Dear Editor,Collecting duct carcinoma(CDC)or Bellini carcinoma originates in the distal collecting ducts.CDC is a markedly aggressive subtype of renal cell carcinoma and accounts for less than 1%of all renal cell carc...Dear Editor,Collecting duct carcinoma(CDC)or Bellini carcinoma originates in the distal collecting ducts.CDC is a markedly aggressive subtype of renal cell carcinoma and accounts for less than 1%of all renal cell carcinomas[1].We described a patient with CDC and psoriasis,who showed complete response(CR)after being treated with combination therapy of nivolumab and ipilimumab(NI).The study was conducted in accordance with and approved by the Ethics Committee of Yamagata University Faculty of Medicine(approval no.2019-35).The need for patient consent was waived by the same institutional review board;all the patients provided written informed consents.展开更多
BACKGROUND Immune checkpoint inhibitors are one of the modern treatment methods for advanced malignancies.However,this group of medications is also associated with various immune-related adverse events,such as colitis...BACKGROUND Immune checkpoint inhibitors are one of the modern treatment methods for advanced malignancies.However,this group of medications is also associated with various immune-related adverse events,such as colitis or pneumonitis.Immune checkpoint inhibitor-induced gastritis is a less common adverse event.CASE SUMMARY We describe a 64-year-old woman presenting with diarrhea,nausea,and discomfort in the upper abdominal region.The patient had a history of metastatic lung cancer,which was treated with nivolumab.During the first endoscopy,an infiltrating gastric tumour was suspected.Later,based on endoscopic,histological and radiological findings,nivolumab-induced gastritis was diagnosed.The patient was successfully treated with three courses of omeprazole.CONCLUSION As a consequence of the increased use of immune checkpoint inhibitors,a growing number of reported immune-related adverse events could be expected.The diagnosis of immune checkpoint inhibitor-induced gastritis should be considered when assessing a patient treated with nivolumab with upper gastrointestinal distress.展开更多
Skin reaction or dermatological toxicities induced by immunotherapy is common.It usually manifests skin rash or erythema and can be cured by skin lotion or steroid.Nivolumab,a human IgG4 programmed cell death protein ...Skin reaction or dermatological toxicities induced by immunotherapy is common.It usually manifests skin rash or erythema and can be cured by skin lotion or steroid.Nivolumab,a human IgG4 programmed cell death protein 1(PD-1)inhibitor,blocks T cells activation preventing signal and allows the immune system to clear cancer cells.Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA,with less than 10%unusual skin reaction,like sensory neuropathy,peeling skin,erythema multiforme,vitiligo,and psoriasis.Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity.The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies,but the risk of side effects may be high.We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy.The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events.Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.展开更多
Dear Editor,I am Dr.Daniel Russell Richardson from the West Virginia University Eye Institute in Morgantown,West Virginia,United States.I write to present a case of uveitis associated with nivolumab,which is a promisi...Dear Editor,I am Dr.Daniel Russell Richardson from the West Virginia University Eye Institute in Morgantown,West Virginia,United States.I write to present a case of uveitis associated with nivolumab,which is a promising new immune checkpoint inhibitor(ICI)for metastatic melanoma and non-small cell lung carcinoma with expanding indications.As the use of nivolumab continues to increase,ophthalmologists must be aware of uveitis as an adverse event.Modulating展开更多
BACKGROUND Sarcomatoid hepatocellular carcinoma(SHC)is a rare subtype of hepatocellular carcinoma(HCC),with a high recurrence rate after surgery.In addition to limited effective treatment for the advanced stage of SHC...BACKGROUND Sarcomatoid hepatocellular carcinoma(SHC)is a rare subtype of hepatocellular carcinoma(HCC),with a high recurrence rate after surgery.In addition to limited effective treatment for the advanced stage of SHC,the prognosis of patients with this malignancy is worse than that of patients with conventional HCC.CASE SUMMARY We present the case of a 54-year-old man with SHC who underwent radical segmental hepatectomy,which relapsed 4 mo after surgery due to lymphatic metastasis in the porta hepatis.Although a second surgery was performed,new metastasis developed in the mediastinal lymph nodes.Therefore,sorafenib and lenvatinib were sequentially administered as first-and second-line systemic therapies,respectively.However,progressive disease was confirmed based on a recurrent hepatic lesion and new metastatic lesion in the abdominal cavity.Percutaneous transhepatic cholangial drainage was performed to alleviate the biliary obstruction.Because the tumor was strongly positive for programmed death-ligand 1,the patient was started on nivolumab.Imaging studies revealed that after two cycles of immunotherapy,the metastatic lesions decreased to undetectable levels.CONCLUSION The patient experienced continuous complete remission for 8 mo.Immune checkpoint inhibitors are useful for the treatment of advanced SHC.展开更多
BACKGROUND A variety of immune-modulating drugs are becoming increasingly used for various cancers. Despite increasing indications and improved efficacy, they are often associated with a wide variety of immune mediate...BACKGROUND A variety of immune-modulating drugs are becoming increasingly used for various cancers. Despite increasing indications and improved efficacy, they are often associated with a wide variety of immune mediated adverse events including colitis that may be refractory to conventional therapy. Although these drugs are being more commonly used by Hematologists and Oncologists, there are still many gastroenterologists who are not familiar with the incidence and natural history of gastrointestinal immune-mediated side effects, as well as the role of infliximab in the management of this condition.CASE SUMMARY We report a case of a 63-year-old male with a history of metastatic renal cell carcinoma who presented to our hospital with severe diarrhea. The patient had received his third combination infusion of the anti-CTLA-4 monoclonal antibody Ipilimumab and the immune checkpoint inhibitor Nivolumab and developed severe watery non-bloody diarrhea the same day. He presented to the hospital where he was found to be severely dehydrated and in acute renal failure. An extensive workup was negative for infectious etiologies and he was initiated on high dose intravenous steroids. However, he continued to worsen. A colonoscopy was performed and revealed no endoscopic evidence of inflammation. Random biopsies for histology were obtained which showed mild colitis, and were negative for Cytomegalovirus and Herpes Simplex Virus. He was diagnosed with severe steroid-refractory colitis induced by Ipilimumab and Nivolumab and was initiated on Infliximab. He responded promptly to it and his diarrhea resolved the next day with progressive resolution of his renal impairment. On follow up his gastrointestinal side symptoms did not recur.CONCLUSION Given the increasing use of immune therapy in a variety of cancers, it is important for gastroenterologists to be familiar with their gastrointestinal side effects and comfortable with their management, including prescribing infliximab.展开更多
BACKGROUND Immunotherapy has revolutionized the clinical outcomes of intractable cancer patients.Little is known about the intestinal nonpathogenic bacterial composition of hepatocellular carcinoma(HCC)patients treate...BACKGROUND Immunotherapy has revolutionized the clinical outcomes of intractable cancer patients.Little is known about the intestinal nonpathogenic bacterial composition of hepatocellular carcinoma(HCC)patients treated by immunotherapy.AIM To determine whether there is a correlation between gut bacterial composition and prognosis in HCC patients.METHODS From September 2019 to March 2020,we prospectively collected fecal samples and examined the gut microbiome of 8 advanced HCC patients treated with nivolumab as a second-or third-line systemic treatment.Fecal samples were collected before the start of immunotherapy.Fecal samples of patients with progression during treatment were collected at the time of progression,and fecal samples of patients who showed good response to nivolumab were collected after 5-7 mo as follow-up.Metagenomic data from 16S ribosomal RNA sequencing were analyzed using CLC Genomics Workbench.Microbiome data were analyzed according to therapeutic response.RESULTS All 8 patients were male,of which 6 had underlying chronic hepatitis B.A higher Shannon index was found in the responders than in the non-responders after nivolumab therapy(P=0.036).The unweighted beta diversity analysis also showed that the overall bacterial community structure and phylogenetic diversity were clearly distinguished according to therapeutic response.There was no significant difference in the diversity or composition of the patient gut microbiome according to the immunotherapy used.Several taxa specific to therapeutic response were designated as follows:Dialister pneumosintes,Escherichia coli,Lactobacillus reteri,Streptococcus mutans,Enterococcus faecium,Streptococcus gordonii,Veillonella atypica,Granulicatella sp.,and Trchuris trichiura for the nonresponders;Citrobacter freundii,Azospirillum sp.and Enterococcus durans for the responders.Of note,a skewed Firmicutes/Bacteroidetes ratio and a low Prevotella/Bacteroides ratio can serve as predictive markers of non-response,whereas the presence of Akkermansia species predicts a good response.CONCLUSION The current presumptive study suggests a potential role for the gut microbiome as a prognostic marker for the response to nivolumab in treatment of HCC patients.展开更多
BACKGROUND Immune checkpoint inhibitors have significantly improved survivals for an increasing range of malignancies but at the cost of several immune-related adverse events,the management of which can be challenging...BACKGROUND Immune checkpoint inhibitors have significantly improved survivals for an increasing range of malignancies but at the cost of several immune-related adverse events,the management of which can be challenging due to its mimicry of other autoimmune related disorders such as immunoglobulin G4(IgG4)related disease when the pancreaticobiliary system is affected.Nivolumab,an IgG4 monoclonal antibody,has been associated with cholangitis and pancreatitis,however its association with IgG4 related disease has not been reported to date.CASE SUMMARY We present a case of immune-related pancreatitis and cholangiopathy in a patient who completed treatment with nivolumab for anal squamous cell carcinoma.Patients IgG4 levels was normal on presentation.She responded to steroids but due to concerns for malignant biliary stricture,she opted for surgery,the pathology of which suggested IgG4 related disease.CONCLUSION We hypothesize this case of IgG4 related cholangitis and pancreatitis was likely triggered by nivolumab.展开更多
BACKGROUND Checkpoint-Inhibition has revolutionized the treatment for several entities such as melanoma and renal cell carcinoma.The first encouraging experience in ovarian cancer was reported for nivolumab,a fully hu...BACKGROUND Checkpoint-Inhibition has revolutionized the treatment for several entities such as melanoma and renal cell carcinoma.The first encouraging experience in ovarian cancer was reported for nivolumab,a fully humanized anti-programmed death-1 antibody.Pseudoprogression is a new phenomenon associated with these novel immuno-oncologic agents.It can be explained by infiltrating leucocytes and edema that result in a temporary increase in tumor size and delayed subsequent shrinkage due to tumor cell destruction.CASE SUMMARY We report on a 47-year old patient with platinum-resistant ovarian cancer that was treated off-label with nivolumab 3mg/kg iv d1q14d.She first experienced classic pseudoprogression with inguinal lymph node swelling after cycle two and subsequent shrinkage.After 6 cycles she presented with rectal bleeding and progressive disease was diagnosed due to new tumor infiltration into the rectum.CONCLUSION Clinicians should be aware of pseudoprogression,its underlying mechanisms and strategies to discriminate pseudo-from real progression in ovarian cancer.展开更多
文摘Dear Editor,Collecting duct carcinoma(CDC)or Bellini carcinoma originates in the distal collecting ducts.CDC is a markedly aggressive subtype of renal cell carcinoma and accounts for less than 1%of all renal cell carcinomas[1].We described a patient with CDC and psoriasis,who showed complete response(CR)after being treated with combination therapy of nivolumab and ipilimumab(NI).The study was conducted in accordance with and approved by the Ethics Committee of Yamagata University Faculty of Medicine(approval no.2019-35).The need for patient consent was waived by the same institutional review board;all the patients provided written informed consents.
文摘BACKGROUND Immune checkpoint inhibitors are one of the modern treatment methods for advanced malignancies.However,this group of medications is also associated with various immune-related adverse events,such as colitis or pneumonitis.Immune checkpoint inhibitor-induced gastritis is a less common adverse event.CASE SUMMARY We describe a 64-year-old woman presenting with diarrhea,nausea,and discomfort in the upper abdominal region.The patient had a history of metastatic lung cancer,which was treated with nivolumab.During the first endoscopy,an infiltrating gastric tumour was suspected.Later,based on endoscopic,histological and radiological findings,nivolumab-induced gastritis was diagnosed.The patient was successfully treated with three courses of omeprazole.CONCLUSION As a consequence of the increased use of immune checkpoint inhibitors,a growing number of reported immune-related adverse events could be expected.The diagnosis of immune checkpoint inhibitor-induced gastritis should be considered when assessing a patient treated with nivolumab with upper gastrointestinal distress.
文摘免疫检查点抑制剂(immune checkpoint inhibitors,ICI)是肿瘤免疫治疗的最新药物及重要手段之一。免疫检查点的功能是保持自身耐受并防止自身免疫。ICI通过阻断免疫系统中的抑制性信号通路,重新激活并促进机体对肿瘤的免疫应答,起到杀伤肿瘤细胞的作用。细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte antigen-4,CTLA-4)抑制剂是首个广泛应用于临床的ICI,近年来程序性死亡受体1(programmed cell death protein-1,PD-1)抑制剂Nivolumab(纳武利尤单抗)、Pembrolizumab及程序性死亡配体1(programmed death ligand 1,PD-L1)抑制剂Atezolizumab、Avelumab和Durvalumab等ICI逐渐应用于治疗黑色素瘤、肺非小细胞肺癌(non-small cell lung cancer,NSCLC)和转移性肾癌等不同类型的肿瘤[1]。
文摘Skin reaction or dermatological toxicities induced by immunotherapy is common.It usually manifests skin rash or erythema and can be cured by skin lotion or steroid.Nivolumab,a human IgG4 programmed cell death protein 1(PD-1)inhibitor,blocks T cells activation preventing signal and allows the immune system to clear cancer cells.Nivolumab was approved in the second-line therapy in squamous cell lung cancer by FDA,with less than 10%unusual skin reaction,like sensory neuropathy,peeling skin,erythema multiforme,vitiligo,and psoriasis.Radiotherapy could aggravate this skin reaction through inflammatory response and promotion of immunity.The combined treatment of anti-PD-1 and radiotherapy represented a new promising therapeutic approach in many studies,but the risk of side effects may be high.We reported a patient with advanced squamous cell lung cancer who suffered from serious skin immune-related adverse events when he was treated with nivolumab and radiotherapy.The immune overreaction of the treatment of anti-PD-1 treatment and radiotherapy might cause these serious skin adverse events.Our report warranted careful workup to reduce the risk of side effects by combinative therapy with anti-PD-1 and radiotherapy.
文摘Dear Editor,I am Dr.Daniel Russell Richardson from the West Virginia University Eye Institute in Morgantown,West Virginia,United States.I write to present a case of uveitis associated with nivolumab,which is a promising new immune checkpoint inhibitor(ICI)for metastatic melanoma and non-small cell lung carcinoma with expanding indications.As the use of nivolumab continues to increase,ophthalmologists must be aware of uveitis as an adverse event.Modulating
基金The National 13th Five-Year Science and Technology Plan Major Projects of China,No.2017ZX10203205-006-001.
文摘BACKGROUND Sarcomatoid hepatocellular carcinoma(SHC)is a rare subtype of hepatocellular carcinoma(HCC),with a high recurrence rate after surgery.In addition to limited effective treatment for the advanced stage of SHC,the prognosis of patients with this malignancy is worse than that of patients with conventional HCC.CASE SUMMARY We present the case of a 54-year-old man with SHC who underwent radical segmental hepatectomy,which relapsed 4 mo after surgery due to lymphatic metastasis in the porta hepatis.Although a second surgery was performed,new metastasis developed in the mediastinal lymph nodes.Therefore,sorafenib and lenvatinib were sequentially administered as first-and second-line systemic therapies,respectively.However,progressive disease was confirmed based on a recurrent hepatic lesion and new metastatic lesion in the abdominal cavity.Percutaneous transhepatic cholangial drainage was performed to alleviate the biliary obstruction.Because the tumor was strongly positive for programmed death-ligand 1,the patient was started on nivolumab.Imaging studies revealed that after two cycles of immunotherapy,the metastatic lesions decreased to undetectable levels.CONCLUSION The patient experienced continuous complete remission for 8 mo.Immune checkpoint inhibitors are useful for the treatment of advanced SHC.
文摘BACKGROUND A variety of immune-modulating drugs are becoming increasingly used for various cancers. Despite increasing indications and improved efficacy, they are often associated with a wide variety of immune mediated adverse events including colitis that may be refractory to conventional therapy. Although these drugs are being more commonly used by Hematologists and Oncologists, there are still many gastroenterologists who are not familiar with the incidence and natural history of gastrointestinal immune-mediated side effects, as well as the role of infliximab in the management of this condition.CASE SUMMARY We report a case of a 63-year-old male with a history of metastatic renal cell carcinoma who presented to our hospital with severe diarrhea. The patient had received his third combination infusion of the anti-CTLA-4 monoclonal antibody Ipilimumab and the immune checkpoint inhibitor Nivolumab and developed severe watery non-bloody diarrhea the same day. He presented to the hospital where he was found to be severely dehydrated and in acute renal failure. An extensive workup was negative for infectious etiologies and he was initiated on high dose intravenous steroids. However, he continued to worsen. A colonoscopy was performed and revealed no endoscopic evidence of inflammation. Random biopsies for histology were obtained which showed mild colitis, and were negative for Cytomegalovirus and Herpes Simplex Virus. He was diagnosed with severe steroid-refractory colitis induced by Ipilimumab and Nivolumab and was initiated on Infliximab. He responded promptly to it and his diarrhea resolved the next day with progressive resolution of his renal impairment. On follow up his gastrointestinal side symptoms did not recur.CONCLUSION Given the increasing use of immune therapy in a variety of cancers, it is important for gastroenterologists to be familiar with their gastrointestinal side effects and comfortable with their management, including prescribing infliximab.
文摘BACKGROUND Immunotherapy has revolutionized the clinical outcomes of intractable cancer patients.Little is known about the intestinal nonpathogenic bacterial composition of hepatocellular carcinoma(HCC)patients treated by immunotherapy.AIM To determine whether there is a correlation between gut bacterial composition and prognosis in HCC patients.METHODS From September 2019 to March 2020,we prospectively collected fecal samples and examined the gut microbiome of 8 advanced HCC patients treated with nivolumab as a second-or third-line systemic treatment.Fecal samples were collected before the start of immunotherapy.Fecal samples of patients with progression during treatment were collected at the time of progression,and fecal samples of patients who showed good response to nivolumab were collected after 5-7 mo as follow-up.Metagenomic data from 16S ribosomal RNA sequencing were analyzed using CLC Genomics Workbench.Microbiome data were analyzed according to therapeutic response.RESULTS All 8 patients were male,of which 6 had underlying chronic hepatitis B.A higher Shannon index was found in the responders than in the non-responders after nivolumab therapy(P=0.036).The unweighted beta diversity analysis also showed that the overall bacterial community structure and phylogenetic diversity were clearly distinguished according to therapeutic response.There was no significant difference in the diversity or composition of the patient gut microbiome according to the immunotherapy used.Several taxa specific to therapeutic response were designated as follows:Dialister pneumosintes,Escherichia coli,Lactobacillus reteri,Streptococcus mutans,Enterococcus faecium,Streptococcus gordonii,Veillonella atypica,Granulicatella sp.,and Trchuris trichiura for the nonresponders;Citrobacter freundii,Azospirillum sp.and Enterococcus durans for the responders.Of note,a skewed Firmicutes/Bacteroidetes ratio and a low Prevotella/Bacteroides ratio can serve as predictive markers of non-response,whereas the presence of Akkermansia species predicts a good response.CONCLUSION The current presumptive study suggests a potential role for the gut microbiome as a prognostic marker for the response to nivolumab in treatment of HCC patients.
文摘BACKGROUND Immune checkpoint inhibitors have significantly improved survivals for an increasing range of malignancies but at the cost of several immune-related adverse events,the management of which can be challenging due to its mimicry of other autoimmune related disorders such as immunoglobulin G4(IgG4)related disease when the pancreaticobiliary system is affected.Nivolumab,an IgG4 monoclonal antibody,has been associated with cholangitis and pancreatitis,however its association with IgG4 related disease has not been reported to date.CASE SUMMARY We present a case of immune-related pancreatitis and cholangiopathy in a patient who completed treatment with nivolumab for anal squamous cell carcinoma.Patients IgG4 levels was normal on presentation.She responded to steroids but due to concerns for malignant biliary stricture,she opted for surgery,the pathology of which suggested IgG4 related disease.CONCLUSION We hypothesize this case of IgG4 related cholangitis and pancreatitis was likely triggered by nivolumab.
文摘BACKGROUND Checkpoint-Inhibition has revolutionized the treatment for several entities such as melanoma and renal cell carcinoma.The first encouraging experience in ovarian cancer was reported for nivolumab,a fully humanized anti-programmed death-1 antibody.Pseudoprogression is a new phenomenon associated with these novel immuno-oncologic agents.It can be explained by infiltrating leucocytes and edema that result in a temporary increase in tumor size and delayed subsequent shrinkage due to tumor cell destruction.CASE SUMMARY We report on a 47-year old patient with platinum-resistant ovarian cancer that was treated off-label with nivolumab 3mg/kg iv d1q14d.She first experienced classic pseudoprogression with inguinal lymph node swelling after cycle two and subsequent shrinkage.After 6 cycles she presented with rectal bleeding and progressive disease was diagnosed due to new tumor infiltration into the rectum.CONCLUSION Clinicians should be aware of pseudoprogression,its underlying mechanisms and strategies to discriminate pseudo-from real progression in ovarian cancer.
