In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarc...In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.展开更多
BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens b...BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 50%and 56%of the cases,respectively.Deficient MMR(dMMR)was 14%of the cases.T-PD-L1,I-PD-L1 and PD-L1 CPS≥10 were all significantly associated with dMMR(P=0.037,P=0.009,and P=0.005,respectively).T-PD-L1,I-PD-L1,and PD-L1 CPS≥10 were all associated with deeper depth of invasion(P=0.001,P=0.024,and P=0.002,respectively).I-PD-L2 expression and PD-L2 CPS≥10 were significantly higher in the differentiated histological type(P=0.015 and P=0.030,respectively).The I-PD-L1 and IPD-L2 levels were significantly associated with better CSS(P=0.037 and P=0.015,respectively).CD8-high was significantly associated with less lymph node metastasis(P=0.047),less distant metastasis(P=0.024),less peritoneal dissemination(P=0.034),and earlier TNM stage(P=0.047).The CD8-high group had better prognosis than the CD8-low group(P=0.018).FoxP3 expression was not associated with any clinicopathological factors or prognosis.We found that patients with PD-L2 CPS≥10 tended to have worse prognosis in the FoxP3/CD8-low group(P=0.088).CONCLUSION The clinicopathological significance of PD-L1/2 expression may differ depending on the TME status.Immune checkpoint inhibitors may improve the prognosis of SBA patients with low FoxP3/CD8 ratio and PD-L2 expression.展开更多
BACKGROUND Small bowel adenocarcinomas(SBA) are rare malignancies with exceedingly low survival rates, with different presentation in Crohn’s disease(CD). CD-induced SBA poses diagnostic challenges given overlapping ...BACKGROUND Small bowel adenocarcinomas(SBA) are rare malignancies with exceedingly low survival rates, with different presentation in Crohn’s disease(CD). CD-induced SBA poses diagnostic challenges given overlapping presentation with stricturing CD and lack of diagnostics for early detection. Moreover, guidance is lacking on the impact of recently approved therapeutics in CD on SBA management. Here, we aim to highlight the future of CD-induced SBA management and discuss the potential merit of balloon enteroscopy and genetic testing for earlier detection.CASE SUMMARY We report the case of a 60-year-old female with longstanding Crohn’s ileitis, presenting with acute obstructive symptoms attributed to stricturing phenotype. Her obstructive symptoms were refractory to intravenous(Ⅳ) steroids, with further investigation via computed tomography enterography not providing additional diagnostic yield. Ultimately, surgical resection revealed SBA in the neoterminal ileum, with oncologic therapy plan created. However, this therapy plan could not be initiated due to continued obstructive symptoms attributed to active CD. Ultimately, infused biologic therapy was initiated, but her obstructive symptoms continued to remain dependent on Ⅳ corticosteroids. Review of diagnostics by a multidisciplinary care team suggested metastatic disease in the peritoneum, lending to a shift in the goals of care to comfort.CONCLUSION With the diagnostic and therapeutic challenges of concurrent SBA and CD, multidisciplinary care and algorithmic management can optimize outcomes.展开更多
BACKGROUND Epstein–Barr virus(EBV)-positive mucocutaneous ulcers(MCUs)are an uncommon disorder characterized by ulcerative lesions in the skin,oral cavity or gastrointestinal tract in patients with iatrogenic or agin...BACKGROUND Epstein–Barr virus(EBV)-positive mucocutaneous ulcers(MCUs)are an uncommon disorder characterized by ulcerative lesions in the skin,oral cavity or gastrointestinal tract in patients with iatrogenic or aging-induced immunosuppression.The nonspecific lesions are difficult to differentiate from small bowel adenocarcinomas.We present the case of a 69-year-old woman who was initially misdiagnosed with a small bowel adenocarcinoma but was later surgically diagnosed with and treated for EBV-MCU.Through this case,we aim to emphasize the importance of accurately distinguishing between the two conditions.CASE SUMMARY The patient presented with an incidental finding of a small bowel tumor during computed tomography(CT)examination performed for hematuria.The CT scan showed irregular thickening of the distal ileum,which was suggestive of a malignant small bowel tumor.An exploratory laparotomy revealed an 8-cm mass in the distal ileum;thus,a segment of the small intestine,including the mass,was resected.Histopathological analysis revealed an ulceroinfiltrative mass-like lesion with luminal narrowing,marked inflammatory cell infiltration,and large atypical lymphoid cells(positive for EBV-encoded small RNA).A final diagnosis of an EBV-MCU was established.The postoperative course was uneventful,and the patient was discharged on postoperative day 7.The patient remained recurrencefree until 12 mo after surgery.CONCLUSION This case highlights the diagnostic challenges for EBV-MCUs and emphasizes the importance of comprehensive evaluation and accurate histopathological analysis.展开更多
Small bowel adenocarcinomas are remarkable for their rarity, difficult diagnosis and poor prognosis. Here we report an unusual case of a 33-year-old patient in whom infiltrative adenocarcinoma of the small bowel was d...Small bowel adenocarcinomas are remarkable for their rarity, difficult diagnosis and poor prognosis. Here we report an unusual case of a 33-year-old patient in whom infiltrative adenocarcinoma of the small bowel was diagnosed after a 10-year history of Crohn＇s disease. In most previously reported cases, detection of Crohn＇s disease was subsequent tothat of carcinoma of the small bowel or the patients involved had an even longer history of the disease. Our literature review suggests that the risk of small bowel adenocarcinoma is higher in patients with Crohn＇s disease than in the overall population. We present details on epidemiology as well as clinical and diagnostic aspects of this rare disease entity.展开更多
A 40-year-old male, diagnosed with mild Crohn's disease (CD) 11 years ago but with no prior abdominal surgeries, was diagnosed with a small bowel stricture, due to ongoing abdominal pain and intolerance of enteral...A 40-year-old male, diagnosed with mild Crohn's disease (CD) 11 years ago but with no prior abdominal surgeries, was diagnosed with a small bowel stricture, due to ongoing abdominal pain and intolerance of enteral diet, and referred for surgical treatment. Exploratory laparoscopy revealed a white solid mass causing a near total jejunal obstruction with significant proximal dilatation. An adjacent small node was sampled for frozen biopsy, revealing a lymph node infiltrated with adenocarcinoma. Laparoscopic assisted small bowel resection and appendectomy were carried out. Final pathological results supported the initial report of diffuse small bowel adenocarcinoma. In conclusion, once a small bowel stricture associated with CD is suspected, rapid action should be considered to avoid late diagnosis of a neoplasia.展开更多
Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity, previous studies have traditionally combined duodenal adenocarcinoma(DA) with either other periampullary cancers or small bowel adenocarci...Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity, previous studies have traditionally combined duodenal adenocarcinoma(DA) with either other periampullary cancers or small bowel adenocarcinomas, limiting the available data to guide treatment decisions. Nevertheless, management primarily involves complete surgical resection when technically feasible. Surgery may require pancreaticoduodenectomy or segmental duodenal resection; either are acceptable options as long as negative margins are achievable and an adequate lymphadenectomy can be performed. Adjuvant chemotherapy and radiation are important components of multi-modality treatment for patients at high risk of recurrence. Further research would benefit from multiinstitutional trials that do not combine DA with other periampullary or small bowel malignancies. The purpose of this article is to perform a comprehensive review of DA with special focus on the surgical management and principles.展开更多
目的：分析原发性小肠腺癌（primary small bowel adenocarcinoma,PSBA）的临床表现、诊断治疗及预后因素。方法：回顾性分析31例PSBA患者的临床资料并进行生存分析。结果：31例患者中男性17例,女性14例,中位发病年龄为67岁,好发于十二...目的：分析原发性小肠腺癌（primary small bowel adenocarcinoma,PSBA）的临床表现、诊断治疗及预后因素。方法：回顾性分析31例PSBA患者的临床资料并进行生存分析。结果：31例患者中男性17例,女性14例,中位发病年龄为67岁,好发于十二指肠并以贫血为主要表现。术前确诊率为38.7%,Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期患者分别占9.7%、22.6%、35.5%、32.2%。31例患者中20例行根治性手术,5例行姑息性手术,11例接受化疗,中位生存期为22个月,5年生存率仅为19%。年龄〉65岁、Ⅲ~Ⅳ期、局部淋巴结转移数≥4个患者的中位生存期分别低于年龄≤65岁、Ⅰ~Ⅱ期、局部淋巴结转移数≤3个患者的中位生存期,差异有统计学意义（P〈0.05）;性别、病理分级、肿瘤原发部位、肿瘤标志物及根治术后有无化疗等因素对患者中位生存期影响的差异无统计学意义（P值分别为0.396、0.141、0.082、0.877、0.599）。结论：PSBA临床表现无特异性,确诊时多为进展期,预后差。外科手术是主要的治疗方式。年龄、临床分期及局部淋巴结转移数目等因素可能成为临床评估生存期的指标。展开更多
文摘In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.Small bowel adenocarcinoma(SBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,SBA accounts for less than 3%of such tumors.Early detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor prognosis.Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor prognosis.SBAs are linked to genetic disorders and risk factors,including chronic inflammatory conditions.The unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis.Programmed cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic value.Microsatellite instability(MSI)in SBA is associated with a high tumor mutational burden,affecting the prognosis and response to immunotherapy.The presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis,especially in the context of high MSI tumors.Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.
基金The study was reviewed and approved by the Nippon Medical School Institutional Review Board(Approval No.B-2020-164).
文摘BACKGROUND Comprehensive genomic analysis has shown that small bowel adenocarcinoma(SBA)has different genomic profiles from gastric and colorectal cancers.Hence,it is essential to establish chemotherapeutic regimens based on SBA characteristics.The expression of programmed cell death-ligand 1(PD-L1)and programmed cell death-ligand 2(PD-L2)in SBA is not fully understood.Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes(TILs);therefore,the status of TILs in the tumor microenvironment(TME)may influence their efficacy.The ratio of FoxP3+to CD8+T cells has been reported to be useful in predicting the prognosis of digestive system cancers.AIM To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.METHODS We performed immunohistochemical analysis for PD-L1,PD-L2,CD8,FoxP3,and DNA mismatch repair(MMR)proteins using formalin-fixed,paraffin-embedded tissues from 50 patients diagnosed with primary SBA.The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins,and finally evaluated using the combined positive score(CPS).We assessed CD8+and FoxP3+T cells in the intratumoral and tumor-surrounding stroma.Subsequently,we calculated and summed the ratio of FoxP3 to CD8+T cell counts.Immune-related cell densities were graded as low or high.Immunohistochemical results were compared with clinicopathological factors and patient prognosis.The distribution of cancer-specific survival(CSS)was estimated using the Kaplan–Meier method,and the log-rank test was used to test for significant differences in CSS.A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.RESULTS PD-L1 expression was positive in 34%in tumor cells(T-PD-L1)and 54%in tumor-infiltrating immune cells(I-PDL1)of the cases examined.T-PD-L2 was positive in 34%and I-PD-L2 was positive in 42%of the cases.PD-L1 CPS≥10 and PD-L2 CPS≥10 were observed in 50%and 56%of the cases,respectively.Deficient MMR(dMMR)was 14%of the cases.T-PD-L1,I-PD-L1 and PD-L1 CPS≥10 were all significantly associated with dMMR(P=0.037,P=0.009,and P=0.005,respectively).T-PD-L1,I-PD-L1,and PD-L1 CPS≥10 were all associated with deeper depth of invasion(P=0.001,P=0.024,and P=0.002,respectively).I-PD-L2 expression and PD-L2 CPS≥10 were significantly higher in the differentiated histological type(P=0.015 and P=0.030,respectively).The I-PD-L1 and IPD-L2 levels were significantly associated with better CSS(P=0.037 and P=0.015,respectively).CD8-high was significantly associated with less lymph node metastasis(P=0.047),less distant metastasis(P=0.024),less peritoneal dissemination(P=0.034),and earlier TNM stage(P=0.047).The CD8-high group had better prognosis than the CD8-low group(P=0.018).FoxP3 expression was not associated with any clinicopathological factors or prognosis.We found that patients with PD-L2 CPS≥10 tended to have worse prognosis in the FoxP3/CD8-low group(P=0.088).CONCLUSION The clinicopathological significance of PD-L1/2 expression may differ depending on the TME status.Immune checkpoint inhibitors may improve the prognosis of SBA patients with low FoxP3/CD8 ratio and PD-L2 expression.
文摘BACKGROUND Small bowel adenocarcinomas(SBA) are rare malignancies with exceedingly low survival rates, with different presentation in Crohn’s disease(CD). CD-induced SBA poses diagnostic challenges given overlapping presentation with stricturing CD and lack of diagnostics for early detection. Moreover, guidance is lacking on the impact of recently approved therapeutics in CD on SBA management. Here, we aim to highlight the future of CD-induced SBA management and discuss the potential merit of balloon enteroscopy and genetic testing for earlier detection.CASE SUMMARY We report the case of a 60-year-old female with longstanding Crohn’s ileitis, presenting with acute obstructive symptoms attributed to stricturing phenotype. Her obstructive symptoms were refractory to intravenous(Ⅳ) steroids, with further investigation via computed tomography enterography not providing additional diagnostic yield. Ultimately, surgical resection revealed SBA in the neoterminal ileum, with oncologic therapy plan created. However, this therapy plan could not be initiated due to continued obstructive symptoms attributed to active CD. Ultimately, infused biologic therapy was initiated, but her obstructive symptoms continued to remain dependent on Ⅳ corticosteroids. Review of diagnostics by a multidisciplinary care team suggested metastatic disease in the peritoneum, lending to a shift in the goals of care to comfort.CONCLUSION With the diagnostic and therapeutic challenges of concurrent SBA and CD, multidisciplinary care and algorithmic management can optimize outcomes.
文摘BACKGROUND Epstein–Barr virus(EBV)-positive mucocutaneous ulcers(MCUs)are an uncommon disorder characterized by ulcerative lesions in the skin,oral cavity or gastrointestinal tract in patients with iatrogenic or aging-induced immunosuppression.The nonspecific lesions are difficult to differentiate from small bowel adenocarcinomas.We present the case of a 69-year-old woman who was initially misdiagnosed with a small bowel adenocarcinoma but was later surgically diagnosed with and treated for EBV-MCU.Through this case,we aim to emphasize the importance of accurately distinguishing between the two conditions.CASE SUMMARY The patient presented with an incidental finding of a small bowel tumor during computed tomography(CT)examination performed for hematuria.The CT scan showed irregular thickening of the distal ileum,which was suggestive of a malignant small bowel tumor.An exploratory laparotomy revealed an 8-cm mass in the distal ileum;thus,a segment of the small intestine,including the mass,was resected.Histopathological analysis revealed an ulceroinfiltrative mass-like lesion with luminal narrowing,marked inflammatory cell infiltration,and large atypical lymphoid cells(positive for EBV-encoded small RNA).A final diagnosis of an EBV-MCU was established.The postoperative course was uneventful,and the patient was discharged on postoperative day 7.The patient remained recurrencefree until 12 mo after surgery.CONCLUSION This case highlights the diagnostic challenges for EBV-MCUs and emphasizes the importance of comprehensive evaluation and accurate histopathological analysis.
文摘Small bowel adenocarcinomas are remarkable for their rarity, difficult diagnosis and poor prognosis. Here we report an unusual case of a 33-year-old patient in whom infiltrative adenocarcinoma of the small bowel was diagnosed after a 10-year history of Crohn＇s disease. In most previously reported cases, detection of Crohn＇s disease was subsequent tothat of carcinoma of the small bowel or the patients involved had an even longer history of the disease. Our literature review suggests that the risk of small bowel adenocarcinoma is higher in patients with Crohn＇s disease than in the overall population. We present details on epidemiology as well as clinical and diagnostic aspects of this rare disease entity.
文摘A 40-year-old male, diagnosed with mild Crohn's disease (CD) 11 years ago but with no prior abdominal surgeries, was diagnosed with a small bowel stricture, due to ongoing abdominal pain and intolerance of enteral diet, and referred for surgical treatment. Exploratory laparoscopy revealed a white solid mass causing a near total jejunal obstruction with significant proximal dilatation. An adjacent small node was sampled for frozen biopsy, revealing a lymph node infiltrated with adenocarcinoma. Laparoscopic assisted small bowel resection and appendectomy were carried out. Final pathological results supported the initial report of diffuse small bowel adenocarcinoma. In conclusion, once a small bowel stricture associated with CD is suspected, rapid action should be considered to avoid late diagnosis of a neoplasia.
文摘Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity, previous studies have traditionally combined duodenal adenocarcinoma(DA) with either other periampullary cancers or small bowel adenocarcinomas, limiting the available data to guide treatment decisions. Nevertheless, management primarily involves complete surgical resection when technically feasible. Surgery may require pancreaticoduodenectomy or segmental duodenal resection; either are acceptable options as long as negative margins are achievable and an adequate lymphadenectomy can be performed. Adjuvant chemotherapy and radiation are important components of multi-modality treatment for patients at high risk of recurrence. Further research would benefit from multiinstitutional trials that do not combine DA with other periampullary or small bowel malignancies. The purpose of this article is to perform a comprehensive review of DA with special focus on the surgical management and principles.
文摘目的：分析原发性小肠腺癌（primary small bowel adenocarcinoma,PSBA）的临床表现、诊断治疗及预后因素。方法：回顾性分析31例PSBA患者的临床资料并进行生存分析。结果：31例患者中男性17例,女性14例,中位发病年龄为67岁,好发于十二指肠并以贫血为主要表现。术前确诊率为38.7%,Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期患者分别占9.7%、22.6%、35.5%、32.2%。31例患者中20例行根治性手术,5例行姑息性手术,11例接受化疗,中位生存期为22个月,5年生存率仅为19%。年龄〉65岁、Ⅲ~Ⅳ期、局部淋巴结转移数≥4个患者的中位生存期分别低于年龄≤65岁、Ⅰ~Ⅱ期、局部淋巴结转移数≤3个患者的中位生存期,差异有统计学意义（P〈0.05）;性别、病理分级、肿瘤原发部位、肿瘤标志物及根治术后有无化疗等因素对患者中位生存期影响的差异无统计学意义（P值分别为0.396、0.141、0.082、0.877、0.599）。结论：PSBA临床表现无特异性,确诊时多为进展期,预后差。外科手术是主要的治疗方式。年龄、临床分期及局部淋巴结转移数目等因素可能成为临床评估生存期的指标。
