Clinical Evaluation of Targeted Arterial Infusion of Verapamil in the Interventional Chemotherapy of Primary Hepatocellular Carcinoma

This study evaluates the clinical effectiveness of targeted arterial infusion of verapamil in interventional treatment of primary hepatocellular carcinoma. For this purpose, in 273 patients with middle- or late-stage primary hepatocellular carcinoma, verapamil, IL-2, and chemotherapeutic agents were infused into the target tumor vasculature through femoral artery using Seldinger technique. The medications were infused as serial dilutions, and effectiveness was evaluated after two treatment cycles. Among these 273 patients, 76 cases showed clinical cure or significant improvement, 119 cases improved, 64 cases stabilized, while 14 cases progressed or deteriorated. In 238 patients, KPS score and body weights were stabilized. Regarding side effects, 99 patients (36.3%) developed leukopenia; 160 patients had gastrointestinal reactions (58.6%); 80 patients (29.3%) presented with elevated ALT/AST profile; and 65 cases (23.8%) had pyrexia; however, these side effects abated quickly. No elevations in BUN/Cr and/or allergic reactions were observed. Pre- and post-intervention cardiac function did not change in all the patients. No significant change was observed in ECG. Liver function was also improved after two cycles of treatment. It was concluded that verapamil management via targeted arterial infusion could effectively reverse the multidrug resistance in cancer cells in primary hepatocellular carcinoma patients and therefore enhanced the efficacy of chemotherapy.     

Clinical Efficacy of Chemotherapy Combined with Verapamil in Metastatic Colorectal Patients

In order to determine the clinical efficacy and adverse reactions of chemotherapy and verapamil infusion through a target artery to treat colorectal cancer patients with metastasis after failure with previous conventional treatments. Patients with metastatic colon cancer (n = 36) received an infusion of verapamil, interleukin-2, oxaliplatin (or hydroxy camptothecin or irinotecan hydrochloride), fluorouracil and calcium folinate through target artery using the Seldinger puncture technique. From the second day of infusion, the patients were treated with fluorouracil and calcium folinate via systematic intravenous injection for 2–3 days. Efficacy was evaluated after at least two treatment courses. The objective response including complete or partial response was 58.3% in the 36 patients; clinical benefit rate, evaluated by Karnofsky Performance Status score was 91.7%; by weight was 83.3%; by the amount of painkiller consumed was 80.6%. No patient experienced side effects associated with heart function. Post-treatment, the P–R period, Q–T period, QRS, and heart rate were not significantly different than before treatment. Liver function was significantly improved. Side effects of chemotherapy were minor in comparison to those observed with intravenous chemotherapy. Infusion of verapamil and chemotherapy directly into pelvic tumor tissue can increase treatment efficacy and has been shown to be a relatively safe technique.     

中晚期肝癌患者采用超声介入治疗引发并发症影响因素分析

摘要 目的：分析中晚期肝癌患者采用超声介入治疗引发并发症影响因素。方法：选取2019年2月～2023年2月在本院接受超声介入治疗的120例中晚期肝癌患者进行研究,治疗后记录患者的并发症发生率,并根据并发症发生情况将患者分为有并发症组（36例）和无并发症组（84例）,分别对两组患者的一般特征{性别、年龄、有无基础疾病、TNM分期、Child-Pugh分级、形态分型、肿瘤体积、腹水、门静脉高压、血供情况、白蛋白（ALB）及血清学指标[血红蛋白（Hb）、血小板（PLT）、凝血酶原时间（PT）、总胆红素（TBIL）、谷丙转氨酶（ALT）、谷草转氨酶（AST）]}进行分析,并建立logistic模型,对一般特征在中晚期肝癌患者超声介入治疗后引发并发症的影响中进行单因素和多因素分析。结果：120例患者经超声介入治疗后的并发症发生率为30.00%。有并发症组Child-Pugh B级、腹水+、ALB＜30 g/L的患者明显高于无并发症组,差异有统计学意义（P＜0.05）。单因素分析结果显示,Child-Pugh分级、腹水、ALB是导致中晚期肝癌患者超声介入治疗后引发并发症的影响因素（P＜0.05）。多因素logistic分析结果显示,Child-Pugh B级、腹水、ALB＜30 g/L均是导致中晚期肝癌患者超声介入治疗后引发并发症的独立危险因素（P＜0.05）。结论：Child-Pugh分级、腹水和ALB均是导致中晚期肝癌患者超声介入治疗后引发并发症的独立因素,只有尽早针对该类影响因素加强防治干预,才能有效降低中晚期患者的并发症发生率。     

Efficacy of Chemotherapy Combined with Targeted Arterial Infusion of Verapamil in Patients with Advanced Gastric Cancer

The present study evaluated the efficacy of chemotherapy combined with targeted arterial infusion of verapamil in patients with advanced gastric cancer. Forty patients were enrolled. Targeted arterial infusion of verapamil was done once a month, 3–5 times per patient, along with chemotherapy. After 2 bouts of combined treatment, the efficacy was evaluated. Primary gastric tumor was confirmed in 38/40 patients, and unconfirmed in 2/40 patients due to adhesion of tumors to surrounding tissue. Combined treatment was administered in 38 patients with defined tumors. Complete response to the treatment was in 5/38 (13.1 %) patients, partial response in 27/38 (71.1 %) patients, stable disease in 4/38 (10.5 %) patients, and progressive disease in 2/38 (5.26 %) patients. The effective rate (i.e., complete + partial response) comprised 84.2 %. There were 31 patients with liver metastases; 10/31 (32.3 %) patients showed complete response, 16/31 (51.6 %) patients showed partial response, 3/31 (9.7 %) patients had stable disease, and 2/31 (6.5 %) patients had progressive disease. The effective rate in these patients was 83.8 %. Thirty-seven patients were followed up, and 27/37 (73.0 %) patients were alive for 6 months or longer, 19/37 (51.3 %) for 12 months, 8 (35.1 %) for 18 months, and 8/37 (21.6 %) for 24 months. In conclusion, in patients with advanced gastric cancer, chemotherapy is more effective when combined with targeted arterial infusion of verapamil, leading to extended patients’ survival and improved quality of life.     

三氧化二砷栓塞联合肝动脉介入治疗转移性肝癌的疗效并33例临床观察

目的：观察并探讨三氧化二砷碘油栓塞联合置管介入化疗治疗转移性肝癌的临床效果。方法：选取辽宁省肿瘤医院介入治疗科2008-2010年收治的转移性肝癌患者33例,进行肝动脉造影及间接门脉造影,根据肝动脉造影或门脉造影结果,根据肝动脉供血情况分别采取肝动脉化疗栓塞及肝动脉灌注化疗方法治疗,3．4周为1治疗周期,共完成4个治疗周期,治疗结束后评价患者,陆床有效率,随访半年、1年、2年患者生存率。结果：①介入治疗后,患者,临床症状均改善,KPS得分明显高于化疗前（P〈0．05）,临床总有效率81．82％。②随访半年、1年、2年生存率分别为90．9l％、66．67％、33.33％,肝动脉化疗栓塞组患者中远期生存率明显高于肝动脉灌注化疗的患者。结论：三氧化二砷可从多角度抑制癌细胞,临床应用安全有效;对于不能手术和不适宜手术的转移性肝癌患者,根据肝动脉供血情况和特点选择合适的介入治疗,可获得满意疗效。     

La scintigraphie de perfusion hépatique dans la prise en charge des patients traités par chimiothérapie intra-artérielle hépatique

Nearly 50 % of patients with colorectal cancer (CRC) develop liver metastases (LM) during their disease. Only 10 % of these patients are candidates for an initial surgical resection. Compared to systemic chemotherapy alone, intra-arterial hepatic chemotherapy showed a benefit in overall survival in patients with unresectable LM. This treatment requires surgical or endovascular introduction of an intra-arterial hepatic catheter (IAHC). A precise vascular assessment is necessary due to the frequency of anatomic variations of hepatic arterial vasculature. Complications of intra-arterial hepatic chemotherapy are related to both IAHC and chemotherapy. ^99mTc-MAA hepatic perfusion scanning plays a key role before treatment initiation and during follow-up. Moreover, intra-hepatic distribution of tracer can be analysed and objectify a possible extra-hepatic spread that may lead to increased toxicity and/or less effective treatment. The different protocols, the place of ^99mTc-MAA scanning compared with other imaging techniques, or frequency of checks are still debated. A literature review is presented, illustrated with some cases of normal and pathological liver perfusion scans from the department of Nuclear Medicine, Val d’Aurelle Regional Cancer Center, Montpellier.     

Efficiency of adjuvant active specific immunization with Newcastle disease virus modified tumor cells in colorectal cancer patients following resection of liver metastases: results of a prospective randomized trial

Purpose  Metastatic disease is a major cause of mortality in colorectal cancer patients. Even after complete resection of isolated liver metastases, recurrence develops in the majority of patients. Therefore, development of strategies to prevent recurrent liver metastases is of major clinical importance. The present prospectively randomised phase III trial investigates the efficiency of active specific immunotherapy (ASI) after liver resection for hepatic metastases of colorectal cancer. Methods  Patients with histologically confirmed liver metastases from colorectal cancer were randomised to the vaccination or control group. After complete resection of liver metastases, patients randomised to the vaccination group received six doses of Newcastle disease virus (NDV) infected autologous tumour cell vaccine (ATV-NDV). The primary end-point was overall survival, secondary end-points were disease-free survival and metastases-free survival. Results  Fifty-one patients were enrolled in the study with 50 patients available for analysis. The follow-up period was 116.1 ± 23.8 month in the vaccination arm and 112.4 ± 18.5 month in the control group. In the total patient group, no differences in the primary and secondary end-points were detected. Most interestingly, subgroup analysis revealed a significant advantage for vaccinated colon cancer patients with respect to overall survival [hazard ratio: 3.3; 95%, confidence interval (CI): 1.0–10.4; P = 0.042] and metastases-free survival (hazard ratio: 2.7; 95%, CI: 1.0–7.4; P = 0.047) in the intention-to-treat analysis. Conclusion  Active specific immunotherapy in unselected colorectal cancer patients was not effective for prevention of recurrent metastatic disease. However, in colon cancer patients, ASI with ATV-NDV appears to be beneficial prolonging overall and metastases-free survival.     

SelSA,selenium analogs of SAHA as potent histone deacetylase inhibitors

Cancer treatment and therapy has moved from conventional chemotherapeutics to more mechanism-based targeted approach. Disturbances in the balance of histone acetyltransferase (HAT) and deacetylase (HDAC) leads to a change in cell morphology, cell cycle, differentiation, and carcinogenesis. In particular, HDAC plays an important role in carcinogenesis and therefore it has been a target for cancer therapy. Structurally diverse group of HDAC inhibitors are known. The broadest class of HDAC inhibitor belongs to hydroxamic acid derivatives that have been shown to inhibit both class I and II HDACs. Suberoylanilide hydroxamic acid (SAHA) and Trichostatin A (TSA), which chelate the zinc ions, fall into this group. In particular, SAHA, second generation HDAC inhibitor, is in several cancer clinical trials including solid tumors and hematological malignancy, advanced refractory leukemia, metastatic head and neck cancers, and advanced cancers. To our knowledge, selenium-containing HDAC inhibitors are not reported in the literature. In order to find novel HDAC inhibitors, two selenium based-compounds modeled after SAHA were synthesized. We have compared two selenium-containing compounds; namely, SelSA-1 and SelSA-2 for their inhibitory HDAC activities against SAHA. Both, SelSA-1 and SelSA-2 were potent HDAC inhibitors; SelSA-2 having IC50 values of 8.9 nM whereas SAHA showed HDAC IC₅₀ values of 196 nM. These results provided novel selenium-containing potent HDAC inhibitors.     

A new animal model of continuous catheterization for investigating mechanisms of arteritis associated with chemotherapy

Although superselective continuous intra-arterial infusion has advantages for cancer therapy, intra-arterial chemotherapy is often interrupted by arterial damage due to arteritis. Therefore, an animal model must be developed to elucidate the mechanism of arteritis associated with continuous anti-cancer drug infusion. We developed a new rat model with which to investigate the causal mechanism(s) of vascular damage associated with continuous catheterization chemotherapy. Chemotherapeutic agents (fluorouracil (5-FU) or peplomycin (PEP)) were continuously administered for 7 days into the abdominal aorta of male Sprague-Dawley rats through a catheter fixed in situ. We found that the incidence of apoptotic endothelial cells of the aorta was higher nearer the tip of the catheter. The incidence of apoptosis was higher in the group treated with 5-FU than with PEP. This animal model will be useful to improve arterial damage among patients undergoing chemotherapy using continuous catheterization.     

Use of a transjugular intrahepatic portosystemic shunt combined with autologous bone marrow cell infusion in patients with decompensated liver cirrhosis: an exploratory study

Background aimsCurrently, there is no treatment for decompensated liver cirrhosis except for liver transplantation. The safety and effect on liver function of a transjugular intrahepatic portosystemic shunt (TIPS) with and without autologous bone marrow cell (BMC) infusion in patients with decompensated liver cirrhosis were determined.MethodsTen patients who were diagnosed with decompensated liver cirrhosis during the period from September 2011 to July 2012 were enrolled in this study. The patients underwent TIPS (TIPS group) or combined treatment with TIPS and BMC infusion through the hepatic artery (TIPS+BMC group). All patients were monitored for adverse events, liver function and complications caused by portal hypertension during a period of 52 weeks.ResultsThe number of infused BMCs was 2.65 ± 1.20 ×10⁹. Significant improvements in the serum levels of albumin and total bilirubin and decreased Child-Pugh scores were observed in patients treated with both TIPS and BMCs (P < 0.05), whereas no such changes were observed in the TIPS group. Endoscopic findings showed that varices in the esophagus and the gastric fundus were alleviated after either treatment. All 10 patients showed a complete or partial resolution of ascites at 4 weeks. No major adverse effects were noted during the follow-up period for patients in either group.ConclusionsTIPS combined with BMC infusion is clinically safe; the treatment improved liver function and alleviated complications caused by portal hypertension; therefore, this combination has potential for treatment of patients with decompensated liver cirrhosis.     

手术切除与介入栓塞治疗肝癌术后复发患者的临床对比研究

目的:比较手术切除与介入栓塞治疗肝癌术后复发患者的临床疗效。方法:选择2010年6月到2011年6月本院收治的92例肝癌手术切除术后复发患者,按随机数字表法分为手术切除组和介入栓塞组,各46例。手术切除组患者给予再次切除治疗,介入栓塞组患者给予介入栓塞治疗。记录并比较两组患者治疗后1年、3年及5年的生存率。检测并比较两组患者治疗前后血清肝纤维化指标,包括血清透明质酸(HA)、层黏蛋白(LN)、人Ⅲ型前胶原(HPC-Ⅲ)及IV型胶原(IV-C)水平。检测并比较两组患者治疗前后血清白细胞(WBC)、甲胎蛋白(AFP)及癌胚抗原(CEA)水平。结果:手术切除组患者治疗后1年、3年、5年的生存率均明显高于介入栓塞组,差异均具有统计学意义(P0.05)。治疗后,介入栓塞组血清HA、LN、HPC-Ⅲ及IV-C明显高于治疗前,且均明显高于手术切除组,差异均具有统计学意义(P0.05)。两组患者治疗后血清WBC、AFP及CEA水平均明显低于治疗前,且手术切除组患者血清WBC明显高于介入栓塞组,而血清AFP、CEA水平明显低于介入栓塞组,差异均具有统计学意义(P0.05)。结论:手术切除治疗肝癌术后复发能够明显提高患者生存率,降低肝纤维化程度,改善血清AFP及CEA水平,值得在临床上推广应用。     

Clinical trials of intrasplenic arterial infusion of interleukin-2 (IS-IL-2) to patients with advanced cancer

We tried a infusion of interleukin-2 (IL-2) of a relatively low dose via an intrasplenic arterial catheter connected to a chronometric infusion (IS-IL-2). Eighteen patients of colorectal cancer with metastases to the liver or lung or of unresectable hepatoma received a 24 hour continuous infusion with low dose recombinant of IL-2 (mainly 8 × 10⁵ JRU/day) for 25–40 days. All patients tolerated this protocol of the therapy and the main toxic effects were fever and general fatigue. Such serious toxicity as previously reported by high dose IL-2 therapy was not observed. Data of hepatic and renal functions were normal. IS-IL-2 therapy induced a high incidence of eosinophilia (12/18) and thrombocythemia (12/18). Peripheral natural killer (NK) and LAK activities were augmented in all patients and total white blood cell counts were increased during IS-IL-2 therapy. An increase in IL-2 receptor expression of peripheral blood mononuclear cells and significant rises in numbers of Leull (CD16)+, OKMl(CD11)+ and OKIal(HLA-DR)+ were observed. Of 18 patients 12 were evaluable for their response to therapy. Partial response (PR) was observed in one unresectable hepatoma and 11 demonstrated no change (NC) or progressive disease (PD). Six patients were not evaluable because of additional therapy (3 cases) or decreasing tumor cell markers having no measurable lesions (3 cases). Three patients of colorectal cancer from an unresectable group were presumed to have micrometastases to the liver as suggested by an elevated serum CEA level. After receiving IS-IL-2 therapy they demonstrated a decrease in the serum CEA level for more than 3 years after treatment. We conclude that continuous IS-IL-2 administration can result in an increase of their therapeutic efficacy of IL-2 administration and in a decrease its toxicity.     

Early detection of gastric cancer after Helicobacter pylori eradication due to endoscopic surveillance

Background

Helicobacter pylori eradication therapy is commonly performed to reduce the incidence of gastric cancer. However, gastric cancer is occasionally discovered even after successful eradication therapy. Therefore, we examined the prognosis of gastric cancer patients, diagnosed after successful H. pylori eradication therapy.

Materials and Methods

All‐cause death rates and gastric cancer‐specific death rates in gastric cancer patients who received successful H. pylori eradication treatment was tracked and compared to rates in patients who did not receive successful eradication therapy.

Results

In total, 160 gastric cancer patients were followed‐up for up to 11.7 years (mean 3.5 years). Among them, 53 gastric cancer patients received successful H. pylori eradication therapy prior to gastric cancer diagnosis. During the follow‐up period, 11 all‐cause deaths occurred. In the successful eradication group, the proportion of patients with cancer stage I was higher. The proportions of patients who received curative endoscopic therapy and endoscopic examination in the 2 years prior to gastric cancer diagnosis were also higher in the successful eradication group. Kaplan–Meier analysis of all‐cause death and gastric cancer‐specific death revealed a lower death rate in patients in the successful eradication group (P = .0139, and P = .0396, respectively, log‐rank test). The multivariate analysis showed that endoscopy within 2 years before cancer diagnosis is associated with stage I cancer.

Conclusions

Possible early discovery of gastric cancer after H. pylori eradication due to regular endoscopic surveillance may contribute to better prognosis of patients with gastric cancer.     

The clinical application of 68Ga-PSMA PET/CT and regulating mechanism of PSMA expression in patients with brain metastases of lung cancer

Brain metastases (BMs) of lung cancer are common malignant intracranial tumours associated with severe neurological symptoms and an abysmal prognosis. Prostate-specific membrane antigen (PSMA) has been reported to express significantly in a variety of solid tumours. However, the clinical applications of ⁶⁸Ga-PSMA PET/CT and the mechanism of PSMA expression in patients with BMs of lung cancer have rarely been reported. Experiments with ⁶⁸Ga-PSMA PET/CT and immunohistochemical staining were conducted to evaluate the expression of PSMA from seven patients with BMs of lung cancer who accepted surgical treatment in Fudan University Shanghai Cancer Center between October 2020 and October 2021. The mechanism of PSMA expression in BMs of lung cancer was explored by using single-cell RNA sequencing. The median maximum standardized uptake value (SUVmax) in BMs was higher than that in primary lung cancer (8.6 ± 2.8 vs. 3.6 ± 1.3, P < 0.01). The mean SUVmax in BMs was 1.76-fold higher than that in the liver, which indicated the potential of PSMA radioligand therapy (PSMA-RLT) for BMs. BMs showed intense PSMA staining, while normal lung tissue had no PSMA staining and there was only faint primary lung cancer staining by immunohistochemistry (IHC). Single-cell RNA sequencing (scRNA-seq) analysis found that PSMA was mainly expressed in oligodendrocytes of BMs, whereas it was expressed at lower levels in solid cells of lung cancer. PSMA expression in oligodendrocytes might be regulated by the factors ATF3 and NR4A1, which were associated with ER stress.     

Autologous bone marrow mononuclear cell infusion and hyperbaric oxygen therapy in type 2 diabetes mellitus: an open-label,randomized controlled clinical trial

Background aimsThe use of bone marrow mononuclear cells (BM-MNCs) has achieved great outcomes in clinical practice. We aim to evaluate the efficacy and safety of autologous BM-MNC infusion and hyperbaric oxygen therapy (HOT) in type 2 diabetes mellitus.MethodsThis single-center, randomized, open-label, controlled clinical trial with a factorial design included two phases. The patients received standard medical therapy in the run-in phase; in the treatment phase, patients with glycated hemoglobin of 7.5–9.5% were randomly assigned into four groups and underwent BM-MNC infusion along with HOT (BM-MNC+HOT group), BM-MNC infusion (BM-MNC group), HOT (HOT group) and standard medical therapy (control group), respectively. The area under the curve of C-peptide was recorded as a primary end point. Our research is registered at ClinicalTrials.gov (NCT00767260).ResultsA total of 80 patients completed the follow-up. At 12 months after treatment, the area under the curve of C-peptide (ng/mL per 180 min) of the BM-MNC+HOT group and the BM-MNC group were significantly improved (34.0% and 43.8% from the baseline, respectively). The changes were both significant compared with that in the control group, but no remarkable change was observed in the HOT group. Treatment-related adverse events were mild, including transient abdominal pain (n = 5) and punctual hemorrhage (n = 3).ConclusionsBM-MNC infusion for type 2 diabetes mellitus improves islet function and metabolic control, with mild adverse effects. HOT does not synergize with BM-MNC infusion.     

Incidence of radiation toxicity in cervical cancer and endometrial cancer patients treated with radiotherapy alone versus adjuvant radiotherapy

AimThe study was made to evaluate early and late toxicity in a diversified group of patients receiving definitive or adjuvant radiotherapy in terms of clinical diagnosis and treatment methods.BackgroundRadiotherapy is a standard way of treatment in cervical and endometrial cancer patients, both as definitive and adjuvant therapy. But every radiation treatment may be involved with toxicity.Materials and methodsA detailed analysis was performed of 263 patients with gynaecological cancer treated with definitive (90 patients with cervical cancer received radiochemotherapy or radiotherapy exclusively) and adjuvant radiotherapy (38 with cervical and 135 with endometrial cancer).ResultsAcute reactions were found in 51.3% and late reactions were found in 14.8% of patients. It was stated that early (p < 0.007) and late (p < 0.003) post radiation reaction appear more frequently in women treated with definitive than adjuvant radiotherapy. The analysis of the whole group revealed higher rate of toxicity, both early and late, in the gastrointestinal tract than in the urinary system (p < 0.004). Comparing the subgroups, it was found that intestinal reactions occurred more frequently in the definitive radiotherapy group than in the adjuvant one.The occurrence of side effects was associated with the prolongation of total irradiation time due to necessary interruptions of radiotherapy. The comparison of the subgroups showed that interruptions occurred more frequently in patients receiving definitive rather than adjuvant radiotherapy (17.7–2.9%).ConclusionsDefinitive radiotherapy compared with adjuvant treatment may by associated with higher percentage of side effects caused by dose of therapy and correlation with chemotherapy.     

Improvement of microcirculation after percutaneous transluminal angioplasty in the lower limb with prostaglandin E1

OBJECTIVE: The aim of the study was to investigate prospectively the microcirculation after angioplasty and its improvement with additional Prostaglandin E1 (PGE1) therapy assessed by transcutaneous pressure of oxygen. PATIENTS AND METHODS: 45 patients with intermittent claudication eligible for angioplasty were enrolled in a prospective randomised controlled clinical trial. Patients received either intra-arterial bolus of 40 microg PGE1 in addition to angioplasty or a 40 microg PGE1 intravenous infusion. Control group received no trial medication. Additional 15 patients undergoing intra-arterial angiography were also investigated. tcpO(2) values were recorded distal to the PTA region before, during the intervention, 24h, 2 and 4 weeks after intervention. Clinical endpoint was the change of tcpO(2) values 4 weeks after intervention. RESULTS: During the 4 week follow-up tcpO(2) values decreased in patients treated with angioplasty. At the same time tcpO(2) increased significantly in those patients additionally treated with intra-arterial PGE1 bolus injection as well as with intravenous PGE1 infusion. CONCLUSIONS: Impaired microcirculation after angioplasty can be improved with additional intravenous as well as intra-arterial PGE1 administration.     

Early serial circulating tumor DNA sequencing predicts the efficacy of chemohormonal therapy in patients with metastatic hormone-sensitive prostate cancer

Chemohormonal therapy is a standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC); however, there are no biomarkers to guide clinical decisions regarding therapeutic options. We aimed to evaluate the clinical utility of serial circulating tumor DNA (ctDNA) sequencing in early prediction of the efficacy of chemohormonal therapy in patients with mHSPC. We conducted a retrospective observational study of 66 patients with mHSPC receiving chemohormonal therapy who underwent serial targeted gene-panel ctDNA sequencing. Peripheral blood samples were collected before treatment and after one cycle of chemotherapy. Kaplan–Meier and log-rank analyses were used to analyze the association between ctDNA status and disease progression-free survival. Serial changes in the ctDNA fraction and genetic alterations were also observed. After one cycle of chemotherapy, 23 (34.8%) patients displayed elevated ctDNA levels, whereas the other patients (65.2%, n = 43) did not. The median time to castration resistance in the group with reduced ctDNA levels was significantly longer than that in the group with increased ctDNA levels (17.70 vs. 8.43 months [mo], p < 0.001). Interestingly, patients with de novo alterations in homologous recombination pathway genes after treatment experienced a shorter time to castration resistance than that experienced by the remaining patients (8.02 vs. 13.20 mo, p = 0.011). The increased ctDNA levels or de novo alterations detected in homologous recombination pathway genes are a harbinger of disease progression. Early serial ctDNA sequencing could aid clinicians in making accurate treatment decisions.     

Differential block by 1-hyoscyamine of the salivary and vascular responses of the dog mandibular gland to prostaglandin F2alpha.

Prostaglandin F_2α (PGF_2α) (3–300 pmol) administered to the dog mandibular gland $\text{via}$ the glandular artery produced salivation and an increase in blood flow rate in a dose-related manner. The salivary responses to PGF_2α and to electrical stimulation of the chorda-lingual nerve were abolished by intra-arterial infusion of $\text{1}$-hyoscymine (30 nmol/min), whereas the vascular responses to both were not affected. The salivary and vasodilator responses to PGF_2α were not affected by intra-arterial infusion of hexamethonium (0.6–2 μmol/min) which abolished those to stimulation of the chordalingual nerve. These results support the prevous conclusion that PGF_2α produces the two responses by exciting the parasympathetic ganglion or postganglionic neurons in the dog mandibular gland.     

The management of cancer in the elderly: targeted therapies in oncology

Cancer is universally considered a disease of ageing. Today the management of elderly cancer patients poses many specific problems and it should be revisited in the light of the most recent advances in both diagnosis and treatment of human malignancies. In particular, the potential use of novel therapeutic options, based on therapeutic agents raised against molecular targets (the so called targeted therapy), appears to be promising in this clinical settings especially in view of the limited side-effects. The mainstays of cancer treatment during the twentieth century were surgery, radiation and chemotherapy. However, surgery is not curative in metastatic disease, radiation and chemotherapy are limited by side effects because they can't discriminate between healthy and cancerous cells. When key molecular changes responsible for malignant transformation were identified (e.g. growth factors and their receptors), it was hoped that new targeted agents, by inhibiting cancer-specific pathways, would spare normal cells and thereby offer improved safety benefits and a higher therapeutic index over standard chemotherapeutics. The most common targeted therapies used in clinical practice, i.e. monoclonal antibodies and small molecules, are described.