Preoperative profiles of plasma amino acids and derivatives distinguish periampullary cancer and benign disease.

Periampullary cancers, including pancreatic ductal adenocarcinoma, ampullary-, cholangio-, and duodenal carcinoma, are frequently diagnosed in an advanced stage and are associated with poor overall survival. They are difficult to differentiate from each other and challenging to distinguish from benign periampullary disease preoperatively. To improve the preoperative diagnostics of periampullary neoplasms, clinical or biological markers are warranted.In this study, 28 blood plasma amino acids and derivatives from preoperative patients with benign (N = 45) and malignant (N = 72) periampullary disease were analyzed by LC-MS/MS.Principal component analysis and consensus clustering both separated the patients with cancer and the patients with benign disease. Glutamic acid had significantly higher plasma expression and 15 other metabolites significantly lower plasma expression in patients with malignant disease compared with patients having benign disease. Phenylalanine was the only metabolite associated with improved overall survival (HR = 0.50, CI 0.30-0.83, P < 0.01).Taken together, plasma metabolite profiles from patients with malignant and benign periampullary disease were significantly different and have the potential to distinguish malignant from benign disease preoperatively.

Germline Pathogenic Variants in Patients With Pancreatic and Periampullary Cancers.

PURPOSE: Inherited cancer susceptibility is often not suspected in the absence of a significant cancer family history. Pathogenic germline variants in pancreatic cancer are well-studied, and routine genetic testing is recommended in the guidelines. However, data on rare periampullary cancers other than pancreatic cancer are insufficient. We compared the prevalence of germline susceptibility variants in patients with pancreatic cancer and nonpancreatic periampullary cancers. MATERIALS AND METHODS: Six hundred and eight patients who had undergone pancreaticoduodenal resection at a tertiary referral hospital were studied, including 213 with pancreatic ductal adenocarcinoma, 172 with ampullary cancer, 154 with distal common bile duct cancer, and 69 with duodenal adenocarcinoma. Twenty cancer susceptibility and candidate susceptibility genes were sequenced, and variant interpretation was assessed by interrogating ClinVar and PubMed. RESULTS: Pathogenic or likely pathogenic, moderate- to high-penetrant germline variants were identified in 46 patients (7.7%), including a similar percentage of patients with pancreatic (8.5%) and nonpancreatic periampullary cancer (7.1%). Low-penetrant variants were identified in an additional 11 patients (1.8%). Eighty-nine percent of the moderate- to high-penetrant variants involved the major cancer susceptibility genes BRCA2, ATM, BRCA1, CDKN2A, MSH2/MLH1, and PALB2; the remaining 11% involved other cancer susceptibility genes such as BRIP1, BAP1, and MSH6. Almost all pathogenic variant carriers had a family history of cancer. CONCLUSION: Patients with pancreatic and nonpancreatic periampullary cancer have a similar prevalence of pathogenic cancer susceptibility variants. Germline susceptibility testing should be considered for patients with any periampullary cancer.

Comparison of the two histological subtypes of ampullary adenocarcinoma: a retrospective study.

OBJECTIVES: This study aimed to compare the intestinal and pancreatobiliary subtypes of ampullary adenocarcinoma in a large patient group due to limited data on survival and risk factors. METHODS: A retrospective analysis of the clinical and pathological findings and the survival of 184 patients with ampullary adenocarcinoma who underwent curative operation between 2007 and 2018 was performed. RESULTS: Pancreatobiliary subtype had a higher prevalence of jaundice before operation than the intestinal subtype (p < 0.05). Pancreatobiliary subtype had a larger tumor size (> 2 mm) (p < 0.01) and poorer differentiation (p < 0.05) than the intestinal subtype. Perineural invasion more frequently occurred in pancreatobiliary subtype than the intestinal subtype (p < 0.01) and pancreatobiliary subtype had a higher prevalence of positive dissected lymph nodes (p < 0.05) with an advanced disease stage (p < 0.01) than the intestinal subtype. Patients of the pancreatobiliary subtype had poorer disease-free and overall survival than patients of the intestinal subtype. No survival benefit of adjuvant chemotherapy was found in either patients of the intestinal subtype or pancreatobiliary subtype. No significant difference was found in any subtypes regarding the recurrent regions. CONCLUSIONS: Pancreatobiliary subtype exhibited a higher recurrence rate and a poorer overall survival rate with more unfavorable pathological characteristics than the intestinal subtype.

OBJETIVOS: Los datos sobre la supervivencia y los factores de riesgo del adenocarcinoma ampular son limitados debido a su rareza. Este estudio buscó comparar el subtipo intestinal y el subtipo pancreático-biliar en pacientes con adenocarcinoma ampular. MÉTODOS: Análisis retrospectivo de hallazgos clínicos y patológicos y la supervivencia de 184 pacientes con adenocarcinoma ampular tratados entre 2007 y 2018. RESULTADOS: El subtipo pancreático-biliar tuvo una mayor prevalencia de ictericia antes de la operación y un tamaño de tumor mayor, y una peor diferenciación, que el subtipo intestinal. La invasión perineural fue más frecuente en el subtipo pancreático-biliar, con una mayor prevalencia de linfonodos disecados positivos y un estadio avanzado de la enfermedad. Los pacientes del subtipo pancreático-biliar tuvieron una supervivencia libre de enfermedad y una supervivencia general peores que los pacientes del subtipo intestinal. No se encontró ningún beneficio de la quimioterapia adyuvante en pacientes del subtipo intestinal o pancreático-biliar. No hubo diferencia significativa en las regiones recurrentes. CONCLUSIÓN: El subtipo pancreático-biliar mostró una tasa de recurrencia y una tasa de supervivencia general peores, con características patológicas más desfavorables que el subtipo intestinal.

[Intraductal radiofrequency ablation under endosonography and cholangioscopy for residual adenoma of the major duodenal papilla with intraductal component]. / Vnutriprotokovaya radiochastotnaya ablyatsiya pod kontrolem endosonografii i kholangioskopii pri rezidual'noi adenome bol'shogo sosochka dvenadtsatiperstnoi kishki s vnutriprotokovym komponentom. Obzor literatury.

All adenomas of the major duodenal papilla (MDP) require resection regardless of morphological structure due to high risk of malignancy. Currently, intraluminal endoscopic interventions are preferable for these adenomas. MDP neoplasms with intraductal spread (type III and IV) are of particular difficulty for endoscopic techniques. Intraductal radiofrequency ablation provides new opportunities for minimally invasive treatment of patients with MDP adenomas and intraductal component. A 72-year-old patient after previous endoscopic papillectomy for MDP adenoma admitted to the Vishnevsky National Research Medical Center of Surgery due to residual adenomatous growths within the papillectomy zone extending to the common bile duct throughout 13 mm. The patient underwent intraductal RFA under endosonography and cholangioscopy. Despite difficult localization of residual growths extending to the common bile duct, endosonography-guided intraductal RFA provided total destruction of residual tumor that was confirmed by cholangioscopy. Length of treatment was 4 months, relapse-free period - 10 months. Minimally invasive endoscopic technology for residual MDP adenoma provided good clinical results.

Clinicopathologic Analysis and Prognostic Factors for Survival in Patients with Operable Ampullary Carcinoma: A Multi-Institutional Retrospective Experience.

Background and Objectives: In ampullary cancer, 5-year survival rates are 30-50%, even with optimal resection and perioperative systemic therapies. We sought to determine the important clinicopathological features and adjuvant treatments in terms of the prognosis of patients with operable-stage ampullary carcinomas. Materials and Methods: We included 197 patients who underwent pancreaticoduodenectomy to treat ampullary carcinomas between December 2003 and May 2019. Demographics, clinical features, treatments, and outcomes/survival were analyzed. Results: The median disease-free survival (mDFS) and median overall survival (mOS) were 40.9 vs. 63.4 months, respectively. The mDFS was significantly lower in patients with lymphovascular invasion (p < 0.001) and lymph node involvement (p = 0.027). Potential predictors of decreased OS on univariate analysis included age ≥ 50 years (p = 0.045), poor performance status (p = 0.048), weight loss (p = 0.045), T3-T4 tumors (p = 0.018), surgical margin positivity (p = 0.01), lymph node involvement (p = 0.001), lymphovascular invasion (p < 0.001), perineural invasion (p = 0.007), and poor histological grade (p = 0.042). For the multivariate analysis, only nodal status (hazard ratio [HR]1.98; 95% confidence interval [CI], 1.08-3.65; p = 0.027) and surgical margin status (HR 2.61; 95% CI, 1.09-6.24; p = 0.03) were associated with OS. Conclusions: Nodal status and a positive surgical margin were independent predictors of a poor mOS for patients with ampullary carcinomas. Additional studies are required to explore the role of adjuvant therapy in patients with ampullary carcinomas.

Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

A rare case of neuroendocrine cell tumor mixed with a mucinous component in the ampulla of Vater.

BACKGROUND: A rare case of neuroendocrine cell tumor (NET) having both conventional and mucinous components was reported. Mucinous NET is rarely encountered in the pathological diagnosis of gastrointestinal (GI) tumors. Here we examined the mechanism for transformation of conventional NETs into mucinous NETs. CASE PRESENTATION: Macroscopic examination revealed a tumor with ulceration in the ampulla of Vater that measured 1.7 cm in its largest diameter. Histologically, the tumor comprised two components: a tubular/ribbon-like feature and small nests floating in a mucinous lake. The tumor nests showed sheet, nest and ribbon-like structures of small cells having eosinophilic cytoplasm as well as small-sized nuclei with dense hyperchromatin. Immunohistochemical analysis showed tumor cells positive for pan-endocrine markers (synaptophysin, CD56, INSM1 and chromogranin). Based on the histological findings, the solid and mucinous components were diagnosed as conventional and mucinous NETs, respectively. Grading was NET G2 based on 12.8% and 13.2% Ki-67-positive cells in the solid and mucinous components, respectively. Immunohistochemically, the mucin phenotype of this tumor was gastric and intestinal. Only the mucinous NET component had cytoplasmic CD10 expression. Examination using a customized gene panel detected only a DPC4 mutation, which was limited to the mucinous component. CONCLUSIONS: Coexistence of conventional and mucinous NETs could provide important insight into evaluating the NET subtype histogenesis. Moreover, molecular alterations including cytoplasmic expression of CD10 and the DPC4 mutation can contribute to interpretation of tumor pathogenesis.

Early and Long-Term Morbidity and Mortality Following Pancreaticoduodenectomy for Periampullary Tumors in Elderly Patients.

AIM: The growing elderly population is facing an increasing risk of cancers, consequently raising the pancreatic cancer surgery rate. This study aimed to determine whether advanced age is a risk factor for morbidity and mortality following pancreaticoduodenectomy (PD) for periampullary tumors. MATERIALS AND METHODS: The present study included 90 patients who underwent PD for periampullary tumors. Patients were divided into two age-related groups, including those aged 60-74 years (n = 60) (Group 1) and those aged ≥75 years (n = 30) (Group 2). Each patient's characteristics, perioperative features, morbidity, and long-term results were evaluated retrospectively. RESULTS: In both univariate and multivariate logistic regression analyses, old age (≥75 years) was not a risk factor for morbidity and hospital mortality. The multivariate analysis demonstrated that male gender (p = 0.008), pancreatic duct diameter (<3 mm) (p < 0.001), and length of hospital stay (p = 0.005) were independent risk factors for pancreatic fistula post-operation and reoperation. Additionally, hospital mortality was significantly associated with reoperation (p = 0.011). The overall median survival was 27 ± 4.1 (18.8-35.1) months. Lymph node positivity (p < 0.001), neural tumor invasion (p = 0.026), and age ≥75 years (p = 0.045) were risk factors affecting the overall survival rate. Moreover, there was no statistically significant difference in terms of PD rates during the Coronavirus disease-19 (COVID-19) period among groups, and PD during this period was not related to the occurrence of pancreatic fistula. CONCLUSION: PD can be performed effectively in selected elderly patients with tolerable morbidity and mortality rates.

[Efficacy analysis of 7 cases of mixed neuroendocrine-nonneuroendocrine neoplasm of the duodenal papilla].

The clinical data of 7 patients diagnosed with mixed neuroendocrine-nonneuroendocrine neoplasm were analyzed in the Department of Hepatobiliary Surgery of Hunan Provincial People's Hospital from January 2016 to December 2022. Among the 7 patients, 5 were male and 2 were female, with an average age of 59.3 years. Its clinical characteristics are similar to malignant ampulla tumors, and it is difficult to differentiate them. The preoperative puncture biopsy positivity rate is low, making it difficult to diagnose preoperatively, and the prognosis is worse.Comprehensive treatment including surgery, chemotherapy, and radiotherapy can be the preferred treatment option for this disease.

Metastatic Melanoma of the Common Bile Duct Presented with Dyspepsia.

Malignant melanoma (MM) is an aggressive tumor that can metastasize to any organ, but biliary tract metastasis is scarce. We describe a very rare case of MM metastasis to the common bile duct (CBD), presented with only dyspeptic symptoms. The patient had mildly elevated alkaline phosphatase and gamma-glutamyl transferase levels. Magnetic resonance cholangiopancreatography demonstrated a dilated common bile duct with a distal stricture. The MM diagnosis was established with the ampulla of Vater biopsy specimens obtained by endoscopic retrograde cholangiopancreatography (ERCP), and the patient's symptoms were resolved after biliary stenting. Both primary CBD cancer and other cancer types like MM that metastasize to CBD can cause obstruction and can be manifested only by dyspeptic symptoms. MM metastasis to CBD can cause obstruction manifested only by dyspeptic symptoms without obstructive jaundice. ERCP can be employed as a promising option for treatment and diagnosis. New-onset dyspeptic symptoms in patients with a history of MM should be investigated thoroughly, especially in the context of biliary metastasis.

Assessing the genomic feature of Chinese patients with ampullary adenocarcinoma: potential therapeutic targets.

BACKGROUNDS: Ampullary adenocarcinoma (AMPAC) is a rare malignancy, treated as pancreatic or intestinal cancer based on its histologic subtype. Little is known about the genomic features of Chinese patients with AMPAC. MATERIALS AND METHODS: We enrolled 145 Chinese AMPAC patients in our local cohort and performed a compressive somatic and germline genetic testing using a 156 gene panel. Expression of PD-L1 (clone 28 - 8) was also assessed in tumor specimens from 64 patients. RESULTS: The frequency of genetic alterations (GAs) in Chinese patients with AMPAC was found to be distinctive, with TP53, KRAS, SMAD4, APC, CTNNB1, ARID1A, and CDKN2A emerged as the most frequently mutated genes. Comparing with Western patients, significant differences were observed in the prevalence of PIK3CA and ARID2. Furthermore, the incidence of MSI-H was lower in the Chinese cohort, with only two patients identified as MSI-H. Conversely, 11 patients (8.27%) had pathogenic/likely pathogenic germline alterations, all of which were in the DNA damage response (DDR) pathway. In our cohort, 34.48% (22/64) of patients exhibited positive PD-L1 expression in tumor cells, and this expression was associated with GAs in CTNNB1 and BLM. Importantly, over three-fourths of Chinese AMPAC patients in our study had at least one actionable GA, with more than one-fifth of them having actionable GAs classified as Level 3. These actionable GAs were primarily involved in the DDR and PI3K pathways. Notably, GAs in the DDR pathway were detected in both Chinese and Western patients, and regardless of their functional impact, these alterations demonstrated enhanced overall survival rates and higher tumor mutational burden (TMB) levels. CONCLUSION: These findings underscore the distinct genomic landscape of Chinese AMPAC patients and highlight the potential for targeted therapies based on the identified GAs.

New gel immersion endoscopic ultrasonography technique for accurate periampullary evaluation.

BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.

Evaluation of Malignancy Risk of Ampullary Tumors Detected by Endoscopy Using 2-[18F]FDG PET/CT.

OBJECTIVE: We aimed to investigate whether 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. MATERIALS AND METHODS: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[18F]FDG PET/CT for endoscopy-detected ampullary tumors 5-87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. RESULTS: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in early-phase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13-36.18; P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80-13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41-19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00-14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16-21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874-0.956] vs. 0.815 [0.732-0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816-0.967) in candidates for endoscopic papillectomy. CONCLUSION: Adding 2-[18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Prognostic value of nodal staging classification and number of examined lymph nodes among patients with ampullary cancer.

BACKGROUND: Metastatic disease in the regional lymph nodes (LNs) is a strong indicator of worse outcomes among patients after curative-intent resection of ampullary cancer (AC). This study aimed to ascertain the threshold number of examined LNs (ELNs) for AC to compare the prognosis accuracy of various nodal classification schemes relative to long-term prognosis. METHODS: Patients who underwent pancreatoduodenectomy (PD) for AC (2004-2019) were identified using the National Cancer Database. Locally weighted regression scatter plot smoothing (LOWESS) curves were used to ascertain the optimal cut point for ELNs. The accuracy of the American Joint Committee on Cancer N classification, LN ratio, and log odds transformation (LODDS) ratio to stratify patients relative to survival was examined. RESULTS: Among 8127 patients with AC, 67% were male with a median age of 67 years (IQR, 59-74). Tumors were most frequently classified as T3 (34.9%), followed by T2 (30.6%); T1 (12.9%) and T4 (17.6%) were less common. LN metastasis was identified in 4606 patients (56.7%). Among patients with nodal disease, 37.0% and 19.7% had N1 and N2 disease, respectively. The LOWESS curves identified an inflection cutoff point in the hazard of survival at 20 ELNs. The survival benefit of 20 ELNs was more pronounced among patients without LN metastasis vs patients with N1 disease (median overall survival [OS]: 54.1 months [IQR, 45.9-62.1] in ≥20 ELNs vs 39.0 months [IQR, 35.8-42.2] in <20 ELNs; P < .001) or N2 disease (median OS: 22.5 months [IQR, 18.9-26.2] in ≥20 ELNs vs 25.4 months [IQR, 23.3-27.6] in <20 ELNs; P < .001). When comparing the 4 different N classification schemes, the LODDS classification scheme yielded the highest predictive ability. CONCLUSIONS: Evaluation of a minimum of 20 LNs was needed to stratify patients with AC relative to the prognosis and to minimize stage migration. The LODDS nodal classification scheme had the highest prognostic accuracy to differentiate survival among patients after PD for AC.

Bile ductal mucosal dysplasia is a possible risk factor for adenocarcinoma in patients with adenomyomatous hyperplasia of the Vaterian system: a single-centre study from China.

BACKGROUND: The relationship between adenomyomatous hyperplasia of the Vaterian system(AV) and cancer is unclear, some reports suggest that AV is often combined with mucosal glandular dysplasia, but it is not clear whether mucosal glandular dysplasia is a risk factor for carcinogenesis of AV. The aim of this study was to retrospective analysis of role of ductal glandular dysplasia as a risk factor in the development of carcinoma in AV. METHODS: A total of 328 cases who underwent surgery with a final pathological diagnosis of adenomyomatous hyperplasia (AH) in the Chinese PLA General Hospital in BeiJing, China, between January 2005 and December 2021 were retrospectively collected. There were Seventeen cases(5%) in which the lesions were located in the common bile duct as well as the ampulla of Vater, and their clinical (age, sex, etc.), imaging (cholelithiasis, etc.) and pathological data (mucosal glandular dysplasia, etc.) were collected. Clinical data and pathological features of AV with or without mucosal glandular dysplasia were analyzed. RESULTS: There were 17 out of 328 cases of AH occurring in the Vaterian system (5%). Three of seventeen AV cases were associated with carcinoma (18%). Of three cases, two (12%) with the tumor lesions in the mucosal glands adjacent to the AH (biliary tract cancer and ampullary cancer), and one (6%) with carcinoma developed from AH itself in the ampulla of Vater. All carcinomas had adenomyomatous hyperplasia with nearby mucosal glandular dysplasia (MGD). The percentage of BTC or AC was higher in patients with concurrent AH and MGD compared to AH patients without MGD. The results show tendency toward statistical significance (P = 0.082). This difference was more obvious among AH with severe dysplasia compared to adenomyomatous hyperplasia with mild-moderate dysplasia (P = 0.018). CONCLUSION: This study is the first to find that AV is associated with biliary tract cancer and ampullary cancer. In AV, the mucosal glandular dysplasia may be a risk factor for the development of malignancy. The underlying mechanism for carcinogenesis of AV could be AH itself or its secretions stimulating mucosal glands hyperplasia, then mucosal glands dysplasia. AV may be a precancerous lesion.

Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining.

BACKGROUND: The histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance. METHODS: Seventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors. RESULTS: Classifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI. CONCLUSIONS: Classification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.

Revolutionizing anti-HER2 therapies for extrahepatic cholangiocarcinoma and gallbladder cancer: Current advancements and future perspectives.

Biliary tract cancers (BTCs) encompass a heterogeneous group of rare tumors, including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC) and ampullary cancer (AC). The present first-line palliative treatment regimen comprises gemcitabine and cisplatin in combination with immunotherapy based on two randomized controlled studies. Despite the thorough investigation of these palliative treatments, long-term survival remains low. Moving beyond conventional chemotherapies and immunotherapies, the realm of precision medicine has demonstrated remarkable efficacy in malignancies such as breast and gastric cancers, characterized by notable HER2 overexpression rates. In the context of biliary tract cancer, significant HER2 alterations are observed, particularly within eCCA and GBC, heightening the interest in precision medicine. Various anti-HER2 therapies, including trastuzumab, pertuzumab, trastuzumab-deruxtecan, zanidatamab and neratinib, have undergone investigation. The objective of this review is to summarize the current evidence and outline future directions of targeted HER2 treatment therapy in patients with biliary tract tumors, specially extrahepatic cholangiocarcinoma and gallbladder cancer.

Establishment and characterization of DPC-X4: a novel mixed-type ampullary cancer cell line.

Mixed-type ampullary cancer is a distinct subtype of ampullary cancer that manifests a merging of the biological characteristics of both intestinal and pancreaticobiliary subtypes. The absence of established cell lines specific to this subtype has resulted in a concomitant scarcity of research on its tumorigenic mechanisms and the development of novel therapeutic modalities. The present study achieved the successful establishment of a novel mixed-type ampullary cancer cell line, designated DPC-X4 through primary culture techniques. Subsequent analyses pertaining to phenotypic characteristics, molecular profiling, biomarker identification, and histological features validated the DPC-X4 cell line as a potent model for delineating the pathogenesis of mixed-type ampullary cancer and facilitating the development of new pharmacological agents. This newly established cell line was subjected to continuous cultivation for 1 year, with stable passaging for over 50 generations. Notably, the DPC-X4 cell line manifested typical morphological features associated with epithelial tumors. Furthermore, the population doubling time for the DPC-X4 cell line was determined at 70 h. Short tandem repeat (STR) analysis confirmed that the DPC-X4 cell line exhibited a high genetic concordance with the primary tumor from the patient. Karyotypic profiling indicated an abnormal sub-triploid karyotype, with representative karyotypes of 57, XXY inv (9), 14p + , 15p + , der (17), + mar. The DPC-X4 cell line demonstrated a high capacity for efficient organoid formation under suspension culture conditions. In addition, the subcutaneous inoculation of DPC-X4 cells into NXG mice led to the formation of xenografted tumors. The results of drug sensitivity testing indicated that DPC-X4 cells were sensitive to paclitaxel and resistant to oxaliplatin, 5-fluorouracil, and gemcitabine. Immunohistochemistry revealed positive expression of CK7, CK19, and CK20 in DPC-X4 cells, while CDX2 demonstrated negative expression. In addition, positive expression of E-cadherin and vimentin was identified in DPC-X4 cells, with a proliferation index indicated by Ki-67 at 70%. The findings of our study establish DPC-X4 as a novel mixed-type ampullary cancer cell line, which can serve as a potential experimental model for exploring the pathogenesis of ampullary cancer and the development of therapeutic drugs.