RESUMO
BACKGROUND: PDAC cells upregulate carbonic anhydrase 9 (CA9) expression in order to survive in hypoxic tumor environments, which plays a key role in tumor progression. However, the relationship between CA9 expression and preoperative treatment has not been clarified. We evaluated the clinical impact of CA9 expression on the efficacy of neoadjuvant chemoradiotherapy (NACRT) in pancreatic ductal adenocarcinoma (PDAC). METHODS: We investigated CA9 expression in 273 surgical specimens and 20 serum samples obtained from patients with PDAC and evaluated their clinical outcomes. We analyzed the function of CA9 using human pancreatic cancer cell lines. RESULTS: CA9 was positively expressed in 36.2 % of patients who underwent NACRT, which was significantly lower than those who underwent upfront surgery (US) (58.9 %, p < 0.001). Interestingly, patients who were CA9-positive in the US group had a significantly poorer prognosis than that of those in the NACRT group (median survival time [MST], 21.5 months vs. 49.2 months, p < 0.001), while there was no significant difference between patients who were CA9-negative in the US and NACRT groups (MST, 45.8 months vs. 46.3 months, p = 0.357). Moreover, serum CA9 levels tended to correlate positively with CA9 expression in cancer tissues. In-vitro experiments demonstrated that CA9 expression was reduced after treatments with radiation and chemoradiation therapy (RT/CRT), and that CA9 knockdown suppressed the impact of RT/CRT on cancer cell proliferation. CONCLUSIONS: CA9 may act as a target molecule for RT/CRT, highlighting its clinical importance as a valuable biomarker for more stringent indications for NACRT.
RESUMO
BACKGROUND: The management of malignant ascites is critical for treating patients with advanced pancreatic cancer. The purpose of this study was to assess the safety of cell-free and concentrated ascites reinfusion therapy (CART) and its impact on the prognosis of patients with advanced pancreatic cancer who have massive malignant ascites. METHODS: This study analyzed 47 procedures in 29 patients who underwent CART for ascites caused by pancreatic cancer between 2015 and 2022. Among them, 7 patients who received chemotherapy following CART were classified as the chemotherapy group, while 22 patients without chemotherapy after CART were classified as the palliative care group. RESULTS: Among the 47 procedures, adverse events (AEs) were observed in 9 procedures (19 %). Grade 2 adverse events were observed only in one procedure, manifested as fever. There were no grade 3 or 4 AEs, nor were there any treatment-related deaths. The median survival time was 4.0 months in the chemotherapy group and 0.7 months in the palliative care group (p = 0.004). The albumin level in the chemotherapy group was significantly higher than that in the palliative care group. CONCLUSION: CART is feasible and might be the optimal option to enable prolonged use of chemotherapy to improve the prognosis for late-stage pancreatic cancer patients.
RESUMO
BACKGROUND: Hyperglycemia is involved in malignant transformation of pancreatic cancer via the hexosamine biosynthetic pathway (HBP). However, few studies have verified this mechanism based on clinical data. This study investigated the complementary effects of hyperglycemia and HBP on pancreatic cancer prognosis using detailed clinical data. METHODS: The study analyzed data of 477 patients with pancreatic cancer who underwent pancreatectomy between 2006 and 2020. The patients were divided into normoglycemia and hyperglycemia groups based on their HbA1c levels. Immunostaining for glutamine fructose-6-phosphate transaminase-1 (GFAT-1), the rate-limiting enzyme in HBP, CD4, CD8, and Foxp3, was performed to evaluate the association between survival outcomes, HBP, and local tumor immunity. RESULTS: Overall survival (OS) was significantly poorer in the hyperglycemia group than in the normoglycemia group (mean survival time [MST]: 35.0 vs. 47.9 months; p = 0.007). The patients in the hyperglycemia group with high GFAT-1 expression had significantly poorer OS than those with low GFAT-1 expression (MST, 49.0 vs. 27.6 months; p < 0.001). However, the prognosis did not differ significantly between the patients with high and low GFAT-1 expression in the normoglycemia group. In addition, the patients with hyperglycemia and high GFAT-1 expression had fewer CD4+ (p = 0.015) and CD8+ (p = 0.017) T cells and a lower CD8+/Foxp3+ ratio (p = 0.032) than those with hyperglycemia and low GFAT-1 expression. CONCLUSIONS: The patients with hyperglycemia and high GFAT-1 expression levels had an extremely poor prognosis. Furthermore, the tumors in these patients were characterized as immunologically cold tumors.
RESUMO
BACKGROUND: Ehlers-Danlos syndrome (EDS) is a genetic disorder that causes fragility of the systemic connective tissues. Of the 13 subtypes, vascular EDS (vEDS) is associated with abnormalities in collagen production, resulting in arterial rupture and intestinal perforation. Herein, we report the case of a man with confirmed vEDS who survived a ruptured dissected splenic artery aneurysm triggered by perforation of the sigmoid colon. CASE PRESENTATION: A 48-year-old man presented to our hospital with sudden severe lower abdominal pain. The patient was genetically diagnosed with vEDS at the age of 43 years. Abdominal computed tomography (CT) showed fluid and free air surrounding the sigmoid colon. These findings suggested sigmoid colon perforation, and emergency surgery was needed. Hartmann's procedure was performed. The resected specimen showed a 2-cm-sized depression around the perforation. Histopathological findings showed an abscess and exudate in the serosa of the perforation and thinning of the intrinsic muscular layer in the depressed area. The patient was doing well postoperatively; however, on the ninth postoperative day, sudden upper abdominal pain developed. CT revealed an intra-abdominal hemorrhage due to rupture of a dissecting splenic artery aneurysm. The aneurysm was not observed on preoperative CT and was distant from the surgical site. Urgent transcatheter arterial embolization was performed. Although embolization of the splenic artery was attempted during the procedure, the arterial dissection spread to the common hepatic artery. Moreover, the proper hepatic and gastroduodenal arteries were poorly visualized, probably due to vasospasm. Although complications associated with extensive embolization were a concern, embolization of the splenic and common hepatic arteries was necessary to save the patient's life. After embolization, angiography showed that the left hepatic blood flow was maintained from the inferior phrenic artery, and the right hepatic inflow was maintained from the superior mesenteric artery via the peribiliary vascular plexus in the hilar area. The patient recovered well and was discharged on the 19th postoperative day. CONCLUSIONS: vEDS can cause arterial rupture after intestinal surgery. Therefore, careful post-operative management is necessary. Moreover, cooperation with interventional radiologists is important for prompt treatment of vascular complications.
RESUMO
Aim: This study aimed to evaluate the prognostic impact of total neoadjuvant therapy (TNT) for borderline resectable pancreatic cancer with arterial involvement (BR-A) pancreatic cancer. Methods: We analyzed 81 patients initially diagnosed as BR-A who received initial treatments between 2007 and 2021. Among them, 18 patients who received upfront surgery were classified as the UFS group, while 30 patients who were treated with neoadjuvant chemoradiotherapy were classified as the NACRT group. Furthermore, 33 patients who planned to receive a combination treatment of over 6 months of systemic chemotherapies followed by chemoradiotherapy before surgery were classified as the TNT group. Results: There were no significant differences in the patients' backgrounds between the three groups at the time of initial treatment. The resection rates of the UFS, NACRT, and TNT groups were 89%, 77%, and 67%, respectively. NACRT had no impact on the prognosis compared to upfront surgery. In sharp contrast, the TNT group had a significantly better prognosis compared to the other groups, especially after pancreatic resection. Multivariate analysis demonstrated that TNT and resection were independent prognostic factors for the patients of BR-A. Conclusion: TNT can be a promising therapeutic strategy for patients with BR-A.
RESUMO
BACKGROUND: Although the overall survival rate of patients with resectable pancreatic cancer has gradually improved, some patients relapse early and have a poor prognosis. This study aimed to identify the preoperative risk factors for early recurrence after neoadjuvant chemoradiotherapy in patients with resectable pancreatic cancer. METHODS: This study analyzed patients who underwent pancreatectomy after receiving neoadjuvant chemoradiotherapy for resectable pancreatic cancer between January 2009 and June 2021 and excluded those with borderline resectable and unresectable pancreatic cancers. Early recurrence was defined as recurrence within 6 months after surgery. RESULTS: This study included 203 patients, of whom 22 experienced early recurrence. The median survival time of patients with early recurrence was 18.3 months, which was significantly worse than that of patients with late recurrence (44.0 months, p < 0.001) or no recurrence (not reached, p < 0.001). Logistic regression analysis revealed that a carbohydrate antigen 19-9 level of >100 units/mL and a T status of ≥T2 after neoadjuvant chemoradiotherapy were independent predictive risk factors for early recurrence. The median recurrence-free survival time of patients with two risk factors was 9.7 months and significantly worse than that of those with either risk factors (20.5 months, p = 0.024) and those with no risk factor (26.2 months, p < 0.001). CONCLUSIONS: A combination of a high-level carbohydrate antigen 19-9 and a T status of ≥T2 after neoadjuvant chemoradiotherapy are predictors of early recurrence and may be helpful for selecting patients who require a stronger preoperative treatment.
Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Terapia Neoadjuvante/efeitos adversos , Carcinoma Ductal Pancreático/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/patologia , Pancreatectomia/efeitos adversos , Adenocarcinoma/patologia , Estudos Retrospectivos , CarboidratosRESUMO
PURPOSE: This study investigated the role of sarcopenia in the long-term outcomes of patients with early-stage intrahepatic recurrent hepatocellular carcinoma (HCC). METHODS: The study included 136 patients with intrahepatic recurrent Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC following liver resection diagnosed between 2006 and 2020 and underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial chemoembolization (TACE). Sarcopenia was defined based on the skeletal muscle index using computed tomography at the time of recurrence, and its association with long-term outcomes was evaluated. Tumor-infiltrating lymphocytes (CD4 + , CD8 + , and CD45RO + T cells) were assayed using immunohistochemistry on specimens obtained from repeat hepatectomies, and their association with sarcopenia was evaluated. RESULTS: The overall survival (OS) and recurrence-free survival (RFS) rates after initial recurrence of patients with sarcopenia were significantly lower than those without sarcopenia (p < 0.001 and p < 0.001, respectively). Multivariate analysis identified sarcopenia as an independent prognostic factor for RFS (p < 0.001). In patients without sarcopenia, surgery resulted in better RFS than RFA or TACE. Contrastingly, in patients with sarcopenia, the RFS was extremely poor regardless of the treatment type: surgery, RFA, or TACE (median RFS, 11.7, 12.7, and 10.1 months). Significantly low levels of tumor-infiltrating CD4 + , CD8 + , and CD45RO + lymphocytes were observed in patients with sarcopenia (p = 0.001, p = 0.001, and p = 0.001, respectively). CONCLUSIONS: This study suggests that patients with sarcopenia have poor RFS regardless of the treatment type for early-stage intrahepatic recurrent HCC. Impaired host immunity might be one of the underlying mechanisms.
Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas , Sarcopenia , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Sarcopenia/complicações , Resultado do Tratamento , Estudos Retrospectivos , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Ablação por Cateter/métodos , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: The influence of prolonged intermittent Pringle maneuver (IPM) on post-hepatectomy liver failure (PHLF) remains unclear. We evaluated the impact of the prolonged IPM on PHLF in patients undergoing open and laparoscopic hepatectomy. METHODS: We retrospectively included 546 patients who underwent hepatectomy using IPM. The patients were divided into open (n = 294) and laparoscopic (n = 252) groups. Odds ratios for PHLF occurrence were estimated in each group according to cumulative Pringle time (CPT). The cut-off value was set at CPT of 120 min. Risk factors for PHLF were evaluated in the open and laparoscopic groups. Additionally, we analyzed the post-operative outcomes in the open and laparoscopic groups with CPT ≥ 120 min and performed propensity score matching analysis based on PFLF-associated factors. RESULTS: In the open group, the risk of PHLF increased as CPT increased, particularly after 120 min. However, in the laparoscopic group, PHLF did not occur at less than 60 min, and the risk of PHLF was not significantly different at more than 60 min. Multivariate analysis identified CPT ≥ 120 min as an independent risk factor for PHLF in the open group (p < 0.001), but not in the laparoscopic group. Propensity score matching analysis showed that the PHLF rate was significantly lower in the laparoscopic group with CPT ≥ 120 min (p = 0.027). The post-operative transaminase levels were significantly lower in the laparoscopic group with CPT ≥ 120 min. CONCLUSIONS: Laparoscopic hepatectomy may cause less PHLF with prolonged IPM compared with open hepatectomy.
Assuntos
Carcinoma Hepatocelular , Laparoscopia , Falência Hepática , Neoplasias Hepáticas , Humanos , Hepatectomia/efeitos adversos , Neoplasias Hepáticas/complicações , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Falência Hepática/epidemiologia , Falência Hepática/etiologia , Falência Hepática/prevenção & controle , Laparoscopia/efeitos adversos , Carcinoma Hepatocelular/complicaçõesRESUMO
INTRODUCTION/AIMS: Intravenous (IV) edaravone is a US Food and Drug Administration-approved treatment for amyotrophic lateral sclerosis (ALS), shown in clinical trials to slow physical functional decline. In this study we compared the effect of IV edaravone (edaravone-first group) versus placebo followed by IV edaravone (placebo-first group) on survival and additional milestone events. METHODS: This work is a post hoc analysis of Study 19/MCI186-19, which was a randomized, placebo-controlled, phase 3 study investigating IV edaravone versus placebo. Study 19 and its 24-week extension have been described previously (NCT01492686). Edaravone-first versus placebo-first group time to events for specific milestone(s) were analyzed post hoc. Time-to-event composite endpoints were time to death; time to death, tracheostomy, or permanent assisted ventilation (PAV); and time to death, tracheostomy, PAV, or hospitalization. RESULTS: The risk for death, tracheostomy, PAV, or hospitalization was 53% lower among patients in the edaravone-first vs placebo-first groups (hazard ratio = 0.47 [95% confidence interval 0.25 to 0.88], P = .02). The overall effect of IV edaravone on ALS progression could be seen in the significant separation of time-to-event curves for time to death, tracheostomy, PAV, or hospitalization. ALS survival composite endpoint analyses (ALS/SURV) suggested a treatment benefit (least-squares mean difference) for the edaravone-first versus the placebo-first group at week 24 (0.15 ± 0.05 [95% confidence interval 0.06 to 0.25], P < .01) and week 48 (0.11 ± 0.05 [95% confidence interval 0.02 to 0.21], P = .02). DISCUSSION: These analyses illustrate the value of timely and continued IV edaravone treatment, as earlier initiation was associated with a lower risk of death, tracheostomy, PAV, or hospitalization in patients with ALS.
Assuntos
Esclerose Lateral Amiotrófica , Humanos , Edaravone/uso terapêutico , Esclerose Lateral Amiotrófica/tratamento farmacológico , Traqueostomia , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
BACKGROUND: Pancreatic lipomas (PLs) arising from the adipose tissue in the pancreatic parenchyma are rare among pancreatic tumors. Coexisting pancreatic ductal adenocarcinoma (PDAC) and PLs have not been previously reported. Herein, we report a case of PDAC arising from the pancreatic parenchyma with chronic pancreatitis compressed by a large PL. CASE PRESENTATION: The patient was a 69-year-old male. He had been diagnosed with a PL using computed tomography (CT) 12 years previously. The tumor had been slowly growing and was followed up carefully because of the possibility of well-differentiated liposarcoma. During follow-up, laboratory data revealed liver damage and slightly elevated levels of inflammatory markers. Contrast-enhanced CT revealed the previously diagnosed 12 cm pancreatic head tumor and an irregular isodensity mass at the upper margin of the tumor that invaded and obstructed the distal common bile duct. Magnetic resonance cholangiopancreatography demonstrated no specific findings in the main pancreatic duct. Based on these imaging findings, the patient underwent endoscopic retrograde biliary drainage and bile duct brushing cytology, which revealed indeterminate findings. The differential diagnosis of the tumor at that time was as follows: (1) pancreatic liposarcoma (focal change from well-differentiated to dedifferentiated, not lipoma), (2) distal cholangiocarcinoma, and (3) pancreatic cancer. After the cholangitis improved, a pancreatoduodenectomy was performed. Histologically, hematoxylin-eosin staining revealed moderately differentiated PDAC compressed by proliferating adipose tissue. The adipose lesion showed homogeneous adipose tissue with no evidence of sarcoma, which led to a diagnosis of lipoma. Additionally, extensive fibrosis of the pancreatic parenchyma and atrophy of the acinar cells around the lipoma was suggestive of chronic pancreatitis. The pathological diagnosis was PDAC (pT2N0M0 pStage Ib) with chronic pancreatitis and PL. The postoperative course was uneventful, and the patient was discharged on the 15th day after surgery. The patient received adjuvant chemotherapy and has remained recurrence-free for more than 6 months. CONCLUSIONS: PL may be associated with the development of PDAC in the surrounding inflammatory microenvironment of chronic pancreatitis. In cases of growing lipomas, careful radiologic surveillance may be needed not only for the possibility of liposarcoma but also for the coincidental occurrence of PDAC.
RESUMO
BACKGROUND: This study aimed to evaluate the significance of multiple tumor markers (TMs) measurements in determining the indications for conversion surgery (CS) in the management of unresectable locally advanced pancreatic cancer (UR-LAPC). METHODS: A total of 103 patients with UR-LAPC, treated between 2008 and June 2021, were enrolled in this study. Three TMs, including carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and Duke pancreatic monoclonal antigen type 2 (DUPAN-2), were measured. RESULTS: Twenty-five patients (24%) underwent CS. The median preoperative treatment period was 9.5 months. The median survival time (MST) from the initial treatment for patients with CS was significantly longer than that for patients without surgery (34.6 vs. 18.9 months, P < 0.001). The number of elevated TMs before CS was one in five patients and two in five patients, while 15 patients had normal levels of all three TMs. Notably, the MST from the initial treatment for patients with all three preoperative normal TMs levels was favorable for 70.5 months. In contrast, patients with one or two preoperatively elevated TMs levels had a significantly worse prognosis (25.4 and 21.0 months, respectively, P < 0.001). Furthermore, the relapse-free survival of patients with three preoperative normal TMs levels was significantly longer than those with one or two elevated TMs levels (21.9 vs. 11.3 or 3.0 months, respectively, P < 0.001). Non-normal values of all TMs before CS were identified as independent poor prognostic factors. CONCLUSIONS: Simultaneous measurement and assessment of the three TMs levels may help determine the surgical indications for UR-LAPC after systemic anticancer treatment.
Assuntos
Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Prognóstico , Antígenos de Neoplasias , Hormônios Pancreáticos , Estudos Retrospectivos , Biomarcadores Tumorais , Antígeno CA-19-9 , Neoplasias PancreáticasRESUMO
INTRODUCTION/AIMS: An intravenous (IV) formulation of edaravone has been shown to slow the rate of physical functional decline in amyotrophic lateral sclerosis (ALS). An oral suspension formulation of edaravone was recently approved by the United States Food and Drug Administration for use in patients with ALS. This study assessed the safety and tolerability of oral edaravone. METHODS: This global, open-label, phase 3 study evaluated the long-term safety and tolerability of oral edaravone in adults with ALS who had a baseline forced vital capacity ≥70% of predicted and disease duration ≤3 y. The primary safety analysis was assessed at weeks 24 and 48. Patients received a 105-mg dose of oral edaravone in treatment cycles replicating the dosing of IV edaravone. RESULTS: The study enrolled 185 patients (64.3% male; mean age, 59.9 y; mean disease duration, 1.56 y). The most common treatment-emergent adverse events (TEAEs) at week 48 were fall (22.2%), muscular weakness (21.1%) and constipation (17.8%). Serious TEAEs were reported by 25.9% of patients; the most common were worsening ALS symptoms, dysphagia, dyspnea, and respiratory failure. Twelve TEAEs leading to death were reported. Forty-six (24.9%) patients reported TEAEs that were considered related to study drug; the most common were fatigue, dizziness, headache, and constipation. Sixteen (8.6%) patients discontinued study drug due to TEAEs. No serious TEAEs were related to study drug. DISCUSSION: This study indicated that oral edaravone was well tolerated during 48 wk of treatment, with no new safety concerns identified.
Assuntos
Esclerose Lateral Amiotrófica , Edaravone , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Administração Oral , Esclerose Lateral Amiotrófica/tratamento farmacológico , Constipação Intestinal , Edaravone/administração & dosagem , Edaravone/efeitos adversosRESUMO
Typically, sulfate-reducing bioreactors used to treat acid mine drainage (AMD) undergo an initial incubation period of a few weeks to acclimatize sulfate-reducing bacteria (SRB), although necessity of this preincubation has rarely been evaluated. To reduce time and economic cost, we developed an SRB acclimatization method using the continuous flow of AMD into bioreactors fed with rice bran, and compared with the conventional acclimatization method. We found that the SRB sufficiently acclimatized without the preincubation phase. Furthermore, we examined the performance and SRB communities in bioreactors operated for >200 days under seven different conditions, in which the amount of rice bran added and hydraulic retention times (HRTs) were varied. A comparison of the various bioreactor conditions revealed that the lowest rice bran amount (50 g) and the shortest HRT (6 h) caused a deterioration in reactor performance after day 144 and 229, respectively. In both cases, relatively aerobic environments developed due to the lack of organic matter seemed to inhibit sulfate reduction. Of the conditions tested, operation of the bioreactors with 200 g of rice bran and an HRT of 12.5 h was the most effective in treating AMD, showing a sulfate reduction rate of 20.7-77.9% during days 54-242. DATA AND MATERIALS AVAILABILITY: All data needed to evaluate the conclusions of this study are presented in the paper and/or the appendix.
Assuntos
Microbiota , Sulfatos , Ácidos , Reatores Biológicos , MineraçãoRESUMO
BACKGROUND: A limb symmetry index (LSI) of ≥90% for the quadriceps is recommended for return to sports activity after anterior cruciate ligament reconstruction (ACLR). However, there is no information on differences in muscle fatigability between patients with LSI of <90% and ≥90%. The aim of this study was to assess the difference in quadriceps muscle fatigability on the involved side between post-ACLR patients with LSI of <90% and ≥90%. We hypothesized that there were differences between the two groups in muscle fatigability on the involved side reflecting difference in muscle fiber composition in the vastus medialis (VM) muscle. METHODS: The study subjects were 18 adult men who had undergone ACLR followed by rehabilitation therapy. LSI was <90% in 10 and ≥90% in 8 adult men. Surface electromyography (EMG) of the VM muscle was recorded during sustained quadriceps muscle isometric contraction. The median frequency (MF) was computed from the raw EMG signal using fast Fourier transform spectrum analysis. The MF slope was also calculated. RESULTS: There were no differences in anthropometric characteristics, time since ACLR, anterior tibial translation and peak torque of knee extension on the involved side between the two groups. However, MF slope was significantly lower in the LSI ≥ 90% group than the <90% group. CONCLUSION: Our results demonstrated fatigue-resistant vastus medialis in post-ACLR patients with LSI ≥90% compared to those with LSI <90%. The finding adds support to the use of ≥90% as the cutoff value for LSI for return of post-ACLR patients to sports activity.
Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Fadiga Muscular , Adulto , Lesões do Ligamento Cruzado Anterior/cirurgia , Humanos , Masculino , Força Muscular , Músculo Quadríceps , Volta ao EsporteRESUMO
Patients with advanced unresectable hilar cholangiocarcinoma have poor prognosis, and the survival is usually short. Herein, we report a 9-year survival case of unresectable hilar cholangiocarcinoma treated with chemoradiotherapy. A 64-year-old male patient presented with hilar cholangiocarcinoma. The tumor was located in the right hepatic duct, and it extended from the bifurcation of the anterior and posterior branches to the periphery. In the left side, the tumor extended from the umbilical portion to B2 and B3. However, there was no distant metastasis. The patient was then diagnosed with locally advanced, unresectable hilar cholangiocarcinoma and was treated with chemoradiotherapy. He received a total dose of 60 Gy in 30 daily fractions via intensity-modulated radiation therapy. In addition, he received gemcitabine chemotherapy for 5 years. There has been neither re-elevation of carbohydrate antigen 19-9 levels nor tumor relapse for 5 years during chemotherapy. Therefore, gemcitabine treatment was discontinued. However, the patient experienced tumor relapse 3 years after the last chemotherapy. Hence, chemotherapy with gemcitabine and cisplatin was initiated. At present, 1 year has passed after treatment for recurrence, and the patient has survived for 9 years since the initial treatment. Herein, we report a rare case of long-term survival with chemoradiotherapy in locally advanced unresectable hilar cholangiocarcinoma.
RESUMO
Sulfate-reducing bioreactors, also called biochemical reactors, represent a promising option for passive treatment of mining-influenced water (MIW) based on similar technology to aerobic/anaerobic-constructed wetlands and vertical-flow wetlands. MIW from each mine site has a variety of site-specific properties related to its treatment; therefore, design factors, including the organic substrates and inorganic materials packed into the bioreactor, must be tested and evaluated before installation of full-scale sulfate-reducing bioreactors. Several full-scale sulfate-reducing bioreactors operating at mine sites provide examples, but holistic understanding of the complex treatment processes occurring inside the bioreactors is lacking. With the recent introduction of high-throughput DNA sequencing technologies, microbial processes within bioreactors may be clarified based on the relationships between operational parameters and key microorganisms identified using high-resolution microbiome data. In this review, the test design procedures and precedents of full-scale bioreactor application for MIW treatment are briefly summarized, and recent knowledge on the sulfate-reducing microbial communities of field-based bioreactors from fine-scale monitoring is presented.Key points⢠Sulfate-reducing bioreactors are promising for treatment of mining-influenced water.⢠Various design factors should be tested for application of full-scale bioreactors.⢠Introduction of several full-scale passive bioreactor systems at mine sites.⢠Desulfosporosinus spp. can be one of the key bacteria within field-based bioreactors.
Assuntos
Reatores Biológicos/microbiologia , Microbiota , Mineração , Sulfatos/metabolismo , Purificação da Água/métodos , Bactérias/classificação , Bactérias/metabolismo , Peptococcaceae/metabolismo , Poluentes Químicos da Água/análise , Purificação da Água/instrumentaçãoRESUMO
The role of L-type amino-acid transporter 1 (LAT1), an oncofetal protein, in tumor progression is not well known, although it is important for the survival and proliferation of cancer cells. LAT1 expression was immunohistochemically analyzed and compared in sporadic (conventional) colorectal tumors and ulcerative colitis (UC)-associated neoplasia development and progression. LAT1 expression showed a significant stepwise increase in the order: conventional low-grade tubular adenoma, high-grade tubular adenoma, and invasive adenocarcinoma. Similarly, the same increasing trend in LAT1 expression was found in UC-associated low-grade dysplasia, high-grade dysplasia, and adenocarcinoma, whereas expression was significantly lower compared with that in an adenoma-adenocarcinoma series. LAT1 expression was predominant in the upper half of mucosal lesions in low-grade adenoma. This localized difference in LAT1 expression between the upper and lower halves of mucosal lesions disappeared in conventional high-grade adenoma and adenocarcinoma. LAT1 expression in the colorectal mucosa was significantly increased in the order: nontumor mucosa, quiescent phase of UC, and active phase of UC. Considering the histological pattern of Ki-67 labeling, LAT1 expression appeared partly related to cell proliferation, but this was not significant. In relation to the prognosis of patients with sporadic phase IV colorectal adenocarcinoma, this was significantly poorer in the group with high LAT1 expression compared with that with low LAT1 expression. This suggests LAT1 expression may be used as a companion biomarker for anti-cancer therapy targeting the LAT1 molecule in colorectal cancers.
Assuntos
Adenocarcinoma/patologia , Biomarcadores Tumorais/metabolismo , Colite Ulcerativa/complicações , Neoplasias Colorretais/patologia , Transportador 1 de Aminoácidos Neutros Grandes/biossíntese , Adenocarcinoma/etiologia , Adulto , Idoso , Neoplasias Colorretais/etiologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
The objective of the present multicenter randomized study was to compare weekly teriparatide with alendronate in their inhibition of vertebral collapse, effects on delayed union, pain relief, and improvement of quality of life (QOL) in women with new osteoporotic vertebral fractures within 1 week after onset of the fracture. Patients were randomly allocated to the teriparatide and alendronate groups. Vertebral collapse, low back pain assessed by a visual analog scale, and QOL assessed by EuroQol 5 dimension at weeks 1, 2, 4, 8, and 12 after the start of the treatment were compared between the groups. Lumbar bone mineral density (BMD) at baseline and week 12 and the rate of delayed union at week 12 were also compared. Each group consisted of 48 subjects. Vertebral collapse progressed over time in both groups, with no significant difference between the groups. Pain on rising up from lying position, turning over in bed, and resting in the lying position improved over time in both groups, with no significant difference between the groups. There were no significant differences in increase in BMD and delayed union. QOL in the teriparatide group showed significant improvement in comparison with that in the alendronate group at week 12. The weekly formulation of teriparatide showed comparable inhibition of vertebral collapse, increase in BMD, promotion of bone union, and improvement of pain and significant improvement of QOL at week 12 in comparison with alendronate in patients with a new osteoporotic vertebral fracture within 1 week after onset of the fracture. The weekly formulation of teriparatide may have improved components of QOL other than pain at week 12.
Assuntos
Alendronato/uso terapêutico , Fraturas da Coluna Vertebral/tratamento farmacológico , Teriparatida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Alendronato/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Qualidade de Vida , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/fisiopatologia , Teriparatida/farmacologia , Escala Visual AnalógicaRESUMO
Five types of sulfate-reducing passive bioreactors with rice bran as substrate were operated at three different mine sites under various operating conditions to investigate and compare the dominant sulfate-reducing bacteria (SRBs) involved in acid mine drainage (AMD) treatment. In all bioreactors, AMD was properly treated under the national effluent standard of Japan when 16 samples in total were taken from different depths of the bioreactors at different sampling times. Analysis of the microbiomes in the five bioreactors by Illumina sequencing showed that Desulfosporosinus spp. were dominant SRBs in all bioreactors (the relative abundances were ~ 26.0% of the total population) regardless of reactor configurations, sizes, and operating conditions. This genus is known to comprise spore-forming, acid-tolerant, and oxygen-resistant SRBs with versatile metabolic capabilities. Microbial populations of AMD water and soil samples (as inocula) from the respective mine sites were also analyzed to investigate the origin of the genus Desulfosporosinus. Desulfosporosinus spp. were detectable in most AMD water samples, even at low relative abundances (0.0025 to 0.0069% of total AMD population), suggesting that the genus Desulfosporosinus is present within the AMD water that flows into the bioreactor. These data strongly imply that the passive treatment system is a versatile and widely applicable process for AMD treatment.
Assuntos
Ácidos/metabolismo , Reatores Biológicos/microbiologia , Mineração , Peptococcaceae/metabolismo , Sulfatos/metabolismo , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Sequenciamento de Nucleotídeos em Larga Escala , Japão , Microbiota , Oryza , Peptococcaceae/genética , Projetos PilotoRESUMO
Flecainide, an anti-arrhythmic drug, undergoes renal excretion through active renal tubular secretion in addition to passive glomerular filtration. The contribution of renal uptake and efflux transporters in active renal tubular secretion of flecainide remains unclear except that flecainide is a substrate of human multidrug resistance protein 1 (MDR1). To elucidate renal efflux and uptake transporters involved with active renal tubular secretion of flecainide, we conducted in vitro interaction studies of flecainide using organic cation transporter 2 (OCT2), multidrug and toxin extrusion (MATE) 1, and MATE2-K. Uptake transporter inhibition assays using hOCT2-Chinese hamster ovary (CHO), hMATE1-CHO, and hMATE2-K-Madin Darby canine kidney strain II (MDCKII) cells revealed that flecainide (2.5 µM) inhibited hMATE1-mediated transport by 40% with an IC50 value of 6.7 µM; however, it showed no or weak inhibitory effects on hOCT2- and hMATE2-K-mediated transport. For investigating flecainide as a substrate of hMATE1, the accumulation of flecainide in hMATE1-CHO was compared with that in control cells. Uptake transporter substrate assay revealed that flecainide (1 µM) showed 1.11-fold accumulation though the hMATE1-related active transport was significantly decreased in the presence of quinidine (42.0 ± 23.9 vs. 11.8 ± 4.1 pmol/mg in transfected cells; p < 0.05). These results suggest that flecainide is a weak substrate of hMATE1, which is involved in the renal tubular secretion of cationic drugs, and hMATE1 may be less important in the pharmacokinetic drug-drug interaction for renal excretion of flecainide. However, in vivo drug-drug interaction studies of flecainide with substrates of hMATE1 may be needed because flecainide has the potential to inhibit hMATE1.