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BACKGROUND: The development of immunohistochemical staining has revealed that gastric adenocarcinoma with the gastric phenotype can be divided into the foveolar, fundic gland, and pyloric gland phenotypes. Gastric adenocarcinoma of the pyloric gland type is difficult to diagnose using biopsy because of its low atypia and rarity. Herein, we describe a case of gastric adenocarcinoma of the pyloric gland type that was diagnosed immunohistochemically after endoscopic resection. CASE PRESENTATION: A 67-year-old man was referred to our hospital for the diagnosis and treatment of a 30-mm elevated lesion on the lesser curvature side of the middle of the gastric body. Although four biopsies were performed, it was difficult to determine whether the lesion was benign or malignant. Therefore, endoscopic submucosal dissection was performed, and the presence of tumor cells infiltrating the submucosa with venous invasions was identified. Immunohistochemical staining revealed that the tumor cells were positive for MUC5AC and MUC6 and negative for Pepsinogen I and H + /K + -ATPase. From the above findings, he was diagnosed as having gastric adenocarcinoma with pyloric gland type. The patient underwent a laparoscopic distal gastrectomy and was discharged without any adverse events. CONCLUSIONS: Gastric adenocarcinoma of the pyloric gland type is a rare disease, and endoscopic resection can serve as a viable diagnostic option for this condition when it is difficult to diagnose using biopsy. Immunohistochemical pathology images can aid in the diagnosis of gastric adenocarcinoma of the pyloric gland type.
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Pseudomyxoma peritonei (PMP) of pancreatic origin arising from an intraductal papillary mucinous neoplasm (IPMN) is rare. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established as the optimal treatment for PMP. However, the benefits and safety of CRS with HIPEC for treating PMP of pancreatic origin remain unclear. Herein, we describe a case of PMP of pancreatic origin that was treated with CRS and HIPEC without postoperative complications. A 75-year-old woman was referred to our department. Computed tomography (CT) revealed a multilocular cystic tumor in the pancreatic tail, notable mucinous ascites in the abdominal cavity, and scalloping of the liver and spleen. CT did not reveal the appendix, and the ovaries were normal in size. The patient was diagnosed with PMP of pancreatic origin, and CRS and HIPEC were performed. Intraoperatively, the pancreatic tumor was perforated, and there was a large amount of mucinous ascites. We performed distal pancreatectomy in addition to CRS and HIPEC, with no intraoperative complications. The postoperative course was uneventful, and the patient survived after 6 months without recurrence. CRS with HIPEC may be a feasible treatment option for PMP of pancreatic origin.
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Hipertermia Induzida , Neoplasias Pancreáticas , Neoplasias Peritoneais , Pseudomixoma Peritoneal , Feminino , Humanos , Idoso , Pseudomixoma Peritoneal/cirurgia , Pseudomixoma Peritoneal/diagnóstico , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/patologia , Ascite , Procedimentos Cirúrgicos de Citorredução/métodos , Hipertermia Induzida/métodos , Neoplasias Pancreáticas/terapia , Estudos RetrospectivosRESUMO
BACKGROUND: Preoperative chemotherapy/chemoradiotherapy has been generally considered for the treatment of esophageal squamous cell carcinoma (ESCC) to improve prognosis. We examined the effects of anticancer drugs on the expression of kallikrein-related peptidase 13 (KLK13), a potential ESCC prognostic marker, and its clinical relevance in patients who received chemotherapy/chemoradiotherapy for ESCC. METHODS: Overall, 105 patients with ESCC who received chemotherapy or chemoradiotherapy before esophagectomy were enrolled. The expression of KLK13 in biopsy samples obtained before chemotherapy/chemoradiotherapy and resected ESCC tumors was assessed by immunohistochemical staining. The effects of 5-fluorouracil (5-FU) and/or cisplatin (CDDP) exposure on the expressions of KLK13 and ten-eleven translocation dioxygenases (TET) in ESCC cells were examined by reverse transcription-polymerase chain reaction. RESULTS: Immunohistochemical staining of paired ESCC specimens before (biopsy samples) and after (resected specimens) chemotherapy/chemoradiotherapy demonstrated a change in KLK13 expression. KLK13 and TET2/3 transcriptions were induced when human ESCC cell lines were treated with 5-FU and/or CDDP. Among patients with KLK13-negative status before chemotherapy/chemoradiotherapy, those with KLK13-positive resected tumors had a significantly poorer prognosis than those with KLK13-negative resected tumors (p = 0.0477). By using tumor cells isolated from ESCC biopsy tissues obtained before chemotherapy/chemoradiotherapy, we established a primary culture system and detected the induction of KLK13 expression by anticancer drugs. CONCLUSIONS: Preoperative treatments alter KLK13 expression in ESCC. The conversion of KLK13 expression from a negative status in biopsy samples to a positive status in resected tumor samples is a predictor of poor prognosis. KLK13 status is a potential marker for decision making to avoid harmful chemotherapy/chemoradiotherapy in patients with ESCC.
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Antineoplásicos , Dioxigenases , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/farmacologia , Proteínas de Ligação a DNA , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Fluoruracila , Calicreínas , Prognóstico , Terapia NeoadjuvanteRESUMO
Lung squamous cell carcinoma (LSCC) is associated with poor prognosis. Molecular targeting drugs have been demonstrated to be effective for lung adenocarcinoma; however, they are often not effective for LSCC. Kallikrein-related peptidase 13 (KLK13) expression enhances the malignancy of lung adenocarcinoma; however, its expression and crucial role in LSCC remain largely unknown. The present study examined the relationship between the KLK13 expression and clinicopathological features of LSCC. A total of 94 patients diagnosed with LSCC who underwent lobectomy, segmentectomy or wedge resection were selected. KLK13 expression was evaluated through immunostaining of formalin-fixed paraffin-embedded sections of surgical specimens. Of the 94 LSCC samples, 70 exhibited no KLK13 expression, while the remaining 24 exhibited ectopic expression. KLK13 expression in tumors was focal and restricted to the cytoplasm of keratinized cells. LSCC cases were classified into KLK13-negative and KLK13-positive groups, and KLK13 expression was positively associated with E-cadherin expression (P=0.0143). Associations between KLK13 expression and keratinization (P=0.0052) or absence of lymphatic vessel invasion (P=0.0603) were observed; however, these trends did not reach statistical significance. The present findings indicated that KLK13 expression in keratinized LSCC may have a protective role in lymphatic vessel invasion of LSCC, which suggests its significance for therapeutic applications against LSCC.
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A 41-year-old man presented with chronic cough and chest pain. Laboratory tests revealed anemia, inflammation, hypoalbuminemia, polyclonal hypergammaglobulinemia, and elevated interleukin-6 levels. Computed tomography revealed diffuse bilateral pulmonary nodules and multicentric lymphadenopathy. Histopathology of the pulmonary nodule resembled pulmonary hyalinizing granuloma (PHG), whereas lymph node histopathology was consistent with idiopathic multicentric Castleman disease (iMCD). The patient was diagnosed with iMCD involving PHG-like pulmonary nodules. Little is known about the association between these two diseases, and the present case provides insights regarding the relationship between PHG and iMCD.
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Hiperplasia do Linfonodo Gigante , Nódulos Pulmonares Múltiplos , Pneumonia , Fibrose Pulmonar , Masculino , Humanos , Adulto , Hiperplasia do Linfonodo Gigante/complicações , Hiperplasia do Linfonodo Gigante/diagnóstico por imagem , Nódulos Pulmonares Múltiplos/diagnóstico , Diagnóstico Diferencial , Granuloma/complicações , Granuloma/diagnóstico , Fibrose Pulmonar/complicaçõesRESUMO
A 78-year-old man presented with a large abdominal mass detected by ultrasonography during a regular checkup. Even if the mass was > 10 cm in diameter, he was asymptomatic. Computed tomography detected an oval-shaped mass, with a maximum diameter of 12 cm, adjacent to the greater curvature of the stomach. Esophagogastroduodenoscopy revealed a 20 mm slightly depressed (type 0-IIc) lesion on the posterior wall of the gastric antrum, which was confirmed to be adenocarcinoma. Three cycles of combination chemotherapy with S-1 and oxaliplatin were administered as neoadjuvant chemotherapy. After neoadjuvant chemotherapy, the patient underwent distal gastrectomy, and a histopathological study identified the 12 cm giant mass as a lymph node metastasis. The postoperative course was uneventful, and thus far, the patient has completed adjuvant chemotherapy without relapse. Cases of gastric cancer with a giant lymph node metastasis are extremely rare. In this study, we report the present case and review the previous literature.
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Neoplasias Gástricas , Masculino , Humanos , Idoso , Neoplasias Gástricas/patologia , Metástase Linfática/patologia , Gastrectomia , Recidiva Local de Neoplasia/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfonodos/diagnóstico por imagem , Linfonodos/patologiaRESUMO
BACKGROUND: Esophageal gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal interstitium, and comprise less than 0.7% of all GISTs. The presentation of esophageal GIST is relatively benign, commonly characterized by symptoms of dysphagia and gastrointestinal bleed. On the contrary, it is highly unusual for these tumors to present as surgical emergencies. CASE PRESENTATION: Here, we describe a case of hemothorax secondary to the rupture of a massive (19 cm) esophageal GIST in a 79-year-old male. The patient presented with mild back pain, vomiting, and hypotension. A CT scan revealed significant mediastinal enlargement and left hemothorax. We conducted an emergency thoracotomy which revealed a 19 × 15 × 7 cm ruptured esophageal tumor that was bleeding profusely into the left thoracic cavity. Piecemeal resection without esophagectomy was performed to achieve hemostasis. Pathological evaluation of resected tissue confirmed the diagnosis of GIST. The patient was provided adjuvant imatinib therapy and remains progression-free at the 10-month follow-up. CONCLUSIONS: To the best of our knowledge, this is the first reported case of life-threatening hemothorax caused by a ruptured esophageal GIST. Findings from this case may aid in the diagnosis and management of these rare tumors.
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We report a rare case of duodenal gangliocytic paraganglioma accompanied with lymph node metastasis. An asymptomatic 58-year-old woman was admitted for the evaluation of abnormal liver enzyme test results. Abdominal computed tomography and upper gastrointestinal endoscopy revealed a 27-mm pedunculated tumor of the papilla of Vater. Adenocarcinoma of the papilla with muscularis propria invasion was suspected; therefore, pancreaticoduodenectomy with lymph node dissection was performed. There were no perioperative complications. A definitive diagnosis of gangliocytic paraganglioma of the papilla of Vater with lymph node metastases was confirmed by pathological examinations, which is a rare condition. The patient was discharged on her 16th postoperative day, and no recurrence or metastases were identified during the 18-month follow-up period. We herein discuss the surgical treatment for this rare case and present a review of related literature.
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Neoplasias Duodenais , Paraganglioma , Neoplasias Duodenais/diagnóstico por imagem , Neoplasias Duodenais/cirurgia , Endoscopia Gastrointestinal , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Pancreaticoduodenectomia , Paraganglioma/diagnóstico por imagem , Paraganglioma/cirurgiaRESUMO
Extracorporeal membrane oxygenation (ECMO) therapy in patients with coronavirus disease 2019 (COVID-19) has a low frequency of use, and thus pathological findings in such patients are valuable. In this case report, a 62-year-old man with a history of hypertension presented with a runny nose. After an at-home COVID-19 positive test, he developed dyspnea and fever. Once admitted to our hospital, his oxygenation worsened, and ECMO was initiated. He died from respiratory failure 69 days after ECMO induction. Macroscopically, the lungs gained mass, were partially consolidated, and were airless. Histological analysis revealed diffuse bronchial epithelial metaplasia and adenoid metaplasia in the alveolar epithelium. Although the lung parenchyma was partially preserved, there was organizing and fibrosis that filled pulmonary alveolus due to COVID-19 and changes resulting from disuse and long-term ECMO.
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Glutathione S-transferase omega 2 (GSTO2) lacks any appreciable GST activity, but it exhibits thioltransferase activity. The significance of GSTO2 in lung function has been reported; however, the precise expression and molecular function of GSTO2 in the lungs remain unclear. In the present study, we found that GSTO2 is expressed in airway basal cells, non-ciliated, columnar Clara cells, and type II alveolar cells, which have self-renewal capacity in the lungs. Contrastingly, no GSTO2 expression was observed in 94 lung squamous cell carcinoma (LSCC) samples. When human LSCC cell lines were treated with 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant GSTO2 hypermethylation in LSCC is the cause of its downregulation. Forced GSTO2 expression in LSCC cell lines inhibited cell growth and colony formation in vitro. In a subcutaneous xenograft model, GSTO2-transfected cells formed smaller tumors in nude mice than mock-transfected cells. Upon intravenous injection into nude mice, the incidence of liver metastasis was lower in mice injected with GSTO2-transfected cells than in those injected with mock-transfected cells. In addition, GSTO2 induction suppressed the expression of ß-catenin and the oxygen consumption rate, but it did not affect the extracellular acidification rate. Furthermore, GSTO2-transfected cells displayed lower mitochondrial membrane potential than mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, ß-catenin expression and mitochondrial membrane potential were recovered. Our study indicated that the loss of GSTO2 via DNA hypermethylation contributes to the growth and progression of LSCC, probably by modulating cancer metabolism via the p38/ß-catenin signaling pathway.
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Carcinoma de Células Escamosas/patologia , Regulação para Baixo , Glutationa Transferase/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/patologia , Animais , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Metilação de DNA/efeitos dos fármacos , Decitabina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Epigênese Genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicólise , Humanos , Neoplasias Hepáticas/genética , Neoplasias Pulmonares/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Camundongos Nus , Transplante de Neoplasias , Fosforilação OxidativaRESUMO
INTRODUCTION: Aortogastric tube fistula is a rare and fatal complication of esophagectomy. The treatment for aortogastric tube fistula with active infection is challenging, wherein a contamination around the fistula can cause a high risk of aneurysm and recurrence of bleeding, even if large amount of bleeding is controlled immediately. PRESENTATION OF CASE: We present a case of a 54-year-old male patient who underwent lower esophagectomy for esophageal squamous cell carcinoma 22 years ago. He developed aortogastric tube fistula on postoperative day 46. The patient underwent two surgeries and stenting for aortogastric tube fistula and pseudoaneurysm between days 46 and 120 following the first surgery, and digestive reconstruction was performed 6 months after the first surgery. Computed tomography and esophagogastroduodenoscopy were performed periodically, and the postoperative course was uneventful for 22 years. However, the patient died from pneumonia at the age of 76 years. Autopsy findings revealed no recurrence of esophageal cancer, anastomotic complications, or stent issues. The fistula between the aorta and gastric tube was closed with a stent and connective tissue. Intrathoracic findings revealed that the cause of death was severe bilateral pneumonia. DISCUSSION: Immediate hemodynamics stabilization and interval infection control enabled successful disease management. CONCLUSION: Tenting for aneurysm was performed under aseptic conditions, and the patient did not experience recurrence of esophageal cancer and stent issues, which contributed to the long-term survival of 22 years.
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Pseudomyxoma peritonei is a rare disease with a reported prevalence of about 1-3 per million people annually. Cytoreductive surgery and perioperative hyperthermic intraperitoneal chemotherapy are considered as treatment options improving disease control or long-term survival. However, for patients with incomplete cytoreduction or debulking surgery, outcomes are significantly poorer compared with patients who have obtained complete or optimal cytoreduction. In cases of high-grade pseudomyxoma peritonei that are considered inoperable and/or unresectable, combination chemotherapy regimen with a neo-angiogenesis inhibitor such as bevacizumab is recommended. In this report, a 62-year-old Japanese man presented with abdominal distention. Examination of ascites demonstrated a jelly-like consistency and peritoneal pseudomyxoma was suspected. To relieve progressive symptoms, palliative debulking surgery with total colectomy was performed. Postoperative pathology confirmed high-grade appendiceal mucinous neoplasm with high-grade pseudomyxoma peritonei. In our case, combination chemotherapy with trifluridine/tipiracil (TAS-102) and bevacizumab was initiated after palliative debulking surgery. As a result, carcinoembryonic antigen level was kept stable and the volume of ascites remained almost the same as at the beginning of treatment for more than 2 years. In conclusion, combination chemotherapy comprising TAS-102 and bevacizumab in patients with palliative debulking could be a useful option for patients with high-grade mucinous appendiceal neoplasm and high-grade pseudomyxoma peritonei.
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Neoplasias Peritoneais , Pseudomixoma Peritoneal , Bevacizumab/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Combinação de Medicamentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/tratamento farmacológico , Pseudomixoma Peritoneal/cirurgia , Pirrolidinas/uso terapêutico , Timina/uso terapêutico , Trifluridina/uso terapêuticoRESUMO
A 70-year-old Japanese man contracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and required oxygen to maintain oxygen saturation (>90%), 5 weeks after onset of coronavirus disease 2019 (COVID-19) symptoms. Transbronchial lung cryobiopsy revealed pathological features of organizing pneumonia with alveolar epithelial injury, and prednisolone administration led to alleviation of respiratory symptoms and recovery of respiratory function. This case report is the first to demonstrate the use of corticosteroids to successfully treat post-COVID-19 respiratory failure in a patient with biopsy-proven organizing pneumonia. We propose that steroid treatment be considered for patients with persistent respiratory dysfunction as COVID-19 pneumonia sequelae.
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Tratamento Farmacológico da COVID-19 , Prednisolona/administração & dosagem , Administração Oral , Idoso , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/patologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Oxigenoterapia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: A previous study conducted a transcriptome analysis of paired normal and esophageal squamous cell carcinoma (ESCC) tissue samples. The results showed that the expression of serine protease 27 (PRSS27) was perturbed in tumor samples. Hence, this retrospective study aimed to validate the prognostic significance of PRSS27 in patients with preoperative treatment for ESCC. METHODS: We enrolled 86 patients who received preoperative treatment before esophagectomy for ESCC. The expression of PRSS27 in resected ESCC and biopsy tissue samples obtained before preoperative treatment was evaluated via immunostaining, and its relationship with clinicopathological features and prognosis was analyzed. RESULTS: In normal esophageal mucosa tissue samples, PRSS27 was expressed in the cytoplasm of spinous cells in the suprabasal layer and basal cells in the basal layer. Of 64 resected ESCC tissue samples, 35 (54.7%) expressed PRSS27 and 29 (45.3%) did not. Moreover, ectopic nuclear expression of PRSS27 was observed. Based on multivariate analysis, PRSS27 expression in resected tumor samples was a predictor of poor prognosis. In cases in which PRSS27 expression was observed in biopsy samples, patients with PRSS27-negative resected tumors had a better postoperative prognosis than those with PRSS27-positive resected tumors. CONCLUSIONS: PRSS27 expression in resected ESCC tissue samples is a poor prognostic factor in ESCC patients with preoperative treatment. Furthermore, conversion of PRSS27 expression from positive in biopsy samples to negative in resected tumor samples is a predictor of good prognosis in these patients. Hence, PRSS27 status is an effective tool for decision making regarding adjuvant treatment in ESCC patients.
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Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Humanos , Prognóstico , Estudos Retrospectivos , Serina Endopeptidases , Serina ProteasesRESUMO
Ectopic intrapulmonary thyroid tissue is extremely rare and considerably difficult to diagnose without surgery. Ectopic thyroid tissue, described as a mediastinal tumor, and intrapulmonary lesions are infrequent. An abnormal shadow was detected upon chest X-ray in a 60-year old woman with a history of benign thyroid goiter. A computed tomography scan revealed a solitary nodule measuring 27 mm in diameter in the left lower lobe, the diameter of which had increased by 5 mm since initial observation eight years ago. A thoracoscopic wedge resection was performed and the lesion was determined to be a non-invasive, soft-tissue tumor. It was pathologically diagnosed as an ectopic thyroid follicular adenoma. The course of the tumor was uneventful. A diagnosis of ectopic intrapulmonary thyroid should be made cautiously and only after ruling out metastasis of a follicular adenoma or thyroid carcinoma. This diagnosis of ectopic thyroid tissue was made possible by the surgical approach.
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Adenoma , Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Feminino , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Diffuse pulmonary lymphangiomatosis (DPL) is a rare lymphatic disease that can cause diverse respiratory symptoms. A 22-year-old man, whose chest CT had shown an abnormality for years, presented with acute respiratory failure due to the abrupt onset of hemoptysis. The diagnosis of DPL was confirmed by surgical lung biopsy and lymphangiography. Histopathological investigation showed dilated vascular and lymphatic vessels. DPL can cause acute and life-threatening symptoms during its chronic clinical course. A coexisting anomaly in the venous system may be present in DPL patients with hemoptysis.
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BACKGROUND/OBJECTIVES: Pseudomyxoma peritonei (PMP) arising from an intraductal papillary mucinous neoplasm of the pancreas (IPMN) is a rare condition. The diagnosis of IPMN as the origin of PMP is mainly inferred from the clinical course and the exclusion of PMP from other organs. The pathological diagnosis has not yet been established. To evaluate the usefulness of immunohistochemical staining for the diagnosis of the primary lesion of PMP as IPMN. METHODS: There are 2 cases of PMP arising from IPMN between March 2010 and December 2019 at National Center for Global Health and Medicine. A PubMed search that reported PMP arising from IPMN identified 16 additional cases. Diagnostic methods and clinicopathological features of 18 cases were compared. RESULTS: Four cases including our two cases used immunohistochemical staining for the diagnosis of PMP arising from IPMN. The correspondence of the immunohistochemical staining between PMP and IPMN was shown in the three cases including previously reported two cases and one of our two cases to identify the primary lesion of PMP as IPMN. In addition, we revealed that the comparison of the immunostaining pattern of PMP with the representative immunostaining pattern of the candidate primary lesions is helpful for the diagnosis of the primary lesion of PMP. CONCLUSIONS: Immunohistochemical staining is helpful to identify the primary lesion of PMP as IPMN.
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Imuno-Histoquímica/métodos , Neoplasias Pancreáticas/patologia , Papiloma Intraductal/patologia , Pseudomixoma Peritoneal/patologia , Idoso , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Papiloma Intraductal/diagnóstico , Papiloma Intraductal/cirurgia , Valor Preditivo dos Testes , Pseudomixoma Peritoneal/diagnóstico , Pseudomixoma Peritoneal/cirurgia , Esplenectomia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Glutathione S-transferase omega 2 (GSTO2), which belongs to the superfamily of GST omega class, lacks any appreciable GST activity. Although GSTO2 exhibits thioltransferase and glutathione dehydrogenase activities, its precise expression and physiological functions are still unclear. In the present study, we found that GSTO2 is exclusively expressed in the basal cell layer in Ki67-negative non-proliferative cells in the human esophageal mucosa. GSTO2 overexpression in esophageal squamous cell carcinoma (ESCC) cell lines inhibited cell growth and colony formation, and GSTO2-transfected cells formed smaller tumors in nude mice compared with mock-transfected cells. Interestingly, GSTO2 induction suppressed the expressions of E-cadherin and ß-catenin at the cell-cell contact site. We quantified the phosphorylation levels of key proteins of MAPK signaling pathway and identified phosphorylation of p38. Additionally, HSP27, a downstream molecule of p38, was accelerated in GSTO2-transfected cells, unlike in mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, the expression of ß-catenin and the membrane localization of E-cadherin was recovered. We next examined GSTO2 expression in 61 ESCC tissues using quantitative reverse transcription polymerase chain reaction and immunostaining. The results showed that GSTO2 mRNA and protein were significantly reduced in ESCC compared with normal tissues. When human ESCC cell lines were treated with 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant hypermethylation is the cause of the down-regulated expression. Our results indicate that GSTO2 expression inhibits the membrane localization of E-cadherin, probably by modulation of the p38 signaling pathway. Down-regulation of GSTO2 by DNA hypermethylation contributes to the growth and progression of ESCC.
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Caderinas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Glutationa Transferase/genética , beta Catenina/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células/genética , Metilação de DNA/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Camundongos , Transdução de Sinais/genéticaRESUMO
OBJECTIVES: The peritoneal cancer index (PCI) is widely used for assessing pseudomyxoma peritonei (PMP) in surgery. The aim of this study was to evaluate the utility of a modified PCI using 18F-fluorodeoxyglucose (18F-FDG)-PET/CT (PET-PCI) for predicting pathologic grade and progression-free survival (PFS) in patients with PMP. METHODS: Thirty-five patients who underwent 18F-FDG-PET/CT before cytoreductive surgery and/or hyperthermic intraperitoneal chemotherapy were enrolled. PET-PCI was determined by summing up the visually scored 18F-FDG uptake of PMP lesions in 13 specific abdominal-pelvic regions. Uptake score was defined as 0, no lesion or lesion without uptake; 1, slight uptake less than or equivalent to mediastinal blood pool; 2, moderate uptake above mediastinal but below or equal to liver; and 3, intense uptake moderately to markedly higher than liver. SUVmax of the lesion was also evaluated. RESULTS: Pathologic diagnosis revealed 19 patients with low-grade PMP and 16 patients with high-grade PMP. Patients with high-grade PMP showed significantly higher PET-PCI and SUVmax than patients with low-grade PMP (PET-PCI 14.8 vs. 8.7, p = 0.007; SUVmax 3.6 vs. 2.6, p = 0.013). Using a cutoff PET-PCI of 12, Kaplan-Meier analyses showed a significant difference in PFS between patients with high and low PET-PCI (p < 0.001; hazard ratio (HR), 12.4). For SUVmax, the optimal cutoff was 2.7 and the correlation with PFS was also significant (p = 0.008; HR, 4.7). In multivariate Cox proportional-hazards regression, PET-PCI was independently and significantly correlated with PFS. CONCLUSIONS: PET-PCI can reflect histopathologic features and appears useful for predicting recurrence in patients with PMP. KEY POINTS: ⢠Peritoneal cancer index using 18F-FDG-PET/CT (PET-PCI) has great potential for predicting progression-free survival in patients with pseudomyxoma peritonei. ⢠PET-PCI provides higher prognostic performance than maximum standardized uptake value (SUVmax). ⢠PET-PCI shows high correlation with histopathologic grade of pseudomyxoma peritonei.