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1.
Gan To Kagaku Ryoho ; 51(2): 181-183, 2024 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-38449406

RESUMEN

A 38-year-old woman was admitted to our hospital due to severe anemia. CT showed a 13×12 cm tumor with moderately enhanced wall thickening in the right upper abdomen. The huge tumor located adjacent to the jejunum and compressed the right transverse colon. Hemorrhagic necrosis and air were observed within the tumor, suspecting tumor penetration into the jejunum. The patient was diagnosed with abdominal GIST with jejunal infiltration. Laparotomy revealed a 13× 11 cm solid mass with intra-tumoral hemorrhage and invasion into the jejunum, located in the transverse mesocolon. Tumor resection combined with partial jejunectomy and transverse colectomy were performed. Immunohistochemical findings of the resected specimen was positive for c-kit and DOG-1, and the MIB-1 positive rate was 10%. Three weeks after the operation, re-anastomosis was performed due to transverse colon anastomotic stricture. She was discharged 45 days after first operation. Currently, 9 months after the operation, patient has been prescribed imatinib and is alive without recurrence.


Asunto(s)
Colon Transverso , Neoplasias , Femenino , Humanos , Adulto , Colon Transverso/cirugía , Yeyuno/cirugía , Mesenterio , Hemorragia
2.
Gan To Kagaku Ryoho ; 51(2): 193-195, 2024 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-38449410

RESUMEN

BACKGROUND: Watch and wait(W & W)for rectal cancer after chemoradiotherapy(CRT)is attracting attention. PURPOSE: To examine regimens and indications from the results of follow-up of cases undergoing W & W in our department. MATERIALS AND METHODS: CRT(SOX therapy 2-5 cycles, 45 Gy)was performed on patients with lower rectal cancer over a period of 2016 to 2020, and 7 patients with clinical complete response(cCR)were followed up. RESULTS: With a median follow-up of 33 months(10-74), 4 of 7 patients(57.1%)remained in cCR. Two patients had local relapse more than a year after the start of treatment, were able to undergo salvage surgery, and are alive after surgery. Patients with lateral lymph node metastasis before CRT had para-aortic lymph node metastasis at 8 months. CONCLUSIONS: Patients with maintained cCR were those with localized, node-negative disease. On the other hand, in patients with lymph node metastasis, including lateral metastasis, it was not possible to perform salvage surgery due to distant metastasis. Careful case selection and follow-up are necessary in the future.


Asunto(s)
Neoplasias Primarias Secundarias , Neoplasias del Recto , Humanos , Metástasis Linfática , Neoplasias del Recto/terapia , Quimioradioterapia , Ganglios Linfáticos
3.
Cancers (Basel) ; 16(5)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38473211

RESUMEN

The sphingolipid metabolic pathway, an important signaling pathway, plays a crucial role in various physiological processes including cell proliferation, survival, apoptosis, and immune regulation. The liver has the unique ability to regenerate using bioactive lipid mediators involving multiple sphingolipids, including ceramide and sphingosine 1-phosphate (S1P). Dysregulation of the balance between sphingomyelin, ceramide, and S1P has been implicated in the regulation of liver regeneration and diseases, including liver fibrosis and hepatocellular carcinoma (HCC). Understanding and modulating this balance may have therapeutic implications for tumor proliferation, progression, and metastasis in HCC. For cancer therapy, several inhibitors and activators of sphingolipid signaling, including ABC294640, SKI-II, and FTY720, have been discussed. Here, we elucidate the critical roles of the sphingolipid pathway in the regulation of liver regeneration, fibrosis, and HCC. Regulation of sphingolipids and their corresponding enzymes may considerably influence new insights into therapies for various liver disorders and diseases.

4.
Surg Case Rep ; 10(1): 25, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38252200

RESUMEN

BACKGROUND: Ampullary adenomas are premalignant lesions. However, biliary obstruction causing jaundice is rare. Duodenal intussusception secondary to an ampullary adenoma rarely occurs because of the fixed position of the duodenum in the retroperitoneum. Herein, we have described a rare case of ampullary adenoma with jaundice caused by duodenal intussusception. CASE PRESENTATION: A 40-year-old woman presenting with vomiting and yellowish discoloration of the skin was admitted to another hospital. The patient had experienced recurrent epigastric pain and vomiting for the past 18 months. Blood test results showed elevated levels of bilirubin (3.9 mg/dL), and abdominal computed tomography (CT) showed a 60-mm hypovascular mass in the third part of the duodenum and a left lateral shift of the dilated common bile duct. The patient was referred to our hospital for further evaluation. She recovered from hyperbilirubinemia spontaneously (levels of bilirubin, 1.0 mg/dL), and the CT showed a tumor shift from the third part of the duodenum to the second part and improvement of the dilated common bile duct. Hypotonic duodenography revealed a tumor that moved easily from the second to the third portion of the patient's position. Upper gastrointestinal endoscopy revealed a large papillary tumor occupying the second part of the duodenum, which was diagnosed as an adenoma through biopsy. The possibility of malignancy could not be negated owing to the presence of jaundice and an elevated carbohydrate antigen 19-9 level (76.0 U/mL). Pancreaticoduodenectomy was performed. The resected specimen showed a 60 × 40 × 40-mm pedunculated ampullary mass with submucosal elongation. The pathological examination indicated that the ampullary tumor was a high-grade intestinal adenoma. The postoperative course was uneventful, and the patient was discharged 26 days postoperatively. CONCLUSIONS: This report describes a rare case of a patient with an ampullary adenoma presenting with jaundice resulting from duodenal intussusception. Owing to the possibility of a postoperative cancer diagnosis which may have caused the biliary obstruction and the difficulty in making an accurate preoperative diagnosis, it is imperative to choose the appropriate surgical procedure such as a pancreaticoduodenectomy.

5.
Kidney Int Rep ; 8(7): 1407-1416, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37441472

RESUMEN

Introduction: Peroxisome proliferator-activated receptor δ (PPARδ) plays a central role in modulating mitochondrial function in ischemia-reperfusion injury. The novel PPARδ modulator, ASP1128, was evaluated. Methods: A randomized, double-blind, placebo-controlled, biomarker assignment-driven, multicenter study was performed in adult patients at risk for acute kidney injury (AKI) following cardiac surgery, examining efficacy and safety of a 3-day, once-daily intravenous dose of 100 mg ASP1128 versus placebo (1:1). AKI risk was based on clinical characteristics and postoperative urinary biomarker (TIMP2)•(IGFBP7). The primary end point was the proportion of patients with AKI based on serum creatinine within 72 hours postsurgery (AKI-SCr72h). Secondary endpoints included the composite end point of major adverse kidney events (MAKE: death, renal replacement therapy, and/or ≥25% reduction of estimated glomerular filtration rate [eGFR]) at days 30 and 90). Results: A total of 150 patients were randomized and received study medication (81 placebo, 69 ASP1128). Rates of AKI-SCr72h were 21.0% and 24.6% in the placebo and ASP1128 arms, respectively (P = 0.595). Rates of moderate/severe AKI (stage 2/3 AKI-SCr and/or stage 3 AKI-urinary output criteria) within 72 hours postsurgery were 19.8% and 23.2%, respectively (P = 0.609). MAKE occurred within 30 days in 11.1% and 13.0% in the placebo and ASP1128 arms (P = 0.717), respectively; and within 90 days in 9.9% and 15.9% in the placebo and ASP1128 arms (P = 0.266), respectively. No safety issues were identified with ASP1128 treatment, but rates of postoperative atrial fibrillation were lower (11.6%) than in the placebo group (29.6%). Conclusion: ASP1128 was safe and well-tolerated in patients at risk for AKI following cardiac surgery, but it did not show efficacy in renal endpoints.

6.
Gan To Kagaku Ryoho ; 50(1): 84-86, 2023 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-36759994

RESUMEN

An 81-year-old woman was admitted to our hospital due to frequent bleeding and hemorrhagic shock. Blood tests revealed anemia and contrast-enhanced abdominal CT revealed a pancreatic tail tumor with a diameter of 60 mm. The boundary between pancreatic tumor and the transverse colon, stomach and spleen was unclear, and invasion of the transverse colon as well as the stomach and spleen was suspected. Hemorrhage due to colon invasion of the pancreatic tail cancer and intra-tumoral hemorrhage were suspected. Due to persistent bleeding, the patient had emergency surgery to control bleeding. The pancreatic tail tumor invaded not only the colon but also stomach and spleen, distal pancreatectomy, partial gastrectomy and splenectomy was performed in combination with resection of the transverse colon, and transverse colon colostomy. We report a case of gastrointestinal bleeding caused by transverse colon invasion of pancreatic tail cancer, which resulted in emergency surgery.


Asunto(s)
Colon Transverso , Neoplasias Pancreáticas , Femenino , Humanos , Anciano de 80 o más Años , Colon Transverso/cirugía , Colon Transverso/patología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Estómago/patología , Pancreatectomía/efectos adversos , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/cirugía , Neoplasias Pancreáticas
7.
Gan To Kagaku Ryoho ; 50(1): 102-104, 2023 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-36760000

RESUMEN

An 83-year-old woman developed jaundice, and was diagnosed as perihilar cholangiocarcinoma. Abdominal contrast- enhanced CT revealed coexisting portosystemic shunt between portal vein and inferior vena cava, however, her blood ammonia level was normal. She underwent right hemihepatectomy and caudate lobectomy combined with extrahepatic bile duct resection and portal vein resection. Postoperatively, hyperammonemia refractory to conservative treatment was observed. The blood ammonia level increased to 180µg/dL and she was suffered from grade Ⅲ hepatic encephalopathy on the 20th postoperative day. CT showed an increase in the diameter of the portosystemic shunt, while there was only a slight increase in the remnant left lobe of the liver. These findings indicated that hepatic encephalopathy was caused by increased portosystemic shunt blood flow and decreased portal venous flow. Hepatic encephalopathy was rapidly improved by percutaneous transhepatic portosystemic shunt obliteration.


Asunto(s)
Neoplasias de los Conductos Biliares , Encefalopatía Hepática , Tumor de Klatskin , Derivación Portosistémica Intrahepática Transyugular , Humanos , Femenino , Anciano de 80 o más Años , Tumor de Klatskin/complicaciones , Encefalopatía Hepática/etiología , Encefalopatía Hepática/terapia , Amoníaco , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología
8.
World J Clin Cases ; 10(24): 8709-8717, 2022 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-36157792

RESUMEN

BACKGROUND: Bronchogenic cysts are congenital cysts caused by abnormal sprouting from the ventral foregut during fetal life. They usually occur in the mediastinum or lung, but there are very rare cases of ectopic bronchogenic cysts that develop in the abdominal cavity. A unique intra-abdominal ectopic bronchogenic cyst with a mucinous neoplasm that was producing carcinoembryonic antigen (CEA), harboring a GNAS mutation, is reported. The present case may contribute to clarifying the mechanism of tumorigenesis and malignant transformation of ectopic bronchogenic cysts. CASE SUMMARY: In 2007, a man in his 50s was incidentally found to have an intra-abdominal cystic mass, 8 cm in diameter. Surgical resection was recommended, but he preferred to remain under observation. In 2020, his serum CEA level increased to 26.7 ng/mL, and abdominal computed tomography showed a 15 cm × 12 cm, multifocal, cystic mass located predominantly on the lesser curvature of the stomach. Since malignancy could not be ruled out, he finally underwent surgical resection. Histologically, the cystic wall was lined by ciliated columnar epithelium, accompanied by bronchial gland-like tissue, bronchial cartilage, and smooth muscle. Part of the cyst consisted of atypical columnar epithelium with an MIB-1 index of 5% and positive for CEA. Moreover, a GNAS mutation (p.R201C) was detected in the atypical epithelium, leading to a diagnosis of an ectopic bronchogenic cyst with a low-grade mucinous neoplasm. The patient is currently undergoing outpatient follow-up without recurrence. CONCLUSION: An extremely rare case of an abdominal bronchogenic cyst with a low-grade mucinous neoplasm harboring a GNAS mutation was reported.

9.
Front Med (Lausanne) ; 9: 1092879, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36687430

RESUMEN

Background: Invasive Klebsiella-associated liver abscesses can progress rapidly and cause severe metastatic infections such as meningitis and hydrocephalus, which are associated with high morbidity and mortality. In patients with large multiloculated liver abscesses after failure of percutaneous drainage, rapid diagnosis of the abscess followed by hepatic resection is necessary for early recovery and to prevent severe secondary metastatic complications. Case presentation: An 84-year-old woman with a large liver abscess and in septic shock was transferred to our hospital. Abdominal CT showed multiloculated liver abscesses 15 cm in diameter in the right lobe of the liver. We first performed percutaneous liver abscess drainage. The patient was managed in the intensive care unit, as well as treated with intravenous administration of meropenem followed by cefozopran according to the antibiogram. Klebsiella pneumoniae with invasive infection was confirmed by a string test in an isolated colony of K. pneumoniae; the K1 serotype with the rmpA and magA genes was determined by polymerase chain reaction and Sanger sequencing. Additional percutaneous liver abscess drainage was performed due to initial inadequate drainage. Although the abscess had shrunk to a diameter of 8 cm after drainage in 4 weeks, the patient recovered from sepsis, but still had low-grade fever (occasionally 38°C) and continued to have symptoms of chronic inflammation with persistent hyper mucus discharge from the liver abscess. Surgical resection was chosen to prevent prolonged hospitalization and ensure early recovery. A right posterior sectionectomy of the liver, including liver abscess, was performed. The post-operative course was uneventful, with no complications, and she was discharged after 18 days. There were no signs of abscess recurrence 1 year after surgery. Conclusion: We present a case of successful hepatic resection after percutaneous drainage failure in a patient with invasive K. pneumoniae multiloculated liver abscess.

10.
J Surg Res ; 259: 200-210, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33307511

RESUMEN

BACKGROUND: It remains unknown whether epithelial-mesenchymal transition (EMT)-mediated vascular invasion and cancer stemness are associated with sphingosine-1-phosphate receptor-1 (S1PR1) expression in human hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between S1PR1 expression and prognosis of patients with primary HCC and to define the potential of S1PR as a therapeutic target. MATERIALS AND METHODS: We investigated 108 patients who underwent primary surgical resection for HCC treatment. Expression of S1PR1 and EMT markers was analyzed to predict prognosis of patients with HCC. Furthermore, three-dimensional organotypic culture, anoikis assay, and cell invasion were performed to validate the association of S1PR1 with EMT and cancer stemness. RESULTS: Among patients with HCC, the high S1PR1 expression group had significantly shorter overall survival than the low expression group. Moreover, high S1PR1 expression was significantly associated with shorter recurrence-free survival, increased risk of portal and hepatic vein invasion, and intrahepatic metastasis. Multivariate analyses revealed that S1PR1 overexpression was an independent prognostic factor in patients with HCC. S1PR1 overexpression positively correlated with vimentin and MMP-9 expression and negatively correlated with E-cadherin. In addition, S1PR1 overexpression induced EMT and enhanced tumor invasion and cancer stemness. CONCLUSIONS: S1PR1 overexpression, via EMT-induced vascular invasion and increased cancer stem cell properties, establishes a metastatic niche, enhances the capacity of hematogenous metastasis, and associates with poor outcomes in patients with HCC. Hence, S1PR1 may serve as a therapeutic target for patients with HCC with vascular invasion.


Asunto(s)
Carcinoma Hepatocelular/patología , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas/patología , Receptores de Esfingosina-1-Fosfato/fisiología , Anciano , Carcinoma Hepatocelular/mortalidad , Línea Celular Tumoral , Femenino , Venas Hepáticas/patología , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Metaloproteinasa 9 de la Matriz/análisis , Persona de Mediana Edad , Invasividad Neoplásica , Vena Porta/patología , Vimentina/análisis
11.
Pancreatology ; 20(6): 1205-1212, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32819845

RESUMEN

BACKGROUND: This study aimed to assess the prognostic values of preoperative maximum standardized uptake value (SUVmax) of primary pancreatic tumors and Glut-1 expression in patients with resectable pancreatic ductal adenocarcinoma (R-PDAC), and to investigate whether Glut-1 expression is more effective than SUVmax in predicting survival in patients with R-PDAC. METHODS: We investigated 101 R-PDAC patients who underwent pancreatectomy for pancreatic cancer treatment. SUVmax analyzed through 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), and Glut-1 expression, were assessed for predicting the prognosis of patients with R-PDAC. RESULTS: In patients with R-PDAC, the high SUVmax group (≥4.25) had significantly shorter overall survival (OS) and disease-free survival (DFS) than the low SUVmax group (<4.25). Surprisingly, Glut-1 expression was not significantly correlated with SUVmax. Moreover, the high Glut-1 expression group, which was related to higher levels of CA 19-9, had significantly shorter OS and DFS than the low Glut-1 expression group. Furthermore, among the high SUVmax group, OS and DFS were significantly shorter in the high Glut-1 expression group. Multivariate analyses revealed that Glut-1 overexpression was an independent prognostic factor in patients with R-PDAC. Glut-1 knockdown also induced cell cycle arrest in PDAC cells in vitro. CONCLUSIONS: The study determined that Glut-1 overexpression is a more powerful prognostic factor than SUVmax for predicting OS and higher risk of recurrence in R-PDAC patients. Glut-1 overexpression is also more likely to be associated with malignant activity in PDAC patients.


Asunto(s)
Carcinoma Ductal Pancreático/diagnóstico por imagen , Transportador de Glucosa de Tipo 1/biosíntesis , Neoplasias Pancreáticas/diagnóstico por imagen , Anciano , Antígeno CA-19-9/sangre , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/cirugía , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Reacciones Falso Positivas , Femenino , Fluorodesoxiglucosa F18 , Regulación Neoplásica de la Expresión Génica/genética , Transportador de Glucosa de Tipo 1/genética , Humanos , Masculino , Persona de Mediana Edad , Pancreatectomía , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/cirugía , Tomografía de Emisión de Positrones , Valor Predictivo de las Pruebas , Periodo Preoperatorio , Pronóstico , Análisis de Supervivencia
12.
Gan To Kagaku Ryoho ; 47(4): 685-687, 2020 Apr.
Artículo en Japonés | MEDLINE | ID: mdl-32389984

RESUMEN

A 32-year-old woman presented with epigastric pain and an abdominal mass. Abdominal CT showed a 130mm pancreatic tail mass with an enhanced rim, central necrosis, and small calcification. A 6mm lung tumor was also found via chest CT. Her medical history included surgical resection of cerebral solitary fibrous tumor when she was 24 years old. When she was 31 years old, it had recurred but was cured by gamma knife radiosurgery. We performed distal pancreatectomy and splenectomy with lymph node dissection. According to pathological and immunohistochemical findings, it was diagnosed as an anaplastic carcinoma with osteoclast-like giant cells. She underwent surgical resection of the lung tumor 2 months after pancreatic resection and was diagnosed with metastasis from the solitary fibrous tumor. Fourteen months since undergoing pancreatectomy, the patient experienced no recurrence from both diseases. We report a rare resected case of anaplastic carcinoma of pancreas concomitant with recurrent solitary fibrous tumor.


Asunto(s)
Neoplasias Pulmonares/secundario , Neoplasias Pancreáticas , Tumores Fibrosos Solitarios , Adulto , Femenino , Células Gigantes , Humanos , Recurrencia Local de Neoplasia , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Recurrencia , Tumores Fibrosos Solitarios/secundario , Tumores Fibrosos Solitarios/cirugía , Adulto Joven
13.
Chem Pharm Bull (Tokyo) ; 67(10): 1061-1071, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31582626

RESUMEN

The activation of epidermal growth factor receptor (EGFR) involves the geometrical conversion of the extracellular domain (ECD) from the tethered to the extended forms with the dynamic rearrangement of the relative positions of four subdomains (SDs); however, this conversion process has not yet been thoroughly understood. We compare the two different forms of the X-ray crystal structures of ECD and simulate the ECD conversion process using adiabatic mapping that combines normal mode analysis of the elastic network model (ENM-NMA) and energy optimization. A comparison of the crystal structures reveals the rigidity of the intradomain geometry of the SD-I and -III backbone regardless of the form. The forward mapping from the tethered to the extended forms retains the intradomain geometry of the SD-I and -III backbone and reveals the trends to rearrange the relative positions of SD-I and -III and to dissociate the C-terminal tail of SD-IV from the hairpin loop in SD-II. The reverse mapping from the extended to the tethered forms complements the promotion of ECD conversion in the presence of epidermal growth factor (EGF).


Asunto(s)
Modelos Moleculares , Mapas de Interacción de Proteínas , Cristalografía por Rayos X , Elasticidad , Receptores ErbB/química , Receptores ErbB/metabolismo , Humanos
14.
Hepatol Commun ; 3(7): 954-970, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31304451

RESUMEN

Olfactomedin 4 (OLFM4) induces signal transducer and activator of transcription 3 (STAT3) activation by inhibiting gene associated with retinoid-interferon-induced mortality 19 (GRIM19), a strong STAT3 suppressor gene; however, the mechanisms of OLFM4 for regulating GRIM19-STAT3 cascade in hepatocellular carcinoma (HCC) remain unclear. The functions and regulations of OLFM4, GRIM19, and STAT3 activation in HCC progression were evaluated using surgical specimens collected from 111 HCC patients or 2 HCC cell lines in vitro. Moreover, the cancer stem cell-like property of OLFM4 mediated by leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), known as an intestinal stem cell marker, was investigated. OLFM4 was increased in HCC compared with adjacent liver tissue. The multivariate analysis revealed that high OLFM4 expression was an independent factor for poor prognosis. OLFM4 expression was negatively correlated with GRIM19 expression and positively correlated with STAT3 activation in HCC, thereby increasing cell cycle progression. OLFM4 knockdown in HCC cells increased GRIM19 expression and inhibited STAT3 activation; however, after double knockdown of GRIM19 and OLFM4, STAT3 activation decreased by OLFM4 knockdown was increased again. OLFM4 knockdown increased cell apoptosis, inhibited cell proliferation, and suppressed cancer stem cell-like property in HCC cells. The incidence of hematogenous recurrence was higher in HCC patients with high OLFM4 expression, suggesting that anoikis resistance of HCC was enhanced by OLFM4. In clinical cases, LGR5 expression and CD133 expression was correlated with OLFM4 expression in HCC, leading to poor patient prognosis. In vitro, LGR5 enhanced cancer stem cell-like property by up-regulating OLFM4 through the Wnt signaling pathway. Conclusion: OLFM4 is induced by the LGR5-Wnt signaling pathway and is strongly associated with aggressive tumor progression and poor prognosis in HCC by regulating STAT3-induced tumor cell proliferation and cancer stem cell-like property. Therefore, OLFM4 is a novel prognostic predictor and a potential therapeutic target for patients with HCC.

15.
Mol Clin Oncol ; 10(4): 419-424, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30931110

RESUMEN

Conversion surgery is an attractive strategy to improve the outcomes for locally advanced unresectable (UR-LA) pancreatic ductal adenocarcinoma (PDAC). The present case report, presents a case of successful conversion surgery following the treatment of a patient with UR-LA PDAC, suffering from interstitial pneumonitis (IP), using a combination of gemcitabine and nab-paclitaxel (GnP). A 67-year-old woman presented at the hospital with a high level of carbohydrate antigen 19-9 (CA19-9; 1,713 U/ml). Radiological examination revealed a pancreatic tumor in contact with the superior mesenteric artery, with invasion extending to the most proximal draining jejunal branch into the superior mesenteric vein. The patient was diagnosed with UR-LA PDAC. Following 6 courses of GnP therapy, the tumor size markedly decreased from 50 to 18 mm, and the level of CA19-9 also decreased from 1,713 to 60.1 U/ml. Due to the progression of IP, the patient was administered steroid medication along with a restart of tacrolimus for the treatment of dermatomyositis and IP. After recovery from her lung condition, an additional 3 courses of GnP therapy were administered, and then pancreatoduodenectomy was performed. The patient was still alive 14 months post-surgery with no recurrence. Between July 2009 and September 2017, conversion surgery was performed for 18 cases of UR-LA PDAC treated with gemcitabine plus S-1 (GS) therapy, and 11 cases with GnP therapy. The percentage of median CA19-9 and median tumor volume reductions were 73.7 and 51.6%, respectively, following GS therapy, and 86.7 and 68.8%, respectively, following GnP therapy. Tumor reduction following GnP therapy was significantly higher than that after GS therapy (P=0.02). GnP therapy is a suitable regimen to shrink the tumor mass in patients with UR-LA PDAC. Careful management of systemic conditions is required to treat patients with PDAC and IP when using GnP therapy. Conversion surgery should be considered for recognizing radiological responses (tumor shrinkage adjacent to major arteries) and reductions in CA19-9 levels.

16.
Ann Surg Oncol ; 26(3): 907-917, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30610554

RESUMEN

BACKGROUND: Despite developments in multidisciplinary treatment, the prognosis for advanced gallbladder cancer (GBC) still is poor because of its rapid progression. Epithelial-mesenchymal transition (EMT) plays a central role in promoting tumor invasion and metastasis in malignancies thorough signal transducer and activator of transcription-3 (STAT3) and nuclear factor κB (NF-κB) activation. Whereas Pin1 mediates STAT3 and NF-κB activation, the involvement of Pin1 in GBC progression is unclear. METHODS: Factors regulating Pin1-related STAT3 and NF-κB activation were evaluated using surgical specimens collected from 76 GBC patients, GBC cells, and orthotopic GBC xenograft mice. RESULTS: In the patients with GBC, high Pin1 expression in GBC was associated with aggressive tumor invasion and increased tumor metastasis, and was an independent factor for a poor prognosis. Pin1 expression was correlated with phosphorylation of STAT3(Ser727) and NF-κB-p65(Ser276), thereby activating STAT3 and NF-κB in GBC. Pin1-mediated STAT3 and NF-κB activation induced EMT in GBC. When Pin1 knockdown was performed in GBC cells, the phosphorylation of STAT3(Ser727) and NF-κB-p65(Ser276) was inhibited, and STAT3 and NF-κB activation was suppressed. Inactivation of STAT3 and NF-κB in Pin1-depleted cells decreased snail and zeb-2 expression, thereby reducing the rate of mesenchymal-like cells, suggesting that EMT was inhibited in GBC cells. PiB, a Pin1-specific inhibitor, inhibited EMT and reduced tumor cell invasion by inactivating STAT3 and NF-κB in vitro. Moreover, PiB treatment inhibited lymph node metastasis and intrahepatic metastasis in orthotopic GBC xenograft tumor in vivo. CONCLUSIONS: Pin1 accelerates GBC invasion and metastasis by activating STAT3 and NF-κB. Therefore, Pin1 inhibition by PiB is an excellent therapy for GBC by safely inhibiting its metastasis.


Asunto(s)
Transición Epitelial-Mesenquimal , Neoplasias de la Vesícula Biliar/patología , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/secundario , FN-kappa B/metabolismo , Peptidilprolil Isomerasa de Interacción con NIMA/metabolismo , Factor de Transcripción STAT3/metabolismo , Anciano , Animales , Apoptosis , Biomarcadores de Tumor , Movimiento Celular , Proliferación Celular , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/metabolismo , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirugía , Masculino , Ratones , Ratones SCID , FN-kappa B/genética , Peptidilprolil Isomerasa de Interacción con NIMA/genética , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , Factor de Transcripción STAT3/genética , Transducción de Señal , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Surg Open Sci ; 1(1): 14-19, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33981978

RESUMEN

BACKGROUND: Ischemic gastropathy (IG) is a major complication after distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for locally advanced body/tail pancreatic ductal adenocarcinoma (PDAC), and its incidence is still unknown. METHODS: To evaluate the occurrence of IG, 77 and 18 consecutive patients with body/tail PDAC were analyzed in a retrospective and a prospective study, respectively. We utilized perioperative gastroendoscopy, Gastrointestinal Quality of Life Index (GIQLI) score, and quantitative assessment for gastric arterial blood flow using the HyperEye Medical System (HEMS) with indocyanine green (ICG) fluorescence imaging in the prospective arm. RESULTS: In the retrospective arm, no significant difference was noted in the occurrence rate of IG between the DP-CAR (8.7%) and DP groups (5.5%). In the prospective arm, the postoperative endoscopic scores were significantly higher in the DP-CAR group (45%) than in the DP group (11%) (p < .0007) despite no difference in the GIQLI score. The ICG-HEMS imaging system demonstrated more delayed arterial flow velocity in the IG (+) group (p < .028), but showed no significant difference in arterial flow volume compared to the IG (-) group. CONCLUSION: This is the first demonstration assessing IG incidence after DP-CAR using multiple methods. Despite the high IG rate, gastric arterial flow volume was almost equally maintained in DP-CAR patients with or without IG compared with the DP group. We should note the fact that many of the IG patients do not present with typical symptoms, and proper treatment is required for those "silent" IG patients.

18.
Gan To Kagaku Ryoho ; 46(13): 2548-2550, 2019 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-32156994

RESUMEN

An 81-year-old man was referred to our department because of rapid progression of a cystic lesion in the pancreatic tail. Abdominal CT revealed a heterogeneously enhancing tumor, measuring 70mm in diameter, in the pancreatic tail, encompassing a low-density area with calcification and directly invading the spleen. We diagnosed the patient with malignant transformation of solid-pseudopapillary neoplasm and performed distal pancreatectomy with splenectomy, partial transverse colectomy, and partial resection of the diaphragm. Histopathological examination revealed anaplastic carcinoma of the pancreas of the spindle cell type, and R0 resection was achieved. Anastomotic leakage of the transverse colon occurred on postoperative day 4, and ileostomy was performed. Multiple liver metastases were observed on postoperative day 27, and the patient was orally administered with S-1. Although he was discharged on postoperative day 50, he died of cancer on postoperative day 61. Anaplastic carcinoma of the pancreas has a poor prognosis, and an early multidisciplinary treatment should be performed.


Asunto(s)
Carcinoma/secundario , Neoplasias Hepáticas , Neoplasias Pancreáticas , Anciano de 80 o más Años , Progresión de la Enfermedad , Resultado Fatal , Humanos , Neoplasias Hepáticas/secundario , Masculino , Páncreas , Pancreatectomía
19.
Mol Clin Oncol ; 9(4): 389-393, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30214727

RESUMEN

The standard treatment for locally advanced unresectable (UR-LA) pancreatic ductal adenocarcinoma (PDAC) is chemo-radiotherapy. Surgery following chemo-radiotherapy (conversion surgery), has been considered a useful strategy and has been used for UR-LA PDAC. The current study presents the case of a 43-year-old woman who complained of back pain. A radiological examination revealed a pancreatic tumor in contact with >270 degrees of the superior mesenteric artery (SMA) perimeter, with invasion extending from the superior mesenteric vein (SMV) to the portal vein (PV). An endoscopic ultrasonography-guided fine needle aspiration biopsy revealed adenocarcinoma as the pathological diagnosis and the patient was diagnosed with UR-LA PDAC. Following 12 courses of combined gemcitabine plus nab-paclitaxel (GnP) for 9 months, the extent of tumor invasion to the SMA and SMV was improved and the level of cancer antigen (CA) 19-9 decreased. A pancreatoduodenectomy with PV resection and reconstruction using a left renal vein graft were performed. Pathological examination revealed that the operative outcome was R0 (no residual tumor) resection and the patient was alive 19 months after the initial treatment (9 months post surgery), however, there was local tumor recurrence. Between March 2015 and February 2016 a total of 10 cases of UR-LA PDAC were encountered at the Department of General Surgery, Chiba University Hospital (Chiba, Japan), in which GnP therapy was performed. Including the present case, 6 of the 11 cases (55%) underwent conversion surgery with curative resection. Kaplan-Meier analysis revealed that patients treated with conversion surgery presented significantly longer overall survival (OS) than those treated with no conversion surgery (median OS, 22.5 vs. 11 months; P=0.047, Wilcoxon test). The minimum reduction of CA19-9 was 67%. In conclusion, conversion surgery following GnP therapy is a desirable option for UR-LA PDAC. A significant reduction in the CA19-9 levels may be useful in determining the timing of changeover from medicine to surgery in patients with UR-LA PDAC in whom conversion surgery is being considered.

20.
Surg Case Rep ; 4(1): 43, 2018 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-29721779

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) during pregnancy is rare, with a poor prognosis. Recently, however, increasing resection rates have improved survival rate. Currently, various surgeries are safely performed after the second trimester and termination of pregnancy is not always necessary. However, surgery is sometimes limited by gestational age or the patient's will. When patients with HCC refuse surgery during pregnancy, we face specific problems with respect to curability and fetal life. Meanwhile, previous studies have revealed radiofrequency ablation (RFA) as a possible alternative to surgery for the treatment of early HCC and shown its favorable local control rate for advanced HCC. However, no case of HCC treated with RFA during pregnancy has yet been reported. CASE PRESENTATION: Here, we present the case of a 33-year-old woman, who was a hepatitis B virus carrier. The patient had been followed up because HBV carrier could develop hepatitis or HCC. And she was diagnosed with a 40-mm HCC tumor at 17 weeks of gestation. She refused surgery because she was pregnant and wanted to continue her pregnancy; therefore, we performed RFA for the local control of her HCC at 17 weeks of gestation and radical surgery at postpartum. She delivered a healthy baby and has survived without recurrence for 6 years after the surgery. CONCLUSIONS: Surgery is potentially a curative treatment for HCC whether the patient is pregnant or not. However, various problems unique to pregnancy make it difficult to perform a straightforward surgery. Our case revealed that RFA can be safely performed in pregnant patients during the second trimester, and the combination of RFA and surgery can radically increase the resection rate of HCC during pregnancy.

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