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1.
Artigo em Inglês | MEDLINE | ID: mdl-35486150

RESUMO

PURPOSE: Radical gastrectomy is considered the first choice of curative treatment for older patients with gastric cancer (GC). However, there is limited data on the survival benefits of gastrectomy for older patients with GC. METHODS: This was a retrospective observational study where medical records of patients aged ≥ 75 years with clinically resectable primary GC, comprising 115 patients who underwent radical surgery (S group) and 33 patients who received conservative therapy (non-S group) (total cohort) and 44 propensity-matched patients (matched cohort), were reviewed. Survival and independent risk factors, including comorbidities and systemic nutritional and inflammatory statuses, were evaluated. RESULTS: In the total cohort, the 5-year overall survival (OS) in the S group was significantly higher than that in the non-S group (53.7% vs 19.7%, P < 0.0001). In the matched cohort, the 3-year OS in the S group was significantly higher than that in the non-S group (59.4% vs 15.9%, P < 0.01). Multivariate analysis of the total cohort showed that no surgery was an independent prognostic factor for poor OS (hazard ratio (HR) 3.70, 95% confidence interval (CI) 1.91-7.20, P = 0.0001). In the S group in the total cohort, the multivariate analysis showed that renal disease (HR 2.51, 95% CI 1.23-5.12, P < 0.05) was an independent prognostic factor for poor OS. CONCLUSIONS: Gastrectomy for older patients improved the prognosis; however, careful patient selection is essential, especially among those with renal disease.

2.
Cancer Sci ; 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35363934

RESUMO

CD44 is a widely expressed polymorphic adhesion molecule that has pleiotropic functions in development and tumor progression. Its mRNA undergoes alternative splicing to generate multiple variant (CD44v) isoforms, although the function of each CD44v isoform is not fully elucidated. Here, we show that CD44v plays an important role in the induction of vimentin expression upon transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT). Among multiple CD44v isoforms expressed in NUGC3 gastric cancer cells, CD44v8-10 and CD44v3,8-10 are involved in the acquisition of migratory and invasive properties associated with TGF-ß1-induced EMT, and only CD44v3,8-10 induces the transcription of vimentin mediated by the EMT transcription factor Slug. In primary tumor specimens obtained from patients with gastric cancer, CD44-containing variant exon 9 (CD44v9) expression and EMT features [E-cadherin(-)vimentin(+)] were significantly correlated, and EMT features in the cells expressing CD44v9 was associated with tumor invasion depth, lymph node metastasis, and pStage, which indicate invasive and metastatic properties, and poor prognosis. These results indicate that certain CD44v isoforms promote tumor cell motility and metastasis in gastric cancer in association with EMT features, and CD44v3,8-10 may contribute to these clinical characteristics.

3.
J Atheroscler Thromb ; 29(5): 731-746, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33907060

RESUMO

AIM: To assess the results of a phase I/IIa open-label dose-escalation clinical trial of 5-day repeated intramuscular administration of pitavastatin-incorporated poly (lactic-co-glycolic acid) nanoparticles (NK-104-NP) in patients with chronic limb threatening ischemia (CLTI). METHODS: NK-104-NP was formulated using an emulsion solvent diffusion method. NK-104-NP at four doses (nanoparticles containing 0.5, 1, 2, and 4 mg of pitavastatin calcium, n=4 patients per dose) was investigated in a dose-escalation manner and administered intramuscularly into the ischemic limbs of 16 patients with CLTI. The safety and therapeutic efficacy of treatment were investigated over a 26-week follow-up period. RESULTS: No cardiovascular or other serious adverse events caused by NK-104-NP were detected during the follow-up period. Improvements in Fontaine and Rutherford classifications were noted in five patients (one, three, and one in the 1-, 2-, and 4-mg dose groups, respectively). Pharmacokinetic parameters including the maximum serum concentration and the area under the blood concentration-time curve increased with pitavastatin treatment in a dose-dependent manner. The area under the curve was slightly increased at day 5 compared with that at day 1 of treatment, although the difference was not statistically significant. CONCLUSIONS: This is the first clinical trial of pitavastatin-incorporated nanoparticles in patients with CLTI. Intramuscular administration of NK-104-NP to the ischemic limbs of patients with CLTI was safe and well tolerated and resulted in improvements in limb function.

4.
Ann Transplant ; 26: e909493, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34907151

RESUMO

BACKGROUND Portal vein thrombosis (PVT) after pediatric liver transplantation (LT) is a common but grave complication which could eventually result in life-threatening portal hypertension. A "Rex" shunt between the superior mesenteric vein and the Rex recess of the liver has been reported to be a treatment option for extrahepatic portal vein obstruction; however, its application to living donor liver transplantation (LDLT) is limited due to the availability of appropriate vein grafts. In this study, we retrospectively evaluated the effectiveness of Rex shunt as an option for the treatment of PVT after pediatric LDLT. CASE REPORT Three children underwent the Rex shunt for early (n=2) and late (n=1) PVT after LDLT using the greater saphenous vein (n=2) and the external iliac vein (n=1) from the parents who previously donated their livers. Two of the 3 children are free from symptoms with patent shunt grafts at 14 years after the procedures. One child died at 30 days after LDLT due to repeated episodes of PVT, which finally led to hepatic infarction. CONCLUSIONS The Rex shunt is feasible to treat PVT after LDLT. However, additional surgical insults to the living donor need further discussion.


Assuntos
Transplante de Fígado , Trombose Venosa , Criança , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Veia Porta/cirurgia , Estudos Retrospectivos , Trombose Venosa/etiologia , Trombose Venosa/cirurgia
5.
World J Clin Cases ; 9(24): 7224-7230, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34540982

RESUMO

BACKGROUND: Chronic pancreatitis occasionally requires surgical treatment that can be performed with various techniques. Often, this type of surgery presents with postoperative complications. We report a case of a successful retrograde pancreatojejunostomy for chronic pancreatitis and infected pancreatic cysts. CASE SUMMARY: A 62-year-old male with a 10-year history of chronic pancreatitis presented with epigastric pain for one week and a 20 kg weight loss over one year. Computed tomography showed stones in the pancreas (mainly the head), expansion of the main pancreatic duct, and thinning of the pancreatic parenchyma. Magnetic resonance imaging showed infected pancreatic cysts connected to the stomach with a fistula from the splenic hilum to the caudal portion of the liver's lateral segment. An endoscopic retrograde pancreatography was performed; the guide wires could not pass through the stones in the pancreas and therefore, drainage of the main pancreatic duct was not achieved. Next, a distal pancreatomy and splenectomy were performed; however, the pancreatic juice in the remaining parenchyma was blocked by the stones. Hence, we performed a retrograde pancreatojejunostomy and Roux-en-Y anastomosis. The patient had no postoperative complications and was discharged from the hospital on postoperative day 14. CONCLUSION: A distal pancreatomy, retrograde pancreatojejunostomy, and Roux-en-Y anastomosis could be an effective surgical procedure for intractable chronic pancreatitis.

7.
World J Clin Cases ; 9(17): 4453-4459, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34141813

RESUMO

BACKGROUND: Schwannoma of the pancreas is extremely rare. We report a case of pancreatic schwannoma that was difficult to distinguish from pancreatic carcinoma before surgery. CASE SUMMARY: A 66-year-old male underwent a right-lobe hepatectomy for hepatocellular carcinoma. Post-surgical computed tomography showed a 10 mm long solid mass with ischemia, with no expansion into the main pancreatic duct. Upon magnetic resonance cholangiopancreatography, the tumor had high signal intensity in diffusion weighted images, consistent with pancreatic carcinoma. Endoscopic ultrasound (EUS) was performed to obtain more information about the tumor, and showed a 14 mm solid and hypoechoic mass in the pancreatic body. Contrast enhanced EUS revealed that the tumor showed a hyperechoic mass in the early phase, and the contrasting effect continuation was very short; findings also consistent with pancreatic carcinoma. Thus, we preoperatively diagnosed his condition as a pancreatic carcinoma and performed distal pancreatectomy with splenectomy. Microscopic examination showed that the tumor was in fact a benign schwannoma. Histology showed a proliferation of spindle-shaped cell in a vague fascicular and haphazard pattern, with palisading arrangement. CONCLUSION: Schwannoma of the pancreas is very rare, however, clinicians should consider schwannoma as the differential diagnosis for pancreatic tumors.

8.
BMC Gastroenterol ; 21(1): 226, 2021 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-34011273

RESUMO

BACKGROUND: Percutaneous transhepatic gallbladder drainage (PTGBD) is recommended for acute cholecystitis patients at high risk for surgical treatment. However, there is no evidence about the best timing of surgery after PTGBD. Here, we retrospectively investigated the influence of the interval between PTGBD and surgery on perioperative outcomes and examined the optimal timing of surgery after PTGBD. METHODS: We performed a retrospective analysis of 22 patients who underwent cholecystectomy after PTGBD from January 2008 to August 2019. We examined perioperative factors between patients with an interval of ≤ 7 days between PTGBD and cholecystectomy (≤ 7-day group; n = 12) and those with an interval of ≥ 8 days (≥ 8-day group; n = 10). Moreover, we also examined perioperative factors between patients with an interval of ≤ 14 days from PTGBD to cholecystectomy (≤ 14-day group; n = 10) and those with an interval of ≥ 15 days (≥ 15-day group; n = 12). RESULTS: Of the 22 patients, 9 had Grade I cholecystitis, 12 had Grade II cholecystitis, and 2 had Grade III cholecystitis. Nine patients had high-grade cholecystitis before PTGBD and 13 had a poor general condition. We examined perioperative factors between patients with an interval of ≤ 7 days between PTGBD and cholecystectomy (≤ 7-day group; n = 12) and those with an interval of ≥ 8 days (≥ 8-day group; n = 10). The C-reactive protein (CRP) level before surgery was significantly higher (12.70 ± 1.95 mg/dL vs. 1.13 ± 2.13 mg/dL, p = 0.0007) and the total hospitalization was shorter (17.6 ± 8.0 days vs. 54.1 ± 8.8 days, p = 0.0060) in the ≤ 7-day group than in the ≥ 8-day group. We also examined perioperative factors between patients with an interval of ≤ 14 days from PTGBD to cholecystectomy (≤ 14-day group; n = 14) and those with an interval of ≥ 15 days (≥ 15-day group; n = 8). The CRP level before surgery was significantly higher (11.13 ± 2.00 mg/dL vs. 0.99 ± 2.64 mg/dL, p = 0.0062) and the total hospitalization was shorter (19.5 ± 7.2 days vs. 59.9 ± 9.5 days, p = 0.0029) in the ≤ 14-day group than in the ≥ 15-day group. However, there were no significant differences between the ≤ 14-day group and the ≥ 15-day group in the levels of hepatic enzymes before surgery, adhesion grade, amount of bleeding during surgery, operative duration, frequency of surgical complications, or length of hospitalization after surgery. CONCLUSIONS: The interval between PTGBD and surgery has little influence on perioperative outcomes.


Assuntos
Colecistectomia Laparoscópica , Colecistite Aguda , Colecistectomia , Colecistite Aguda/cirurgia , Drenagem , Vesícula Biliar/cirurgia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
9.
Gastric Cancer ; 24(5): 1089-1099, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33963958

RESUMO

BACKGROUND: CD44 variant 9 (CD44v9) has been reported to suppress reactive oxygen spices (ROS) in association with antioxidant factors such as glutathione (GSH) and glutathione peroxidase 2 (GPx2), resulting in promoted tumor growth. METHODS: CD44v9 and GPx2 expression were investigated by immunohistochemistry in resected specimens from 193 gastric cancer (GC) patients without preoperative chemotherapy and in pretreatment biopsy specimens from 29 GC patients with preoperative chemotherapy. We analyzed the relationship between CD44v9 expression and clinicopathological factors, prognosis, and pathological response to chemotherapy. In GC cell lines, we examined the relationship between CD44v9 expression and chemotherapeutic sensitivity. RESULTS: In patients without preoperative chemotherapy, CD44v9 expression was significantly associated with depth of invasion, lymphatic permeation, vascular invasion, distant metastasis and GPx2 expression. In multivariate analysis, CD44v9 expression was an independent poor prognosis factor for overall survival and recurrence-free survival. In patients with preoperative chemotherapy, CD44v9 expression was significantly associated with worse pathological response and GPx2 expression. In GC cell lines, downregulation of CD44v9 expression enhanced chemotherapeutic sensitivity to 5-fluorouracil with changing GSH and ROS levels. CONCLUSIONS: CD44v9-positive expression was associated with chemotherapeutic resistance by controlling intracellular accumulated ROS, suggesting that CD44v9 may be a predictive biomarker for chemotherapy in GC.


Assuntos
Neoplasias Gástricas , Biomarcadores Tumorais/genética , Resistencia a Medicamentos Antineoplásicos , Humanos , Receptores de Hialuronatos/genética , Oxigênio , Prognóstico , Especiarias , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética
10.
Transplant Proc ; 53(5): 1726-1730, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33993996

RESUMO

BACKGROUND: Biliary stricture (BS) is a severe complication after liver transplantation. It is difficult to treat, especially after living donor liver transplantation (LDLT). We successfully treated 4 patients for intractable BS after LDLT. All patients had developed cholangitis with stenosis of bile ducts anastomosis. CASE 1: . A 65-year-old woman underwent LDLT with right lobe graft and duct-to-duct biliary reconstruction. Internal plastic stents inserted by endoscopic retrograde cholangiography (ERC) were changed quarterly for the next 2 years. CASE 2: A 55-year-old man underwent LDLT with right lobe graft and duct-to-duct biliary reconstruction. Insertion of internal plastic stents by ERC was attempted; however, the posterior bile duct branch showed complete obstruction. After percutaneous transhepatic biliary drainage (PTCD), the stents were inserted using the rendezvous technique of ERC and were changed by ERC quarterly for the next 3 years. CASE 3: A 22-year-old man underwent LDLT with left lobe graft and hepaticojejunostomy. An external drainage tube was inserted by PTCD, and stents were changed quarterly for the next 2 years. CASE 4: A 60-year-old man underwent LDLT with right lobe graft and hepaticojejunostomy. An external drainage tube was inserted by PTCD, and changed to a metallic stent after 1 year. Three months later the stent was extracted using the rendezvous technique of double balloon enteroscopy. CONCLUSION: BS of complete obstruction type after LDLT is difficult to treat. Appropriate procedures should be chosen based on the types of strictures and biliary reconstruction methods.


Assuntos
Ductos Biliares/patologia , Constrição Patológica/diagnóstico , Transplante de Fígado/efeitos adversos , Idoso , Colangiopancreatografia Retrógrada Endoscópica , Colangite/diagnóstico , Colangite/etiologia , Constrição Patológica/etiologia , Drenagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Stents , Adulto Jovem
11.
Front Cardiovasc Med ; 8: 655808, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816581

RESUMO

Cardiac arrest occurred in an 85-year-old female administered osimertinib for advanced lung cancer expressing epidermal growth factor receptor (EGFR) mutations. Electrocardiogram (ECG) recorded at recurrence of spontaneous circulation showed sinus rhythm associated with mild QT prolongation (QTc = 455 ms) to which silent myocardial ischemia and coadministration of itraconazole and herbal drug causing hypokalemia (2.1 mEq/L) may have contributed. Discontinuation of osimertinib, itraconazole and herbal drug, potassium supplementation and percutaneous coronary intervention alleviated QT prolongation (QTc = 432 ms). Osimertinib is the third-generation tyrosine kinase inhibitor lengthening QT interval, and careful monitoring of ECG, serum potassium and drugs coadministered during chemotherapy including osimertinib are highly required.

12.
Eur J Cardiothorac Surg ; 60(2): 393-401, 2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-33668047

RESUMO

OBJECTIVES: The prognostic nutritional index (PNI) is an indicator of systemic immune-nutritional condition and is a well-known prognostic biomarker in lung cancer patients. Tumour-infiltrating lymphocytes (TILs) is a specific histological feature of cancers, influencing an individual's immunological tumour responses. However, whether PNI can reflect lung cancer patients' prognosis through local immunity such as TIL is unclear. METHODS: We selected 64 lung squamous cell carcinoma patients who underwent curative operations. We investigated the significance of preoperative PNI level and evaluated the relationship between PNI and immune cells surrounding the lung cancer tissue using immunohistochemical analysis of a cluster of differentiation (CD)3, CD4, CD8 and CD68. RESULTS: A low-PNI level was significantly associated with a worse postoperative prognosis (P = 0.042). The PNI (hazard ratio 2.768, 95% confidence interval 1.320-5.957; P = 0.007) was an independent prognostic factor. The low-PNI group had a significantly shorter recurrence-free survival and overall survival (P = 0.013 and P = 0.002, log-rank test) compared with the high-PNI group. A significant positive correlation between PNI components including preoperative peripheral blood lymphocyte count and serum albumin concentration, and TILs, was observed. Absolute numbers of TILs in the preoperative high-PNI group were significantly increased compared with those in the preoperative low-PNI group (CD3+ cells; P = 0.002, CD4+ cells; P = 0.049 and CD8+ cells; P = 0.024). CONCLUSIONS: The preoperative PNI level was strongly associated with the postoperative outcome in lung cancer patients. Considering the positive relationship between preoperative PNI level and TIL status, preoperative immune-nutritional condition may influence lung cancer patients' postoperative prognosis through local immunity as well as systemic immune response.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Carcinoma de Células Escamosas/cirurgia , Humanos , Pulmão , Neoplasias Pulmonares/cirurgia , Linfócitos do Interstício Tumoral , Avaliação Nutricional , Estado Nutricional , Prognóstico , Estudos Retrospectivos
13.
Cancer Sci ; 112(6): 2436-2441, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33780084

RESUMO

Trifluridine/tipiracil (FTD/TPI) is an orally administrated anticancer drug with efficacy validated for patients with metastatic colorectal cancer (mCRC) or gastric cancer. FTD, a key component of FTD/TPI, exerts antitumor effects via its incorporation into DNA. Using specific antibodies against bromodeoxyuridine, FTD incorporation into DNA is detected in tumors and peripheral blood mononuclear cells (PBMC) of patients with mCRC who are administered FTD/TPI. The proportion of FTD-positive PBMC fluctuates according to the schedule of treatment, although the association between the proportion of FTD-positive PBMC and the clinical outcomes of patients is unknown. To answer this question, here we monitored the FTD-positive PBMC of 39 elderly patients with mCRC enrolled in KSCC1602, a single-arm phase 2 trial of FTD/TPI plus bevacizumab as a first-line treatment, for 1 month, during the first cycle of treatment. The median values and interquartile ranges of the percentage of FTD-positive PBMC on days 8, 15, and 29 were 39.3% (30.7%-52.2%), 66.9% (40.0%-75.3%), and 13.5% (5.7%-26.0%), respectively. Receiver operating characteristic analysis revealed that the percentage of FTD-positive PBMC on day 8 (the end of the first week of treatment) had moderate ability to accurately diagnose the occurrence of severe neutropenia and leukopenia within 1 month (area under the curve = 0.778 [95% confidence interval, 0.554-0.993]). This result suggests that excess FTD incorporation into PBMC at the initial phase of FTD/TPI plus bevacizumab treatment is a risk factor for early onset of severe hematological adverse events.


Assuntos
Bevacizumab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Leucócitos Mononucleares/química , Pirrolidinas/administração & dosagem , Timina/administração & dosagem , Trifluridina/administração & dosagem , Administração Intravenosa , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , DNA de Neoplasias/sangue , DNA de Neoplasias/química , Esquema de Medicação , Combinação de Medicamentos , Feminino , Humanos , Masculino , Metástase Neoplásica , Pirrolidinas/efeitos adversos , Curva ROC , Timina/efeitos adversos , Trifluridina/efeitos adversos
14.
Clin Colorectal Cancer ; 20(2): e129-e138, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33731288

RESUMO

PURPOSE: The camptothecin (CPT) analogs topotecan and irinotecan specifically target topoisomerase I (topoI) and are used to treat colorectal, gastric, and pancreatic cancer. Response rate for this class of drug varies from 10% to 30%, and there is no predictive biomarker for patient stratification by response. On the basis of our understanding of CPT drug resistance mechanisms, we developed an immunohistochemistry-based predictive test, P-topoI-Dx, to stratify the patient population into those who did and did not experience a response. PATIENTS AND METHODS: The retrospective validation studies included a training set (n = 79) and a validation cohort (n = 27) of gastric cancer (GC) patients, and 8 cohorts of colorectal cancer (CRC) patient tissue (n = 176). Progression-free survival for 6 months was considered a positive response to CPT-based therapy. Formalin-fixed, paraffin-embedded slides were immunohistochemically stained with anti-phospho-specific topoI-Serine10 (topoI-pS10), quantitated, and analyzed statistically. RESULTS: We determined a threshold of 35% positive staining to offer optimal test characteristics in GC. The GC (n = 79) training set demonstrated 76.6% (95% confidence interval, 64-86) sensitivity; 68.8% (41-88) specificity; positive predictive value (PPV) 92.5% (81-98); and negative predictive value (NPV) 42.3% (24-62). The GC validation set (n = 27) demonstrated 82.4% (56-95) sensitivity and 70.0% (35-92) specificity. Estimated PPV and NPV were 82.4% (56-95) and 70.0% (35-92) respectively. In the CRC validation set (n = 176), the 40% threshold demonstrated 87.5% (78-94) sensitivity; 70.0% (59-79) specificity; PPV 70.7% (61-79); and NPV 87.0 % (77-93). CONCLUSION: The analysis of retrospective data from patients (n = 282) provides clinical validity to our P-topoI-Dx immunohistochemical test to identify patients with disease that is most likely to respond to topoI inhibitors.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , DNA Topoisomerases Tipo I/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Retrospectivos , Medição de Risco/métodos
15.
In Vivo ; 35(2): 1151-1155, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33622914

RESUMO

BACKGROUND: Intra-abdominal desmoid-type fibromatosis (DF) rarely necessitates emergency surgery. However, the condition is difficult to diagnose preoperatively and can become life-threatening if left untreated. CASE REPORT: A 46-year-old man complained of fever and right lower quadrant pain. In computed tomography, the mesenteric side of the ascending colon demonstrated air and fluid collections, suggesting diverticulitis with abscess. After 2 weeks of conservative treatment with fasting, the patient started to consume food; nonetheless, fever returned. Colonoscopy and contrast enema detected a fistula extending from the ascending colon to the abscess, with no surrounding lesions. Surgery was then performed because the abscess was refractory. During laparotomy, the scar tissue of the abscess was found to be attached to the lateral wall of the ascending colon. Hence, right colectomy combined with abscess resection was performed. Histopathological findings revealed DF in the mesentery. CONCLUSION: Although rare, DF should be included in the preoperative differential diagnosis of intra-abdominal abscesses.


Assuntos
Diverticulite , Fibromatose Agressiva , Abscesso/diagnóstico , Colectomia , Diagnóstico Diferencial , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade
16.
Ann Surg Oncol ; 28(2): 685-694, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32676867

RESUMO

BACKGROUND: The pack-year index, which is calculated by multiplying a smoking period by the number of cigarette packs smoked per day, is frequently used to investigate the risk of developing lung cancer. Notably, however, whether the smoking period or the number of packs per day is more predictive of postoperative prognosis remains unclear in non-small cell lung cancer (NSCLC) patients who receive curative lung resection. PATIENTS AND METHODS: Initial screening included 2055 consecutive lung cancer patients who had underwent curative lung resection between 2000 and 2016 at a single center in Japan. Data from 1134 NSCLC patients with smoking history were ultimately analyzed. Time-dependent areas under the curve (AUCs) were used to compare diagnostic accuracy. RESULTS: On univariate analysis, the number of packs smoked per day was not a significant predictor of disease-free survival (DFS; p = 0.2387) or overall survival (OS; p = 0.1357). On multivariable analysis, smoking period was an independent predictor of DFS and OS (both p < 0.0001). Time-dependent smoking period AUCs were superior to those of number of packs smoked per day. On subgroup analyses, patients with a smoking period ≥ 40 years had significantly shorter DFS and OS than those with a smoking period of < 40 years, independent of sex, clinical stage, and histological type. CONCLUSIONS: Smoking period was a significant prognostic indicator in NSCLC patients who underwent curative lung resection, which should be validated in further prospective and/or multicenter studies with large sample sizes.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Japão , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fumar/efeitos adversos
17.
Int J Clin Oncol ; 26(2): 345-354, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33085058

RESUMO

BACKGROUND: In a randomized pivotal global phase III study, S-1 and oxaliplatin 100 mg/m2 (SOX100) combination chemotherapy was as effective as S-1 and cisplatin for advanced gastric cancer (AGC) and showed a favorable safety profile. In this phase II study, we analyzed survival outcomes to assess the efficacy and safety of the SOX regimen with oxaliplatin 130 mg/m2 (SOX130) in AGC. METHODS: Patients with HER2-negative AGC received 80 mg/m2/day S-1 orally on days 1-14 and 130 mg/m2 oxaliplatin intravenously on day 1 of each 21-day cycle until the criteria for treatment withdrawal were fulfilled. The primary endpoint was the response rate (RR), and the null hypothesis of RR in the current trial was 45%. The secondary endpoints were progression-free survival (PFS) and overall survival (OS). Adverse events (AEs) were recorded according to CTCAE version 4.0. RESULTS: Seventy-one patients were enrolled from June 2015 to November 2016, but eight were excluded for ineligibility. Therefore, all final analyses were conducted with 63 patients. The confirmed RR was 46.0% (90% confidence interval [CI]: 36.1-56.3), and the disease control rate was 77.8% (90% CI: 68.1-85.1). The median PFS and OS were 4.9 (95% CI: 4.2-7.1) and 14.8 (95% CI: 11.1-18.9) months, respectively. Incidences of grade 3-4 AEs > 10% were anorexia (19.0%), peripheral neuropathy (12.7%), nausea (11.1%), and thrombocytopenia (11.1%). CONCLUSIONS: This study represents the first evaluation of SOX130 in patients with HER2-negative AGC. SOX130 showed an acceptable safety profile, but the prespecified statistical efficacy targets were not achieved.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Junção Esofagogástrica , Recidiva Local de Neoplasia , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Combinação de Medicamentos , Junção Esofagogástrica/patologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Ácido Oxônico/efeitos adversos , Ácido Oxônico/uso terapêutico , Receptor ErbB-2/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Tegafur/efeitos adversos , Tegafur/uso terapêutico
18.
Cancer Med ; 10(2): 454-461, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33249761

RESUMO

BACKGROUND: A previous Phase I/II study demonstrated that TAS-102 (trifluridine/tipiracil [FTD/TPI]) plus bevacizumab (Bev) has encouraging efficacy and controllable safety for patients with previously treated metastatic colorectal cancer. Therefore, we designed for assessing the efficacy and safety of FTD/TPI plus Bev in elderly patients with previously untreated metastatic colorectal cancer. METHODS: This is a multicenter, single-arm Phase II study included patients ≥70 years old with previously untreated, unresectable metastatic colorectal cancer. Treatment consisted of FTD/TPI plus Bev given every 4 weeks. The primary endpoint was progression-free survival (PFS), assuming a null hypothesis of a PFS of 5 months. The secondary endpoints were the overall survival (OS), overall response rate (ORR), and adverse events (AEs). RESULTS: Between 5 January 2017 and 13 March 2018, 39 patients were enrolled from 18 institutions. The median patient age was 76.0 years (range, 70-88); the ECOG-PS was 0 in 24 patients and 1 in 15 patients. The median PFS was 9.4 months as a primary endpoint, and the median OS was 22.4 months. The ORR was 40.5% and the disease control rate was 86.5%. Grade 3-4 AEs included neutropenia (71.8%), leukopenia (51.3%), anorexia (15.4%), febrile neutropenia (10.3%), and fatigue (10.3%). CONCLUSIONS: FTD/TPI plus Bev is an effective and well-tolerated regimen for elderly patients with previously untreated metastatic colorectal cancer. Capecitabine/bevacizumab can be selected as a subsequent maintenance therapy without irinotecan and oxaliplatin because FTD/TPI has no cross-resistance with 5-fluorouracil. CLINICAL TRIAL REGISTRATION: UMIN clinical trials registry (UMIN000025241).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Pirrolidinas/administração & dosagem , Taxa de Sobrevida , Timina/administração & dosagem , Trifluridina/administração & dosagem
19.
Nat Commun ; 11(1): 5292, 2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087715

RESUMO

Recent advances have enabled the direct induction of human tissue-specific stem and progenitor cells from differentiated somatic cells. However, it is not known whether human hepatic progenitor cells (hHepPCs) can be generated from other cell types by direct lineage reprogramming with defined transcription factors. Here, we show that a set of three transcription factors, FOXA3, HNF1A, and HNF6, can induce human umbilical vein endothelial cells to directly acquire the properties of hHepPCs. These induced hHepPCs (hiHepPCs) propagate in long-term monolayer culture and differentiate into functional hepatocytes and cholangiocytes by forming cell aggregates and cystic epithelial spheroids, respectively, under three-dimensional culture conditions. After transplantation, hiHepPC-derived hepatocytes and cholangiocytes reconstitute damaged liver tissues and support hepatic function. The defined transcription factors also induce hiHepPCs from endothelial cells circulating in adult human peripheral blood. These expandable and bipotential hiHepPCs may be useful in the study and treatment of human liver diseases.


Assuntos
Técnicas de Reprogramação Celular/métodos , Células Endoteliais/citologia , Hepatócitos/citologia , Células-Tronco/citologia , Animais , Ductos Biliares/citologia , Ductos Biliares/fisiologia , Agregação Celular , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Reprogramação Celular/genética , Reprogramação Celular/fisiologia , Células Endoteliais/fisiologia , Feminino , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/fisiologia , Fator 3-gama Nuclear de Hepatócito/genética , Fator 3-gama Nuclear de Hepatócito/fisiologia , Fator 6 Nuclear de Hepatócito/genética , Fator 6 Nuclear de Hepatócito/fisiologia , Hepatócitos/fisiologia , Hepatócitos/transplante , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Esferoides Celulares/citologia , Esferoides Celulares/fisiologia , Células-Tronco/fisiologia
20.
Mol Cancer Res ; 18(12): 1876-1888, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33004621

RESUMO

The IL6 family of cytokines, including IL6 and leukemia-inhibitory factor (LIF), are induced during inflammation and are also expressed in many types of cancer where they play an important role in tumor development. IL6 family cytokines mainly activate the JAK-STAT3 pathway via the coreceptor, gp130, and IL6 is known to activate the Src family kinase (SFK)-Yes-associated protein (YAP) pathway. The current study investigated the role of autocrine LIF in human esophageal squamous cell carcinoma (ESCC) that highly expresses LIF. LIF knockdown had various effects on cancer cells, including profound changes in gene expression, suppression of cell proliferation, migration/invasion and sphere formation, and induction of apoptosis. Similar to IL6, LIF activated the SFK-YAP pathway as well as the JAK-STAT3 pathway. LIF-induced YAP activation was more important for cancer cell proliferation than LIF-induced STAT3 activation, and concomitant YAP and STAT3 activation completely compensated for the role of LIF in human ESCC growth. We also confirmed that SFK activation and LIF expression were correlated with YAP activation in human ESCC clinical samples. Furthermore, simultaneous inhibition of the SFK-YAP and JAK-STAT3 pathways in human ESCC cells was more effective at suppressing cell proliferation than single inhibition, and autocrine LIF signaling promoted human ESCC growth in vivo. Therefore, the LIF-SFK-YAP axis may represent a new therapeutic target for human ESCC. IMPLICATIONS: Autocrine LIF signaling promotes human ESCC progression via SFK-dependent YAP activation and is a new potential target of treatment for human ESCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Fator Inibidor de Leucemia/metabolismo , Fator de Transcrição STAT3/metabolismo , Fatores de Transcrição/metabolismo , Quinases da Família src/metabolismo , Animais , Comunicação Autócrina , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas do Esôfago/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Fator Inibidor de Leucemia/genética , Camundongos , Transplante de Neoplasias , Transdução de Sinais , Regulação para Cima
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