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.

Results of diagnosis and surgery of small bowel cancer at Bach Mai Hospital

Tóm tắt Đặt vấn đề: Ung thư ruột non là khối u hiếm gặp, thường được chẩn đoán và phẫu thuật ở giai đoạn muộn khi biến chứng đã xảy ra. Nghiên cứu nhằm mô tả đặc điểm lâm sàng, cận lâm sàng, đánh giá kết quả phẫu thuật ung thư ruột non. Phương pháp nghiên cứu: Nghiên cứu mô tả, hồi cứu 45 người bệnh (NB) ung thư ruột non nguyên phát được phẫu thuật tại Bệnh viện Bạch Mai từ 2012 đến 2016. Thu thập các đặc điểm lâm sàng, cận lâm sàng, chẩn đoán trước mổ, mô bệnh học, kết quả điều trị và thời gian sống thêm. Kết quả: 45 NB gồm 23 nam, 22 nữ, hay gặp ở nhóm 41 đến 60 tuổi. Triệu chứng đa dạng, không đặc hiệu và thay đổi theo thể giải phẫu bệnh, có 64,4% chẩn đoán được trước mổ là u ruột non. Chụp cắt lớp vi tính chẩn đoán chính xác 56,7%. Thể saccom cơ trơn gặp nhiều nhất (51,1%), carcinoid gặp ít nhất (4,4%). Kết quả điều trị không có tử vong, 8,9% nhiễm trùng vết mổ. Thời gian sống thêm sau mổ trung bình là 71,1 ± 1,98 tháng, thể ung thư biểu mô tuyến ngắn nhất 22,1 ± 9,5 tháng, thể u carcinoid dài nhất 54,7 ± 12,2 tháng, tuổi >30 tiên lượng tốt hơn nhóm < 30. Kết luận: Ung thư ruột non vẫn còn khó chẩn đoán đúng trước mổ. Điều trị phẫu thuật có hiệu quả tốt và tiên lượng phụ thuộc lứa tuổi và thể mô bệnh học. Abstract Introduction: Small intestine cancer is a rare tumor that is usually diagnosed and operated at a later stage when complications have occurred. Objectives: Describe clinical, subclinical characteristics and surgical results of small intestine cancer. Tạp chí Phẫu thuật nội soi và Nội soi Việt Nam (2020) Số 5 - Tập 10; 27 - 32 27 Kết quả chẩn đoán và điều trị phẫu thuật ung thư ruột non tại Bệnh viện Bạch Mai Trần Hiếu Học và cộng sự Materials and Methods: Descriptive and longitudinal study on 45 patients of primary small bowel cancer operated at Bach Mai Hospital from 2012 to 2016. Data included clinical, subclinical characteristics, diagnosis, histopathology, results of treatment and survival time. Results: The study has 45 patients (23 males and 22 females), most of them aged 41 - 60. Symptoms are diverse, nonspecific and vary according to disease anatomy, correct preoperative diagnosis of small bowel tumor was 64.4% and sensitivity of CT was 56.7%. Frequency of Sarcoma was highest (51.1%) and of carcinoid was least (4.4%). There was no postoperative mortality, 8.9% incision infection. The survival time is 71.1 ± 1.98 months, shortest belongs to carcinoma (22,1 ± 9,5 months) and longest belongs to carcinoid (54,7 ± 12,2 months), prognosis is better in the age group over 30. Conclusions: Proper preoperative diagnosis of small bowel cancer is still difficult. Surgical treatment is effective and prognosis depends on age and histopathology. Keywords: Small bowel cancer, surgery, survival time.

Clinical outcome after surgical resection of small bowel cancer

Background: Small bowel cancer (SBC) is rare, however there is recent trend toward increased incidence.Methods: Retrospective evaluation of the clinical presentation, diagnosis, management and clinical outcome of adult patients with primary SBC who were admitted at Sohag University Hospital during 2014-2019.Results: Twenty-one patients with SBC were enrolled (14 males and 7 females) with median age of 56 (range 32-83) years. Small bowel mass was identified preoperatively in 13 patients (62%). Thirteen patients (62%) presented with abdominal emergencies after failure of prompt diagnosis of non-specific abdominal pain of variable durations (median: 4, range: 2-11 weeks). Apart from duodenal tumors, histopathological diagnosis for jejunal and ileal tumors was not achieved preoperatively. Tumor types were gastrointestinal stromal tumors, GISTs (9, 43%), lymphoma (8, 38%) and adenocarcinoma (4, 19%). Patients with jejunal and ileal masses were managed by resection and primary anastomosis. Duodenal tumors required local resection in 2 and pancreatico-duodenectomy in 4 patients. Increased risk of aggressive behavior in GISTs, advanced stage and incomplete resection in lymphomas and adenocarcinomas were associated with higher recurrence rates and diminished survival. Follow-up ranged from 5 to 48 months, with survival rate of 76% (16 patients alive).Conclusions: The diagnosis of SBC is difficult and delayed. Appropriate surgical management, even during emergency, could achieve prolonged survival.

Frequency, prognosis and treatment modalities of newly diagnosed small bowel cancer with liver metastases

Background Population-based analysis for the liver metastases of small bowel cancer is currently lacking. This study aimed to analyze the frequency, prognosis and treatment modalities for newly diagnosed small bowel cancer patients with liver metastases. Methods Patients with small bowel cancer diagnosed from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Binary logistic regression analysis was performed to determine predictors for the presence of liver metastases at diagnosis. Kaplan–Meier method and Cox regression analyses were performed for survival analyses. Results A total of 1461 small bowel cancer patients with liver metastases at initial diagnosis were identified, representing 16.5% of the entire set and 63.9% of the subset with metastatic disease to any distant site. Primary tumor with poorer histological type, larger tumor size, later N staging, more extrahepatic metastatic sites, and tumor on lower part of small intestine had increased propensity of developing liver metastases. The combined diagnostic model exhibited acceptable diagnostic efficiency with AUC value equal to 0.749. Patients with liver metastases had significant poorer survival (P < 0.001) than those without liver metastases. In addition, combination of surgery and chemotherapy (HR = 0.27, P < 0.001) conferred the optimal survival for patients with adenocarcinoma, while the optimal treatment options for NEC and GIST seemed to be surgery alone (HR = 0.24, P < 0.001) and chemotherapy alone (HR = 0.08, P = 0.022), respectively. Conclusions The combined predictor had a good ability to predict the presence of liver metastases. In addition, those patients with different histologic types should be treated with distinct therapeutic strategy for obtaining optimal survival.

Prevalence of mismatch repair deficiency and Lynch syndrome in a cohort of unselected small bowel adenocarcinomas

AimsPrevious estimates of the prevalence of mismatch repair (MMR) deficiency and Lynch syndrome in small bowel cancer have varied widely. The aim of this study was to establish the prevalence of MMR deficiency and Lynch syndrome in a large group of small bowel adenocarcinomas.MethodsTo this end, a total of 400 small bowel adenocarcinomas (332 resections, 68 biopsies) were collected through the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief (PALGA)). No preselection criteria, such as family history, were applied, thus avoiding (ascertainment) bias. MMR deficiency status was determined by immunohistochemical staining of MMR proteins, supplemented by MLH1 promoter hypermethylation analysis and next generation sequencing of the MMR genes.ResultsMMR deficiency was observed in 22.3% of resected and 4.4% of biopsied small bowel carcinomas. Prevalence of Lynch syndrome was 6.2% in resections and 0.0% in biopsy samples. Patients with Lynch syndrome-associated small bowel cancer were significantly younger at the time of diagnosis than patients with MMR-proficient and sporadic MMR-deficient cancers (mean age of 54.6 years vs 66.6 years and 68.8 years, respectively, p<0.000).ConclusionsThe prevalence of MMR deficiency and Lynch syndrome in resected small bowel adenocarcinomas is at least comparable to prevalence in colorectal cancers, a finding relevant both for treatment (immunotherapy) and family management. We recommend that all small bowel adenocarcinomas should be screened for MMR deficiency.

Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden

ObjectiveCrohn’s disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD).DesignIn a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969–2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs).ResultsWe identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32).ConclusionSBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.