Low-grade Dysplasia Research Articles

Dysbiosis in gastric mucosal microbiota associated with gastric carcinogenesis.

381 Background: Gastric microbiota, including H. pylori, may play a role in the development of gastric cancer. This study aimed to investigate the gastric microbiota throughout the stages of gastric carcinogenesis, encompassing atrophic gastritis, gastric dysplasia, and gastric adenocarcinoma. Methods: From December 2021 to August 2023, we collected gastric mucosal tissue samples from patients with atrophic gastritis, gastric dysplasia, and early gastric cancer. Subsequently, we conducted 16S rRNA gene profiling through next-generation sequencing. We compared alpha-diversity and beta-diversity within each group and analyzed the taxonomic composition. Results: This study included a total of 98 patients, comprising 16 with atrophic gastritis, 23 with low-grade dysplasia, 15 with high-grade dysplasia, and 44 with early gastric cancer. The H. pylori infection status was comparable across all groups. While there was a difference in alpha diversity between tumor lesions and normal stomach lesions, it did not reach statistical significance. Notably, Phyllobacterium was dominant in early gastric cancer, Prevotella in high-grade dysplasia, and Kocura in low-grade dysplasia. Furthermore, within the early gastric cancer group, Bacillus was widely distributed in cases of undifferentiated type adenocarcinoma. Conclusions: The analysis of microbiota collected from Korean stomach tissue revealed distinct microbial distributions across the various stages of gastric carcinogenesis.

Clinical outcomes of argon plasma coagulation for the treatment of gastric low-grade dysplasia.

336 Background: Argon plasma coagulation (APC) could be considered a treatment modality for small gastric low-grade dysplasia (LGD) instead of endoscopic resection (ER). Our study investigated the clinical outcomes of APC for treating gastric LGD and associated variables with local recurrence. Methods: This study included 911 patients who underwent APC for gastric neoplasms at the tertiary hospital from July 2007 to March 2022 with a minimal follow-up of 12 months. 112 subjects without any information about H. pylori infection status, 164 subjects who underwent APC for salvage therapy, 5 subjects with high grade dysplasia, and 12 subjects with cancer were excluded. Through a retrospective review of medical data, the clinical outcomes and variables associated with the local recurrence were analyzed. Results: A total of 618 patients with LGD (median age of 64 years old) were followed up for a median of 30 months and local recurrence has happened in 21 patients (3.4%). Multivariate analysis showed lesion size (hazard ratio 1.06, 95% confidential interval 1.01–1.12) was associated with the local recurrence. Among 557 lesions smaller than 10 mm, local recurrence was found in 14 cases (2.6%) and local recurrence was in 7 cases (9.5%) of 109 tumors larger than 10 mm ( p <0.004). Conclusions: In gastric LGD smaller than 10 mm without scars, APC is a good treatment modality in place of ER. However, when a lesion is larger, APC should be selected carefully with close monitoring. [Table: see text]

Abstract C011: Detection of circulating tumor cells for the early detection of pancreatic cancer

Abstract Introduction The majority of pancreatic cancer patients are diagnosed with advanced, metastatic disease. Biomarkers to detect pancreatic cancer at earlier stages could drastically improve the poor survival rates. Circulating tumor cells (CTCs) are tumor cells that disseminate or are shed into the vascular system and have been detected in patients at pre-malignant stages. However, detecting these rare cells accurately and reliably remains a challenge. The AccuCyte-CyteFinder system uses density-based enrichment of blood nucleated cells followed by detection of CTCs using fluorescence staining, whole slide scanning and automated image analysis. This study aimed to examine whether CTCs could be used to identify patients with pancreatic lesions likely to malignant. Methods 50 patients undergoing an endoscopic ultrasound procedure for a pancreatic mass were recruited at the Royal Prince Alfred Hospital, Sydney, Australia or Chris O’Brien Lifehouse, Sydney, Australia. Peripheral blood was collected prior to the procedure and processed for CTCs on the AccuCyte-CyteFinder platform using a CK+ EpCAM+ CD45- staining panel. Results 28% (14/50) were found to have an intraductal papillary mucinous neoplasm (IPMN), 10% (5/50) pancreatic ductal adenocarcinoma (PDAC), 6% (3/50) pancreatic neuroendocrine tumor (PNET), 42% (21/50) non-neoplastic pancreatic cyst, and 14% (7/50) normal (no mass found). CTCs were highest in the PDAC group with an average of 5 cells/ml, followed by the IPMN (3 cells/ml), pancreatic cyst (2.5 cells/ml), and PNET (0 cells/ml). 86% (12/14) of IPMN patients had detectable CTCs. 2 IPMN patients with CTC counts of more than 5 cells/ml resulted in a resected sample having high-grade dysplasia while 3 IPMN patients with no/low CTC counts resulted in a resected sample having low-grade dysplasia. There was no correlation with the size of the pancreatic mass and CTC number. Conclusions CTCs could be detected in patients with pre-malignant pancreatic cancer and could determine malignancy. CTCs could potentially be used to detect pancreatic cancer early however, larger patient numbers and longer follow-up are required to validate these findings. Citation Format: Dannel Yeo, Vera Klemm, Payal Saxena, Althea Bastian, Heidi Strauss, Charbel Sandroussi, Sara Wahlroos, Peter Grimison, John E.J. Rasko. Detection of circulating tumor cells for the early detection of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C011.

Abstract A011: Proteomic expression using exosomes in intraductal papillary mucinous neoplasms (IPMN) patients to inform risk stratification

Abstract Introduction Intraductal papillary mucinous neoplasm (IPMN), the most common type of pancreatic mucinous cysts, harbor risks of malignant progression of approximately 50% and 5% when found in the main duct (MD) and branch duct (BD), respectively. Surgical resection is standard of care in patients with high-risk stigmata and in some “indeterminate” cases, while surveillance modalities, which may include invasive imaging, are recommended for cases of cysts with “worrisome features”. Given the poor prognosis of late-stage pancreatic cancer, it is critical to accurately risk-stratify patients with IPMNs. We conducted a pilot study to evaluate the association of IPMN features with protein markers using extracellular vesicles (EVs), including exosomes, isolated from the blood of patients with resected IPMNs. Experimental procedure We evaluated 19 patients with IPMNs who underwent surgical resection (Whipple or distal pancreatectomy). Blood was collected before surgery and the EVs were isolated from plasma using an alternating current electrokinetics (ACE) platform. The concentration of 52 EV proteins was measured using a multiplex immunoassay. Surgical explant pathology reports were available and reviewed on all 19 patients. Data are presented as average concentration and 95% CI, and p-values represent the two-tailed t-test. Results Average age was 69 years (range: 47-83) and, of the 19 patients, 12 (63%) were male. Seventeen patients never smoked or were former smokers (quit > 20 years) before sample collection. A total of 14 patients had acute or chronic pancreatitis (7 historical; 7 found in surgical explant) while 4 patients had previously undiagnosed pancreatic intraepithelial neoplasia (PanIN) at the time of surgery. In our EV analysis, we found multiple EV protein biomarkers to be elevated in patients with various IPMN characteristics. Marker A was significantly elevated in patients with high-grade dysplasia (n=10) compared to low-grade dysplasia (n=9) (10.8 [8.4-13.2] vs. 7.5 [5.8 - 9.2] pg/mL, respectively, p = 0.0241), as defined by surgical explant pathology. When examining 13 patients with main-duct or mixed-type IPMNs, markers B, C, and D were elevated compared to the 6 patients with branch-duct or unspecified IPMNs (marker B: 1.9 [1.4-2.3] vs. 1.1 [0.9-1.4] ng/mL, p=0.0099; marker C: 524.3 [400.2-648.4] vs. 318.8 [209.9-427.7] pg/mL, p=0.0102; marker D: 65.8 [43.8-87.7] vs. 39.9 [31.7-48.1] pg/mL, p=0.0281). Conclusions In this pilot study that evaluated 19 patients with IPMNs, we identified multiple EV proteins that are differentially expressed in subgroups of patients. Our findings suggest that these differentially expressed proteomic markers can lead to the development of an algorithm for IPMN risk-stratification and possibly help discern histopathologic grade. Future studies will expand on these preliminary results with the aim of identifying a panel of biomarkers that can risk-stratify IPMNs to guide medical decision-making. Citation Format: Harmeet Dhani, Roberta V. Alexander, Juan Pablo Hinestrosa, Jesus Izaguirre-Carbonell, Dove Keith, Paul R. Billings, Gregory Cote', Rosalie Sears. Proteomic expression using exosomes in intraductal papillary mucinous neoplasms (IPMN) patients to inform risk stratification [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A011.

Study of Helicobacter pylori infection in patients with chronic atrophic gastritis and its relationship with lifestyle habits and dietary nutrient intake: A retrospective analysis.

To explore Helicobacter pylori (Hp) infection status and its relationship with lifestyle habits and dietary factors in patients with chronic atrophic gastritis. Six hundred thirty-eight patients with chronic atrophic gastritis, who were admitted to our hospital from March 2021 to April 2023, were selected for the study. All patients underwent the 13C urea breath test. The relationship between the detection rate of Hp infection and the clinical characteristics, lifestyle habits, and dietary factors of the patients was analyzed. Among the 638 patients with chronic atrophic gastritis, 531 patients were tested positive for Hp infection, the positive rate for Hp infection was approximately 83.23%. Analyzing the clinical characteristics of the patients, it was found that age, family history of gastric cancer, degree of chronic inflammation, degree of glandular atrophy, presence of low-grade dysplasia, and intestinal metaplasia all have an impact on the positive detection rate of patients (P < .05). Analyzing the patients' lifestyle habits, it was found that BMI, smoking history, alcohol consumption, preference for spicy food, dining location, consumption of pickled foods, frequent consumption of grilled/barbecued foods, preference for strong tea, consumption of sweets, and work-related stress had an impact on the positive rate of Hp infection in patients (P < .05). The discovery showed that the levels of total protein, albumin, hemoglobin, cholesterol, and the intake of livestock and poultry meat, seafood, dairy products, vegetables, fruits, and fats have an impact on the positivity rate of Hp infection in patients (P < .05). A multiple logistic regression analysis was performed, and it was found that patients' age, family history of gastric cancer, degree of chronic inflammation, degree of glandular atrophy, presence of low-grade dysplasia, presence of wasting or obesity, history of alcohol consumption, preference for spicy food, dining location, frequent consumption of strong tea, high work pressure, high intake of fish and seafood, low intake of dairy products, low intake of vegetables, low intake of fruits, and low intake of fats all had an impact on the occurrence of Hp infection in patients (P < .05). There is a certain correlation between patients' lifestyle habits, dietary factors, and clinical characteristics with the occurrence of Hp infection. These factors can assist in the prevention of Hp infection.

Characterization of sessile serrated adenomas with dysplasia including intramucosal adenocarcinoma and colorectal carcinoma with a microsatellite instability phenotype

Recent studies have shown that sessile serrated lesions (SSLs) lead to the development of colorectal cancer (CRC) with a microsatellite instability (MSI) phenotype via a dysplasia-carcinoma sequence. However, the pathological and molecular mechanisms of SSL with dysplasia (SSLD) are unclear. Here, we aimed to examine the clinicopathological and molecular alterations in SSLD and to evaluate the significance of such alterations with regard to lesion progression. Fifty-four SSLDs (20 serrated dysplasia cases and 17 intestinal dysplasia cases, including 30 low-grade dysplasia [LGD] cases, 7 high-grade dysplasia [HGD] cases, and 17 intramucosal adenocarcinomas [IMAs]) were evaluated. Molecular alterations, including immunohistochemical expression of various markers, DNA methylation status, and multiple genetic mutations (using next-generation sequencing), were assessed. Additionally, such alterations were also investigated in 41 CRCs with an MSI phenotype (invasion beyond submucosa). The frequency of mismatch repair (MMR) deficiency in SSLD was 12 of 39 cases (32.4 %), whereas the MMR proficient type was observed in 17 of 39 SSLD cases. SSLD with serrated dysplasia showed a significantly higher frequency of loss of MMR protein expression and methylation status. Moreover, loss of MMR protein expression differed significantly between LGD and IMA. Furthermore, the frequency of TP53 mutation was significantly higher in IMA than in LGD. The current findings demonstrated that SSL with serrated dysplasia may be associated with an increased risk of malignant transformation compared with intestinal dysplasia. Loss of MMR proteins and mutation of TP53 may play important roles in tumor progression from dysplasia to carcinomatous lesions.

Tubular-villous adenoma against the background of ulcerative colitis (clinical case)

A clinical case of the development of tubular-villous adenoma with moderate epithelial dysplasia (high grade) is described, taking into account the presence of foci of squamous metaplasia in the epithelium of the glands. The pathology presented in the article according to ICD-O has code 8263/2.Description of the clinical case. The patient had an initial colonoscopy in 2020 and was diagnosed with chronic ileitis and colitis with moderate and in some areas high inflammation activity, which is most characteristic of nonspecific ulcerative colitis. The patient was treated by a gastroenterologist. In December 2021, she had a follow-up colonoscopy with the histological material sampling. Endoscopic conclusion: ulcerative colitis, total lesion, exacerbation phase.Results and discussion. When the device was inserted into the rectum at a distance of 13 cm, a neoplasm was visualized, the mucosa was pale, shiny, when trying to pass the device through the narrowing of the contact-vulnerable mucosa, with instrumental palpation, the formation was displaced by a conglomerate, a polyfragmentary biopsy was taken. In the study of histological preparations of the recto-sigmoid junction, a tubular-villous adenoma with moderate epithelial dysplasia (high grade) is determined, taking into account the presence of foci of squamous metaplasia in the epithelium of the glands. According to the literature, with ulcerative colitis affecting almost the entire colon for more than 10 years, there is an increased risk of colon cancer formation (10 %), which increases by 2–5 % annually. The possibility of malignancy is present in 10–20 % of patients with ulcerative colitis for more than 20 years. Other researchers describe the identified low-grade dysplasia as progressing to high-grade dysplasia and carcinoma in 29–54 % of cases.Conclusions. The study of patients with this pathology should be carried out against the background of thorough preparation of the large intestine with modern preparations using high-tech verification methods and polyfragmental biopsy with a qualified assessment of biopsy specimens.

Incidence rates of Barrett’s esophagus and esophageal adenocarcinoma: a systematic review and meta-analysis

Background and AimsBarrett’s esophagus (BE) surveillance is commonly performed to detect early dysplasia and esophageal adenocarcinoma (EAC). However, high-quality incidence rates for the development of dysplasia and EAC in patients with BE are limited. This study aims to perform a systematic review and meta-analysis to provide an updated incidence rates for the development of low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC in a population of patients with BE undergoing endoscopic surveillance. MethodsWe performed a systematic search of EMBASE and Medline from inception to September 2022 to identify studies reporting the incidence rates of LGD, EAC, or HGD/EAC as an outcome in patients with non-dysplastic BE (NDBE), LGD, or HGD. Respective pooled incidence rates were estimated using a meta-analysis. ResultsTwenty-five studies were included in this meta-analysis comprising 2,587 patients with a combined follow-up of 218,351 person-years. For patients with NDBE, pooled incidence rates for progression to LGD, HGD, EAC, and HGD/EAC were 4.29, 0.52, 0.21, and 0.57 per 100 person-years, respectively. For patients with LGD, pooled incidence rates were 3.18 (HGD), 1.16 (EAC), and 5.05 (HGD/EAC) per 100 person-years. For those with HGD, the pooled incidence rate for EAC was 14.16 per 100 person-years. ConclusionsProgression to EAC and HGD/EAC remained low for patients with NDBE. Patients with confirmed LGD (≥2 pathologists) may be more likely to develop EAC, prompting a need to assess current BE surveillance strategies in this group.

Preoperative 18F-FDG PET/CT in Patients with Presumed Localized Colon Cancer: A Prospective Study with Long-Term Follow-Up.

We analyzed whether preoperative 18F-FDG PET/CT adds to conventional primary staging in patients with presumed non-metastatic colonic cancer (CC). The prognostic role of 18F-FDG uptake in the primary tumor was evaluated after a mean follow-up of 15 years. Patients with a new diagnosis of presumed localized CC were prospectively enrolled and underwent presurgical 18F-FDG PET/CT. For each colon lesion, SUVmax, SUVpeak, TLG, and MTV were assessed and tested as prognostic factors. Forty-eight patients were included. Post-surgery pathology identified a total of 103 colon lesions, including 58 invasive adenocarcinomas, 4 in situ adenocarcinomas, 3 adenomas with high-grade dysplasia, and 38 adenomas with low-grade dysplasia. Per lesion sensitivity, specificity, positive (PPVs) and negative predictive values (NPVs) for colonic primary tumor detection were 78%, 97%, 98%, and 73% for conventional workup, and 94%, 87%, 92%, and 89% for 18F-FDG PET/CT. Only sensitivity was significantly different between 18F-FDG PET/CT and conventional workup. PET detected an additional ten pathological colonic lesions in seven patients. SUVmax, SUVpeak, and TLG showed significant differences between invasive adenocarcinomas, in situ adenocarcinomas, and high-grade dysplasia compared to low-grade dysplasia. There was a statistically significant difference between pT1-pT2 and pT3-pT4 adenocarcinomas. On patient-based analysis, sensitivity, specificity, PPV, and NPV for nodal staging were 22%, 84%, 44%, and 65% for CECT, and 33%, 90%, 67%, and 70% for 18F-FDG PET/CT, without a statistically significant difference. PET/CT also identified unknown metastatic spread and one synchronous lung cancer in four patients. Overall, 18F-FDG PETCT had an additional diagnostic value in 11 out of 48 patients (23%). 18F-FDG uptake of the primary tumor did not predict nodal or distant metastases. The difference in disease-free survival categorized by median SUVmax, SUVpeak, TLG, and MTV was not significant. Finally, preoperative 18F-FDG PET/CT is valuable in detecting potential colon lesions not visualized by conventional workups, especially in cases of incomplete colonoscopy. It effectively highlights distant metastases but exhibits limitations for N staging. Mainly due to the relatively small sample size, the quantitative analysis of 18F-FDG uptake in the primary tumor did not reveal any association with recurrence or disease-free survival, adding no significant prognostic information.

Comparison of interventions for Barrett's esophagus: A network meta-analysis.

Barrett's esophagus (BE) is a precancerous condition that has the potential to develop into esophageal cancer (EC). Currently, there is a wide range of management options available for individuals at different pathological stages in Barrett's esophagus (BE). However, there is currently a lack of knowledge regarding their comparative efficacy. To address this gap, we conducted a network meta-analysis of published randomized controlled trials to examine the comparative effectiveness of all regimens. Data extracted from eligible randomized controlled trials were utilized in a Bayesian network meta-analysis to examine the relative effectiveness of BE's treatment regimens and determine their ranking in terms of efficacy. The ranking probability for each regimen was assessed using the surfaces under cumulative ranking values. The outcomes under investigation were complete ablation of BE, neoplastic progression of BE, and complete eradication of dysplasia. We identified twenty-three RCT studies with a total of 1675 participants, and ten different interventions. Regarding complete ablation of non-dysplastic BE, the comparative effectiveness ranking indicated that argon plasma coagulation (APC) was the most effective regimen, with the highest SUCRA value, while surveillance and PPI/H2RA were found to be the least efficacious regimens. For complete ablation of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, photodynamic therapy (PDT) had the highest SUCRA value of 94.1%, indicating it as the best regimen. Additionally, for complete eradication of dysplasia, SUCRA plots showed a trend in ranking PDT as the highest with a SUCRA value of 91.2%. Finally, for neoplastic progression, radiofrequency ablation (RFA) and surgery were found to perform significantly better than surveillance. The risk of bias assessment revealed that 6 studies had an overall high risk of bias. However, meta-regression with risk of bias as a covariate did not indicate any influence on the model. In terms of the Confidence in Network Meta-Analysis evaluation, a high level of confidence was found for all treatment comparisons. Endoscopic surveillance alone or PPI/H2RA alone may not be sufficient for managing BE, even in cases of non-dysplastic BE. However, APC has shown excellent efficacy in treating non-dysplastic BE. For cases of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, PDT may be the optimal intervention as it can induce regression of BE metaplasia and prevent future progression of BE to dysplasia and EC.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

Risk Assessment and Radiomics Analysis in Magnetic Resonance Imaging of Pancreatic Intraductal Papillary Mucinous Neoplasms (IPMN).

Intraductal papillary mucinous neoplasms (IPMNs) are a very common incidental finding during patient radiological assessment. These lesions may progress from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and even pancreatic cancer. The IPMN progression risk grows with time, so discontinuation of surveillance is not recommended. It is very important to identify imaging features that suggest LGD of IPMNs, and thus, distinguish lesions that only require careful surveillance from those that need surgical resection. It is important to know the management guidelines and especially the indications for surgery, to be able to point out in the report the findings that suggest malignant degeneration. The imaging tools employed for diagnosis and risk assessment are Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) with contrast medium. According to the latest European guidelines, MRI is the method of choice for the diagnosis and follow-up of patients with IPMN since this tool has a highest sensitivity in detecting mural nodules and intra-cystic septa. It plays a key role in the diagnosis of worrisome features and high-risk stigmata, which are associated with IPMNs malignant degeneration. Nowadays, the main limit of diagnostic tools is the ability to identify the precursor of pancreatic cancer. In this context, increasing attention is being given to artificial intelligence (AI) and radiomics analysis. However, these tools remain in an exploratory phase, considering the limitations of currently published studies. Key limits include noncompliance with AI best practices, radiomics workflow standardization, and clear reporting of study methodology, including segmentation and data balancing. In the radiological report it is useful to note the type of IPMN so as the morphological features, size, rate growth, wall, septa and mural nodules, on which the indications for surveillance and surgery are based. These features should be reported so as the surveillance time should be suggested according to guidelines.

A rare case of intraductal tumor of the pancreas in which an intraductal tubulopapillary neoplasm was mixed with a widely spreading gastric-type intraductal papillary-mucinous neoplasm

A 70-year-old man receiving treatment for diabetes mellitus presented with a cystic mass in the border area of the pancreatic body and tail on plain computed tomography (CT) due to impaired glucose intolerance. Contrast-enhanced CT showed a faint hyperattenuated nodular mass extending from the dilated main pancreatic duct (MPD) to the branch duct. Endoscopic retrograde cholangiopancreatography revealed a mildly dilated orifice of the papilla of Vater and MPD stenosis with entire upstream and immediate downstream dilatations. The patient underwent distal pancreatectomy due to the suspicion of mixed-type intraductal papillary-mucinous carcinoma. A pathological examination showed an intraductal solid-nodular mass measuring 25mm in length, consisting of two types of neoplasms. One showed tubulopapillary growth with entirely high-grade (HG) atypical cuboidal epithelium, in which immunohistochemical examinations were positive for MUC6 but negative for human gastric mucin (HGM), MUC1, MUC2, and MUC5AC, fitting the concept of intraductal tubulopapillary neoplasm (ITPN). The other showed the same growth of low-grade (LG) atypical columnar cells positive for HGM and MUC5AC and negative for MUC1 and MUC2, which corresponded to gastric-type intraductal papillary-mucinous neoplasm (IPMN) -LG. The tumor had not invaded the duct walls, and no metastatic lymph nodes were observed. The ITPN was adjacent to the IPMN mainly composed of tubular glands mimicking pyloric glands with LG dysplasia that corresponded to the so-called IPMN-pyloric gland variant. Moreover, the proliferation of low-papillary gastric-type IPMN spread around the intraductal tumors. Consequently, the patient was diagnosed with an intraductal tubular neoplasm comprising a noninvasive ITPN and gastric-type IPMN-LG. ITPN is a recently identified intraductal neoplasm of the pancreas proposed by Yamaguchi et al. and is distinguished by intraductal tubulopapillary growth with HG cellular atypia without overt mucin production, in contrast to IPMN. To date, no cases of intraductal nodular tumors comprising ITPN and IPMN have been reported. We report this original case with imaging and pathological observations and discuss potential processes via which ITPN and IPMN may arise adjacent to each other in the same pancreatic duct.

Immunohistochemical FAP Expression Reflects 68Ga-FAPI PET Imaging Properties of Low- and High-Grade Intraductal Papillary Mucinous Neoplasms and Pancreatic Ductal Adenocarcinoma.

Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are grossly visible (typically > 5 mm) intraductal epithelial neoplasms of mucin-producing cells, arising in the main pancreatic duct or its branches. According to the current 2-tiered grading scheme, these lesions are categorized as having either low-grade (LG) dysplasia, which has a benign prognosis, or high-grade (HG) dysplasia, which formally represents a carcinoma in situ and thus can transform to pancreatic ductal adenocarcinoma (PDAC). Because both entities require different treatments according to their risk of becoming malignant, a precise pretherapeutic diagnostic differentiation is inevitable for adequate patient management. Recently, our group has demonstrated that 68Ga-fibroblast activation protein (FAP) inhibitor (FAPI) PET/CT shows great potential for the differentiation of LG IPMNs, HG IPMNs, and PDAC according to marked differences in signal intensity and tracer dynamics. The purpose of this study was to biologically validate FAP as a target for PET imaging by analyzing immunohistochemical FAP expression in LG IPMNs, HG IPMNs, and PDAC and comparing with SUV and time to peak (TTP) measured in our prior study. Methods: To evaluate the correlation of the expression level of FAP and α-smooth muscle actin (αSMA) in neoplasm-associated stroma depending on the degree of dysplasia in IPMNs, 98 patients with a diagnosis of LG IPMN, HG IPMN, PDAC with associated HG IPMN, or PDAC who underwent pancreatic surgery at the University Hospital Heidelberg between 2017 and 2023 were identified using the database of the Institute of Pathology, University Hospital Heidelberg. In a reevaluation of hematoxylin- and eosin-stained tissue sections of formalin-fixed and paraffin-embedded resection material from the archive, which was originally generated for histopathologic routine diagnostics, a regrading of IPMNs was performed by a pathologist according to the current 2-tiered grading scheme, consequently eliminating the former diagnosis of "IPMN with intermediate-grade dysplasia." For each case, semithin tissue sections of 3 paraffin blocks containing neoplasm were immunohistologically stained with antibodies directed against FAP and αSMA. In a masked approach, a semiquantitative analysis of the immunohistochemically stained slides was finally performed by a pathologist by adapting the immunoreactive score (IRS) and human epidermal growth factor receptor 2 (Her2)/neu score to determine the intensity and percentage of FAP- and αSMA-positive cells. Afterward, the IRS of 14 patients who underwent 68Ga-FAPI-74 PET/CT in our previous study was compared with their SUVmax, SUVmean, and TTP for result validation. Results: From 98 patients, 294 specimens (3 replicates per patient) were immunohistochemically stained for FAP and αSMA. Twenty-three patients had LG IPMNs, 11 had HG IPMNs, 10 had HG IPMNs plus PDAC, and 54 had PDAC. The tumor stroma was in all cases variably positive for FAP. The staining intensity, percentage of FAP-positive stroma, IRS, and Her2/neu score increased with higher malignancy. αSMA expression could be shown in normal pancreatic stroma as well as within peri- and intraneoplastic desmoplastic reaction. No homogeneous increase in intensity, percentage, IRS, and Her2/neu score with higher malignancy was observed for αSMA. The comparison of the mean IRS of FAP with the mean SUVmax, SUVmean, and TTP of 68Ga-GAPI-74 PET/CT showed a matching value increasing with higher malignancy in 68Ga-FAPI-74 PET imaging and immunohistochemical FAP expression. Conclusion: The immunohistochemical staining of IPMNs and PDAC validates FAP as a biology-based stromal target for invivo imaging. Increasing expression of FAP in lesions with a higher degree of malignancy matches the expectation of a stronger FAP expression in PDAC and HG IPMNs than in LG IPMNs and corroborates our previous findings of higher SUVs and a longer TTP in PDAC and HG IPMNs than in LG IPMNs.

Measuring the concordance between endoscopic and histologic inflammation and its effect on IBD-associated dysplasia.

Background and study aims Chronically inflamed colonic mucosa is primed to develop dysplasia identified at surveillance colonoscopy by targeted or random biopsies. We aimed to explore the effect of mucosal inflammation on detection of visible and "invisible" dysplasia and the concordance between the degree of endoscopic and histologic inflammation. Patients and methods This was a 6-year cross-sectional analysis of endoscopic and histologic data from IBD. A multinomial model was created to estimate the odds for a specific lesion type as well as the odds of random dysplasia relative to the degree of inflammation. Kappa statistics were used to measure concordance between endoscopic and histologic inflammation. Results A total of 3437 IBD surveillance colonoscopies between 2016-2021 were reviewed with 970 procedures from 721 patients containing 1603 visible lesions. Kappa agreement between histologic and endoscopic degree of inflammation was low at 0.4. There was a positive association between increased endoscopic inflammation and presence of tubulovillous adenomas (TVAs) (odds ratio [OR] 2.18; 95% confidence interval [CI] 1.03-4.62; P =0.04). Among cases with visible lesions, the yield of concomitant random dysplasia was 2.7% and 1.9% for random indefinite dysplasia. The odds of random dysplasia significantly increased as the degree of endoscopic and histologic inflammation increased (OR 2.18, 95%CI 1.46-3.26; P <0.001 and OR 2.75; 95%CI 1.65-4.57, P <0.001, respectively. The odds of indefinite random dysplasia also significantly increased as endoscopic and histologic inflammation increased (OR 2.90; 95%CI 1.85, 4.55, P <0.001 and OR 1.98; 95%CI 1.08, 3.62, P <0.035, respectively. Conclusions Endoscopic and histologic inflammation are associated with higher odds of finding TVAs and random low-grade, high-grade, and indefinite dysplasia. Concordance between histologic and endoscopic inflammation severity is low.

Diagnostic Usefulness of p53 Immunostaining in Gastric Cancer and Dysplasia: A Real-world Clinical Experience.

Gastric cancer and its precancerous lesions represent a significant public health concern. A subset of gastric cancers exhibits mutations in the TP53 gene, often accompanying distinctive morphologic alterations. This study aimed to assess the diagnostic efficacy of p53 immunostaining in real-world clinical settings. A retrospective analysis was conducted on 50 cases of gastric tumors and tumor-like lesions, wherein p53 immunostaining played a pivotal diagnostic role. The staining pattern of p53 was examined in conjunction with clinicopathologic parameters. Mutant p53 staining pattern demonstrated a significant association with high-grade nuclear atypia (p<0.001), high-grade dysplasia, and tubular adenocarcinoma (p<0.001), as well as microsatellite instability status (p=0.034). Furthermore, the diagnostic utility of p53 immunostaining was evident in scenarios where: 1) biopsy specimens contained few tumor cells, 2) pathologic evaluation of resection margins was limited by cauterization artifacts, and 3) distinction between low-grade and high-grade gastric dysplasia was challenging. P53 immunostaining can be helpful for the diagnosis of gastric tumor and tumor-like lesions, and accurate pathologic margin evaluation, particularly in lesions demonstrating intestinal-type differentiation and some degree of nuclear atypia.

To minimize invasion - Is it possible to treat a patient's early esophageal cancer and achalasia within one operation?

Patients with achalasia face an increased risk of dysplasia and squamous cell carcinoma due to chronic inflammation. We demonstrated the feasibility of performing endoscopic submucosal dissection (ESD) and well-designed peroral endoscopic myotomy (POEM) within a single operation, aiming to reduce trauma and enhance recovery. A 65-year-old male with progressive dysphagia was diagnosed with type II achalasia and suspected esophageal lesions. Our treatment plan involved addressing both achalasia and the lesions using POEM and ESD during one operation. POEM was initiated with a 2-cm longitudinal incision at 5 o'clock, establishing a submucosal tunnel from 32 cm from the incisors to 2 cm distal to the gastroesophageal junction. A 4 cm myotomy of the esophageal segment was performed, extending 2 cm into the proximal stomach. Subsequently, ESD was conducted on the suspicious lesion in the mid-esophagus. En-bloc resection was achieved and histology revealed high-grade dysplasia with horizontal margin showed low-grade dysplasia. Follow-up assessments demonstrated decreased Eckardt's scores and no evidence of recurrence. By carefully planning the direction and length of the myotomy, we successfully managed POEM and ESD in a single operation. Individualized modifications to endoscopic procedures are crucial for achieving minimally invasive and cost-effective treatment for patients presenting with achalasia combined with esophageal early cancer.

Evaluation of polypus growth among fecal immunochemical test positive patients

Background: Colorectal cancer is a difficult clinical condition to treat all over the world. Adenomatous polyps are thought to be cancer precursors. A colonoscopy is required to detect and confirm ulcerative colitis mucosal healing. Different screening procedures, including as colonoscopy, fecal immunochemistry test (FIT), guaiac fecal occult blood test (gFOBT), computed tomography (CT) colonography, and others, are used to detect polyps or ulcers early. Although the gold standard colonoscopy serves both diagnostic and therapeutic purposes, the FIT can identify advanced adenoma or established cancer, as well as the mucosal condition of ulcerative colitis. The FIT is a less costly approach for detecting colonic disease that is appropriate for our demographic. The aim of the study was to observe the type of polypus growth among FIT positive patients. Methods: This observational cross-sectional study was conducted at the department of colorectal surgery, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. The study duration was 1 year, from July 2019 to August 2020. At the initial stage, a total of 510 participants were selected among the patients attending the outdoor department of BSMMU colorectal surgery following the inclusion and exclusion criteria. Results: The male: female ratio was 1.7:1 in our study. 48.28% were from the age group of 50-59 years. The most common clinical presentation or symptom among the participants was constipation, observed in 81.03% of cases. 39.66% of the participants had abdominal pain, 32.76% had rectal mucus discharge, 12.07% had observed changes in their bowel movement, while 6.90% had a lack of appetite. Among the participants, 42 had pedunculated polyp, while 16 had sessile polyps. A total of 55.17% had non-advanced pedunculated polyp, 22.41% had non-advanced sessile polyp, 17.24% had advanced grade pedunculated polyp, while the remaining 5.17% had advanced grade sessile polyp. Histopathological findings revealed that 44.83% of the participants had tubular adenoma with low grade dysplasia (LGD) among the non-advanced pedunculated polyps’ cases, 17.24% had tubular adenoma with LGD among the non-advances sessile cases. Among the advanced pedunculated polyps’ cases, 6.90% had tubular adenoma with high grade dysplasia (HGD), 3 (5.17%) had villous adenoma with dysplasia, and 2 (3.45%) had tubulovillous with dysplasia. Among the 3 advances sessile polyps cases, 3.45% had tubular adenoma with HGD, while 1 patient had malignancy. Conclusions: It was observed that FIT positive patients had a higher frequency of pedunculated polyps, specifically advanced pedunculated polyps. Both sessile and pedunculated polyps had a high prevalence among patients aged between 50-59 years.

Poor Diagnostic Reproducibility in the Identification of Nonconventional Dysplasia in Colitis Impacts the Application of Histologic Stratification Tools

Due to their increased cancer risk, patients with longstanding inflammatory bowel disease are offered endoscopic surveillance with concomitant histopathologic assessments, aimed at identifying dysplasia as a precursor lesion of colitis-associated colorectal cancer. However, this strategy is beset with difficulties and limitations. Recently, a novel classification criterion for colitis-associated low-grade dysplasia has been proposed, and an association between nonconventional dysplasia and progression was reported, suggesting the possibility of histology-based stratification of patients with colitis-associated lesions. Here, a cohort of colitis-associated lesions was assessed by a panel of 6 experienced pathologists to test the applicability of the published classification criteria and try and validate the association between nonconventional dysplasia and progression. While confirming the presence of different morphologic patterns of colitis-associated dysplasia, the study demonstrated difficulties concerning diagnostic reproducibility between pathologists and was unable to validate the association of nonconventional dysplasia with cancer progression. Our study highlights the overall difficulty of using histologic assessment of precursor lesions for cancer risk prediction in inflammatory bowel disease patients and suggests the need for a different diagnostic strategy that can objectively identify high-risk phenotypes.

Total Proctocolectomy vs Subtotal/total Colectomy for Neoplasia in Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.

Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) frequently undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for medically refractory disease or colonic dysplasia/neoplasia. Subtotal colectomy with ileosigmoid or ileorectal anastomosis may have improved outcomes but is not well studied. Due to increased risk for colorectal cancer in PSC-IBD, there is hesitancy to perform subtotal colectomy. We aim to describe the frequency of colorectal dysplasia/neoplasia following IPAA vs subtotal colectomy in PSC-IBD patients. We completed a retrospective study from 1972 to 2022 of patients with PSC-IBD who had undergone total proctocolectomy with IPAA or subtotal colectomy. We abstracted demographics, disease characteristics, and endoscopic surveillance data from the EMR. Of 125 patients (99 IPAA; 26 subtotal), the indication for surgery was rectal sparing medically refractory disease (51% vs 42%), dysplasia (37% vs 30%) and neoplasia (11% vs 26%) in IPAA vs subtotal colectomy patients, respectively. On endoscopic surveillance of IPAA patients, 2 (2%) had low-grade dysplasia (LGD) in the ileal pouch and 2 (2%) had LGD in the rectal cuff after an average of 8.4 years and 12.3 years of follow-up, respectively. One (1%) IPAA patient developed neoplasia of the rectal cuff after 17.8 years of surgical continuity. No subtotal colectomy patients had dysplasia/neoplasia in the residual colon or rectum. In patients with PSC-IBD, there was no dysplasia or neoplasia in those who underwent subtotal colectomy as opposed to the IPAA group. Subtotal colectomy may be considered a viable surgical option in patients with rectal sparing PSC-IBD if adequate endoscopic surveillance is implemented.