RESUMEN
Elevated autophagy activity enhances the malignancy of pancreatic cancer (PaCa), and autophagy is recognized as a novel therapeutic target. Zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) is a transcription factor that suppresses autophagy, but its association with PaCa is unknown. We analyzed the function of ZKSCAN3 in PaCa and investigated whether autophagy regulation through ZKSCAN3 could become a new therapeutic target for PaCa. Using reverse transcription-quantitative polymerase chain reaction and western blotting, we observed that ZKSCAN3 expression was upregulated in several PaCa cell lines compared with normal pancreatic ductal epithelial cells. Additionally, comparing ZKSCAN3 expression with the prognosis of PaCa patients using web databases, we found that higher ZKSCAN3 expression in PaCa was associated with extended overall survival. Knocking down ZKSCAN3 promoted the proliferation of PaCa cells. Moreover, following ZKSCAN3 knockdown, PaCa cells exhibited significantly enhanced migratory and invasive properties. Conversely, overexpression of ZKSCAN3 significantly suppressed the proliferation, migration and invasion of PaCa cells. Additionally, the knockdown of ZKSCAN3 increased the expression of LC3-II, a marker of autophagy, whereas ZKSCAN3 overexpression decreased LC3-II expression. In a xenograft mouse model, tumors formed by MIA PaCa-2 cells in which ZKSCAN3 was knocked down significantly increased in size compared with the control group. In conclusion, ZKSCAN3 expression was upregulated in several pancreatic cancer cells. Additionally, it was revealed that ZKSCAN3 is negatively correlated with the malignancy of PaCa through autophagy. These results suggest that autophagy regulation via ZKSCAN3 may be a new therapeutic target for PaCa.
Asunto(s)
Autofagia , Movimiento Celular , Proliferación Celular , Invasividad Neoplásica , Neoplasias Pancreáticas , Factores de Transcripción , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Autofagia/genética , Animales , Proliferación Celular/genética , Movimiento Celular/genética , Línea Celular Tumoral , Ratones , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Pronóstico , Femenino , Técnicas de Silenciamiento del Gen , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Microtúbulos/genéticaRESUMEN
A 35-year-old man who had fever and stomachache was referred to our hospital. He underwent surgery and chemoradiotherapy for neuroblastoma as a child and subsequently developed leukemia. Frequent blood transfusions and bone marrow transplants were performed due to anemia. Abdominal contrast CT scan and contrast MRI showed tumorous lesions with a diameter of 60×42 mm in liver S6, and a tendency to increase in a short term. There was also hemochromatosis in the liver. We considered it a malignant tumor and performed a right lobectomy. Pathological examination diagnosed the tumor hepatic angiosarcoma. The postoperative course was fine and he was discharged without complications. But multiple liver metastases appeared 6 months after surgery. We performed chemotherapy but he passed away 10 months after surgery. Hepatic angiosarcoma is a rare disease among liver malignancies and has a very poor prognosis. As for the cause of hepatic angiosarcoma, many of them are unknown, but chronic exposures such as vinyl monomers have been reported in some cases. Hemochromatosis has been reported as a background factor for malignant tumors such as hepatocellular carcinoma. In this case it is possible that it contributed to the development of hepatic angiosarcoma.
Asunto(s)
Carcinoma Hepatocelular , Hemangiosarcoma , Hemocromatosis , Neoplasias Hepáticas , Masculino , Niño , Humanos , Adulto , Hemocromatosis/complicaciones , Hemangiosarcoma/cirugía , Neoplasias Hepáticas/cirugía , Carcinoma Hepatocelular/complicacionesRESUMEN
An-81-year-old man presented to another doctor complaining of epigastric pain. He was referred to us after the laboratory data revealed a high serum CEA and abdominal ultrasonography showed the space occupying lesion in the left liver. Abdominal CT revealed advanced gallbladder cancer infiltrating the liver and colon and found annular pancreas surrounding the descending portion of duodenum. We chose partial hepatectomy(S4a+S5), extrahepatic bile duct resection with hepaticojejunostomy and partial colectomy. Pathological diagnosis of the tumor was pT3N1M0, gallbladder cancer. The patient was discharged on the 21 days after operation. The frequency of malignant tumors in adult annular pancreas are not revealed. But some cases present with adult annular pancreas complicating the biliary tract tumor. We experienced a case of advanced gallbladder cancer with adult annular pancreas and report our case and review the pertinent literature.
Asunto(s)
Neoplasias de la Vesícula Biliar , Enfermedades Pancreáticas , Masculino , Humanos , Adulto , Neoplasias de la Vesícula Biliar/patología , Páncreas/patología , Enfermedades Pancreáticas/cirugía , Hígado/patologíaRESUMEN
The patient described herein was diagnosed with left breast, endometrial, and early gastric cancers at 49, 53, and 57 years of age, respectively. Magnetic resonance cholangiopancreatography performed when she was undergoing treatment for cholecystitis at 50 years of age showed local pancreatic duct dilatation in the pancreatic head. She was followed in the Department of Gastroenterology at our hospital for an intraductal papillary mucinous neoplasm(IPMN). An abdominal computed tomography scan obtained at 59 years of age revealed dilation of the main pancreatic duct in the pancreas body and tail, therefore an endoscopic ultrasound-guided fine needle aspiration was performed. She was diagnosed with pancreatic cancer and underwent a laparoscopic distal pancreatectomy. The postoperative course was uneventful; however, the pancreatic cancer recurred and she died approximately 14 months postoperatively. Reports of multiple cancers associated with IPMNs are rare, yet we managed a patient with a pancreatic head IPMN complicated by metachronous quadruple carcinomas( breast, endometrial, gastric, and pancreatic cancers).
Asunto(s)
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Femenino , Humanos , Carcinoma Ductal Pancreático/patología , Neoplasias Intraductales Pancreáticas/cirugía , Pancreatectomía , Adenocarcinoma Mucinoso/cirugía , Adenocarcinoma Mucinoso/diagnóstico , Recurrencia Local de Neoplasia/cirugía , Neoplasias Pancreáticas/patología , Conductos Pancreáticos/patologíaRESUMEN
BACKGROUND: The treatment of chronic pancreatitis requires a surgical approach in patients who are refractory to medical therapy. During surgical treatment, ductal decompression is required, but a pancreatectomy is necessary for some patients, such as those with severe stenosis of the pancreatic duct. Indeed, suboptimal procedures lead to recurrent pancreatitis. We used a laparoscopic hybrid approach for patients with severe stenosis of the pancreatic duct. In this report, we present the feasibility and outcomes of our approach. METHODS: We selected a laparoscopic approach for the distal pancreatectomy, which is relatively safe and the effect of reducing the length of the wound is substantial. We selected an open approach for the Frey procedure because complete ductal compression has a high risk for injury to the vessels posterior to the pancreas. We recorded the operative outcomes, postoperative complications, and recurrence of pancreatitis. RESULTS: We performed the laparoscopic hybrid approach on 3patients between January and December 2018. There were no major intraoperative complications (Clavien-Dindo classification IIIa or more) and the postoperative course was uneventful in all patients. There were no recurrences of pancreatitis and no postoperative pain in all patients in > 2 years of follow-up. CONCLUSION: Our hybrid method with a focus on complete ductal compression with safety and minimal invasiveness might be the optimal approach for the surgical treatment of chronic pancreatitis that requires a pancreatectomy with the Frey procedure.
Asunto(s)
Laparoscopía , Pancreatectomía , Pancreatitis Crónica , Humanos , Laparoscopía/métodos , Pancreatectomía/métodos , Pancreatitis Crónica/cirugíaRESUMEN
We experienced a case of solitary liver tumor that developed after renal cancer surgery. Before the surgery, the tumor was suspected to be hepatocellular carcinoma and was subsequently diagnosed as renal cancer liver metastasis. An 81-year-old man underwent retroperitoneal laparoscopic nephrectomy for left renal cancer in January 2017. After that, the cancer had not recurred, but a follow-up CT examination 1 year after the operation revealed a 42 mm-sized tumor in the liver S6. Liver biopsy was performed for diagnosis, but in histopathological findings, the diagnosis was difficult to make. Eventually, the preoperative final diagnosis was hepatocellular carcinoma. Laparoscopic partial hepatectomy was performed in June 2018, and in the histopathological findings of the resected specimen, the final diagnosis was the liver metastasis from renal cancer. Generally, the prognosis of renal cancer with liver metastasis is poor, but if complete resection is possible, it is recommended in the Clinical Practical Guideline for Renal Cancer. In recent years, the number of minimally invasive laparoscopic surgeries for hepatectomy has increased, and its safety has also improved. Therefore, resection is diagnostic treatment for cases where, like this case, preoperative diagnosis for solitary liver tumor is difficult. Laparoscopic hepatectomy could be one of the effective treatment strategies.
Asunto(s)
Carcinoma Hepatocelular , Carcinoma de Células Renales , Neoplasias Renales , Laparoscopía , Neoplasias Hepáticas , Anciano de 80 o más Años , Carcinoma Hepatocelular/cirugía , Carcinoma de Células Renales/cirugía , Hepatectomía , Humanos , Neoplasias Renales/cirugía , Neoplasias Hepáticas/cirugía , Masculino , Recurrencia Local de NeoplasiaRESUMEN
BACKGROUND: An epithelial cyst in an intrapancreatic accessory spleen (ECIPAS) is rare. We report a case of ECIPAS that was treated with robot-assisted distal pancreatectomy with splenectomy. CASE PRESENTATION: The case was a 59-year-old woman who was referred to our hospital after a pancreatic tail tumor was found on computed tomography prior to surgery for small bowel obstruction at another hospital. A cystic lesion in the pancreatic tail was discovered and evaluated by magnetic resonance imaging and endoscopic ultrasonography. Based on clinical and radiological features, mucinous cystic neoplasm was included in the differential diagnosis. The patient underwent robot-assisted distal pancreatectomy with splenectomy. The postoperative course was uneventful. Pathological evaluation revealed a 20-mm ECIPAS in the pancreatic tail. CONCLUSIONS: If a pancreatic tail tumor is present, ECIPAS should be included in the differential diagnosis. However, preoperative diagnosis is difficult, and a definitive diagnosis is often not obtained until after surgery. Surgery should be minimally invasive. Laparoscopic distal pancreatectomy has become a standard surgical procedure because it is minimally invasive. Robot-assisted surgery is not only minimally invasive, but also advantageous, because it has a stereoscopic magnifying effect and allows the forceps to move smoothly. Robot-assisted distal pancreatectomy may be a good option, when performing surgery for a pancreatic tail tumor.
Asunto(s)
Coristoma , Quiste Epidérmico , Enfermedades Pancreáticas , Procedimientos Quirúrgicos Robotizados , Bazo , Enfermedades del Bazo , Anciano , Coristoma/diagnóstico por imagen , Endosonografía , Quiste Epidérmico/diagnóstico por imagen , Quiste Epidérmico/cirugía , Femenino , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Pancreatectomía , Enfermedades Pancreáticas/diagnóstico por imagen , Enfermedades Pancreáticas/cirugía , Bazo/diagnóstico por imagen , Bazo/cirugía , Esplenectomía , Enfermedades del Bazo/diagnóstico por imagen , Enfermedades del Bazo/cirugía , Tomografía Computarizada por Rayos XRESUMEN
The case presented is a 72-year-old male with no history of hepatitis B or C. Dynamic CT revealed a 2 cm mass in the liver (S8), with arterial phase hyperenhancement and delayed phase washout. The patient underwent an open S8 subsegmentectomy. The mass was pathologically diagnosed as well-to-moderately differentiated hepatocellular carcinoma(T2N0M0, Stage â ¡). At 2 years 10 months postoperatively, MRI showed a 4 cm mass in contact with the pancreatic head, inferior vena cava, and duodenum. The mass had moderate FDG uptake on PET scan, and early phase hyperenhancement and delayed phase washout on dynamic CT. We performed laparoscopic mass resection, suspecting lymph node metastasis of the hepatocellular carcinoma, which was confirmed by the pathological diagnosis. The patient has survived for 1 year without recurrence. Lymph node metastasis of hepatocellular carcinoma is rare. It is unclear whether surgical resection is feasible in such cases. Here, we report a case of lymph node metastasis of hepatocellular carcinoma resected by laparoscopic surgery.
Asunto(s)
Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Anciano , Carcinoma Hepatocelular/cirugía , Humanos , Neoplasias Hepáticas/cirugía , Ganglios Linfáticos , Metástasis Linfática , Masculino , Recurrencia Local de NeoplasiaRESUMEN
The case is a 59-year-old woman. A medical examination revealed a high CA19-9, she visited a nearby hospital. Abdominal echo showed thickening of the gallbladder wall, and she was referred to our hospital for further examination. EUS-FNA was performed and a biopsy of #12 lymph node revealed undifferentiated cancer, which was diagnosed as gallbladder cancer. FDG-PET showed accumulation of FDG in the gallbladder lumen and swollen lymph nodes around the aorta. Therefore, the cancer was considered unresectable and chemotherapy was performed. FDG-PET was re-examined after 4 courses of gemcitabine plus cisplatin combination chemotherapy. As a result, the lymph node swelling contracted, the accumulation of FDG disappeared, and surgery was scheduled. Extended cholecystectomy and extrahepatic bile duct resection were performed. She was discharged 22 days after the surgery without complications. Histopathological examination showed fibrotic tissue at the gallbladder and lymph nodes, but no residual tumor cells. There are no recurrences 11 months after surgery. Although the prognosis of gallbladder cancer with para-aortic lymph node metastasis is generally poor, it is suggested that conversion surgery with multimodality treatment including preoperative chemotherapy may be a useful therapeutic strategy.
Asunto(s)
Cisplatino , Neoplasias de la Vesícula Biliar , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/uso terapéutico , Desoxicitidina/análogos & derivados , Femenino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Ganglios Linfáticos , Metástasis Linfática , Persona de Mediana Edad , GemcitabinaRESUMEN
A 60's man came to our hospital for jaundice. Contrast-enhanced CT showed irregular thickening of the hilar bile duct, and the lymph nodes(LN)were swollen from the hilar to the abdominal aorta. These LNs showed similar findings in endoscopic ultrasonography(EUS), and fine needle aspiration cytology(FNA)was performed on the enlarged No.13LN to diagnose LN metastasis of hilar cholangiocarcinoma. Since the peri-aortic LN was also markedly enlarged, it was considered to be metastasis, and was diagnosed as unresectable hilar cholangiocarcinoma with distant LN metastasis. When gemcitabine/cisplatin therapy(GC therapy)was started, tumor markers normalized and LN decreased in 4 months. We performed GC therapy for a total of 12 cycles and did not re-exacerbate. Cholangioscopy revealed that bile duct stenosis at the hilar portion had improved. We have determined that curative resection is possible and performed surgery. We confirmed that No.16b1LN was negative by pathological diagnosis during surgery and performed left hepatic caudate lobectomy, extrahepatic cholangectomy, and biliary reconstruction. Diagnosis was pT2aN1(n8a)M0, fStage â ¢B, and pR0. After surgery, adjuvant chemotherapy with S-1 was continued.
Asunto(s)
Neoplasias de los Conductos Biliares , Conductos Biliares Intrahepáticos , Tumor de Klatskin , Terapia Neoadyuvante , Hepatectomía , Humanos , MasculinoRESUMEN
Stoma creation through the extraperitoneal route reportedly reduces the risk of parastomal hernia and stomal prolapse after abdominoperineal resection (APR) for rectal cancer. We describe a new technique for laparoscopic extraperitoneal sigmoid colostomy following APR. After the rectus abdominis muscle is separated, Lap ProtectorTM and EZ AccessTM devices are placed. An extraperitoneal stoma tunnel is created laparoscopically as much as possible. Next, the peritoneum is separated from the inside of the abdominal cavity, and the extraperitoneal tunnel is opened. At the time of writing, we had performed laparoscopic extraperitoneal sigmoid colostomy in eight patients, without any complications or conversion to the conventional procedure. Thus, laparoscopic extraperitoneal sigmoid colostomy is a useful and safe technique for the laparoscopic creation of an extraperitoneal stoma tunnel after APR.
Asunto(s)
Colon Sigmoide/cirugía , Colostomía/métodos , Hernia/prevención & control , Herniorrafia/métodos , Laparoscopía/métodos , Complicaciones Posoperatorias/prevención & control , Proctectomía/métodos , Neoplasias del Recto/cirugía , Estomas Quirúrgicos , Humanos , Peritoneo/cirugía , Recto/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A 56-year-old man underwent distal pancreatectomy due to pancreatic body carcinoma in 2009, at the age of 46. There had been no sign of metastasis and recurrence until levels of tumor markers began to increase in January 2014. PET scan, CT scan, and other examinations showed a possible carcinoma in the pancreas head. The patient underwent total remnant pancreatectomy. The tumor was located in the uncinate process of the pancreas with infiltration of the portal vein. The pathological diagnosis of the tumor was moderately differentiated adenocarcinoma. The ductal lumen structure was relatively maintained and the cytoplasm was comparatively clear. Since its pathological findings were similar to those observed in 2009, the tumor appeared to be a recurrence of the tumor resected at that time. The patient had received postoperative chemotherapy and remains alive in 2019 without recurrence. While there is evidence that surgical resection for the recurrence of other cancers such as colon cancer may improve patient survival, it remains unclear if surgical resection of recurrence in the remnant pancreas after pancreatectomy of pancreatic cancer is feasible. We report a case with long survival after surgical resection of a pancreatic carcinoma recurrence in the remnant pancreas.
Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Páncreas , Pancreatectomía , Neoplasias Pancreáticas/cirugíaRESUMEN
We report a case of conversion surgery for a locally advanced unresectable(UR-LA)pancreatic cancer that was radically resected after S-1 therapy. A 65-year-old man visited a referral physician because of fatigue and liver dysfunction. A CT scan revealed a mass in the pancreatic uncinate process that was suspected to be superior mesenteric artery(SMA)infiltration and was diagnosed as UR-LA pancreatic cancer. GEM nab-PTX therapy was initiated but was discontinued after 2 courses because of adverse events. The treatment was switched to S-1 monochemotherapy. After that, the tumor did not progress for around 1.5 years, and the patient was referred to our hospital for surgical treatment. As the contact between the tumor and the SMA was considered to be less than half-round, we made a diagnosis of borderline resectable(BR-A)pancreatic cancer. Subsequently, we performed a pancreaticoduodenectomy with partial resection of the portal vein and achieved R0 resection. The patient received adjuvant chemotherapy with S-1 and showed no signs of recurrence for 10 months after surgery.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Ácido Oxónico/uso terapéutico , Neoplasias Pancreáticas , Tegafur/uso terapéutico , Anciano , Combinación de Medicamentos , Humanos , Masculino , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , PancreaticoduodenectomíaRESUMEN
Xantohumol, a prenylated chalcone from hops (Humulus lupulus L.), has been shown to inhibit proliferation in some cancers. However, little is known regarding the effects of xanthohumol in pancreatic cancer. We have previously reported that activation of the transcription factor nuclear factor-κB (NF-κB) plays a key role in angiogenesis in pancreatic cancer. In this study, we investigated whether xanthohumol inhibited angiogenesis by blocking NF-κB activation in pancreatic cancer in vitro and in vivo. We initially confirmed that xanthohumol significantly inhibited proliferation and NF-κB activation in pancreatic cancer cell lines. Next, we demonstrated that xanthohumol significantly suppressed the expression of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) at both the mRNA and protein levels in pancreatic cancer cell lines. We also found that coculture with BxPC-3 cells significantly enhanced tube formation in human umbilical vein endothelial cells, and treatment with xanthohumol significantly blocked this effect. In vivo, the volume of BxPC-3 subcutaneous xenograft tumors was significantly reduced in mice treated with weekly intraperitoneal injections of xanthohumol. Immunohistochemistry revealed that xanthohumol inhibited Ki-67 expression, CD31-positive microvessel density, NF-κB p65 expression, and VEGF and IL-8 levels. Taken together, these results showed, for the first time, that xanthohumol inhibited angiogenesis by suppressing NF-κB activity in pancreatic cancer. Accordingly, xanthohumol may represent a novel therapeutic agent for the management of pancreatic cancer.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Flavonoides/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Propiofenonas/administración & dosificación , Factor de Transcripción ReIA/metabolismo , Inhibidores de la Angiogénesis/farmacología , Animales , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Técnicas de Cocultivo , Flavonoides/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Ratones , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Propiofenonas/farmacología , Factor de Transcripción ReIA/genética , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
We report a case of a malignant lymphoma that was treated with laparoscopic resection of the pericardium. A 43-year-old woman was diagnosed with asymptomatic extrahepatic nodule by medical examination. CT, MRI, and PET-CT examination indicated a solitary fibrous tumor(SFT). Therefore, we performed laparoscopic resection for definitive diagnosis and treatment. The tumor was located in the upper abdominal wall and adhered to the liver; hence, we additionally performed partial resection of the liver. Thereafter, we dissected the tumor from the abdominal wall alongwith a part of the diaphragm. Because intraoperative pathological examination revealed more malignancy than was preoperatively expected, we also resected a part of the pericardium. The laparoscopic approach to the pericardium can be performed safely because of its magnification effect, which is an advantage of laparoscopic surgery.
Asunto(s)
Laparoscopía , Linfoma , Adulto , Antimetabolitos Antineoplásicos/uso terapéutico , Femenino , Humanos , Linfoma/cirugía , Metotrexato/uso terapéutico , Pericardio/cirugía , Tomografía Computarizada por Tomografía de Emisión de PositronesRESUMEN
BACKGROUND: The CXCL12-CXCR4 signaling axis in malignant tumor biology has increased in importance, and these peptides are implicated in tumor growth, invasion and metastasis. The aim of our study was to examine the important role of the axis in pancreatic cancer (PaCa) cells' relationship with stromal cells in gemcitabine-resistant (GEM-R) tumors and to confirm the effectiveness of CXCR4 antagonists for the treatment of GEM-R PaCa cells. METHODS: We established two GEM-R PaCa cell lines using MIA PaCa-2 and AsPC-1 cells. The expression of CXCR4 mRNA in PaCa cells and the expression of CXCL12 mRNA in fibroblasts were examined by reverse transcription polymerase chain reaction (RT-PCR). The expression of CXCR4 protein in PaCa cells was examined by immunosorbent assay (ELISA) and immunocytochemistry. Using Matrigel invasion assays and animal studies, we then examined the effects of two CXCR4 antagonists, AMD11070 and KRH3955, on the invasiveness and tumorigenicity of GEM-R PaCa cells stimulated by CXCL12. RESULTS: We found that the expression of CXCR4 in GEM-R PaCa cells was significantly enhanced by GEM but not in normal GEM-sensitive (GEM-S) PaCa cells. In RT-PCR and ELISA assays, the production and secretion of CXCL12 from fibroblasts was significantly enhanced by co-culturing with GEM-R PaCa cells treated with GEM. In Matrigel invasion assays, the invasiveness of GEM-R PaCa cells treated with GEM was significantly activated by fibroblast-derived CXCL12 and was significantly inhibited by CXCR4 antagonists, AMD11070 and KRH3955. In vivo, the tumorigenicity of GEM-R PaCa cells was activated by GEM, and it was significantly inhibited by the addition with CXCR4 antagonists. CONCLUSIONS: Our findings demonstrate that the CXCL12-CXCR4 signaling axis plays an important role in PaCa cells' resistance to GEM. CXCR4 expression was significantly enhanced by the exposure to GEM in GEM-R PaCa cells but not in GEM-S PaCa cells. Furthermore, CXCR4 antagonists can inhibit the growth and invasion of GEM-R PaCa cells. These agents may be useful as second-line chemotherapy for GEM-R PaCa in the future.
Asunto(s)
Quimiocina CXCL12/metabolismo , Desoxicitidina/análogos & derivados , Compuestos Heterocíclicos con 1 Anillo/farmacología , Neoplasias Pancreáticas/metabolismo , Receptores CXCR4/antagonistas & inhibidores , Receptores CXCR4/metabolismo , Aminoquinolinas , Animales , Antimetabolitos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Bencimidazoles , Butilaminas , Proliferación Celular/efectos de los fármacos , Desoxicitidina/farmacología , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Células del Estroma/patología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , GemcitabinaRESUMEN
BACKGROUND: We have established a standard procedure for Roux-en-Y (RY) reconstruction in laparoscopic total gastrectomy (LTG) using esophagojejunostomy by the overlap method (OL). We report on our RY reconstruction technique and special approaches, and evaluate the usefulness of our reconstruction method based on the surgical results of 100 patients we have experienced to date. METHODS: We performed LTG in 100 patients with gastric cancer. After total gastrectomy using five ports, the resected stomach was extracted through a small laparotomy. Through that, we performed sacrifice of the jejunum, Y limb anastomosis, creation of the lifted jejunum. As the OL, a side-to-side anastomosis of the lifted jejunum to the esophageal stump was laparoscopically performed using a linear stapler in an isoperistaltic direction, and the entry hole was closed with full-thickness suturing. The lifted jejunum was fixed with suture to the duodenal stump at a location where the esophagojejunostomy site was made linear, and the duodenal stump was buried. The mesenteric gap was laparoscopically closed with suture. RESULTS: The median operative time in 100 patients undergoing LTG was 385 min, the median blood loss was 65 mL, and the median time required for the OL was 32 min. The mean hospitalization period was 10 days, and postoperative complications included bleeding requiring reoperation in one patient; other complications such as pancreatic fistula in five patients (5 %) were treated conservatively. No complication associated with anastomosis occurred. CONCLUSION: In RY reconstruction using the OL, there were no complications associated with the anastomosis site in 100 consecutive patients, such as anastomotic leak or stenosis, indicating that it is a very useful and safe reconstruction method.
Asunto(s)
Anastomosis en-Y de Roux/métodos , Carcinoma/cirugía , Esófago/cirugía , Gastrectomía/métodos , Yeyuno/cirugía , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica/métodos , Fuga Anastomótica/epidemiología , Femenino , Humanos , Laparoscopía/métodos , Laparotomía , Tiempo de Internación , Masculino , Persona de Mediana Edad , Tempo Operativo , Fístula Pancreática/epidemiología , Complicaciones Posoperatorias/epidemiología , SuturasRESUMEN
BACKGROUND: Situs inversus totalis is a relatively rare condition and is an autosomal recessive congenital defect in which an abdominal and/or thoracic organ is positioned as a "mirror image" of the normal position in the sagittal plane. We report our experience of laparoscopic-assisted total gastrectomy with lymph node dissection performed for gastric cancer in a patient with situs inversus totalis. CASE PRESENTATION: A 58-year-old male was diagnosed with cT1bN0N0 gastric cancer. There were no vascular anomalies on abdominal angiographic computed tomography with three-dimensional reconstruction. laparoscopic-assisted total gastrectomy was performed with D1+ lymph node dissection, in accordance with the Japanese Gastric Cancer Treatment Guidelines. There were no intraoperative issues, and no postoperative complications. CONCLUSIONS: This was the first report describing laparoscopic-assisted total gastrectomy with the standard typical lymph node dissection in the English literature. We emphasize that the position of trocars and the standing side of the primary surgeon during the lymph node dissection are critical.
Asunto(s)
Adenocarcinoma/cirugía , Gastrectomía/métodos , Laparoscopía/métodos , Situs Inversus/complicaciones , Neoplasias Gástricas/cirugía , Adenocarcinoma/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Gástricas/complicacionesRESUMEN
BACKGROUND: Various methods of reconstruction after laparoscopic distal gastrectomy (LDG) have been developed and published, whereas only a limited number of reports are available on the utility of the delta-shaped anastomosis (Delta). This study compared Delta and Roux-en-Y anastomoses (RY), with the aim to clarify the utility of Delta. METHODS: Stage 1 gastric cancer patients who had undergone LDG with Delta (group D, n = 68) and those who had undergone LDG with RY (group RY, n = 60) were compared in terms of operative outcomes, postoperative clinical symptoms, gastrointestinal fiberscopic findings, and changes in body weight. RESULTS: Both the operative and anastomotic times were significantly shorter in group D (230 and 13 min, respectively) than in group RY (258 and 38 min, respectively) (p < 0.001). Among the complications observed at the anastomotic site, obstruction was seen in one group D patient and two group RY patients but was relieved with conservative management. Postoperative clinical symptoms were reported for 26.4% of the group D patients but had decreased to 5.9% 1 year later. Group RY yielded similar results. Upper gastrointestinal fiberscopy performed 1 year postoperatively showed no intergroup differences in the incidence of gastritis or residual retention and a significantly more frequent occurrence of bile reflux in group D. Postoperative weight changes did not differ between the two groups. CONCLUSIONS: Delta reconstruction after LDG is a safe and effective procedure that is totally laparoscopic, less time consuming, and associated with a favorable postoperative course and a better quality of life.
Asunto(s)
Anastomosis en-Y de Roux , Anastomosis Quirúrgica/métodos , Gastrectomía/métodos , Laparoscopía , Adulto , Anciano , Reflujo Biliar/etiología , Pérdida de Sangre Quirúrgica , Síndrome de Vaciamiento Rápido/etiología , Duodenostomía , Femenino , Derivación Gástrica , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND: Laparoscopic procedures are increasingly being applied to gastric cancer surgery, including total gastrectomy for tumors located in the upper gastric body. Even for expert surgeons, esophagojejunostomy after laparoscopy-assisted total gastrectomy (LATG) can be technically challenging. We perform the overlap method of esophagojejunostomy after LATG for gastric cancer. However, technical questions remain. Is the overlap method safer and more useful than other anastomosis techniques, such as methods using a circular stapler? In addition, while we perform this overlap reconstruction after LATG in a deep and narrow operative field, can the overlap method be performed safely regardless of body habitus? This study aimed to evaluate these issues retrospectively and to review the literature. METHODS: From October 2005 to August 2013, we performed LATG with lymph-node dissection and Roux-en-Y reconstruction using the overlap method in 77 patients with gastric cancer. This study examined pre-, intra- and postoperative data. RESULTS: Mean operation time, time to perform anastomosis, and estimated blood loss were 391.4 min, 36.3 min, and 146.9 ml, respectively. There were no deaths, and morbidity rate was 13%, including one patient (1%) who developed anastomotic stenosis. Mean postoperative hospitalization was 13.4 days. Surgical outcomes did not differ significantly by body mass index. CONCLUSIONS: First, the overlap method for esophagojejunostomy after LATG is safe and useful. Second, this method can be performed irrespective of the body type of the patient. In particular, in a deep and narrow operative field, the overlap method is more versatile than other anastomosis methods. We believe that the overlap method can become a standard reconstruction technique for esophagojejunostomy after LATG.