Long-term Survival Of Cancer Patients Research Articles

Glucose and Amino Acid Metabolic Dependencies Linked to Stemness and Metastasis in Different Aggressive Cancer Types.

Malignant cells are commonly characterised by being capable of invading tissue, growing self-sufficiently and uncontrollably, being insensitive to apoptosis induction and controlling their environment, for example inducing angiogenesis. Amongst them, a subpopulation of cancer cells, called cancer stem cells (CSCs) shows sustained replicative potential, tumor-initiating properties and chemoresistance. These characteristics make CSCs responsible for therapy resistance, tumor relapse and growth in distant organs, causing metastatic dissemination. For these reasons, eliminating CSCs is necessary in order to achieve long-term survival of cancer patients. New insights in cancer metabolism have revealed that cellular metabolism in tumors is highly heterogeneous and that CSCs show specific metabolic traits supporting their unique functionality. Indeed, CSCs adapt differently to the deprivation of specific nutrients that represent potentially targetable vulnerabilities. This review focuses on three of the most aggressive tumor types: pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC) and glioblastoma (GBM). The aim is to prove whether CSCs from different tumour types share common metabolic requirements and responses to nutrient starvation, by outlining the diverse roles of glucose and amino acids within tumour cells and in the tumour microenvironment, as well as the consequences of their deprivation. Beyond their role in biosynthesis, they serve as energy sources and help maintain redox balance. In addition, glucose and amino acid derivatives contribute to immune responses linked to tumourigenesis and metastasis. Furthermore, potential metabolic liabilities are identified and discussed as targets for therapeutic intervention.

Does nutrition support during chemotherapy increase long-term survival of cancer patients? Lessons from the past and future perspectives.

The aim of this review was to analyze the potential effect of the nutritional support (oral supplementation/counseling, tube feeding, parenteral nutrition) combined with chemotherapy on long-term survival of cancer patients. Using various electronic databases, we retrieved all English language papers on the combination nutritional support and chemotherapy and including data on long-term survival. 29 trials (4 non-RCT) were retrieved. No significant benefit was observed except for a longer survival in a few selected subgroups of patients, depending on the tumor stage and compliance with the nutritional support. However, no study included survival as primary endpoint or was adequately powered for this purpose, and patients were seldom affected by malnutrition, a condition which would have made them extremely vulnerable and unsafe during an intensive chemotherapy with significant gastrointestinal toxicity. Finally, nutritional regimens were often inappropriate as regards quality and quantity of nutrients or too similar in the two arms of the trial to expect a result. From the review of these trials, it appears clear that there is absence of evidence morethan evidence of absence of effect of the supplemental nutritional support. This poor scenario should not discourage future large multicenter trials to assess the potential of an early versus a delayed support in mildly malnourished patients. From the practical point of view, a nutritional supplementation should be considered when severe malnutrition caused by the disease or following repeated oncologic treatments can make the patients poorly compliant with further chemotherapy cycles, as recommended by the international guidelines.

Quality and Cost of Care by Hospital Teaching Status: What Are the Differences?

The relative performance of teaching hospitals has been discussed for decades. For private and public insurers with provider networks, an issue is whether having a major teaching hospital in the network is a "must." For traditional fee-for-service Medicare, there is an issue of adequacy of payment of hospitals with various attributes, including graduate medical education (GME) provision. Much empirical evidence on relative quality and cost has been published. This paper aims to (1) evaluate empirical evidence on relative quality and cost of teaching hospitals and (2) assess what the findings indicate for public and private insurer policy. Complementary approaches were used to select studies for review. (1) Relevant studies highly cited in Web of Science were selected. (2) This search led to studies cited by these studies as well as studies that cited these studies. (3) Several literature reviews were helpful in locating pertinent studies. Some policy-oriented papers were found in Google under topics to which the policy applied. (4) Several papers were added based on suggestions of reviewers. Quality of care as measured in process of care studies and in longitudinal studies of long-term survival of cancer patients tends to be higher at major teaching hospitals. Evidence on survival at 30 days post admission for common conditions and procedures also tends to favor such hospitals. Findings on other dimensions of relative quality are mixed. Hospitals with a substantial commitment to graduate medical education, major teaching hospitals, are about 10% to 20% more costly than nonteaching hospitals. Private insurers pay a differential to major teaching hospitals at this range's lower end. Inclusive of subsidies, Medicare pays major teaching hospitals substantially more than 20% extra, especially for complex surgical procedures. Based on the evidence on quality, there is reason for patients to be willing to pay more for inclusion of major teaching hospitals in private insurer networks at least for some services. Medicare payment for GME has long been a controversial policy issue. The actual indirect cost of GME is likely to be far less than the amount Medicare is currently paying hospitals.

The effect of pentoxifylline on radiation-induced bone loss in C3H/HeN mice

Developments in cancer therapies and diagnostic techniques have improved the long-term survival of cancer patients. Certain cancer treatments, such as radiotherapy, often harm normal tissue as well as the specifically targeted cancer cells. High doses of radiation induce bone loss. This study investigated the effects of pentoxifylline (PTX) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham and irradiation (3 Gy, gamma-ray, IR) groups. The irradiated mice were treated for 12 weeks with vehicle, PTX (p.o.) or PTX (s.c.). Grip strength, uterus weight, serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) level were measured. Tibiae were analyzed using micro-computed tomography. There were no significant differences in the degree of grip strength, body weight and uterine weight between IR group and PTX-treated group. Treatment of PTX significantly preserved trabecular bone volume, trabecular number, trabecular separation and bone mineral density of proximal tibia metaphysic. The administration of PTX lowered serum TRAP in IR mice, suggesting that PTX can reduce the bone resorptive rate in mice. Our experimental data support the protective role of PTX against bone loss in irradiated mice. Based on the findings of this study, development of PTX-based treatments is anticipated to address bone loss after radiotherapy. Prospective dose escalation studies are required to determine the appropriate dosage of PTX.

The effect of pentoxifylline on radiation-induced bone loss in C3H/HeN mice

Developments in cancer therapies and diagnostic techniques have improved the long-term survival of cancer patients. Certain cancer treatments, such as radiotherapy, often harm normal tissue as well as the specifically targeted cancer cells. High doses of radiation induce bone loss. This study investigated the effects of pentoxifylline (PTX) on radiation-induced bone loss in C3H/HeN mice. C3H/HeN mice were divided into sham and irradiation (3 Gy, gamma-ray, IR) groups. The irradiated mice were treated for 12 weeks with vehicle, PTX (p.o.) or PTX (s.c.). Grip strength, uterus weight, serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) level were measured. Tibiae were analyzed using micro-computed tomography. There were no significant differences in the degree of grip strength, body weight and uterine weight between IR group and PTX-treated group. Treatment of PTX significantly preserved trabecular bone volume, trabecular number, trabecular separation and bone mineral density of proximal tibia metaphysic. The administration of PTX lowered serum TRAP in IR mice, suggesting that PTX can reduce the bone resorptive rate in mice. Our experimental data support the protective role of PTX against bone loss in irradiated mice. Based on the findings of this study, development of PTX-based treatments is anticipated to address bone loss after radiotherapy. Prospective dose escalation studies are required to determine the appropriate dosage of PTX.

The oncolytic Newcastle disease virus as an effective immunotherapeutic strategy against glioblastoma.

Glioblastoma is the most frequent primary brain tumor in adults, with a dismal prognosis despite aggressive resection, chemotherapeutics, and radiotherapy. Although understanding of the molecular pathogenesis of glioblastoma has progressed in recent years, therapeutic options have failed to significantly change overall survival or progression-free survival. Thus, researchers have begun to explore immunomodulation as a potential strategy to improve clinical outcomes. The application of oncolytic virotherapy as a novel biological to target pathogenic signaling in glioblastoma has brought new hope to the field of neuro-oncology. This class of immunotherapeutics combines selective cancer cell lysis prompted by virus induction while promoting a strong inflammatory antitumor response, thereby acting as an effective in situ tumor vaccine. Several investigators have reported the efficacy of experimental oncolytic viruses as demonstrated by improved long-term survival in cancer patients with advanced disease. Newcastle disease virus (NDV) is one of the most well-researched oncolytic viruses known to affect a multitude of human cancers, including glioblastoma. Preclinical in vitro and in vivo studies as well as human clinical trials have demonstrated that NDV exhibits oncolytic activity against glioblastoma, providing a promising avenue of potential treatment. Herein, the authors provide a detailed discussion on NDV as a mode of therapy for glioblastoma. They discuss the potential therapeutic pathways associated with NDV as demonstrated by in vitro and in vivo experiments as well as results from human trials. Moreover, they discuss current challenges, potential solutions, and future perspectives in utilizing NDV in the treatment of glioblastoma.

Positive Impact of Intraoperative Epidural Ropivacaine Infusion on Oncologic Outcomes in Pancreatic Cancer Patients Undergoing Pancreatectomy: A Retrospective Cohort Study.

Background: Previous literatures have demonstrated that regional anesthesia such as epidural anesthesia may affect long-term survival of cancer patients. In the present study, we conducted a retrospective cohort study to investigate the survival impact of intraoperatively epidural ropivacaine infusion on pancreatic ductal adenocarcinoma (PDAC) patients.Methods: PDAC patients who underwent pancreatic surgery in Zhongshan Hospital Fudan University from January, 2015 to June, 2018 were included. The surgical procedure was performed under combined endotracheal general anesthesia and thoracic epidural anesthesia, and patient-controlled epidural analgesia (PCEA) with 0.12% ropivacaine was given after surgery for further pain control. Patients were divided into two groups according to their intraoperative epidural ropivacaine concentration: high (0.375%-0.5%) and low (0.15%-0.25%). Survival outcome was compared between groups.Results: A total of 215 patients were enrolled and their baseline characteristics were balanced between groups, except that patients with high concentration ropivacaine received higher total dose opioid and had longer operative time. Resected PDAC patients who were administrated with high concentration ropivacaine through epidural catheter intraoperatively had improved overall survival (median overall survival, mOS, high VS low, 37.6 VS 23.7 months, p=0.04). High epidural ropivacaine concentration was an independent prognostic factor (hazard ratio [HR]=0.65, 95% confidence interval [CI], 0.44-0.94; p=0.03). Subgroups analyses shown that T3M0 PDAC patients with preoperative CA 19-9 higher than 200 U/ml, negative resection margin, and those without tumor deposit and adjuvant radiotherapy could benefit from high concentration of ropivacaine.Conclusion: Intraoperatively epidural infusion with high concentration of ropivacaine was associated with improved OS in PDAC patients undergoing pancreatectomy.

Quercetin Prevents Radiation-Induced Oral Mucositis by Upregulating BMI-1.

Radiation-induced oral mucositis is a major adverse event of radiotherapy. Severe oral mucositis may cause unwanted interruption in radiotherapy and reduce long-term survival in cancer patients receiving radiotherapy, but until now, there have been no effective options for preventing radiation-induced oral mucositis. Quercetin is a flavonoid that is widely found in food species and has anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated a new role of quercetin in preventing radiation-induced oral mucositis. Quercetin exerted preventive effects against radiation-induced oral mucositis induced by single-dose (25 Gy) ionizing radiation or fractionated ionizing radiation (8 Gy × 3) in C57BL/6 mice and maintained the proliferation ability of basal epithelial cells. Quercetin pretreatment alleviated reactive oxygen species generation, NF-κB pathway activation, and downstream proinflammatory cytokine production and reduced DNA double-strand breaks and cellular senescence induced by ionizing radiation. Quercetin also upregulated BMI-1 expression in oral epithelial cells and promoted ulcer repair. In addition, quercetin exerted similar radioprotective effects in irradiated primary cultured normal human keratinocytes, reduced reactive oxygen species generation and proinflammatory cytokine release, and promoted DNA double-strand break repair and wound healing by upregulating the expression of BMI-1, which is a polycomb group protein. Thus, quercetin can block multiple pathological processes of radiation-induced oral mucositis by targeting BMI-1 and may be a potential treatment option for preventing radiation-induced oral mucositis.

Cancer Therapeutics-Related Cardiac Dysfunction - Insights From Bench and Bedside of Onco-Cardiology.

Improvements in the long-term survival of cancer patients have led to growing awareness of the clinical importance of cancer therapeutics-related cardiac dysfunction (CTRCD), which can have a considerable effect on the prognosis and quality of life of cancer patients and survivors. Under such circumstances, onco-cardiology/cardio-oncology has emerged as a new discipline, with the aim of best managing cardiovascular complications, including CTRCD. Despite the recent accumulation of epidemiological and clinical information regarding CTRCD, the molecular mechanisms underlying the pathogenesis of CTRCD by individual drugs remain to be determined. To achieve the goal of preventing cardiovascular complications in cancer patients and survivors, it is important to elucidate the pathogenic mechanisms and to establish diagnostic strategies with risk prediction and mechanism- and evidence-based therapies against CTRCD.

Third Place Award: Reconstruction of metastatic bone loss of the proximal femur and acetabulum: A literature review

Background: Improved rates of long-term survival in cancer patients has led to an increasing prevalence of metastatic disease, notably to osseous structures. The proximal femur and acetabulum are vital weight-bearing surfaces of the lower extremity and common regions of metastatic spread. There are many reconstructive options that depend on several factors including the location of the lesion, type of lesion, and the prognosis of the patient. Methods: An extensive literature review was conducted searching Pubmed.gov with the key words metastatic, proximal femur, acetabulum, reconstruction, and fixation. This identified pathologic characteristics for various metastatic processes, anatomic considerations for the proximal femur, and periacetabular metastatic lesions. This also identified treatment-sensitive tumors compared to treatment-resistant conditions. Reconstruction was usually recommended specifically considering renal, lung, and gastrointestinal carcinomas as well as previously irradiated bone where healing was unlikely. In addition, this study provides a technique guide for implementation of a proximal femoral prosthetic replacement (PFR). Results: The management of femoral head or neck lesions are frequently managed by hemiarthroplasty with overall reasonable outcomes. In intertrochanteric or subtrochanteric regions, there have been high failure rates of intramedullary fixation, and 2-year reoperation rate of up to 35% was reported with conversion to endoprosthesis. In comparison to an 85% implant survival in intramedullary constructions, there was a 100% 5-year survival in endoprosthesis reconstruction. Periacetabular lesions that do not impact structural stability can be managed with palliative measures. Those patients experiencing significant pain with contained defects may be managed with cement augmentation. Support of the columns may be required with fixation into the ilium, and those with extensive disease may require en bloc internal hemipelvectomy. Conclusions: Management of lesions of the proximal femur and acetabulum can be managed with a variety of treatment constructions. The utilization of PFR is increasingly more common especially in the setting of destructive metastatic lesions in the proximal femur as soft-tissue repairs improve ambulatory function. Additionally, the survivorship of endoprosthesis is greater than intramedullary fixation and is recommended for reconstruction for individuals with an expected survivorship greater than 7 mo. Lesions within the periacetabular region that are refractory to nonoperative management may benefit anywhere on the spectrum from intralesional cementation to en bloc hemipelvectomy depending the primary tumor type and degree of osseous involvement. Level of Evidence: Level IV.

4164 Body mass index, not chemotherapy is the major predictor of insulin resistance in patients with hematological malignancies

OBJECTIVES/GOALS: Cancer survivors are at increased risk for type 2 diabetes mellitus.It is not clear if diabetes susceptibility is due to shared risk factors for cancer and diabetes, such as obesity, or if it is directly related to cancer and its treatment. We investigated the association between malignancy and insulin resistance, a major risk factor for diabetes. METHODS/STUDY POPULATION: 20 adult patients with treated hematological malignancies and 21 controls without cancer were included in the study. Individuals with pre-existing diabetes were excluded. All patients underwent a 2-hour 75-gram oral glucose tolerance test (OGTT). Hyperinsulinemic-euglycemic clamps were performed to measure the steady-state glucose infusion rate (M-value) as an indicator of whole-body glucose utilization during insulin stimulation. Insulin sensitivity index was calculated by dividing M-value over the steady-state plasma insulin (M/I). RESULTS/ANTICIPATED RESULTS: Fasting or postprandial plasma glucose levels during the OGTT did not differ significantly between malignancy patients and controls (Table 2). Difference in the insulin-stimulated glucose utilization (M-value) was not statistically significant among cancer patients and controls (median, 7.2 [IQR, 6.2-10.4] vs. 7.3 [IQR, 5.5-8.9] mg/kg/min; P = 0.261). M/I index was significantly higher in malignancy patients compared to controls (median, 42.4 mg/kg/min/(µU/ml) [IQR, 33.9-67.2] vs. 23.4 mg/kg/min/(µU/ml) [IQR, 12.9-29.2], P <0.001), however insulin clearance was also lower in the controls. In multivariate analysis, only BMI was significantly associated with M-value (β = −0.2 (95% CI −0.4, −0.1), P = 0.004), and M/I (β = −2 (95% CI −3.4, −0.5), P = 0.009). DISCUSSION/SIGNIFICANCE OF IMPACT: Our data suggest that the major contributor to diabetes development after diagnosis of cancer in adults is obesity-induced insulin resistance, not malignancy related factors. These findings emphasize the importance of obesity management in long-term survival of cancer patients, as diabetes is a risk factor for mortality in this patient population.

Troponins and Natriuretic Peptides in Cardio-Oncology Patients-Data From the ECoR Registry.

BackgroundThe long-term survival of cancer patients has significantly improved over the past years. Despite their therapeutic efficacy, various cancer therapies are associated with cardiotoxicity. Therefore, timely detection of cardiotoxic adverse events is crucial. However, the clinical assessment of myocardial damage caused by cancer therapy remains difficult.MethodsThis retrospective study was performed to evaluate the diagnostic value of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for monitoring cancer therapy-induced cardiomyopathy. A total of 485 cancer patients referred to our cardio-oncology unit between July 2018 and January 2020 were selected from our Essen Cardio-oncology Registry (ECoR). We included patients with all types of cancer. Plasma concentrations of cTnI and NT-proBNP were measured by radioimmunoassay, and two-dimensional left ventricular ejection fraction (2D-LVEF), diastolic function, and global longitudinal strain (GLS) were measured by transthoracic echocardiography. In 116 patients, assessment was conducted before the induction of cancer therapy and during a short-term follow-up period; n = 42 of these were treated for malignant melanoma, and n = 42 with serial measurements were under treatment for breast cancer.ResultsIn cross-sectional data, elevated NT-proBNP was associated with reduced LVEF and pathological GLS in the total cohort. A total of 116 patients had serial LVEF and biomarker measurements, and changes in NT-proBNP and troponin correlated with changes in LVEF during follow-up investigations. Similar to the total cohort, a subgroup of patients treated for malignant melanoma showed a correlation between the change in cTnI and the change in LVEF. In a subgroup analysis of patients undergoing breast cancer therapy, a correlation between the change in NT-proBNP and the change in LVEF could be detected. Thirty patients presented with chemotherapy-induced cardiomyopathy, defined as a significant LVEF decrease (> 10%) to a value below 50%. The number of patients with increased cTnI and NT-proBNP was significantly higher in patients with chemotherapy-induced cardiomyopathy than in patients without cardiotoxicity. Patients with positive cTnI and NT-proBNP were more likely to have a history of coronary heart disease, atrial fibrillation, and arterial hypertension.ConclusionOur data suggest that cardiac biomarkers play an important role in the detection of cancer therapy-induced cardiotoxicity. Larger systematic assessment in prospective cohorts is mandatory.

Electrochemical Biosensors for Determination of Colorectal Tumor Biomarkers.

The accurate determination of specific tumor markers associated with cancer with non-invasive or minimally invasive procedures is the most promising approach to improve the long-term survival of cancer patients and fight against the high incidence and mortality of this disease. Quantification of biomarkers at different stages of the disease can lead to an appropriate and instantaneous therapeutic action. In this context, the determination of biomarkers by electrochemical biosensors is at the forefront of cancer diagnosis research because of their unique features such as their versatility, fast response, accurate quantification, and amenability for multiplexing and miniaturization. In this review, after briefly discussing the relevant aspects and current challenges in the determination of colorectal tumor markers, it will critically summarize the development of electrochemical biosensors to date to this aim, highlighting the enormous potential of these devices to be incorporated into the clinical practice. Finally, it will focus on the remaining challenges and opportunities to bring electrochemical biosensors to the point-of-care testing.

Mechanisms of Resistance to Monoclonal Antibodies (mAbs) in Lymphoid Malignancies.

Passive immunotherapy with therapeutic monoclonal antibodies (mAbs) has revolutionized the treatment of cancer, especially hematological malignancies over the last 20years. While use of mAbs has improved outcomes, development of resistance is inevitable in most cases, hindering the long-term survival of cancer patients. This review focuses on the available data on mechanisms of resistance to rituximab and includes some additional information for other mAbs currently in use in hematological malignancies. Mechanisms of resistance have been identified that target all described mechanisms of mAb activity including altered antigen expression or binding, impaired complement-mediated cytotoxicity (CMC) or antibody-dependent cellular cytotoxicity (ADCC), altered intracellular signaling effects, and inhibition of direct induction of cell death. Numerous approaches to circumvent identified mechanisms of resistance continue to be investigated, but a thorough understanding of which resistance mechanisms are most clinically relevant is still elusive. In recent years, a deeper understanding of the tumor microenvironment and targeting the apoptotic pathway has led to promising breakthroughs. Resistance may be driven by unique patient-, disease-, and antibody-related factors. Understanding the mechanisms of resistance to mAbs will guide the development of strategies to overcome resistance and re-sensitize cancer cells to these biological agents.

Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes

Recent developments of novel targeted therapies are contributing to the increased long-term survival of cancer patients; however, drug-induced cardiotoxicity induced by cancer drugs remains a serious problem in clinical settings. Nevertheless, there are few in vitro cell-based assays available to predict this toxicity, especially from the aspect of morphology. Here, we developed a simple two-dimensional (2D) morphological assessment system, 2DMA, to predict drug-induced cardiotoxicity in cancer patients using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with image-based high-content analysis in a high-throughput manner. To assess the effects of drugs on cardiomyocytes, we treated iPSC-CMs with 28 marketed pharmaceuticals and measured two key parameters: number of cell nuclei and sarcomere morphology. Drugs that significantly perturbed these two parameters at concentrations ≤30 times the human Cmax value were regarded as positive in the test. Based on these criteria, the sensitivity and specificity of the 2DMA system were 81% and 100%, respectively. Moreover, the translational predictability of 2DMA was comparable with that of a three-dimensional cardiotoxicity assay. RNA sequencing further revealed that the expression levels of several genes related to sarcomere components decreased following treatment with sunitinib, suggesting that inhibition of the synthesis of proteins that comprise the sarcomere contributes to drug-induced sarcomere disruption. Based on these features, the 2DMA system provides mechanistic insight with high predictability of cancer drug-induced cardiotoxicity in humans, and could thus contribute to the reduction of drug attrition rates at early stages of drug development.

Optimal timing of pancreaticoduodenectomy following preoperative biliary drainage considering major morbidity and postoperative survival

Introduction: The present study aims to assess the impact of preoperative biliary drainage (PBD) on postoperative outcomes and to investigate optimal timing of pancreaticoduodenectomy (PD) following PBD in terms of postoperative morbidity and survival. Method: Between January 2007 and December 2015, consecutive 1568 patients underwent PD at a single institute. Clinicopathological and survival data were reviewed retrospectively. Result: Of all, 831 patients underwent PBD. Mean duration between drainage and surgery was 16.9 days. When the duration was subdivided weekly, 196 underwent PD in 1st week, 300 in 2nd week, 170 in 3rd week, 91 in 4th week, 27 in 5th week and 47 beyond 6th week. In postoperative outcomes, length of stay was longer in drainage group (p=0.028). Postoperative pancreatic fistula was not significantly different between non-drainage and drainage groups (p=0.162), but major complications occurred significantly more in drainage group (p=0.002). Multivariable analysis showed major complications occurred significantly in weekly interval 3 and 4 weeks (odds ratios, 1.863 and 2.523), whereas early (1 to 2 weeks) or late (beyond 4weeks) periods were not associated with complications. In multivariable survival comparison, weekly interval beyond 6 weeks was associated with poor survival in pancreatic cancer, and 4 weeks interval showed worse prognosis in bile duct cancer. Conclusion: Considering the long-term survival of cancer patients, early surgery that reduces the operative delay after PBD may enhance postoperative outcomes if preoperative biliary infection is recovered through biliary drainage.

Recent advances in thoracoscopic esophagectomy for esophageal cancer.

Technical advances and developments in endoscopic equipment and thoracoscopic surgery have increased the popularity of minimally invasive esophagectomy (MIE). However, there is currently no established scientific evidence supporting the use of MIE as an alternative to open esophagectomy (OE). To date, a number of single-institution studies and several meta-analyses have demonstrated acceptable short-term outcomes of thoracoscopic esophagectomy for esophageal cancer, and we recently reported one of the largest propensity score-matched comparison studies between MIE and OE for esophageal cancer, based on a nationwide Japanese database. We found that, in general, MIE had a longer operative time and less blood loss than OE. Moreover, compared to OE, MIE was associated with a lower rate of pulmonary complications such as pneumonia, and both methods had similar mortality rates. Although MIE may reduce the occurrence of postoperative respiratory complications, MIE and OE seem to have comparable short-term outcomes. However, the oncological benefit to patients undergoing MIE remains to be scientifically proven, as no randomized controlled trials have been conducted to verify each method's impact on the long-term survival of cancer patients. An ongoing randomized phase III study (JCOG1409) is expected to determine the impact of each method with regard to short- and long-term outcomes.

Molecular-targeted therapies and precision medicine for endometrial cancer

The overall survival rate of patients with early-stage endometrial cancer is relatively high; however, there are few treatment options for patients with advanced or recurrent endometrial cancer, and the prognosis of such patients remains poor. Recent progress in molecular-targeted therapies demonstrated that they have the potential to improve the long-term survival of cancer patients with appropriate biomarkers. However, the median progression-free survival of patients who received single-agent molecular-targeted therapy was <5 months, and the development of molecular-targeted therapies for endometrial cancer patients is urgently needed. This review highlights the previous efforts, including antiangiogenesis therapy, PI3K/AKT/mTOR pathway inhibitor treatment and epidermal growth factor receptor inhibitor treatment and reports on ongoing phase 2 clinical trials, including immune checkpoint inhibitor and PARP inhibitor. We also summarized the genetic background of endometrial cancer according to The Cancer Genome Atlas data and considered the theoretical background for future efforts to prolong the survival of patients with refractory endometrial cancer and for other interesting challenges.

Beneficial effects of curcumin and capsaicin on cyclophosphamide-induced premature ovarian failure in a rat model

BackgroundIn recent years, cancer rates have been rising among reproductive-age women. Thus, chemotherapy exposure has become an important cause of premature ovarian failure (POF). There has been growing interest regarding the preservation and restoration of ovarian function before and after oncological treatment because of the reproductive risk of chemotherapeutics and improved long-term survival of cancer patients. In this study, we sought to analyze the effects of curcumin (CRC) and capsaicin (CPS) on cyclophosphamide-induced POF in a rat model.MethodsPOF in rats was induced by intraperitoneal injection of 200 mg/kg cyclophosphamide on day 1 and then 8 mg/kg/day for the following 14 days. After 14 days of cyclophosphamide administration, rats were randomly divided into three groups as follows (n = 10/group): POF, POF + CRC (100 mg/kg/day), and POF + CPS (0.5 mg/kg/day) to determine the effects of CRC and CPS on the cyclophosphamide-induced POF rat model. Biochemical, hormonal, and histopathological evaluations were performed on blood and tissue samples 14 days after the CRC and CPS treatments.ResultsMalonaldehyde levels were significantly reduced, and glutathione levels and superoxide dismutase activity were significantly increased, in ovarian tissues in the POF + CRC and POF + CPS groups compared with the POF group. In the POF group, we observed hemorrhage and prominent mononuclear cell infiltration beneath the germinative epithelium, vascular congestion in ovarian stroma, hemorrhage around the corpus luteum, and atresia in ovarian follicles. This histopathological damage was significantly improved by treatment with CRC and CPS. There was a significant reduction in serum follicle-stimulating hormone and luteinizing hormone levels in rats treated with CRC and CPS compared with the POF group. Moreover, the levels of estradiol and anti-mullerian hormone in rats treated with CRC and CPS were significantly increased compared with the control group.ConclusionsIn conclusion, CRC and CPS treatment of rats with cyclophosphamide-induced POF had a beneficial effect on reducing ovarian damage by improving tissue oxidative stress marker levels, ovarian reserve marker levels, and histopathological parameters. The significant improvements in ovarian tissue histopathological damage and hormonal levels detected in this study indicate that treatment with CRC or CPS might be a conservative treatment approach for cyclophosphamide-induced POF.

Methodology for survival assessment of cancer patients using population-based cancer registration data

Evaluating and monitoring long-term survival of cancer patients and reporting the survival rate are routinely employed by cancer registries. Long-term survival rate is a necessary indicator in evaluating the effect of cancer therapy and cancer burden. Cohort method is a traditional approach for survival analysis, but it essentially reflects the survival expectations of patients diagnosed many years ago, therefore survival status of cancer patients was often disclosed with delay. Given the limitation of cohort method, period analysis and model-based period analysis are subsequently proposed and gradually applied in assessment of survival rates in recent years. Period analysis includes the patients of interest period, which reflects more up-to-date estimates of long-term survival of cancer patients. While model-based period analysis can use the existing data to calculate survival rates and to assess the trend, and predict survival rates in the future. Compared with cohort approach, period analysis and model-based period analysis are better in timeliness and precision in survival analysis. This article reviews the definition and theory, calculation and application of cohort method, period analysis and model-based period analysis, in order to provide a basis on up-to-date and precise assessment of survival rates of cancer patients.