Incidental Finding of an Asymptomatic Jejunal Schwannoma: A Rare Case Report and Review of Literature.

BACKGROUND Schwannomas are tumors that arise from Schwann cells that surround and support nerve cells. Most common sites for presentations are head, neck, and extremities. Schwannomas of gastrointestinal tract are rare, slow-growing tumors, usually benign, arising from gastrointestinal tract's neural plexus. They are histologically distinguishable from conventional schwannomas that arise in soft tissue or the central nervous system. Preoperative diagnosis of gastrointestinal schwannoma is challenging, requiring immunohistological confirmation of the nature of the tumor. Here, we report a case of 57-year-old woman with an incidental finding of an asymptomatic submucosal jejunal schwannoma. CASE REPORT A 57-year-old woman with a medical history of hematological disorder underwent a contrast abdominal computed tomography as part of medical follow-up. The imaging revealed the presence of a jejunal mass. The patient underwent laparoscopic surgical resection of the lesion, followed by side-to-side jejuno-jejunal anastomosis with 4-cm clear surgical margins. The final pathologic study revealed the presence of jejunal schwannoma, as tested positive for S-100 protein. The patient was discharged home on the fourth postoperative day, having an uneventful recovery. CONCLUSIONS Jejunal schwannoma are usually benign and asymptomatic, and they are often discovered incidentally during diagnostic tests for other conditions; therefore, it should be included in the differential diagnosis of gastrointestinal tumors. Surgical treatment appears to be necessary to achieve a definitive diagnosis through a biopsy of the tumor tissue. Benign jejunal schwannomas have a good prognosis.

Immunotherapy in small bowel adenocarcinoma: a potential role?

Small bowel adenocarcinoma (SBA) is a rare tumor with an unfavorable prognosis, and due to its rarity, few studies on its treatment are available. Chemotherapy remains the standard of treatment in advanced disease. Recently immunotherapy has demonstrated to be a valid therapeutic option for many solid tumors. We reviewed the data published in literature to understand the impact of immunotherapy in this cancer.

FDG PET/CT in Follicular Dendritic Cell Sarcoma of the Jejunum With Hepatic Metastasis.

ABSTRACT: Follicular dendritic cell sarcoma of the gastrointestinal tract is a rare malignancy. We describe contrast-enhanced CT and FDG PET/CT findings in a case of jejunal follicular dendritic cell sarcoma with hepatic metastasis. The primary jejunal tumor showed inhomogeneous enhancement on contrast-enhanced CT and intense FDG uptake on PET/CT mimicking adenocarcinoma or gastrointestinal stromal tumor. The hepatic metastatic tumor showed hypovascularity on contrast-enhanced CT and mild FDG uptake on PET/CT. This case indicates that follicular dendritic cell sarcoma should be included in the differential diagnosis of the hypermetabolic intestinal lesions.

Small intestinal angiosarcoma on clinical presentation, diagnosis, management and prognosis: A case report and review of the literature.

BACKGROUND: Angiosarcoma is a highly malignant soft-tissue sarcoma derived from vascular endothelial cells that mainly occurs in the skin and subcutaneous tissues. Small-intestinal angiosarcomas are rare, and the prognosis is poor. CASE SUMMARY: We reported a case of primary multifocal ileal angiosarcoma and analyze previously reported cases to improve our understanding of small intestinal angiosarcoma. Small intestinal angiosarcoma is more common in elderly and male patients. Gastrointestinal bleeding, anemia, abdominal pain, weakness, and weight loss were the common symptoms. CD31, CD34, factor VIII-related antigen, ETS-related gene, friend leukemia integration 1, and von Willebrand factor are valuable immunohistochemical markers for the diagnosis of small-intestinal angiosarcoma. Small-intestinal angiosarcoma most commonly occurs in the jejunum, followed by the ileum and duodenum. Radiation and toxicant exposure are risk factors for angiosarcoma. After a definite diagnosis, the mean and median survival time was 8 mo and 3 mo, respectively. Kaplan-Meier survival analysis showed that age, infiltration depth, chemotherapy, and the number of small intestinal segments invaded by tumor lesions were prognostic factors for small intestinal angiosarcoma. Multivariate Cox regression analysis showed that chemotherapy and surgery significantly improved patient prognosis. CONCLUSION: Angiosarcoma should be considered for unexplained melena and abdominal pain, especially in older men and patients with a history of radiation exposure. Prompt treatment, including surgery and adjuvant chemotherapy, is essential to prolonging patient survival.

Characteristics and outcome of patients with small bowel adenocarcinoma (SBA).

BACKGROUND: Small bowel adenocarcinoma (SBA) remains a rare malignancy accounting for less than 5% of all the gastrointestinal tract cancers. However, only limited data and expert guidelines are available for this entity. As a result, treatment concepts are predominantly derived from colorectal cancer. METHODS: To substantiate data on the course of disease, diagnosis and treatment of SBA, we performed a population-based analysis from a Bavarian population of 2.2 million people. RESULTS: We identified 223 patients with SBA. Mean age at diagnosis was 67.8 years and patients were diagnosed rather late (34.5% UICC stage IV). Largest proportion of these patients were diagnosed with adenocarcinoma of the duodenum (132 patients, 59.2%) and most patients were diagnosed with late stage cancer, stage IV (70 patients, 31.4%). With respect to treatment, most patients underwent primary surgery (187 patients, 84.6%). Systemic therapy seemed to have an impact in UICC stage IV patients but not in UICC stage IIB or III. The 5-year survival rate was 29.0%. This was significantly less compared to colon cancer in the same cohort, which was 50.0%. Furthermore, median survival of patients with small bowel cancer was only 2.0 years (95% CI 1.4-2.5) compared to 4.9 years (95% CI 4.8-5.1) of patients with colon cancer. CONCLUSION: SBA showed a distinct epidemiology compared to colon cancer. Thus, data acquisition particularly on systemic treatment are paramount, with the objective to complement the available guidelines.

The Number of Lymph Nodes Examined is Associated with Survival Outcomes of Neuroendocrine Tumors of the Jejunum and Ileum (siNET): Development and Validation of a Prognostic Model Based on SEER Database.

PURPOSE: The number of neuroendocrine tumors (NETs) is gradually increasing worldwide, and those located in the small intestine (siNETs) are the most common. As some biological and clinical characteristics of tumors of the jejunum and the ileum differ, there is a need to assess the prognosis of individuals with siNETs of the jejunum and ileum separately. We generated a predictive nomogram by assessing individuals with siNETs from the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: We used univariate Cox regression analysis to determine both the overall survival (OS) and the cancer-specific survival (CSS) of 2501 patients with a pathological confirmation of siNETs of the jejunum and ileum. To predict 3-, 5-, and 10-year OS of siNETs, a nomogram was generated based on a training cohort and validated with an external cohort. Accuracy and clinical practicability were evaluated separately by Harrell's C-indices, calibration plots, and decision curves. The correlation was examined between dissected lymph nodes and positive lymph nodes. RESULTS: Dissection of 7 or more lymph nodes significantly improved patient OS and was found to be a protective factor for patients with siNETs. In Cox regression analyses, age, primary site, tumor size, N stage, M stage, and regional lymph node examination were significant predictors in the nomogram. A significant positive correlation was found between dissected lymph nodes and positive lymph nodes. CONCLUSIONS: Patients with 7 or more dissected lymph nodes showed an accurate tumor stage and a better prognosis. Our nomogram accurately predicted the OS of patients with siNETs.

Current Oncologic Standards for Surgery of Small Bowel Cancers.

PURPOSE: The last 2 decades has witnessed efforts towards standardization of surgery for small bowel cancers. The proposed recent guidelines/recommendations pertaining to choice of procedure and extent of lymphadenectomy are based on analysis of data from high volume centres of excellence. We evaluated whether these recently proposed oncologic recommendations can be replicated in the setting of single centre/team. METHODS: This was a retrospective analysis of consecutive adult patients (age ≥ 18 years) who underwent surgery for tumours of small intestine (duodenum, jejunum, and ileum) by the same team of surgeons from 01/01/2010 to 12/31/2019. The procedure performed and lymph nodes harvested during pathologic examination were compared with recent recommendations. RESULTS: Of the 32 patients (20 males and 12 females), mean age was 52.4 (range 31-77) years. Twenty-nine (90.6%) patients underwent surgery for small bowel cancers. Duodenum was the most common site, while NET was the commonest cancer. Whipple's procedure was performed for tumours of II part of duodenum, while for the rest, segmental resection was performed. The median number of lymph nodes examined for duodenal adenocarcinoma and NET was 14 and 9, respectively. For jejunal/ileal adenocarcinoma, median lymph node number examined was 11. CONCLUSION: Our study shows that these recently proposed standards for surgery of small bowel cancers are achievable if basic principles of oncologic surgery are followed.

Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma.

BACKGROUND: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. METHODS: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, ß-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. RESULTS: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. CONCLUSION: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

How to Manage Small Intestine (Jejunal and Ileal) Neuroendocrine Neoplasms Presenting with Liver Metastases?

PURPOSE OF REVIEW: Small intestinal neuroendocrine neoplasms (siNENs) are slowly growing tumours with a low malignant potential. However, more than half of the patients present with distant metastases (stage IV) and nearly all with locoregional lymph node (LN) metastases at the time of surgery. The value of locoregional treatment is discussed controversially. RECENT FINDINGS: In stage I to III disease, locoregional surgery was currently shown to be curative prolonging survival. In stage IV disease, surgery may prolong survival in selected patients with the chance to cure locoregional disease besides radical/debulking liver surgery. It may improve the quality of life and may prevent severe local complications resulting in a state of chronic malnutrition and severe intestinal ischaemia or bowel obstruction. Locoregional tumour resection offers the opportunity to be curative or to focus therapeutically on liver metastasis, facilitating various other therapeutic modalities. Risks and benefits of the surgical intervention need to be balanced individually.

Genomic analysis for the prediction of prognosis in small-bowel cancer.

The current understanding of clinicopathological features and genomic variants of small-bowel cancer is limited, in part due to the rarity of the disease. However, understanding of these factors is necessary for the development of novel therapeutic agents for small-bowel cancer. Thus, we aimed to identify the clinicopathological features and genomic variants associated with its prognosis and recurrence. We retrospectively examined 24 consecutive patients with primary small-bowel cancer surgically treated between May 2005 and August 2018 and collected 29 tumor specimens. The 29 lesions were subjected to mismatch repair status evaluation, using immunohistochemistry (IHC), and targeted genomic sequencing, after which they were analyzed using a panel of 90 cancer-related genes. IHC revealed that 45% (13/29) of the lesions exhibited deficient mismatch repair. The most common genomic variants in small-bowel cancers were in TP53 (48%, 13/27), followed by KRAS (44%, 12/27), ARID1A (33%, 9/27), PIK3CA (26%, 7/27), APC (26%, 7/27), and SMAD4, NOTCH3, CREBBP, PTCH1, and EP300 (22%, 6/27 each). Overall survival and disease-specific survival of patients with tumor mutational burden (TMB) ≥10 mutations/Mb (n = 17) were significantly better than those of patients with TMB <10 mutations/Mb (n = 6). Additionally, patients with a mutant SMAD4 had poorer recurrence-free survival than those with wild-type SMAD4. Our results suggested that TMB and SMAD4 mutations were associated with the prognosis of small-bowel cancer patients. Thus, cancer genomic analysis could be useful in the search for biomarkers of prognosis prediction in small-bowel cancers.

Clinical features, treatment, and prognosis of different histological types of primary small bowel adenocarcinoma: A propensity score matching analysis based on the SEER database.

PURPOSE: This aim of this study was to provide a comprehensive understanding of the clinical characteristics, treatment, and prognosis of patients with small bowel adenocarcinoma (SBA), mucinous small bowel adenocarcinoma (MSBA), and signet ring cell carcinoma of the small bowel (SRCSB). METHODS: Information on patients with SBA, MSBA, and SRCSB (2004-2015) was obtained from the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional hazards models and Kaplan-Meier curves were used for the survival analyses. Propensity-score matching (PSM) was implemented to determine the differences among these tumors. RESULTS: In all, 3697 patients with SBA (n = 3196), MSBA (n = 325) and SRCSB (n = 176) were ultimately eligible for this study. Poor differentiation, local invasion, and lymph node metastasis were more likely to be observed in SRCSB than in SBA and MSBA. Surgery was the most common treatment modality in all groups. The prognosis of SBA was similar to that of MSBA, but better than that of SRCSB in both unmatched and matched cohorts. M stage, surgery, and chemotherapy were identified as independent predictors of survival in all patients. Surgery and chemotherapy could significantly improve outcomes in all groups before and after PSM. Radiotherapy was associated with a survival benefit in patients with SBA, but this trend was not maintained after PSM. Survival advantages of SBA and MSBA were remarkable in the stratified analysis of surgery after PSM. CONCLUSION: Patients with SRCSB had the worst prognosis among all histological types examined. However, surgery and chemotherapy could improve patients survival, regardless of histological type.

ZEBRA: A Multicenter Phase II Study of Pembrolizumab in Patients with Advanced Small-Bowel Adenocarcinoma.

PURPOSE: Small-bowel adenocarcinoma (SBA) is rare, and no standard of care exists for metastatic disease beyond first-line FOLFOX/CAPOX. SBA has higher rates of microsatellite instability (MSI-H) and T-lymphocyte infiltration than other gastrointestinal cancers. We hypothesize that pembrolizumab, a PD-1 inhibitor, will induce antitumor response. PATIENTS AND METHODS: Patients with previously treated advanced SBA received pembrolizumab 200 mg i.v. every 3 weeks until disease progression (PD), toxicity, or 35 doses maximum. Primary endpoint was confirmed overall response rate (ORR) with secondary progression-free survival (PFS), overall survival (OS), and toxicity assessment endpoints. Outcomes were stratified by tumor location, microsatellite stability (MSS) or instability (MSI-H), and PD-L1 level. RESULTS: Forty patients were treated for a median duration of four cycles (range, 1-35). All patients are off study treatment due to PD (75%), death (10%), 35 cycles completed (8%), refusal (3%), and adverse effects (AEs, 5%). Three confirmed partial responses [PRs; 8%; 95% confidence interval (CI), 2-20] did not meet predefined success criteria of ORR 30%. Median OS (7.1 months; 95% CI, 5.1-17.1) and median PFS (2.8 months; 95% CI, 2.7-4.2) were similar across primary tumor sites. One confirmed PR (3%) was seen in patients with low MSS/MSI tumors and correlated with high tumor mutation burden (TMB). Fifty percent of patients with MSI-H tumors achieved PR and remain alive without progression. Twenty-five patients (63%) had grade ≥3 AEs and 11 patients (28%) had grade 4/5 AEs. CONCLUSIONS: In the largest study of SBA to date, pembrolizumab did not induce the hypothesized response rate; however, we did identify responses in key biomarker-selected cohorts.

Time trends in incidence and survival of small intestinal cancer in Sweden.

BACKGROUND: Small intestinal cancer is less common than some other gastrointestinal malignancies. Tumours of different histological types and anatomical sites of origin have therefore often been described together. The aim of this study was to investigate the epidemiology for each of the four main subtypes: duodenal adenocarcinoma (D-AC), duodenal neuroendocrine tumour (D-NET), jejunoileal adenocarcinoma (J/I-AC), and jejunoileal neuroendocrine tumour (J/I-NET). METHODS: All patients with small intestinal cancer diagnosed between 1960 and 2015 were identified from the Swedish Cancer Register. The age-adjusted incidence rate with incidence rate ratios, as well as overall (OS) and net (NS) survival, were determined and temporal trends were analysed. RESULTS: The incidence rate was highest for J/I-NET, with 9.98 clinical diagnoses per million in 2010-2015. Clinical diagnosis of D-AC increased more than 10-fold and surpassed J/I-AC as the second most common subtype. D-NET was by far the least common subtype. Diagnosis at autopsy became less common over time, whereas clinical diagnoses increased significantly for all four subtypes. All subtypes except J/I-AC affected men more often than women. The age distribution was similar between subtypes, although patients with adenocarcinomas were slightly older. Survival was generally much better for patients with NET than for those with adenocarcinoma. Both OS and NS showed a negative association with advancing age. Survival improved only for J/I-NET from a 5-year NS of 0.69 in the 1960s to 0.81 in 2010-2015. CONCLUSION: The incidence of small intestinal cancer is increasing, particularly for D-AC and in the elderly. Survival of patients with small intestinal cancer has improved only for J/I-NET over the last decades.

Tumor Microenvironmental Prognostic Risk in Primary Operable Small Intestinal Adenocarcinoma.

The tumor microenvironment (TME) has become an important area of investigation with respect to improving prognosis in malignancies. Here we evaluated TME prognostic risk in small intestinal adenocarcinomas based on histologic assessment of tumor budding at the peritumoral-invasive front (pTB) and stromal tumor-infiltrating lymphocytes (sTILs). pTB and sTILs were analyzed in 230 surgically resected small intestinal adenocarcinomas, as recommended by the International Tumor Budding Consensus Conference (ITBCC) and the International TILs Working Group (ITWG). On the basis of high levels of pTB count (≥10) and sTIL density (≥20%), we combined pTB and sTIL to produce a collective TME-based prognostic risk index: low-risk (pTBLow/sTILHigh; n=39, 17.0%), intermediate-risk (pTBLow/sTILLow or pTBHigh/sTILHigh; n=99, 43.0%), and high-risk groups (pTBHigh/sTILLow; n=92, 40.0%). TME risk index provided better prognostic stratification than the individual pTB and sTIL (14.9 vs. 6.7 vs. 10.3). Tumors with higher TME prognostic risk were associated with an infiltrative growth pattern and nonintestinal immunophenotype (both P=0.001), pancreatic invasion (P=0.010), lymphovascular (P<0.001) or perineural invasion (P=0.006), higher T-category (P<0.001), N-category (P=0.004), and stage grouping (P=0.002), and KRAS mutation (P=0.008). In multivariate analysis, higher TME prognostic risk index (P<0.001), distal tumor location and nonintestinal immunophenotype (both P=0.001), higher N-category (P<0.001), and microsatellite stable (P=0.015) were worse-independent prognosticators. TME prognostic risk index consistently stratified patient survival regardless of tumor location (P<0.001 in proximal; P=0.002 in distal), stages (P<0.001 in lower stages I to II; P=0.028 in stage III), and DNA mismatch repair gene status (P<0.001 in microsatellite stable; P=0.001 in microsatellite instability). TME risk index is a powerful prognostic predictor for risk stratification of patients with small intestinal adenocarcinoma.

A Rare Case of Well-Differentiated Neuroendocrine Tumor Arising From a Jejunal Pancreatic Heterotopia.

Pancreatic heterotopia is a well-described entity occurring at multiple abdominal sites, most commonly the stomach and small intestine. They can develop similar disease processes as the pancreas ranging from acute pancreatitis, cyst formation, or neoplasms, most commonly ductal adenocarcinoma. Neuroendocrine tumors (NETs) arising in pancreatic heterotopias are exceedingly rare with only 3 prior published cases. In this article, we describe the first reported case of a NET arising in a jejunal pancreatic heterotopia in a 59-year-old woman presenting with abdominal pain and diarrhea. The submucosal tumor was composed of a well-differentiated NET (World Health Organization grade 1) directly intermixed with a heterotopic pancreas consisting of acinar cells, islet cells, and ducts. This case illustrates that NETs can occur in association with pancreatic heterotopias at any site. Also, the importance for pathologists to recognize that pancreatic heterotopias can give rise to a variety of neoplasms and is not limited to ductal adenocarcinoma.

Jejunal schwannoma detected by video capsule endoscopy

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