.278, 95% CI: 1.162-4.466; p = 0.016). In summary, CA 19-9 and, to a lesser extent, CEA, show promise as prognostic markers in DA. Larger studies are needed to validate their use and to evaluate their performance as markers of recurrence.

Salvage endoscopic ultrasound-guided gastrojejunostomy as a bridge to definitive surgical therapy for duodenal adenocarcinoma presenting with duodenal stent obstruction

The utilization of endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) in the setting of an obstructed (ingrown) duodenal stent as a bridge to pancreaticoduodenectomy (PD) remains undescribed. Herein, we report a case study of a 51-year-old patient who underwent EUS-GJ using lumen apposing metal stent (LAMS) for an obstructed duodenal stent during neoadjuvant treatment for duodenal adenocarcinoma. The patient ultimately underwent surgical resection by a classic PD 14 weeks after LAMS placement. EUS-GJ using LAMS represents a potential option as a salvage bridge to surgery for duodenal obstruction in the setting of an obstructed duodenal stent.

Hybrid Organomineral Carriers for Therapeutic Proteins

—Drug delivery systems are developed to provide a necessary concentration and prolonged effect of the active substance in the organism. Orally administered protein preparations require a protection from the proteolysis in the gastrointestinal tract. Biocompatible hydrophilic polysaccharides in the composition of the matrix are especially promising, since they do not irritate the intestine and are gradually cleaved by specific glycosidases, releasing a therapeutic agent. The introduction of an insoluble porous mineral matrix into the composition of the carrier allows us to increase the concentration of the therapeutic agent in the matrix without a significant increase in the volume of the drug tablet form. In this work, a new original organomineral carrier was created based on heat-treated crushed clinoptilolite zeolite in combination with natural polysaccharides of red algae (agar–agar, agarose, and carrageenan). Granular and finely dispersed clinoptilolites in the composition of the matrix are loaded with a promising therapeutic agent (Bacillus pumilus ribonuclease (binase)), which shows a selective cytotoxicity to tumor cells. It was established that both granular and finely dispersed zeolites in a complex with polysaccharides retain the protein better as compared with pure zeolites and provide a gradual complete release of the enzyme in 18 h; at the same time, binase retains a catalytic activity and causes apoptosis in up to 23.8% of the population of HuTu80 human duodenal adenocarcinoma cells. Data obtained substantiate the prospects of designing dosage forms based on the studied organomineral carriers.

Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes

The subtypes of duodenal cancer (DC) are complicated and the carcinogenesis process is not well characterized. We present comprehensive characterization of 438 samples from 156 DC patients, covering 2 major and 5 rare subtypes. Proteogenomics reveals LYN amplification at the chromosome 8q gain functioned in the transmit from intraepithelial neoplasia phase to infiltration tumor phase via MAPK signaling, and illustrates the DST mutation improves mTOR signaling in the duodenal adenocarcinoma stage. Proteome-based analysis elucidates stage-specific molecular characterizations and carcinogenesis tracks, and defines the cancer-driving waves of the adenocarcinoma and Brunner’s gland subtypes. The drug-targetable alanyl-tRNA synthetase (AARS1) in the high tumor mutation burden/immune infiltration is significantly enhanced in DC progression, and catalyzes the lysine-alanylation of poly-ADP-ribose polymerases (PARP1), which decreases the apoptosis of cancer cells, eventually promoting cell proliferation and tumorigenesis. We assess the proteogenomic landscape of early DC, and provide insights into the molecular features corresponding therapeutic targets.

Diverse Biological Activity of Benzofuroxan/Sterically Hindered Phenols Hybrids.

Combining two pharmacophores in a molecule can lead to useful synergistic effects. Herein, we show hybrid systems that combine sterically hindered phenols with dinitrobenzofuroxan fragments exhibit a broad range of biological activities. The modular assembly of such phenol/benzofuroxan hybrids allows variations in the phenol/benzofuroxan ratio. Interestingly, the antimicrobial activity only appears when at least two benzofuroxan moieties are introduced per phenol. The most potent of the synthesized compounds exhibit high cytotoxicity against human duodenal adenocarcinoma (HuTu 80), human breast adenocarcinoma (MCF-7), and human cervical carcinoma cell lines. This toxicity is associated with the induction of apoptosis via the internal mitochondrial pathway and an increase in ROS production. Encouragingly, the index of selectivity relative to healthy tissues exceeds that for the reference drugs Doxorubicin and Sorafenib. The biostability of the leading compounds in whole mice blood is sufficiently high for their future quantification in biological matrices.

Hybrid Organomineral Carriers for Therapeutic Proteins

Drug delivery systems are designed to provide the necessary concentration and prolonged effect of the active substance in the body. Orally administered protein preparations require protection from proteolysis in the gastrointestinal tract. Biocompatible hydrophilic polysaccharides in the matrix are especially promising, since they do not irritate the intestines and are gradually cleaved by specific glycosidases, releasing the therapeutic agent. The introduction of an insoluble porous mineral matrix into composition of carrier makes it possible to increase the concentration of therapeutic in matrix without a significant increase in the volume of drug tablet form. In this work, a new original organic mineral carrier based on heat-treated crushed clinoptiolite zeolite in combination with natural polysaccharides from red seaweeds – agar-agar, agarose, and carrageenan was created. Granular and finely dispersed clinoptiolites in the matrix are loaded with a promising therapeutic agent, Bacillus pumilus ribonuclease (binase), which exhibits selective cytotoxicity to tumor cells. It has been established that both granular and finely dispersed zeolites in combination with polysaccharides retain protein better than pure zeolites and provide a gradual complete release of enzyme in 18 hours. At the same time, the enzyme retains its catalytic activity and induces apoptosis up to 23.8% cells of the human duodenal adenocarcinoma HuTu80. The data obtained substantiate the prospects of dosage forms based on the used organomineral carriers designing.