Schwannoma in the Rectum: A Case Report.

A woman in her 60s with a past medical history of recurrent Helicobacter pylori (H. pylori) presented for surgical consultation after a colonoscopy revealed a mass in the rectum. Preoperative biopsy revealed mucosal excrescence with no dysplasia or malignant changes. The final pathology showed a solid, submucosal rectal mass that was positive for SOX10 and S100 on immunohistochemistry, supporting our diagnosis of Schwannoma. This case emphasizes the importance of considering schwannomas in the differential diagnosis of patients presenting with a rectal mass no matter how rare it may be.

A Case Report of an Unusually Large Heterotopic Pancreas.

Heterotopic pancreas (HP) is the presence of pancreatic tissue outside of its normal anatomical position without vascular continuity from the main pancreas. HP is most commonly found within the gastrointestinal tract, particularly the stomach through the jejunum. This report shares the case of a 57-year-old man who presented with persistent vomiting despite medical therapy. Given the nonspecific and broad differential diagnosis, a histopathological examination was warranted for a definitive diagnosis that showed a uniquely large and well-differentiated type I HP in the lesser curvature of the stomach. Resection was completed which was followed with resolution of symptoms.

Development of high-quality artificial intelligence for computer-aided diagnosis in determining subtypes of colorectal cancer.

BACKGROUND AND AIM: There are no previous studies in which computer-aided diagnosis (CAD) diagnosed colorectal cancer (CRC) subtypes correctly. In this study, we developed an original CAD for the diagnosis of CRC subtypes. METHODS: Pretraining for the CAD based on ResNet was performed using ImageNet and five open histopathological pretraining image datasets (HiPreD) containing 3 million images. In addition, sparse attention was introduced to improve the CAD compared to other attention networks. One thousand and seventy-two histopathological images from 29 early CRC cases at Kyoto Prefectural University of Medicine from 2019 to 2022 were collected (857 images for training and validation, 215 images for test). All images were annotated by a qualified histopathologist for segmentation of normal mucosa, adenoma, pure well-differentiated adenocarcinoma (PWDA), and moderately/poorly differentiated adenocarcinoma (MPDA). Diagnostic ability including dice sufficient coefficient (DSC) and diagnostic accuracy were evaluated. RESULTS: Our original CAD, named Colon-seg, with the pretraining of both HiPreD and ImageNET showed a better DSC (88.4%) compared to CAD without both pretraining (76.8%). Regarding the attentional mechanism, Colon-seg with sparse attention showed a better DSC (88.4%) compared to other attentional mechanisms (dual: 79.7%, ECA: 80.7%, shuffle: 84.7%, SK: 86.9%). In addition, the DSC of Colon-seg (88.4%) was better than other types of CADs (TransUNet: 84.7%, MultiResUnet: 86.1%, Unet++: 86.7%). The diagnostic accuracy of Colon-seg for each histopathological type was 94.3% for adenoma, 91.8% for PWDA, and 92.8% for MPDA. CONCLUSION: A deep learning-based CAD for CRC subtype differentiation was developed with pretraining and fine-tuning of abundant histopathological images.

Metastatic Hepatoblastoma in Adolescence: A Clinical Case Report and Literature Review.

Hepatoblastoma is the most common hepatic neoplasm in children. However, its incidence is infrequent beyond age five. We present the case of a 15-year-old female diagnosed with metastatic hepatoblastoma during hospitalization for liver function deterioration. The patient presented with abdominal distension, jaundice, and other symptoms indicative of advanced disease. Imaging and biopsy confirmed stage IV epithelial hepatoblastoma with pulmonary metastases. This case underscores the importance of considering hepatoblastoma in older pediatric patients or young adults presenting with hepatic masses despite lacking traditional risk factors for liver malignancies.

Skull Metastasis With Orbital Invasion as a Primary Manifestation of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common worldwide cancer with a poor prognosis despite treatment advancements. Patients typically exhibit signs and symptoms pertaining to the liver. Extrahepatic metastasis of HCC is documented to be as low as 5% of cases. Bone metastasis ranks third following lungs and regional lymph nodes. The typical locations for bone metastasis include the vertebral column, pelvis, femora, and ribs, with skull metastasis, being reported in less than 1.6% of cases. Herein, we describe a case of HCC presenting with skull metastases and orbital invasion as the initial manifestation.

Stroma AReactive Invasion Front Areas (SARIFA): a novel histopathologic biomarker in colorectal cancer patients and its association with the luminal tumour proportion.

BACKGROUND: Stroma AReactive Invasion Front Areas (SARIFA) is a novel prognostic histopathologic biomarker measured at the invasive front in haematoxylin & eosin (H&E) stained colon and gastric cancer resection specimens. The aim of the current study was to validate the prognostic relevance of SARIFA-status in colorectal cancer (CRC) patients and investigate its association with the luminal proportion of tumour (PoT). METHODS: We established the SARIFA-status in 164 CRC resection specimens. The relationship between SARIFA-status, clinicopathological characteristics, recurrence-free survival (RFS), cancer-specific survival (CSS), and PoT was investigated. RESULTS: SARIFA-status was positive in 22.6% of all CRCs. SARIFA-positivity was related to higher pT, pN, pTNM stage and high grade of differentiation. SARIFA-positivity was associated with shorter RFS independent of known prognostic factors analysing all CRCs (RFS: hazard ratio (HR) 2.6, p = 0.032, CSS: HR 2.4, p = 0.05) and shorter RFS and CSS analysing only rectal cancers. SARIFA-positivity, which was measured at the invasive front, was associated with PoT-low (p = 0.009), e.g., higher stroma content, and lower vessel density (p = 0.0059) measured at the luminal tumour surface. CONCLUSION: Here, we validated the relationship between SARIFA-status and prognosis in CRC patients and provided first evidence for a potential prognostic relevance in the subgroup of rectal cancer patients. Interestingly, CRCs with different SARIFA-status also showed histological differences measurable at the luminal tumour surface. Further studies to better understand the relationship between high luminal intratumoural stroma content and absence of a stroma reaction at the invasive front (SARIFA-positivity) are warranted and may inform future treatment decisions in CRC patients.

Pancreatic Adenosquamous Carcinoma Presenting as a Gastric Lesion.

Pancreatic adenosquamous carcinoma, an uncommon subtype of pancreatic adenocarcinoma, is characterized by an aggressive course and poor prognosis, with the only method of cure being surgical resection at the time of diagnosis. It is a complex condition, as it presents nonspecifically and remains indistinguishable from pancreatic adenocarcinoma without imaging techniques despite its aggressive nature. We report an atypical case of pancreatic adenosquamous carcinoma, presenting with marked anemia, found on endoscopy to have a gastric mass. This is of interest to readers as a reminder that pancreatic cancers may present with gastric invasion and should remain on the differential diagnosis for gastric lesions.

Using machine learning models to predict synchronous genitourinary cancers among gastrointestinal stromal tumor patients.

Objectives: Gastrointestinal stromal tumors (GISTs) can occur synchronously with other neoplasms, including the genitourinary (GU) system. Machine learning (ML) may be a valuable tool in predicting synchronous GU tumors in GIST patients, and thus improving prognosis. This study aims to evaluate the use of ML algorithms to predict synchronous GU tumors among GIST patients in a specialist research center in Saudi Arabia. Materials and Methods: We analyzed data from all patients with histopathologically confirmed GIST at our facility from 2003 to 2020. Patient files were reviewed for the presence of renal cell carcinoma, adrenal tumors, or other GU cancers. Three supervised ML algorithms were used: logistic regression, XGBoost Regressor, and random forests (RFs). A set of variables, including independent attributes, was entered into the models. Results: A total of 170 patients were included in the study, with 58.8% (n = 100) being male. The median age was 57 (range: 9-91) years. The majority of GISTs were gastric (60%, n = 102) with a spindle cell histology. The most common stage at diagnosis was T2 (27.6%, n = 47) and N0 (20%, n = 34). Six patients (3.5%) had synchronous GU tumors. The RF model achieved the highest accuracy with 97.1%. Conclusion: Our study suggests that the RF model is an effective tool for predicting synchronous GU tumors in GIST patients. Larger multicenter studies, utilizing more powerful algorithms such as deep learning and other artificial intelligence subsets, are necessary to further refine and improve these predictions.

Beyond the Expectation: Pembrolizumab-Associated Tumor Lysis Syndrome in Metastatic Gastric Adenocarcinoma.

Tumor lysis syndrome (TLS) emerges as a critical oncological emergency, a consequence of the body's struggle to manage the intense cellular turnover and release of cytotoxins induced by treatments such as chemotherapy, radiation, targeted immune therapy, or hormonal therapy. While commonly associated with hematological malignancies, the heightened risk also extends to advanced-stage solid tumors and instances of liver metastasis. Although TLS is a rare occurrence in gastric adenocarcinoma, reported cases are usually linked to the initiation of chemotherapy. Remarkably, the incidence of TLS following the commencement of pembrolizumab in gastric adenocarcinoma remains undocumented in the existing literature. In this context, we present a compelling case involving a 73-year-old gentleman diagnosed with advanced-stage metastatic gastric adenocarcinoma. Strikingly, the patient developed TLS subsequent to the initiation of pembrolizumab (Keytruda®). This unique scenario not only accentuates the atypical manifestation of TLS in the context of gastric adenocarcinoma but also underscores the need for heightened awareness and exploration of potential complications associated with immunotherapeutic agents in solid tumor settings. The detailed analysis of this case contributes valuable insights that may prove instrumental in refining our understanding of the intricate interplay between immunotherapy and tumor lysis syndrome in the specific landscape of gastric adenocarcinoma.

FAP-targeted PET imaging in gastrointestinal malignancies: a comprehensive review.

F18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) plays a crucial role in tumour diagnosis, staging, and therapy response evaluation of various cancer types and has been a standard imaging modality used in clinical oncology practice for many years. However, it has certain limitations in evaluating some particular gastrointestinal cancer types due to low FDG-avidity or interphering physiological background activity. Fibroblast activation protein (FAP), a protein of the tumour microenvironment, is overexpressed in a wide range of cancers which makes it an attractive target for both tumour imaging and therapy. Recently, FAP-targeted radiopharmaceuticals are widely used in clinical research and achieved great results in tumour imaging. Considering the limitations of FDG PET/CT and the lack of physiological FAP-targeted tracer uptake in liver and intestinal loops, gastrointestinal cancers are among the most promising indications of FAP-targeted imaging. Herein, we present a comprehensive review of FAP-targeted imaging in gastrointestinal cancers in order to clarify the current and potential future role of this class of molecules in gastrointestinal oncology.

Clinical and endoscopic features of primary small bowel lymphoma: a single-center experience from mainland China.

Objective: The worldwide incidence of primary small intestinal lymphoma (PSIL) is increasing. However, little is known about the clinical and endoscopic characteristics of this disease. The aim of this study was to investigate the clinical and endoscopic data of patients with PSIL, with the goal of enhancing our understanding of the disease, improving diagnostic accuracy, and facilitating more accurate prognosis estimation. Methods: Ninety-four patients diagnosed with PSIL were retrospectively studied at Qilu Hospital of Shandong University between 2012 and 2021. The clinical data, enteroscopy findings, treatment modalities, and survival times were collected and analyzed. Results: Ninety-four patients (52 males) with PSIL were included in this study. The median age of onset was 58.5 years (range: 19-80 years). Diffuse large B-cell lymphoma (n=37) was the most common pathological type. Abdominal pain (n=59) was the most frequent clinical presentation. The ileocecal region (n=32) was the most commonly affected site, and 11.7% of patients had multiple lesions. At the time of diagnosis, the majority of patients (n=68) were in stages I-II. A new endoscopic classification of PSIL was developed, including hypertrophic type, exophytic type, follicular/polypoid type, ulcerative type, and diffusion type. Surgery did not show a significant increase in overall survival; chemotherapy was the most commonly administered treatment. T-cell lymphoma, stages III-IV, "B" symptoms, and ulcerative type were associated with poor prognosis. Conclusion: This study provides a comprehensive analysis of the clinical and endoscopic features of PSIL in 94 patients. This highlights the importance of considering clinical and endoscopic characteristics for accurate diagnosis and prognosis estimation during small bowel enteroscopy. Early detection and treatment of PSIL is associated with a favorable prognosis. Our findings also suggest that certain risk factors, such as pathological type, "B" symptoms, and endoscopic type, may affect the survival of PSIL patients. These results underscore the need for careful consideration of these factors in the diagnosis and treatment of PSIL.

Solitary Extramedullary Plasmacytoma With Development of T-cell Anaplastic Large-Cell Lymphoma: A Rare Case Report and Literature Review.

Solitary extramedullary plasmacytomas are an exceedingly rare form of malignant neoplasms characterized by a single localized mass located in any soft tissue that consists of abnormal plasma cells. This type of tumor is characterized by the absence of plasmacytosis on bone marrow biopsy, the absence of other lesions on imaging, and no clinical signs of multiple myeloma. They usually present with mass effect, so the clinical picture varies based on the location of the tumor. In cases where the tumor is located in the gastrointestinal tract, patients may experience abdominal pain, small bowel obstruction, or gastrointestinal bleeding. The diagnostic process typically involves imaging to identify the tumor and its location, followed by a biopsy of the lesion with subsequent immunohistochemical analysis, as well as fluorescence in situ hybridization, and finally, bone marrow biopsy. Treatment options vary depending on the tumor's location and may include radiation therapy, surgical resection, and chemotherapy. Currently, radiation therapy is the preferred first-line treatment, with the best outcomes reported in the literature. Surgery is also frequently used and is often followed by radiation therapy. While chemotherapy has not been shown to have significant benefits, the available data is insufficient, and further studies are required to make better conclusions. Disease progression is often associated with transformation to multiple myeloma, but due to the rarity of the disease, data is limited, and it remains unclear if other forms of progression exist.   We report a case of a 63-year-old male who presented to the hospital with symptoms of abdominal pain, nausea, and vomiting. A computed tomography scan revealed a mass causing bowel obstruction, which was subsequently resected and evaluated by pathology. The final diagnosis was determined to be a solitary extramedullary plasmacytoma. Since the margins of the resected mass were clear, the patient was managed with solely clinical observation. Approximately eight months later, the patient was diagnosed with T-cell anaplastic large-cell lymphoma, ultimately leading to his passing 15 months after the initial diagnosis of solitary extramedullary plasmacytoma. We present this case to increase awareness of the rare condition of solitary extramedullary plasmacytoma and to highlight the potential association with T-cell anaplastic large-cell lymphomas, as demonstrated in this patient's case. Given the possibility of malignant transformation, close monitoring is warranted in similar cases.

Can Ki-67 predict radiotherapy response in neuroendocrine tumors? Retrospective analysis of a monocentric series of patients.

BACKGROUND: The impact of radiotherapy (RT) in neuroendocrine neoplasms is still unknown, and outcomes could be improved by a better insight in RT response predictors. This retrospective analysis investigates the potential correlation between Ki-67 and RT response to evaluate its role as biological marker of radiosensitivity. MATERIAL AND METHODS: Data from patients treated at an Italian NET-referral center between 2015 and 2020 were retrieved. Inclusion criteria included: histologically-proven diagnosis of NEN, Ki-67 status, indication (symptomatic and/or ablative) and at least one post-RT radiological assessment. RESULTS: Forty-two patients and 63 different treatment lines were included. Primary tumors presented Ki-67 values < 3% in 21% of cases, between 3 and 20% in 45% and >20% in the remaining 33%. Almost all patients were metastatic at the time of RT, which was performed with symptomatic purpose in 43% of cases. At a median time of three months, a complete response on the target lesion was observed in nine cases (14%), a partial response in 17 (27%), stability in 23 (37%) and local progression in 14 (22%). With median FU of 22.8 months, OS does not show statistically significant differences among three Ki-67 groups. Considering all lines of therapy, the relationship between ORR and Ki-67, did not show statistically significant differences, even following adjustments for drug types and delivered RT doses. CONCLUSION: No association between Ki67 and local tumor response to RT could be observed in the present cohort, regardless of whether the evaluation was performed on a categorical or continuous scale.

TK-1, TP, Ang-2, and Tie-2 mRNA expression in plasma-derived microvesicles of chemo-refractory metastatic colorectal cancer patients.

BACKGROUND: Trifluridine/tipiracil and regorafenib are indicated for metastatic colorectal cancer (mCRC) patients' refractory to standard chemotherapy. No prognostic or predictive biomarkers are available for these agents. METHODS: We assessed messenger ribonucleic acid (mRNA) expression of four biomarkers implicated in the mechanism of action of trifluridine/tipiracil (TK-1 and TP) and regorafenib (Ang-2 and Tie-2) in baseline plasma-derived microvesicles of chemo-refractory mCRC patients treated with these agents (trifluridine/tipiracil cohort and regorafenib cohort), to explore their prognostic and predictive role. RESULTS: Baseline characteristics of the two cohorts were not different. Ang-2 mRNA was not detectable. Only TK-1 expression measured as a continuous variable was associated with progression-free survival (HR=1.09, 95%CI: 0.99-1.21; p=0.07) and overall survival (HR=1.11, 95%CI: 1.00-1.22; p=0.04), confirmed at multivariate analysis for progression-free survival (p=0.02) with a positive trend for overall survival (p=0.08). Baseline mRNA levels of TK-1, TP and Tie-2 were not predictive of trifluridine/tipiracil and regorafenib benefit. CONCLUSION: Baseline mRNA levels of TK-1, TP and Tie-2 on plasma-derived microvesicles were not predictive of trifluridine/tipiracil and regorafenib benefit. Future studies should analyze the early modulation of these biomarkers to assess their potential predictive role.

Global burden of major gastrointestinal cancers and its association with socioeconomics, 1990-2019.

Background: To understand the impact of common cancers of the gastrointestinal tract and help to formulate evidence-based policy, we evaluate the relationship between the burden of GI tract cancers and socioeconomics. Methods: Data on GI tract cancer burden were obtained from the Global Burden of Disease (GBD) 2019 including mortality and incidence rates. According to the Socio-demographic Index (SDI) level, country and territory, and sex, etc., the data were further stratified. The association between the burden of GI tract cancer and socioeconomics, indicated by SDI, was described. Uncertainty analysis was estimated using bootstrap draw. Results: In 2019, five major cancers of the gastrointestinal tract led to an age-standardized incidence rate (ASIR) of 61.9 (95% CI 56.1-67.6) per 100 000 person-years. From 1990 to 2019, five common tumors of the gastrointestinal tract related age-standardized death rates (ASDRs) decreased by -22.7% (-31.1 to -13.5). For the five common tumors, ASIRs and ASDRs were both higher in males than those in females. Globally, Mongolia, and several East Asia countries exhibited the highest ASIRs in 2019. The high SDI, and high-middle SDI locations recorded the highest incidence rate and death rate of colon and rectum cancer and pancreatic cancer. On the contrary, the low-middle SDI, and low SDI locations possessed the highest incidence rate and death rate of stomach cancer and esophageal cancer. Conclusion: There is a profound association between socioeconomics and burden of common cancers of the gastrointestinal tract. It would be helpful for the high SDI, and high-middle SDI locations to pay special attention to the screening of colon and rectum cancer and pancreatic cancer while the low-middle SDI, and low SDI locations should pay more attention to the screening of stomach cancer and esophageal cancer.

Angiogenesis in gastrointestinal stromal tumors: From bench to bedside.

Gastrointestinal stromal tumors (GISTs) are rare neoplasms with an estimated incidence from 0.78 to 1-1.5 patients per 100000. They most commonly occur in the elderly during the eighth decade of life affecting predominantly the stomach, but also the small intestine, the omentum, mesentery and rectosigmoid. The available treatments for GIST are associated with a significant rate of recurrent disease and adverse events. Thorough understanding of GIST's pathophysiology and translation of this knowledge into novel regimens or drug repurposing is essential to counter this challenge. The present review summarizes the existing evidence about the role of angiogenesis in GIST's development and progression and discusses its clinical underpinnings.

Colorectal medullary carcinoma: heterogeneous presentations of a rare clinico-pathological entity. Report of two cases.

Colorectal medullary carcinoma (CMC) is a rare subset of minimally differentiated carcinomas. CMC tend to be right-sided and present at an advanced stage. Despite this, distant metastases are rare at presentation. The liver and the regional lymph nodes represent the most common sites of metastases. Most of the time, CMCs exhibit mismatch repair deficiency and a strong association with high-level microsatellite instability. There is no conspicuous data regarding treatment strategies and short-term outcomes. CMC is supposed to be related to better prognosis compared to poorly-differentiated and undifferentiated colonic adenocarcinomas, but reports are controversial.This lesion, with heterogeneous presentations and unclear prognostic significance, may be unfamiliar to histopathologists and can lead to diagnostic uncertainty and overtreatments.Our aim is to renew the attention to this rare histological subtype through the report of two cases.

Molecular regulatory mechanism of ferroptosis and its role in gastrointestinal oncology: Progress and updates.

Gastrointestinal (GI) tumors, including liver, pancreatic, gastric, and colorectal cancers, have a high incidence rate and low survival rate due to the lack of effective therapeutic methods and frequent relapses. Surgery and postoperative chemoradiotherapy have largely reduced the fatality rates for most GI tumors, but these therapeutic approaches result in poor prognoses due to severe adverse reactions and the development of drug resistance. Recent studies have shown that ferroptosis plays an important role in the onset and progression of GI tumors. Ferroptosis is a new non-apoptotic form of cell death, which is iron-dependent, non-apoptotic cell death characterized by the accumulation of lipid reactive oxygen species (ROS). The activation of ferroptosis can lead to tumor cell death. Thus, regulating ferroptosis in tumor cells may become a new therapeutic approach for tumors, making it become a research hotspot. Current studies suggest that ferroptosis is mainly triggered by the accumulation of lipid ROS. Furthermore, several studies have indicated that ferroptosis may be a new approach for the treatment of GI tumors. Here, we review current research progress on the mechanism of ferroptosis, current inducers and inhibitors of ferroptosis, and the role of ferroptosis in GI tumors to propose new methods for the treatment of such tumors.

Comparing Somatostatin Analogs in the Treatment of Advanced Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: The 2 approved somatostatin analogs (SSAs) in the first-line treatment of advanced, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are octreotide long-acting release (Sandostatin LAR) and somatuline depot (Lanreotide). The study's objective was to compare progression-free survival (PFS) and overall survival (OS) of patients (pts) with GEP-NETs treated with somatuline or octreotide LAR. Pts and Methods: Pts with advanced well-differentiated GEP-NET who received either SSA at Emory University between 1995 and 2019 were included after institutional review board approval. The primary end point was PFS, defined as time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.1, or clinical progression) or death. The secondary end point was OS. Kaplan-Meier curves were generated, and log-rank tests were conducted to compare the survival outcomes. RESULTS: A total of 105 pts were identified. The mean age was 62.1 years (SD ± 11.8). The male-to-female ratio was 51:54. The majority (N = 69, 65.7%) were white. Most pts had grade 2 (G2) disease (N = 44, 41.9%). Primary location was small bowel in 58 (55.2%), pancreas in 27 (25.7%), and other in 20 (19.0%). Functional tumors were defined in 32 pts distributed equally between the 2 groups. Distribution of treatment was similar in the 2 groups, with 54 receiving octreotide LAR and 51 receiving somatuline depot. The median PFS for the octreotide LAR and somatuline depot groups was 12 months (95% CI, 6-18 months) and 10.8 months (95% CI, 6-15.6 months), respectively, and the difference was not statistically significant (p = 0.2665). For pts with G1 disease, the median PFS for the octreotide LAR and somatuline depot was 8.4 versus 32.4 months, respectively, and the difference was not statistically significant (p = 0.159). For G2 disease, the difference in median PFS between octreotide LAR and somutaline depot groups was statistically significant (12 vs. 7.2 months, respectively; p = 0.0372). The mean follow-up time for octreotide LAR was 21.6 months versus 11.3 months for somatuline depot. CONCLUSIONS: Overall, there was no difference in PFS between octreotide LAR and somatuline depot for pts with well-differentiated, metastatic GEP-NETs. A prospective study is worth designing selecting for G.