Personalized medicine for locally advanced rectal cancer: five years of complete clinical response after neoadjuvant radiochemotherapy-a case report with a literature review.

We present a case report of a 73-year-old male patient with a complete clinical response following neoadjuvant radiochemotherapy of mid-rectal adenocarcinoma. The patient was initially diagnosed with stage IIIB microsatellite stable mid-rectal adenocarcinoma in February 2017. During restaging in June 2017, which included rectoscopy, endosonography, computed tomography and magnetic resonance imaging, a complete clinical response was observed. After appropriate consultation, a watch-and-wait strategy was chosen. During stringent follow-up every 3 months for the first 3 years and thereafter every 6 months, no recurrence or regrowth was observed. After the fifth year of complete clinical response, we recommended an annual follow-up. As of November 2023, the patient has no signs of recurrence or late toxicity after radiochemotherapy. The omission of resection in patients with locally advanced rectal cancer and the establishment of a watch-and-wait strategy are currently under discussion as possible treatment courses in patients with complete clinical response. Long-term data on watch-and-wait strategies for patients with a complete clinical response in locally advanced rectal cancer are rare. A clear national and international accepted standardization of follow-up programs for patients managed by a watch-and-wait strategy in the long-term is missing. Here, we report the case of a patient who had undergone a follow-up program for more than five years and discuss the current literature. Our case report and literature review highlights that a watch-and-wait strategy does not seem to increase the risk of systemic disease or compromise survival outcomes in selected locally advanced rectal cancer patients. Thus, our case contributes to the growing body of knowledge on personalized and precision medicine for rectal cancer.

Meta-transcriptomic identification of groundnut RNA viruses in western Kenya and the novel detection of groundnut as a host for Cauliflower mosaic virus.

BACKGROUND: Groundnut (Arachis hypogaea L.) is the 13th most important global crop grown throughout the tropical and subtropical regions of the world. One of the major constraints to groundnut production is viruses, which are also the most economically important and most abundant pathogens among cultivated legumes. Only a few studies have reported the characterization of RNA viruses in cultivated groundnuts in western Kenya, most of which deployed classical methods of detecting known viruses. METHODS: We sampled twenty-one symptomatic and three asymptomatic groundnut leaf samples from farmers' fields in western Kenya. Total RNA was extracted from the samples followed by First-strand cDNA synthesis and sequencing on the Illumina HiSeq 2500 platform. After removing host and rRNA sequences, high-quality viral RNA sequences were de novo assembled and viral genomes annotated using the publicly available NCBI virus database. Multiple sequence alignment and phylogenetic analysis were done using MEGA X. RESULTS: Bioinformatics analyses using as low as ∼3.5 million reads yielded complete and partial genomes for Cauliflower mosaic virus (CaMV), Cowpea polerovirus 2 (CPPV2), Groundnut rosette assistor virus (GRAV), Groundnut rosette virus (GRV), Groundnut rosette virus satellite RNA (satRNA) and Peanut mottle virus (PeMoV) falling within the species demarcation criteria. This is the first report of CaMV and the second report of CPPV2 on groundnut hosts in the world. Confirmation of the detected viruses was further verified through phylogenetic analyses alongside reported publicly available highly similar viruses. PeMoV was the only seed-borne virus reported. CONCLUSION: Our findings demonstrate the power of Next Generation Sequencing in the discovery and identification of novel viruses in groundnuts. The detection of the new viruses indicates the complexity of virus diseases in groundnuts and would require more focus in future studies to establish the effect of the viruses as sole or mixed infections on the crop. The detection of PeMoV with potential origin from Malawi indicates the importance of seed certification and cross-boundary seed health testing.

The impact of resection margin distance on survival and recurrence in pancreatic ductal adenocarcinoma in a retrospective cohort analysis.

BACKGROUND: The prognostic effect of resection margin status following pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) remains controversial, even with the implementation of standardized pathological assessment. We therefore investigated the impact of resection margin (RM) status and RM distance in curative resected PDAC on overall survival (OS), disease-free survival (DFS) and recurrence. METHOD: 108 patients were retrieved from a prospectively maintained database of a certified pancreatic cancer center. Distribution and relationships between circumferential resection margin (CRM) involvement (CRM≤1mm; CRM>1mm; CRM≥2mm) and their prognostic impact on OS and DFS were assessed using Kaplan-Meier statistics and the Log-Rank test. Multivariate logistic regression was used explain the development of a recurrence 12 months after surgery. RESULTS: 63 out of 108 patients had medial RM and 32 posterior RM involvement. There was no significant difference in OS and DFS between CRM≤1mm and CRM>1mm resections. Clearance at the medial margin of ≥2mm had an impact on OS and DFS, (RM≥2mm vs. RM<2mm: median OS 29.8 vs 16.8 months, median DFS 19.6 vs. 10.3 months). Multivariate analysis demonstrated that age, medial RM ≥2mm, lymph node status and chemotherapy were prognostic factors for OS and DFS. Posterior RM had no influence on OS or DFS. CONCLUSION: Not all RM seem to have the same impact on OS and DFS, and a clearance of 1mm for definition of a negative RM (i.e. CRM>1mm) seems not sufficient. Future studies should include more patients to stratify for potential confounders we could not account for. TRIAL REGISTRATION: This study was registered with the German Clinical Trials Registry (reference number DRKS0017425).

Effects of intensive physiotherapy on Quality of Life (QoL) after pancreatic cancer resection: a randomized controlled trial.

BACKGROUND: Patients have significantly lower QoL scores after pancreatic resection due to cancer in the physical and psychological domains compared to healthy controls or other cancer patients. Intensified physiotherapy or physical training can increase QoL by reducing fatigue levels and improving physical functioning. However, data on the long-term effects of intensive or supervised physiotherapy is lacking. The aim of this exploratory study is the assessment of QoL in the intervention group, using various QoL questionnaires in their validated German translations and gather data on its feasibility in the context of chemotherapy with a follow-up of 12 months (and develop concepts to improve QoL after pancreatic cancer resection). METHODS: Fifty-six patients (mean age: 66.4 ± 9.9 years) were randomized in this study to intervention (cohort A, n = 28) or control group (cohort B, n = 28). Intervention of intensified physiotherapy program consisted of endurance and muscle force exercises using cycle ergometer. In the control group physiotherapy was limited to the duration of the hospital stay and was scheduled for 20 min on 5 days per week. The clinical visits took place 2 days preoperatively, 1 week, 3 months, 6 months and 12 months postoperatively. Both groups attended the follow-up program. QoL was evaluated using the Short Physical Performance Battery (SPPB), Short Form-8 Health Survey (SF-8) and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and pancreatic cancer-specific module QLQ-PAN26 questionnaires. The course of QoL was evaluated using a repeated measures ANOVA and a per protocol design. RESULTS: Of the initial 56 randomized patients, 34 finished the 12 months follow-up period. There were no adverse events due to the intervention and 80% of patients in the intervention group where adherent. There was no significant influence on physical performance as measured by SPPB and SF-8 questionnaire. However, after 6 months patients in the intervention group regained their prior physical condition, whereas the control group did not. Intensive physiotherapy significantly influenced various factors of QoL measured with the C30 questionnaire positively, such as physical functioning (p = 0.018), role functioning (p = 0.036), and appetite loss (p = 0.037), even after 6 months. No negative effects in patients undergoing chemotherapy compared to those without chemotherapy was observed. CONCLUSION: This first randomized controlled study with a 12-month follow-up shows that supervised physiotherapy or prescribed home-based exercise after pancreatic cancer resection is safe and feasible and should be proposed and started as soon as possible to improve certain aspects of QoL. TRIAL REGISTRATION: German Clinical Trials Register (No: DRKS00006786 ); Date of registration: 01/10/2014.

Micronutritional status after pylorus preserving duodenopancreatectomy: analysis of data from a randomized controlled trial.

Physical frailty and nutritional malassimilation are often observed after pancreaticoduodenectomy for pancreatic cancer. But long-term data concerning the course of micronutrient status is still missing. Micronutrient status after pylorus preserving pancreaticoduodenectomy with a follow-up of 12 months was evaluated using data of a randomized controlled trial. 47 patients were randomized with respect to the physiotherapy regimen they received (intensified physiotherapy: n = 22; standard physiotherapy: n = 25). Nutritional status was recorded preoperatively and postoperatively after one week, 3, 6 and 12 months. BMI, body fat measurement and albumin, lipid, iron and bone metabolism parameters, vitamins A, B1 B6 and B12, homocysteine, folic acid, and trace elements were measured. Laboratory values were analyzed descriptively. Differences between the groups were analyzed using the t-test in SPSS. For vitamin D, B1, B6 and iron a deficiency over time could be demonstrated with 50% of all patients or more being below normal range. The other laboratory values were in low normal range after 3 months and later. Significant differences between groups were found in cholesterol, HDL and selenium levels (corrected p-values < 0.033 in all cases). Vitamin D and iron should be supplemented postoperatively in the long term, and vitamin B1 and B6 substitution should be considered in symptomatic patients. Levels of malnutrition induced fatigue should be comparable between both groups. However, the role of nutritional status on other health-related aspects such as quality of life should be the focus of further studies.Trial Registration Number in the German Registry for Clinical Studies: DRKS00006786; Date of Registration: 01.10.2014.

Predictive factors for long-term survival after surgery for pancreatic ductal adenocarcinoma: Making a case for standardized reporting of the resection margin using certified cancer center data.

Factors for overall survival after pancreatic ductal adenocarcinoma (PDAC) seem to be nodal status, chemotherapy administration, UICC staging, and resection margin. However, there is no consensus on the definition for tumor free resection margin. Therefore, univariate OS as well as multivariate long-term survival using cancer center data was analyzed with regards to two different resection margin definitions. Ninety-five patients met inclusion criteria (pancreatic head PDAC, R0/R1, no 30 days mortality). OS was analyzed in univariate analysis with respect to R-status, CRM (circumferential resection margin; positive: ≤1mm; negative: >1mm), nodal status, and chemotherapy administration. Long-term survival >36 months was modelled using multivariate logistic regression instead of Cox regression because the distribution function of the dependent data violated the requirements for the application of this test. Significant differences in OS were found regarding the R status (Median OS and 95%CI for R0: 29.8 months, 22.3-37.4; R1: 15.9 months, 9.2-22.7; p = 0.005), nodal status (pN0 = 34.7, 10.4-59.0; pN1 = 17.1, 11.5-22.8; p = 0.003), and chemotherapy (with CTx: 26.7, 20.4-33.0; without CTx: 9.7, 5.2-14.1; p < .001). OS according to CRM status differed on a clinically relevant level by about 12 months (CRM positive: 17.2 months, 11.5-23.0; CRM negative: 29.8 months, 18.6-41.1; p = 0.126). A multivariate model containing chemotherapy, nodal status, and CRM explained long-term survival (p = 0.008; correct prediction >70%). Chemotherapy, nodal status and resection margin according to UICC R status are univariate factors for OS after PDAC. In contrast, long-term survival seems to depend on wider resection margins than those used in UICC R classification. Therefore, standardized histopathological reporting (including resection margin size) should be agreed upon.

Experiences in sub-Saharan Africa with GM crop risk communication: outcome of a workshop.

In tackling agricultural challenges, policy-makers in sub-Saharan Africa (SSA) have increasingly considered genetically modified (GM) crops as a potential tool to increase productivity and to improve product quality. Yet, as elsewhere in the world, the adoption of GM crops in SSA has been marked by controversy, encompassing not only the potential risks to animal and human health, and to the environment, but also other concerns such as ethical issues, public participation in decision-making, socio-economic factors and intellectual property rights. With these non-scientific factors complicating an already controversial situation, disseminating credible information to the public as well as facilitating stakeholder input into decision-making is essential. In SSA, there are various and innovative risk communication approaches and strategies being developed, yet a comprehensive analysis of such data is missing. This gap is addressed by giving an overview of current strategies, identifying similarities and differences between various country and institutional approaches and promoting a way forward, building on a recent workshop with risk communicators working in SSA.

Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer.

BACKGROUND: The chemokine and bone marrow-homing receptor CXCR4 has been implicated in metastatic dissemination of various cancers. We investigated CXCR4 expression in esophageal cancer specimens and its association with survival, lymph node microinvolvement, and bone marrow micrometastasis. METHODS: We analyzed frozen tumor specimens from 136 patients with completely resected esophageal cancer for CXCR4 expression by immunohistochemistry. Lymph node microinvolvement and bone marrow micrometastasis were assessed by immunohistochemistry with monoclonal antibodies Ber-EP4 (against epithelial cell adhesion molecule) and pancytokeratin A45-B/B3 (against several cytokeratins), respectively. Associations between CXCR4 expression and clinicopathologic features, including tumor stage, histologic grade, lymph node metastasis and microinvolvement, bone marrow micrometastasis, and survival, were investigated with Fisher's test, log-rank test, and Cox multivariable analysis. All statistical tests were two-sided. RESULTS: CXCR4 protein was expressed in 75 (55%) of 136 esophageal tumors examined. CXCR4 expression was statistically significantly associated with reduced median overall and disease-specific survival, compared with CXCR4 nonexpression (P < .001; log-rank test). The median overall survival of patients with CXCR4-positive tumors was 20 months and with CXCR4-negative tumors, 76 months (difference = 56 months, 95% confidence interval [CI] = 4 to 108 months; P < .001). The median disease-specific survival of patients with CXCR4-positive tumors was 25 months and with CXCR4-negative tumors was 97 months (difference = 72 months, 95% CI = 34 to 110 months; P < .001). CXCR4 expression was statistically significantly associated with increased lymph node microinvolvement (P < .001) and with increased bone marrow micrometastasis (P < .001). In multivariable analysis, CXCR4 expression, compared with its nonexpression, was identified as the independent variable that was most strongly associated with reduced disease-specific survival (relative risk [RR] of death = 2.03, 95% CI = 1.20 to 3.41; P = .008) and overall survival (RR of death = 2.18, 95% CI = 1.33 to 3.59; P = .002). CONCLUSION: CXCR4 expression was associated with poor clinical outcome in esophageal cancer patients. CXCR4 may have a role in early metastatic spread because its expression was associated with micrometastases to both the lymph nodes and bone marrow. Thus, CXCR4 should be explored further as a target for adjuvant therapy for micrometastatic disease.