Systematic review of risk factors,prognosis,and management of colorectal signet-ring cell carcinoma

BACKGROUND Colorectal signet-ring cell carcinoma(CSRCC)is a rare clinical entity which accounts for approximately 1%of all colorectal cancers.Although multiple studies concerning this specific topic have been published in the past decades,the pathogenesis,associated risk factors,and potential implications on treatment are still poorly understood.Besides the low incidence,historically confusing histological criteria have resulted in confusing data.Nevertheless,the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis,highlight the actual interest to synthesize the known literature regarding CSRCC.AIM To provide an updated overview of risk factors,prognosis,and management of CSRCC.METHODS A literature search in the MEDLINE/PubMed database was conducted with the following search terms used:‘Signet ring cell carcinoma’and‘colorectal’.Studies in English language,published after January 1980,were included.Studies included in the qualitative synthesis were evaluated for content concerning epidemiology,risk factors,and clinical,diagnostic,histological,and molecular features,as well as metastatic pattern and therapeutic management.If possible,presented data was extracted in order to present a more detailed overview of the literature.RESULTS In total,67 articles were included for qualitative analysis,of which 54 were eligible for detailed data extraction.CSRCC has a reported incidence between 0.1%-2.4%and frequently presents with advanced disease stage at the time of diagnosis.CSRCC is associated with an impaired overall survival(5-year OS:0%-46%)and a worse stagecorrected outcome compared to mucinous and not otherwise specified adenocarcinoma.The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised.Surgery is the mainstay of treatment,although the rates of curative resection in CSRCC(21%-82%)are lower compared to those in other histological types.In case of peritoneal metastasis,cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients.CONCLUSION CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation.As such,diagnostic modalities and therapeutic approach should be tailored accordingly.

Colon signet-ring cell carcinoma with chylous ascites caused by immunosuppressants following liver transplantation:A case report

BACKGROUND Chylous ascites is caused by disruption of the lymphatic system,which is characterized by the accumulation of a turbid fluid containing high levels of triglycerides within the abdominal cavity.The two most common causes are cirrhosis and tuberculosis,and colon signer ring cell carcinoma(SRCC)due to the use of immunosuppressants is extremely rare in cirrhotic patients after liver transplantation,making it prone to misdiagnosis and missed diagnosis.CASE SUMMARY A 52-year-old man who underwent liver transplantation and was administered with immunosuppressants for 8 months was admitted with a 3-month history of progressive abdominal distention.Initially,based on lymphoscintigraphy and lymphangiography,lymphatic obstruction was considered,and cystellar chyli decompression with band lysis and external membrane stripping of the lymphatic duct was performed.However,his abdominal distention was persistent without resolution.Abdominal paracentesis revealed allogenic cells in the ascites,and immunohistochemistry analysis revealed adenocarcinoma cells with phenotypic features suggestive of a gastrointestinal origin.Gastrointestinal endoscopy was performed,and biopsy showed atypical signet ring cells in the ileocecal valve.The patient eventually died after a three-month follow-up due to progression of the tumor.CONCLUSION Colon SRCC,caused by immunosuppressants,is an unusual but un-neglected cause of chylous ascites.

Prediction of lymph node metastasis in early gastric signet-ring cell carcinoma:A real-world retrospective cohort study

BACKGROUND Signet-ring cell carcinoma(SRCC)was previously thought to have a worse prognosis than other differentiated gastric cancer(GC),however,recent studies have shown that the prognosis of SRCC is related to pathological type.We hypothesize that patients with SRCC and with different SRCC pathological components have different probability of lymph node metastasis(LNM).AIM To establish models to predict LNM in early GC(EGC),including early gastric SRCC.METHODS Clinical data from EGC patients who had undergone gastrectomy at the First Affiliated Hospital of Nanjing Medical University from January 2012 to March 2022 were reviewed.The patients were divided into three groups based on type:Pure SRCC,mixed SRCC,and non-signet ring cell carcinoma(NSRC).The risk factors were identified through statistical tests using SPSS 23.0,R,and EmpowerStats software.RESULTS A total of 1922 subjects with EGC were enrolled in this study,and included 249 SRCC patients and 1673 NSRC patients,while 278 of the patients(14.46%)presented with LNM.Multivariable analysis showed that gender,tumor size,depth of invasion,lymphovascular invasion,ulceration,and histological subtype were independent risk factors for LNM in EGC.Establishment and analysis using prediction models of EGC showed that the artificial neural network model was better than the logistic regression model in terms of sensitivity and accuracy(98.0%vs 58.1%,P=0.034;88.4%vs 86.8%,P<0.001,respectively).Among the 249 SRCC patients,LNM was more common in mixed(35.06%)rather than in pure SRCC(8.42%,P<0.001).The area under the ROC curve of the logistic regression model for LNM in SRCC was 0.760(95%CI:0.682-0.843),while the area under the operating characteristic curve of the internal validation set was 0.734(95%CI:0.643-0.826).The subgroups analysis of pure types showed that LNM was more common in patients with a tumor size>2 cm(OR=5.422,P=0.038).CONCLUSION A validated prediction model was developed to recognize the risk of LNM in EGC and early gastric SRCC,which can aid in pre-surgical decision making of the best method of treatment for patients.

Update on diagnosis and treatment of early signet-ring cell gastric carcinoma: A literature review

Gastric signet-ring cell gastric carcinoma(GSRC)is an unfavorable subtype of gastric cancer(GC)that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC.However,GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC.Therefore,the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients.In recent years,technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients.Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection(ESD),indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation.This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.

Clinicopathological and prognostic differences between mucinous gastric carcinoma and signet-ring cell carcinoma

Objective： To analyze the differences in clinicopathologic characteristics and prognosis between mucinous gastric carcinoma （MGC） and signet-ring cell carcinoma （SRCC）. Methods： Clinicopathologic and prognostic data of 1,637 patients with histologically confirmed MGC or SRCC who received surgical operations in the Department of Gastroenterological Surgery, Beijing Cancer Hospital between December 2004 and December 2009 were retrospectively collected and analyzed. The clinicopathological features were analyzed statistically using Z2 test. Survival was analyzed using the Kaplan- Meier method and multivariate analysis of Cox proportional hazards regression model （backward, stepwise）. Results： A total of 181 patients with gastric cancer （74 MGC, 107 SRCC） were included. MGC, when compared with SRCC, was featured by senile patients, stage III and I~, upper third stomach, large tumor size, positive lymph node metastasis, and positive lymphatic vascular invasion （P〈0.05）. The overall 5-year survival rate showed no difference between the two groups （48.8% vs. 44.8%, P〉0.05）. However, the survival rate for MGC patients was significant lower than that for SRCC patients when compared among the age 〈60 years, negative distant metastasis, and tumor localized at upper third stomach （P〈0.05）. Multivariate Cox proportional hazards models revealed that distant metastasis was a significant independent prognostic indicator in MGC group, and lymph node metastasis and distant metastasis was significant independent prognostic indicators in SRCC group. Conclusions： While compared with SRCC, MGC is associated with a more aggressive tumor biologic behavior. There is no statistically significant difference in distant metastasis, an independent prognostic indicator for both MGC and SRCC, which might be the reason for no significant difference of the overall survival rate between the patients with MGC and SRCC.

Edema of limbs as the primary symptom of gastric signet-ring cell carcinoma:A case report and literature review

BACKGROUND Metastatic skin cancers are relatively rare dermatological malignancies.They usually present as nodules,erythematous lesions,scar-like lesions or other lesion types.Signet-ring cell carcinoma(SRCC)is an uncommon histological type of gastric cancer that usually behaves aggressively and has a poor prognosis.Skin metastasis may be the first sign of clinically silent visceral cancer or recurrence of an internal malignancy.CASE SUMMARY Herein we report on the case of a 55-year-old man with edema of a lower extremity as the primary symptom which progressed from local to generalized pitting edema in the year following skin involvement.Pathological evidence from gastroscopic specimens and subcutaneous tissue biopsy showed typical signetring cells and gland-like structures.Consistently,immunohistochemical analysis revealed positive pan-cytokeratin expression in tumor cells.A diagnosis of gastric SRCC with skin metastasis was established.Moreover,lymphoscintigraphy showed an obvious accumulation of radiotracer on the anterior and posterior sides of the right leg which indicated lymphedema.We reviewed the relevant literature on subcutaneous metastases of gastric SRCC.CONCLUSION This rare case emphasizes the importance of physical examination as it may help elucidate the etiology of edema.

Gastric signet-ring cell carcinoma with paraneoplastic eosinophilia: A case report and literature review

We report the case of a 40-year-old female Chinese patient with gastric signet-ring cell carcinoma that was first diagnosed because of paraneoplastic eosinophilia.The patient’s eosinophil count reduced markedly to normal levels within 24 h after radical gastrectomy and Billroth II anastomosis.The patient recovered well after the surgery and no abnormalities were found during the regular follow-ups.Paraneoplastic eosinophilia is an unusual manifestation that usually remains asymptomatic;moreover,cases of solid malignant tumors with eosinophilia are uncommon.To our knowledge,this is the first reported case of paraneoplastic eosinophilia in a patient with gastric carcinoma.We considered eosinophilia as a manifestation of a paraneoplastic syndrome,which can be the first clinical manifestation of a malignancy.

Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge

While the incidence of gastric cancer has decreased worldwide in recent decades,the incidence of signetring cell carcinoma(SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has two forms: early gastric cancer,which can be resected endoscopically in some cases and which has a better outcome than non-SRCC,and advanced gastric cancer,which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However,the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified,as the benefit of perioperative chemotherapy and the value of taxanebased chemotherapy are unclear. In this review we analyze recent data on the epidemiology,oncogenesis,prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.

Gastric adenocarcinoma of fundic gland type with signet-ring cell carcinoma component: A case report and review of the literature

A depressed lesion was found at a gastric angle of 76-yearold Japanese woman by esophagogastroduodenoscopy. Four years prior, she was diagnosed with a Helicobacter pylori infection but no eradication was performed. The pathological diagnosis of biopsy specimens was signet-ring cell carcinoma. Endoscopic submucosal dissection(ESD) was performed. Histopathological examination of the ESD specimen revealed proliferation of well-differentiated tubular adenocarcinoma mimicking fundic gland cells at the deep layer of the lamina propria mucosae. These tumor cells expressed focally pepsinogen-Ⅰ, diffusely MUC6, and scattered H^+/K^+ ATPase according to immunohistochemistry. Therefore, we diagnosed this tumor as gastric adenocarcinoma of fundic gland type(GA-FG). Adjacent to the GA-FG, proliferation of signet-ring cell carcinoma which diffusely expressed MUC 2 and MUC 5AC was observed. Intestinal metaplasia was focally observed in the surrounding mucosa of the signet-ring cell carcinoma. To the best of our knowledge, this is the first case report of GA-FG with a signet-ring cell carcinoma component. The origin of signet-ring cell carcinoma, i.e., whether it accidentally arose from a non-neoplastic mucosa and coexisted with the GA-FG or dedifferentiated from the GA-FG is unclear at present. We expect the accumulation of similar cases and further analysis to clarify this issue.

Signet-ring cell carcinoma arising from a fundic gland polyp in the stomach

Fundic gland polyps(FGPs)are currently the most common type of gastric polyps and are usually benign.However,although rare,gastric adenocarcinoma of FGP has been recently proposed as a new variant of gastric adenocarcinoma.Here we report the first case of a49-year-old woman with focal signet ring cell carcinoma that arose from an FGP of the stomach.The tumor was completely excised by endoscopic snare polypectomy.FGPs should therefore be evaluated for malignant changes although they occur rarely,if the FGP has an erosive or irregular surface.

Signet-ring cell carcinoma of ampulla of Vater:Contrast-enhanced ultrasound findings

Signet-ring cell carcinoma(SRCC) of ampulla of Vater is extremely uncommon,and less than 15 cases have been reported so far in literature.It mainly occurs in elderly people(median age 57 years).We report a rare case of SRCC of the ampulla of Vater in a 38-year-old woman who presented with a small tumor at the Vater,discovered by the contrast-enhanced ultrasound(CEUS).Histopathological examination showed prominent signet-ring features.We also describe the imaging features of SRCC of ampulla of Vater in CEUS.

Primary signet-ring cell carcinoma of the colon at early stage: A case report and a review of the literature

经历了外科到将切除的一个 67 岁的人多重胃的癌症 4 年以前，为监视结肠镜检查访问了我们的医院。揭示的结肠镜检查一变色，在直径的 7 公里，有在结肠左曲附近的横向的冒号的中央消沉的提高公寓的损害。尽管内视镜检查法和钡灌肠的调查结果粘膜下层侵略是暗示的，病人选择了经历内视镜的粘膜切除术。resected 标本的病理学的检查揭示了图章戒指房间癌和积极外科的边缘。第二个手术被动，并且到淋巴结的剩余肿瘤或转移都没在 resected 标本被发现。由在一个早阶段检测并且对待的图章戒指房间癌组成的三原色表面的癌症是极其稀罕的。我们在场一个盒子和评论文学。

LINE-1 family member GCRG123 gene is up-regulated in human gastric signet-ring cell carcinoma

AIM:To analyze the expression profiles of a human gastric-cancer-related gene, GCRG123, in human gastric signet-ring cell carcinoma tissues, and to perform bioinformatics analysis on GCRG123. METHODS:In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues, including 15 cases of signet-ring cell carcinoma, 15 of intestinal-type adenocarcinoma, and 15 of normal gastric mucosa. Northern blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues. Online software, including BLAST, Multalin and BLAT, were applied for bioinformatics analysis. National Center for Biotechnology Information (NCBI) and the University of California Santa Cruz (UCSC) databases were used for the analyses. RESULTS:The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm. Ten out of 15 cases of gastric signet ring cell carcinoma, normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression. Low GCRG123 expression was observed in gastric intestinal-type adenocarcinoma and normal gastric glands. Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue. BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons (LINE-1, L1). BLAT analysis indicated that GCRG123 mapped to all chromosomes. GCRG123 was found to integrate in the intron-17 and-23 of Rb, 5' flanking region of IL-2 and clotting factor Ⅸ genes.CONCLUSION:GCRG123, an active member of the L1 family, was up-regulated in human gastric signet-ring cell carcinoma.

Signet-ring cell carcinoma of breast presenting with genital tract metastasis

Objective: To analyze the clinicopathologic features of breast signet-ring cell carcinoma (SRCC) presenting with genital tract metastasis. Methods: A 54-year-old woman presented with metrorrhagia was described and the immunostaining was performed. Results: Histologically, signet ring cells (SRCs) scattered in the stroma of endometrium and cervix, bilateral fallopian tubes, ovaries and left breast. Immunohistochemistry of these SRCs showed strong reactive for cytokertin 7, CEA, GCDFP-15, and weak reactive for CA125 and negative for cytokertin 20. All these information confirmed the breast origin of SRCC. Conclusion: Primary breast SRCC is extremely rare with metrorrhagia as its first symptom. Gynecologist and pathologist should be aware of this possibility when metrorrhagia is the only symptom. Immunohistochemistry can help differentiate the origin of SRCC.

Poorly cohesive cells gastric carcinoma including signet-ring cell cancer:Updated review of definition,classification and therapeutic management

While the incidence of gastric cancer(GC)in general has decreased worldwide in recent decades,the incidence of diffuse cancer historically comprising poorly cohesive cells-GC(PCC-GC)and including signet ring cell cancer is rising.Literature concerning PCC-GC is scarce and unclear,mostly due to a large variety of historically used definitions and classifications.Compared to other histological subtypes of GC,PCC-GC is nevertheless characterized by a distinct set of epidemiological,histological and clinical features which require a specific diagnostic and therapeutic approach.The aim of this review was to provide an update on the definition,classification and therapeutic strategies of PCC-GC.We focus on the updated histological definition of PCC-GC,along with its implications on future treatment strategies and study design.Also,specific considerations in the diagnostic management are discussed.Finally,the impact of some recent developments in the therapeutic management of GC in general such as the recently validated taxane-based regimens(5-Fluorouracil,leucovorin,oxaliplatin and docetaxel),the use of hyperthermic intraperitoneal chemotherapy as well as pressurized intraperitoneal aerosol chemotherapy and targeted therapy have been reviewed in depth for their relative importance for PCC-GC in particular.

Primary signet-ring cell carcinoma of the extrahepatic bile duct:A case report

BACKGROUND Signet ring cell carcinoma(SRCC)is a specific type of mucinous secretory adenocarcinoma,which contains abundant mucus in the cytoplasm and pushes the nucleus to one side of the cell membrane,forming a round or oval,and the nuclear deviations give the cells a signet ring-like appearance.SRCC often originates in the gastrointestinal tract,especially in the stomach.However,primary SRCC of the extrahepatic bile duct is extremely rare.Therefore,little is known about its epidemiology,treatment,and prognosis.CASE SUMMARY An 82-year-old female was admitted with abdominal pain,jaundice,and skin pruritus for 2 mo.She had no specific family history.Physical examination presented normal vital signs,icteric sclera,visible jaundice,and mild tenderness in the right upper abdominal quadrant.Tumor-related cell markers were within normal values.Contrast-enhanced computed tomography revealed a thickened wall of the common bile duct,strengthened with intrahepatic bile duct dilation and multiple round-like lesions in the liver.In addition,the lymph nodes in the hepatic hilum area,the pancreatic head area,and around the abdominal aorta were enlarged.Thus,a preoperative diagnosis of cholangiocarcinoma was established.To alleviate jaundice and prolong the overall survival,percutaneous transhepatic cholangiopancreatic drainage(PTCD)was performed.During the operation,segmental stenosis of the extrahepatic bile duct and a vine-like expansion of the intrahepatic bile duct was observed.Furthermore,a biliary biopsy was performed under fluoroscopy to determine the nature and origin of the lesion.The pathological diagnosis of the biopsy was SRCC.Finally,a diagnosis of primary SRCC of extrahepatic bile duct with distant lymph node metastasis and multiple liver metastases was made based on the radiographic,PTCD,and pathological characteristics.The tumor was diagnosed as T3N1M1 stage IV.Despite our aggressive approach,the patient died of liver failure after 1 mo.CONCLUSION This is the only case report on primary SRCC of the extrahepatic bile duct with distant organ metastasis to date.

Synchronous occurrence of carcinoid, signet-ring cell carcinoma and heterotopic pancreatic tissue in stomach: A case report and literature review

We presented an unusual case with coexistence of carcinoid, signet-ring cell carcinoma (SRC) and heterotopic pancreatic tissue in stomach. Gastroscopic examination of this 63-year-old male patient showed multiple protrusions in gastric corpus near the greater curvature, identified by subsequent biopsy as carcinoid. Distal subtotal gastrectomy was performed. Histological and immunohistochemical examinations showed a carcinoid tumor in gastric corpus near the greater curvature, an intramucosal SRC at the lesser curvature of corpus and heterotopic pancreatic tissue in muscularis propria of the antrum at the lesser curvature with hyperplasia of peripheral endocrine cells producing multiple pancreatic hormones. We reviewed the literatures on clinicopathological characteristics and the differential diagnosis of the above three abnormalities, and concluded that the carcinoid in corpus near the greater curvature and SRC in the lesser curvature are independent lesions; the foci of endocrine cells in the muscularis propria and serosa are hyperplastic lesions from the heterotopic pancreatic tissue, rather than dissemination of carcinoid in corpus.

Clinicopathologic features and survival of patients with colorectal mucinous, signet-ring cell or non-mucinous adenocarcinoma：experience at an institution in southern China

Background Previous studies have shown conflicting results on the relation between clinicopathologic features and prognosis of patients with colorectal mucinous, signet-ring cell, or non-mucinous adenocarcinoma; only few such studies have been performed in China. This retrospective study analyzed data from our department to investigate clinicopathologic characteristics, prognosis and possible correlations of three histologic types - colorectal mucinous, signet-ring cell, and non-mucinous adenocarcinoma, to clarify the bases for observed differences which may lead to development of targeted therapies Methods Of 2079 patients diagnosed with colorectal cancer between 1994 and 2007, 144 had mucinous, 25 had signet-ring cell, and 1837 had non-mucinous adenocarcinoma. Their clinicopathologic parameters and survival were analyzed using established statistical methodologies. Results Mucinous and signet-ring cell adenocarcinomas were common in younger patients （P 〈0.001）. Location, size and disease stage differed significantly among the three types. Signet-ring cell tumors were more commonly found in the rectum than mucinous and non-mucinous adenocarcinoma （P 〈0.001）. Mucinous and signet-ring cell tumors presented in a later stage in life more often than non-mucinous adenocarcinoma, with lymph node involvement, serosal infiltration, peritoneal dissemination, and adjacent organ invasion （P 〈0.01）. The rate of radical resection, hepatic metastasis and local recurrence did not differ among types （P 〉0.05）. Compared with patients with non-mucinous adenocarcinoma, patients with mucinous and signet-ring cell tumors who underwent potentially curative resections or stage Ⅱ/Ⅲ disease had poorer long-term overall survival. Survival did not differ by type for patients with either stage Ⅰ or Ⅳ disease （P 〉0.05）. Conclusions Mucinous and signet-ring cell adenocarcinoma have unique carcinogenesis and similar biologic behavior. Our study confirms that both histologic types, especially signet-ring cell tumors, are independent, negative prognostic factors for patients with colorectal cancer. Type does not appear to have a significant effect on survival when disease is either stage Ⅰ or Ⅳ at presentation.

Endoscopic features of early-stage signet-ring-cell carcinoma of the stomach

AIM: To identify the features of early signet ring cell gastric carcinoma using magnification endoscopy with narrow band imaging(NBI).METHODS: A retrospective review was conducted of 12 cases of early signet ring cell gastric carcinoma who underwent treatment in a single institution between January 2009 and April 2013. All patients had magnification endoscopy with NBI and indigo carmine contrast to closely examine the mucosal architecture, including the microvasculature and arrangement of gastric pits. Histologic examination of the final endoscopic submucosal dissection or gastrectomy specimen was performed and compared with the endoscopic findings to identify patterns specific to signet ring cell carcinoma.RESULTS: Twelve patients with early signet ring cell gastric carcinoma were identified; 75% were male, and average age was 61 years. Most of the lesions were stage T1a(83%), while the remainder were T1b(17%). The mean lesion size was 1.4 cm2. On standard endoscopy, all 12 patients had a pale, flat lesion without any evidence of mucosal abnormality such as ulceration, elevation, or depression. On magnification endoscopywith NBI, all of the patients had irregularities in the glands and microvasculature consistent with early gastric cancer. In addition, all 12 patients exhibited the "stretch sign", an elongation or expansion of the architectural structure. Histologic examination of the resected specimens demonstrated an expanded and edematous mucosal layer infiltrated with tumor cells.CONCLUSION: The "stretch sign" appears to be specific for signet ring cell carcinoma and may aid in the early diagnosis and treatment of this aggressive pathology.

Cell reprogramming therapy for Parkinson’s disease

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.