Case Reports On The Multimodal Management of Refractory Chronic Oncological Pain of The Chest Wall: The Use of The Spinal Erector Plane Neurolysis

Chronic pain of oncological origin is one of the most frequent complications and is difficult to control, that results in a decrease in the quality of life and disability among patients suffering from this pathology. Primary or metastatic tumors originating from lung, colonic, or breast neoplasms can invade the chest wall, causing progressive respiratory pain and symptoms that require multiple interventions to achieve adequate control. Many of these cases presenting with advanced-stage cancer are often incurable; thus, pain management and palliative care are primary objectives. Multimodal management is the strategy of choice in these cases through the participation of a multidisciplinary team. Analgesic therapy covers the use of potent opioids, opioid rotation, adjuvant analgesics, and interventional pain management strategies. We report two cases of chronic oncological pain of the chest wall refractory to pharmacological analgesic management. The optimization of multimodal management and the performance of neurolysis by phenolization of the erector spinae plane achieved an adequate response.

Early Experience of Oncological Reconstructive Surgery at Dharmais National Cancer Center

Background: Oncological reconstructive surgery is a new paradigm in which it combines oncologic principles with reconstruction techniques. This study aims to present patients’ characteristics who had undergone oncological reconstructive surgery at the Department of Surgical Oncology, Dharmais National Cancer Center. Methods: This descriptive study identified patients’ characteristics who underwent oncological reconstructive surgery, their cancer types, and their therapies. All data were obtained from surgery registration and medical records from January 2019 to January 2020. Data were then presented in number and percentage.Results: A total of 174 patients had undergone oncological reconstructive surgery within one year. The mean age of all patients was 48.2 ± 16.7 years old. Most patients were female (72.1%), with breast cancer making up most cases (43.7%). Most of the participants also underwent mastectomy (42.1%), which was later followed by various reconstruction types. Sixty patients received free tissue transfer with microsurgery (34.4%), of which head and neck cancer constituted most cases. In addition, the most common donor site for the free flap was the Anterolateral Thigh (41.7%). Of all 174 patients, 75.2% presented with locally advanced cancer, and 17.8% had metastatic cancer. Within one year of follow-up, the survival rate was 87.4%, while local recurrence was 3%. Conclusions: The oncological reconstructive surgery approach plays a therapeutic and reconstructive role, and such might be the preferred method of choice for patients presenting with advanced-stage cancer

Inhibition of ADAM17 impairs endothelial cell necroptosis and blocks metastasis

Metastasis is the major cause of death in cancer patients. Circulating tumor cells need to migrate through the endothelial layer of blood vessels to escape the hostile circulation and establish metastases at distant organ sites. Here, we identified the membrane-bound metalloprotease ADAM17 on endothelial cells as a key driver of metastasis. We show that TNFR1-dependent tumor cell–induced endothelial cell death, tumor cell extravasation, and subsequent metastatic seeding is dependent on the activity of endothelial ADAM17. Moreover, we reveal that ADAM17-mediated TNFR1 ectodomain shedding and subsequent processing by the γ-secretase complex is required for the induction of TNF-induced necroptosis. Consequently, genetic ablation of ADAM17 in endothelial cells as well as short-term pharmacological inhibition of ADAM17 prevents long-term metastases formation in the lung. Thus, our data identified ADAM17 as a novel essential regulator of necroptosis and as a new promising target for antimetastatic and advanced-stage cancer therapies.

miR-335 Restrains the Aggressive Phenotypes of Ovarian Cancer Cells by Inhibiting COL11A1

High collagen type XI alpha 1 (COL11A1) levels are associated with tumor progression, chemoresistance, and poor patient survival in several cancer types. MicroRNAs (miRNAs) are dysregulated in multiple cancers, including epithelial ovarian carcinoma (EOC); however, the regulation of COL11A1 by miRNAs in EOC remains unclear. We examined the role of miRNAs in regulating COL11A1 expression. We identified miR-509 and miR-335 as the candidate miRNAs through an online database search. EOC cell treatment with miR-335 mimics abrogated COL11A1 expression and suppressed cell proliferation and invasion, besides increasing the sensitivity of EOC cells to cisplatin. Conversely, treatment with miR-335 inhibitors prompted cell growth/invasiveness and chemoresistance of EOC cells. miR-335 inhibited COL11A1 transcription, thus reducing the invasiveness and chemoresistance of EOC cells via the Ets-1/MMP3 and Akt/c/EBPβ/PDK1 axes, respectively. Furthermore, it did not directly regulate PDK1 but increased PDK1 ubiquitination and degradation through COL11A1 inhibition. In vivo findings highlighted significantly decreased miR-335 mRNA expressions in EOC samples. Furthermore, patients with low miR335 levels were susceptible to advanced-stage cancer, poor response to chemotherapy, and early relapse. This study highlighted the importance of miR-335 in downregulating COL11A1-mediated ovarian tumor progression, chemoresistance, and poor survival and suggested its potential application as a therapeutic target.

Helicobacter pylori infection reduces likelihood of death from advanced cancer: A longitudinal analysis from the Japanese DAIKO prospective cohort study

BackgroundParadoxically, patients with advanced stomach cancer who are Helicobacter pylori-positive (HP+) have a higher survival rate than those who are HP-. This finding suggests that HP infection has beneficial effects for cancer treatment. Present study examines whether HP+ individuals have a lower likelihood of death from cancer than those who are HP-.Methods and findingsProspective cohort data (n = 4,982 subjects enrolled in the DAIKO study between 2008-2010) was used to assess whether anti-HP antibody status as a surrogate for past-present HP infection was associated with cancer incidence. The median age in the primary registry was 53 years-old (range 34-69 years-old). Over the 8-year observation period there were 234 (4.7%) cancer cases in the cohort and 88 (1.8%) all-cause deaths. Urine anti-HP antibody data was available for all but one participant (n = 4,981; 99.97%). The number of HP+ and HP- individuals was 1,826 (37%) and 3,156 (63%), respectively. Anti-HP antibody distribution per birth year revealed that earlier birth year was associated with higher HP+ rates. To remove confounding factors associated with birth year, a birth year-matched cohort (n = 3,376) was generated for subsequent analyses. All-cancer incidence was significantly higher in HP+ individuals than those who were HP- (p=0.00328), whereas there was no significant difference in the cancer death rate between HP+ and HP- individuals (p=0.888). Strikingly, we found that HP+ individuals who developed cancer had a better survival rate than would be expected based on cancer incidence. These results suggest that cancer patients who are HP+ may have a higher likelihood of survival than those who are HP-. Cox regression analysis for prognostic factors revealed that the hazards ratio of HP+ was 1.59-fold (95%CI 1.17-2.26) higher than HP- in all-cancer incidence.ConclusionsPotential systemic effects of HP+ status may contribute to reduced likelihood of death for patients with cancer.Data Availability StatementThe data cannot be shared publicly as data sharing is not permitted according to Japanese Government data protection policies. Requests for data analysis may be accepted anonymously and conditionally upon IRB approval from Iwate Medical University and Nagoya University Graduate School of Medicine.FundingThis study is supported by Grants-in-Aid for Scientific Research for Priority Areas of Cancer (No. 17015018); Grants-in-Aid for Innovative Areas (No. 221S0001); and the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant (No. 19K09130 and No. 16H06277 [CoBiA]) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Competing interestsThe authors declare that no competing interests exist.Author summaryWhy was this study done?> Although HP infection is a major cause of gastric diseases including cancer, how HP infection affects prolonged survival of advanced gastric cancer patients is unknown.> Reports of studies carried out in different countries and regions revealed that advanced gastric cancer patients who are HP+ exhibited prolonged post-treatment survival, even though the genetic background of patients, HP strains, and cancer treatment procedures differed.> Since most advanced gastric cancer patients underwent gastrectomy, the favorable prognosis of HP+ patients after multidisciplinary treatment may be due to putative systematic mechanisms associated with HP infection.> If putative systemic mechanisms associated with HP infection reduce the likelihood of death due to cancer, the cancer survival rate in the HP+ population should be lower than that for the HP- population.What did the researchers do and find?> Using data from the DAIKO prospective cohort study in Nagoya, Japan, we analyzed the association between anti-HP antibody status, cumulative cancer incidence and all-cause and cancer-specific deaths.> The HP+ rate increased as birth year decreased. Thus, matching based on birth year between 1935 and 1975 was performed to correct for confounding factors associated with birth year.> Despite a significantly higher all-cancer incidence for HP+ individuals compared to those who were HP-, no difference in the all-cause and cancer death rate was observed between HP+ and HP- individuals.What do these findings mean?> HP+ individuals are less susceptible to death relative to their incidence of cancer.> Patients with advanced stage cancer who are HP+ may have a better treatment response/tolerance than those who are HP-.> Additional longitudinal analyses are warranted to evaluate the effect of HP+ status on prolonged survival of patients with advanced-stage cancer.

Relationship between the depression levels and nutritional statuses of advanced stage cancer patients

Objective This study aimed to determine the depression and nutritional statuses of advanced stage cancer patients and investigate the relationship between depression and malnutrition. Method The descriptive, cross-sectional, and correlational study was conducted with 245 patients with advanced cancer. The data were collected by using an Information Form, the Visual Analog Scale, the NRS-2002-Nutritional Risk Score, and the Beck Depression Inventory. Results The mean NRS-2002 score of the patients was 2.22, and when the cutoff value was accepted as 3, it was determined that 39.2% of the patients had malnutrition. The mean Beck Depression Inventory score of the patients was 35.06, and they were found to experience severe depression. There was a positive and significant relationship between the NRS-2002 scores and the Beck Depression Inventory scores (r = 0.409; p < 0.001). Significance of results These results showed that there was a strong relationship between the depression and malnutrition levels of advanced stage cancer patients. Deterioration in the nutritional status of the advanced stage cancer patients was associated with a significant worsening effect in terms of depression and pain.

Telemedicine as an Acceptable Model of Care in Advanced stage Cancer Patients in the Era of Coronavirus Disease 2019 – An Observational Study in a Tertiary Care Centre

Objectives: The availability of routine care for patients with cancer during the coronavirus disease 2019 (COVID-19) pandemic has become challenging, and the use of telemedicine can be promising in this area. The objective of the study is to evaluate the feasibility of telemedicine-based palliative interventions in cancer patients. Materials and Methods: This retrospective study was conducted in a tertiary care centre with 547 follow-up patients who used palliative medicine teleconsultation services. The following data were retrieved from the records: Patient’s reason for the call, the main barriers to a hospital visit, the assistance given to them by the physician on the call and the patients’ satisfaction with the service on a 4-point scale. The data were analysed using percentages for categorical variables and mean/standard deviation for quantitative variables. Results: Out of the 547 patients, 462 (84.46%) utilised voice calling service, and the major reason for not visiting the hospital were cited to be fear of contracting COVID-19 (37.3%), inability to attend due to health constraints (7.13%) and issues with transportation (48.8%). The majority of the calls (63.62%) calls were regarding uncontrolled symptoms of the primary diseases. A total of 402 (73.49%) patients were very satisfied, and a total of 399 (72.94%) decided to continue to use this medium in the future as well. Conclusion: Telemedicine is a good modality for the assessment of chronic pain and providing symptomatic supportive care in patients with cancer in the COIVD-19 pandemic.

Prospective real-world study on the pharmacokinetics of pembrolizumab in patients with solid tumors

BackgroundDosing schemes of pembrolizumab (anti-programmed cell death protein 1 monoclonal antibody) are solely based on pharmacokinetic (PK) modelling derived from phase I–III trials. The current study aimed to determine factors affecting PK and its relationship with clinical outcome in the real-world setting.MethodsAdvanced-stage cancer patients, who were treated with pembrolizumab monotherapy (2 mg/kg Q3W or 200 mg flat Q3W), were prospectively included for serial sampling to obtain trough concentrations. A PK model was generated, covariate effects assessed and internally validated by a bootstrap procedure. PK parameters were related to overall survival (OS) and the occurrence of immune-related adverse events (irAEs).Results588 serum samples derived from 122 patients with (non-)small-cell lung cancer ([N]SCLC), malignant pleural mesothelioma (MPM), melanoma and urothelial cell cancer (UCC) were analyzed. Median follow-up was 2.2 years. A one-compartment PK model was generated: body surface area (BSA) and serum albumin had a significant effect on drug clearance (CL; covariate estimate 1.46 and −1.43, respectively), and serum lactate dehydrogenase (LDH) on the distribution volume(Vd; 0.34). A significant inverse CL–OS relationship was determined for NSCLC (HR:1.69; 95%CI1.07–2.68; p=0.024) and MPM (HR: 3.29; 95% CI 1.08 to 10.09; p=0.037), after correction for prognostic factors, which could not confirmed for melanoma (p=0.22) or UCC (p=0.34). No relationship could be determined between CL and grade >3 irAEs (p=0.70).ConclusionsHigh interpatient variability of pembrolizumab PK is determined by BSA and serum albumin (on CL) and LDH (on Vd). A strong inverse CL–OS relationship was demonstrated for NSCLC and MPM, which could not be observed for melanoma and UCC. The findings suggest that personalized dosing should be prospectively explored.