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1.
Zhonghua Zhong Liu Za Zhi ; 41(12): 923-931, 2019 Dec 23.
Artigo em Chinês | MEDLINE | ID: mdl-31874550

RESUMO

Objective: To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP. Methods: PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 µl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded. Results: The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%. Conclusion: PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.


Assuntos
Adenocarcinoma Mucinoso/cirurgia , Carcinoma de Células em Anel de Sinete/cirurgia , Pseudomixoma Peritoneal/cirurgia , Adenocarcinoma Mucinoso/patologia , Animais , Biomarcadores Tumorais , Carcinoma de Células em Anel de Sinete/patologia , Xenoenxertos , Humanos , Camundongos , Pseudomixoma Peritoneal/patologia
2.
Urology ; 134: e1-e2, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586569
3.
Medicine (Baltimore) ; 98(40): e17367, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577736

RESUMO

There has been a steady increase in the incidence of signet ring cell (SRC) carcinoma, a distinct histological type with cells containing abundant intracytoplasmic mucin. We aimed to analyze the clinicopathological characteristics and prognostic value of patients with SRC gastric cancer (GC) who underwent gastrectomy.Clinical data of 10,312 GC patients who underwent D2 radical gastrectomy were obtained from the Surveillance, Epidemiology, and End Results database and were retrospectively analyzed. X-tile plots were constructed to illustrate the optimal cut-off points using the minimum P-value from the log-rank Chi-squared test. The Kaplan-Meier method was used for the analysis of the overall cumulative probability of survival. Their differences were evaluated using the log-rank test. The Cox multiple factors analysis was performed using the logistic regression method.In total, 946 (9.17%) SRC GC patients with pT1a-4bN0-3bM0 stage cancer were recruited. The optimal cut-off point for size was 49 mm. The 3-year overall survival (OS) rates of the SRC GC, large-size, and small-size groups were 35.89%, 30.63%, and 44.96%, respectively (P < .05). Cox multivariate analysis showed that tumor size (odds ratio [OR] = 2.032), T3 category (OR = 1.324), T4a category (OR = 1.945), and T4b category (OR = 2.163) were independent hazard prognostic factors.SRC GC has a distinct biological behavior, presents as a large-sized tumor (≥49 mm), and is associated with worse outcomes. SRC GC patients have 2.032 times risk of mortality. SRC patients with larger tumors are at higher risk for infiltrative growth, lymph node metastasis, and distant metastasis.


Assuntos
Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastrectomia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Programa de SEER , Carga Tumoral
4.
Pathol Res Pract ; 215(10): 152566, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31400926

RESUMO

BACKGROUND: The genetic alterations (GAs) in two specific histological subtypes of colorectal cancer (CRC), signet ring cell colorectal carcinoma (SRC) and mucinous colorectal carcinoma (MC), are not well known. In the present study, we employed next-generation sequencing to perform genetic profiling of SRC and MC, and compared the spectrum of GAs with the alterations found in conventional type colorectal cancer (CON). MATERIALS AND METHODS: We selected 46 CRCs comprising 17 SRCs and mucinous carcinoma with signet ring cell component (SRCCs), 17 MCs, and 12 CONs with microsatellite stability or microsatellite instability-low. Deep sequencing was performed using a targeted cancer panel composed of 171 cancer-related genes. SMAD4 protein expression was evaluated by immunohistochemical staining. RESULTS: We detected 108 mutations in 18 different genes. Overall, 2.34 GAs were detected per tumor (range, 0-14). The overall frequency of GA and alteration in targetable genes was less prevalent in SRC/SRCC compared to the frequency of alteration in MC/CON (p = 0.040 and p < 0.001, respectively). The GA profile of SRC/SRCC included TP53 (8/17, 47.1%), SMAD4 (5/17, 29.4%), KRAS (4/17.23.5%), APC (4/17.23.5%), PIK3CA, ATM, BRAF, and PIK3R1 (1/17, 5.9%, each). KRAS mutation was significantly less prevalent in SRC/SRCC compared to the number of KRAS mutations in MC (12/17, 70.6%) and CON (9/12, 75.0%) (p = 0.015 and 0.01, respectively). Compared to the 152 non-hypermutated CONs from TCGA database, SMAD4 alteration was predominant in SRC/SRCC (p = 0.045) with aberrant loss of SMAD4 expression (13/17, 76.5%) compared to the SMAD4 alterations in CON (5/15, 33.3%) (p = 0.031). Accordingly, KRAS (12/17, 70.6%), APC (6/17, 35.3%), SMAD4, TP53 (4/17, 23.5%, each), PIK3CA (3/17, 17.6%), AKT1, ATM, BRAF, EGFR, and EZH2 (1/17, 5.9%, each) were altered in MC. APC and TP53 mutations were less frequent in MC compared to those in TCGA-CON (p < 0.001 and 0.003, respectively) whereas KRAS mutation was prevalent (p = 0.041). CONCLUSION: Alterations of known cancer associated genes and targetable genes in SRC/SRCC are infrequent. The profile of GAs in SRC/SRCC and MC differs from the GA profile of CON. Specifically, SMAD4 mutation and loss of SMAD4 expression is frequently found in SRC/SRCC. The genetic profiles revealed in the present study may aid in developing precision medicine for CRC treatment based on histological subtype.


Assuntos
Adenocarcinoma Mucinoso/genética , Carcinoma de Células em Anel de Sinete/genética , Neoplasias Colorretais/genética , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Genômica , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Adulto Jovem
5.
Acta Med Okayama ; 73(4): 361-365, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31439960

RESUMO

A 35-year-old man was referred to our hospital for chronic abdominal pain and diarrhea. Computed tomography showed wall thickening, poor contrast enhancement and calcification of the ascending colon, which were consistent with phlebosclerotic colitis. Malignant character was not detected from a biopsy specimen. Operatively, we observed a scirrhous mass of the ascending colon invading surrounding tissue, which was diagnosed as signet ring cell carcinoma based on analysis of an intraoperative frozen section. Right hemicolectomy with regional lymph node dissection was performed. This case was extremely similar to phlebosclerotic colitis in clinical findings; surgical resection was required for correct diagnosis.


Assuntos
Carcinoma de Células em Anel de Sinete/diagnóstico , Colite/diagnóstico , Neoplasias do Colo/diagnóstico , Adulto , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/cirurgia , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Humanos , Masculino
6.
Intern Med ; 58(21): 3143-3148, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31292374

RESUMO

Chylothorax is the accumulation of lipid pleural effusion. Few reports have described chylothorax caused by gastric cancer. A 45-year-old woman presented with progressive lymphedema and bilateral chylothorax. Although repetitive thoracentesis was performed to relieve her dyspnea, swelling of her axillary lymph nodes became significant. Positron emission tomography/computed tomography demonstrated the accumulation of 18F-fluorodeoxyglucose in these nodes, and a lymph node biopsy showed signet ring cell carcinoma. The primary site was a 0-IIc type lesion in the gastric body that was only detected by upper gastrointestinal endoscopy. The patient was diagnosed with advanced gastric cancer 3.5 months after presentation for chylothorax.


Assuntos
Carcinoma de Células em Anel de Sinete/complicações , Quilotórax/etiologia , Neoplasias Gástricas/complicações , Adulto , Idoso , Biópsia , Carcinoma de Células em Anel de Sinete/diagnóstico por imagem , Carcinoma de Células em Anel de Sinete/patologia , Quilotórax/terapia , Feminino , Humanos , Linfonodos/patologia , Linfedema/etiologia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Radiografia Torácica , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Toracentese
9.
Diagn Pathol ; 14(1): 73, 2019 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-31279332

RESUMO

BACKGROUND: Ovarian signet ring cell carcinomas are predominantly metastatic. Cases coexisting with endometriotic cysts are extremely rare, and are supposed to be primary. However, such cases have not been well-documented to date. CASE PRESENTATION: A 46-year-old Chinese woman had an incidental small nodule in the right ovarian endometriotic cyst. She underwent a staging surgery due to an unexpected ovarian carcinoma from her frozen section. Laparotomy exploration, MRI and gastrointestinal endoscopy revealed no other abnormalities in the abdominal organs. She had a pelvic recurrence at 7 months and was alive with disease for 13 months at present. Gross examination showed a small mural nodule (l.0 × 0.5 × 0.2 cm) in the wall of the right ovarian cyst (18x15x14 cm). Microscopically, the neoplastic cells arranged in solid nests, crowded small irregular glands and scattered single cells. They had abundant cytoplasmic mucin and contained a significant component of signet ring cells. The stroma was desmoplastic and occasionally contained extracellular mucin deposits. The surrounding endometriotic cyst had several foci of atypical surface epithelium (atypical endometriotic cyst) that was continuous with the mucinous carcinoma. Immunohistochemistry demonstrated that the tumor cells were diffusely positive for CK7 and negative for CK20 and CDX2. CONCLUSIONS: Primary ovarian poorly differentiated mucinous carcinoma with signet ring cells can occur in an atypical endometriotic cyst. This rare case addresses the necessity of careful and extensive pathological examination on large ovarian endometriotic cysts.


Assuntos
Adenocarcinoma Mucinoso/diagnóstico , Carcinoma de Células em Anel de Sinete/diagnóstico , Endometriose/diagnóstico , Cistos Ovarianos/diagnóstico , Neoplasias Ovarianas/diagnóstico , Adenocarcinoma Mucinoso/patologia , Carcinoma de Células em Anel de Sinete/patologia , Diferenciação Celular , Endometriose/patologia , Epitélio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mucinas/metabolismo , Cistos Ovarianos/patologia , Neoplasias Ovarianas/patologia , Ovário/patologia
11.
Pathol Res Pract ; 215(7): 152462, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31146976

RESUMO

Signet ring cell mesothelioma is a rare variant of epithelioid mesothelioma with limited cases published. It has a male predilection and most commonly occurs on pleura; it can also arise in the peritoneal cavity. The signet ring cell morphology can pose a challenge leading to a potential diagnostic error. A variety of benign and malignant diseases, including reactive histiocytic hyperplasia, adenocarcinoma, melanoma, and lymphoma with signet ring cell morphology should be considered in the differential diagnosis. In signet ring cell mesothelioma work up, mucin stains are of limited value. Even though immunohistochemistry is routinely used in mesothelioma diagnosis, there is no sole specific mesothelial marker. Hence, a panel of mesothelial and epithelial markers are used; these should be interpreted with caution especially in this variant. Electron microscopy and genetic testing can be very helpful in distinguishing signet ring cell mesothelioma from its mimickers.


Assuntos
Carcinoma de Células em Anel de Sinete/diagnóstico , Mesotelioma/diagnóstico , Biomarcadores Tumorais/metabolismo , Carcinoma de Células em Anel de Sinete/metabolismo , Carcinoma de Células em Anel de Sinete/patologia , Diagnóstico Diferencial , Humanos , Mesotelioma/metabolismo , Mesotelioma/patologia
13.
Ann Surg Oncol ; 26(7): 2268-2275, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31041628

RESUMO

BACKGROUND: Survival in peritoneal dissemination from appendiceal cancer after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) varies within each histopathologic subtype. Analyzing patients with unique responses may uncover the mechanisms behind their extreme outcomes. We proposed a method to identify retrospectively and to characterize patients who responded exceptionally well or very poorly within each histopathologic subtype. METHODS: Retrospective review of patients with low-grade mucinous carcinoma peritonei (LGMCP), high-grade MCP (HGMCP), and HGMCP with signet ring cells (HGMCP-S) with complete CRS/HIPEC (CC-0/1) was performed. Patients were divided by recurrence status. Median follow-up was calculated for each. Exceptional responders (ExR) were defined as alive without recurrence after median follow-up of the nonrecurrent group. Poor responders (PoR) were defined as disease recurrence before median follow-up of the recurrent group. Perioperative characteristics were analyzed. RESULTS: LGMCP, HGMCP, and HGMCP-S had 48 (41%), 19 (23%), and 7 (14%) ExR and 11 (10%), 20 (24%), and 20 (39%) PoR, respectively. All ExR had lower median PCI (26 vs. 36 [p = 0.004]; 13 vs. 33.5 [p < 0.001]; 3 vs. 29.5 [p = 0.001]). Fewer LGMCP and HGMCP ExR had abnormal tumor markers (36% vs. 90% [p = 0.003]; 22% vs. 74% [p = 0.003]). More HGMCP and HGMCP-S ExR had CC-0 (vs. CC-1) cytoreductions (84% vs. 50%, p = 0.041; 100% vs. 40%, p = 0.008). CONCLUSIONS: Stratifying patients by recurrence status and follow-up time successfully selects ExR and PoR within each histopathologic subtype. Perioperative characteristics of ExR versus PoR differ across histopathologic subtypes, except for disease burden. Genetic analysis may further elucidate differences and aid in the development of novel targeted therapies.


Assuntos
Neoplasias do Apêndice/mortalidade , Quimioterapia do Câncer por Perfusão Regional/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Seleção de Pacientes , Neoplasias Peritoneais/mortalidade , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Carcinoma de Células em Anel de Sinete/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/terapia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/terapia , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
14.
J Int Med Res ; 47(6): 2524-2532, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31039658

RESUMO

OBJECTIVES: We investigated the prognostic value of tumor blood supply in patients with advanced gastric cancer (GC) receiving neoadjuvant chemotherapy. METHODS: We retrospectively reviewed 53 patients with advanced GC treated with FLEEOX chemotherapy. The tumor computed tomography (CT) enhancement value was measured before chemotherapy (CT1; arterial phase CT-plain phase CT). The liver parenchyma CT enhancement value (CT2) was also measured using the same method, to eliminate individual differences. Tumor blood supply was defined as good or poor based on the median CT1/CT2 values. We evaluated the relationships between tumor blood supply and response to chemotherapy, clinicopathologic characteristics, and overall survival (OS). RESULTS: A good blood supply (GBS) was associated with significantly better clinical and pathological responses to chemotherapy than a poor blood supply (PBS). The 3-year OS was 65.8% for the entire cohort. Patients with a GBS had a significantly higher OS (78.57%) than those with a PBS (54.44%). Additionally, patients with Bormann type III GC had a better blood supply than those with type II GC. CONCLUSION: Patients with advanced GC and a GBS are more likely to benefit from neoadjuvant chemotherapy than those with a PBS. Blood supply may thus be a predictor for chemotherapy response.


Assuntos
Adenocarcinoma/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células em Anel de Sinete/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasias Gástricas/mortalidade , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma de Células em Anel de Sinete/irrigação sanguínea , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Carcinoma de Células em Anel de Sinete/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
15.
BMJ Case Rep ; 12(4)2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31040144

RESUMO

Colorectal cancer is the third most common cancer in the world and the fourth most common cause of death related to cancer. Signet ring cell carcinoma represents an uncommon histological type for rectal cancer with less than 1% of all rectal neoplasms. It usually behaves aggressively and has an inferior prognosis. We present the case of a young man diagnosed with signet ring cell rectal carcinoma. He underwent neoadjuvant therapy with partial response, had surgery with curative intent and showed local recurrence after only 3 months. Disease progression happened only weeks after recurrence with metastasis to vertebrae, extraocular muscles, bone marrow and skin. He is currently receiving palliative chemotherapy.


Assuntos
Neoplasias da Medula Óssea/secundário , Carcinoma de Células em Anel de Sinete/secundário , Neoplasias Oculares/secundário , Hemorragia Gastrointestinal/patologia , Neoplasias Retais/patologia , Neoplasias Cutâneas/secundário , Adulto , Carcinoma de Células em Anel de Sinete/diagnóstico por imagem , Carcinoma de Células em Anel de Sinete/patologia , Colonoscopia , Diagnóstico Tardio/efeitos adversos , Progressão da Doença , Hemorragia Gastrointestinal/diagnóstico por imagem , Humanos , Masculino , Cuidados Paliativos , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/tratamento farmacológico , Perda de Peso
17.
Pathology ; 51(4): 384-391, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31029443

RESUMO

Mucinous adenocarcinoma (MAC) is defined by the presence of extracellular mucin covering more than 50% of the tumour area; however, MAC is histologically heterogeneous and some cases exhibit signet ring cell components. The aim of this study was to determine the prognostic impact of such variable morphology. A total of 299 consecutive MAC patients who underwent curative surgery were included. MACs were classified into four categories according to the predominant pattern of floating tumour cells: strips (27.1%), clusters (51.8%), signet ring cells (6.7%), and mixed clusters and signet ring cells (14.4%). In addition, we categorised MACs according to the relative amount of mucin. MACs with signet ring cell component were clearly associated with poor overall and recurrence-free survivals. Moreover, MACs with more than 50% signet ring cell component showed particularly poor clinical outcome just like non-mucinous signet ring cell carcinoma. MACs with a greater amount of extracellular mucin were associated with poor recurrence-free survival, independent of the pathological stage. In addition, lymphovascular and perineural invasion, advanced pathological stage, and old age at diagnosis were also prognostic factors for poor overall survival. MACs with more than 50% signet ring cell component should be classified as signet ring cell carcinoma and the presence of signet ring cells should be included in the pathology report of MACs with 10-50% signet ring cell component.


Assuntos
Adenocarcinoma Mucinoso/classificação , Carcinoma de Células em Anel de Sinete/classificação , Neoplasias Colorretais/classificação , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/patologia , Adulto , Idoso , Carcinoma de Células em Anel de Sinete/diagnóstico , Carcinoma de Células em Anel de Sinete/patologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucinas/metabolismo , Prognóstico
19.
Gastroenterology ; 157(1): 87-96, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30935944

RESUMO

BACKGROUND & AIMS: Pathogenic germline variants in CDH1 are associated with risk for diffuse gastric cancer (DGC) and lobular breast cancer. The reported high incidence of DGC and limited sensitivity of endoscopy in detection have prompted recommendation for total prophylactic gastrectomy for carriers of pathogenic or likely pathogenic (PLP) germline variants of CDH1. Multigene panel tests have identified increasing numbers of carriers of PLP variants in CDH1 who lack a family history of DGC. We evaluated outcomes of endoscopic surveillance for carriers of PLP variants of CDH1 with and without family history of DGC. METHODS: Individuals from 13 families with germline PLP variants of CDH1 were evaluated at the Michigan Medicine Cancer Genetics Clinic from January 1998 through May 2018. Outcomes of esophagogastroduodenoscopy examinations, histopathology analyses, and surgery were compared between individuals with and without a family history of DGC. RESULTS: We identified 20 carriers of germline CDH1 PLP variants; they underwent endoscopic examinations and/or gastrectomy. None had abnormal findings visible during endoscopy. Signet ring cell carcinoma (SRCC) was detected in 12 of 20 subjects. All but 1 of the carcinomas were tiny and confined to the lamina propria, and 1 was transmural. Seven of 12 subjects who had SRCC reported no diagnoses of DGC in first-degree relatives and did not meet established criteria for CDH1 analysis based on a 3-generation family pedigree. CONCLUSIONS: More than half of individuals with germlines variants of CDH1 that are PLP had histopathologic evidence for DGC on endoscopy and/or gastrectomy. Family history of DGC and endoscopic findings therefore do not appear to be reliable determinants of risk of SRCC in individuals with genetic predisposition to DGC.


Assuntos
Carcinoma de Células em Anel de Sinete/diagnóstico , Detecção Precoce de Câncer/métodos , Endoscopia do Sistema Digestório , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Gástricas/diagnóstico , Adulto , Idoso , Antígenos CD/genética , Caderinas/genética , Carcinoma de Células em Anel de Sinete/genética , Carcinoma de Células em Anel de Sinete/patologia , Carcinoma de Células em Anel de Sinete/prevenção & controle , Estudos de Casos e Controles , Feminino , Gastrectomia , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Procedimentos Cirúrgicos Profiláticos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Adulto Jovem
20.
Ann Surg Oncol ; 26(8): 2375-2384, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30941657

RESUMO

BACKGROUND: Little is known about the association between signet ring cell (SRC) differentiation and response to neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) in patients with esophageal and junctional adenocarcinoma (EAC). We aimed to assess if SRC differentiation is associated with survival and response to nCT or nCRT in patients with EAC. METHODS: Patients who underwent nCT and nCRT followed by surgery for EAC from 2000 until 2016 were identified from two institutional prospectively maintained databases. The pretreatment biopsy report or surgical resection specimen was used to differentiate patients into an SRC or non-SRC group. RESULTS: Overall, 129 (19%) of 689 patients included had SRCs (nCT: n = 64; nCRT: n = 65). The SRC group had a more advanced ypT stage (p = 0.003), a higher number of positive lymph nodes in the resection specimen {median (interquartile range [IQR]) 2 [0-5] vs. 1 [0-3]; p = 0.002} and a higher rate of R1/R2 resections (19.4% vs. 12%; p = 0.026). SRC differentiation was not an independent prognostic factor for overall survival (OS) or disease-free survival (DFS). Following nCT, the SRC group had significantly shorter DFS (median [IQR] 12 [5-50] vs. 23 [8-164]; p = 0.013), but not OS, compared with the non-SRC group. In contrast, no differences according to SRC status for OS or DFS were found in patients who underwent nCRT. CONCLUSIONS: SRC differentiation was not independently associated with worse OS in patients with EAC who underwent neoadjuvant therapy and surgery. However, nCRT was associated with greater tumor downstaging and better DFS.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma de Células em Anel de Sinete/patologia , Diferenciação Celular , Quimiorradioterapia Adjuvante/mortalidade , Neoplasias Esofágicas/mortalidade , Junção Esofagogástrica/patologia , Terapia Neoadjuvante/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
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