Behavioural ecology meets oncology: quantifying the recovery of animal behaviour to a transient exposure to a cancer risk factor.

Wildlife is increasingly exposed to sublethal transient cancer risk factors, including mutagenic substances, which activates their anti-cancer defences, promotes tumourigenesis, and may negatively impact populations. Little is known about how exposure to cancer risk factors impacts the behaviour of wildlife. Here, we investigated the effects of a sublethal, short-term exposure to a carcinogen at environmentally relevant concentrations on the activity patterns of wild Girardia tigrina planaria during a two-phase experiment, consisting of a 7-day exposure to cadmium period followed by a 7-day recovery period. To comprehensively explore the effects of the exposure on activity patterns, we employed the double hierarchical generalized linear model framework which explicitly models residual intraindividual variability in addition to the mean and variance of the population. We found that exposed planaria were less active compared to unexposed individuals and were able to recover to pre-exposure activity levels albeit with a reduced variance in activity at the start of the recovery phase. Planaria showing high activity levels were less predictable with larger daily activity variations and higher residual variance. Thus, the shift in behavioural variability induced by an exposure to a cancer risk factor can be quantified using advanced tools from the field of behavioural ecology. This is required to understand how tumourous processes affect the ecology of species.

The impact of food availability on tumorigenesis is evolutionarily conserved.

The inability to control cell proliferation results in the formation of tumors in many multicellular lineages. Nonetheless, little is known about the extent of conservation of the biological traits and ecological factors that promote or inhibit tumorigenesis across the metazoan tree. Particularly, changes in food availability have been linked to increased cancer incidence in humans, as an outcome of evolutionary mismatch. Here, we apply evolutionary oncology principles to test whether food availability, regardless of the multicellular lineage considered, has an impact on tumorigenesis. We used two phylogenetically unrelated model systems, the cnidarian Hydra oligactis and the fish Danio rerio, to investigate the impact of resource availability on tumor occurrence and progression. Individuals from healthy and tumor-prone lines were placed on four diets that differed in feeding frequency and quantity. For both models, frequent overfeeding favored tumor emergence, while lean diets appeared more protective. In terms of tumor progression, high food availability promoted it, whereas low resources controlled it, but without having a curative effect. We discuss our results in light of current ideas about the possible conservation of basic processes governing cancer in metazoans (including ancestral life history trade-offs at the cell level) and in the framework of evolutionary medicine.

The paradox of cooperation among selfish cancer cells.

It is traditionally assumed that during cancer development, tumor cells abort their initially cooperative behavior (i.e., cheat) in favor of evolutionary strategies designed solely to enhance their own fitness (i.e., a "selfish" life style) at the expense of that of the multicellular organism. However, the growth and progress of solid tumors can also involve cooperation among these presumed selfish cells (which, by definition, should be noncooperative) and with stromal cells. The ultimate and proximate reasons behind this paradox are not fully understood. Here, in the light of current theories on the evolution of cooperation, we discuss the possible evolutionary mechanisms that could explain the apparent cooperative behaviors among selfish malignant cells. In addition to the most classical explanations for cooperation in cancer and in general (by-product mutualism, kin selection, direct reciprocity, indirect reciprocity, network reciprocity, group selection), we propose the idea that "greenbeard" effects are relevant to explaining some cooperative behaviors in cancer. Also, we discuss the possibility that malignant cooperative cells express or co-opt cooperative traits normally expressed by healthy cells. We provide examples where considerations of these processes could help understand tumorigenesis and metastasis and argue that this framework provides novel insights into cancer biology and potential strategies for cancer prevention and treatment.

Spontaneously occurring tumors in different wild-derived strains of hydra.

Hydras are freshwater cnidarians widely used as a biological model to study different questions such as senescence or phenotypic plasticity but also tumoral development. The spontaneous tumors found in these organisms have been so far described in two female lab strains domesticated years ago (Hydra oligactis and Pelmatohydra robusta) and the extent to which these tumors can be representative of tumors within the diversity of wild hydras is completely unknown. In this study, we examined individuals isolated from recently sampled wild strains of different sex and geographical origin, which have developed outgrowths looking like tumors. These tumefactions have common features with the tumors previously described in lab strains: are composed of an accumulation of abnormal cells, resulting in a similar enlargement of the tissue layers. However, we also found diversity within these new types of tumors. Indeed, not only females, but also males seem prone to form these tumors. Finally, the microbiota associated to these tumors is different from the one involved in the previous lineages exhibiting tumors. We found that tumorous individuals hosted yet undescribed Chlamydiales vacuoles. This study brings new insights into the understanding of tumor susceptibility and diversity in brown hydras from different origins.

Re-defining 18 F-DCFPyl prostate-specific membrane antigen positron emission tomography detected local recurrence from radical prostatectomy histopathology.

OBJECTIVE: To assess topographic concordance between the histopathological features of patients' radical prostatectomy (RP) specimens and the location of the prostate-specific membrane antigen positron emission tomography (PSMA PET) local recurrences, qualitatively and quantitatively. PATIENTS AND METHODS: Our cohort was selected from the 100 men who received a 18 F-DCFPyL PET scan in the IMPPORT trial (Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213), a prospective non-randomised study completed by GenesisCare Victoria. Eligibility included patients with a rising prostate-specific antigen (PSA) level (>0.2 ng/mL) after RP and PSMA PET detected local recurrence. Histopathological parameters collated included the location of tumour, extraprostatic extension (EPE), and positive margins. Criteria for the location and 'concordance' between histopathological features and local recurrences were pre-defined. RESULTS: A total of 24 patients were eligible; the median age was 71 years, the median PSA level was 0.37 ng/mL, and the time between RP and PSMA PET was 2.6 years. In all, 15 patients had recurrences within the vesicourethral anastomotic region and nine within the lateral surgical margins. There was 100% concordance in the left-right plane between tumour location and local recurrence, with 79% of these lesions concordant three-dimensionally; across craniocaudal, left-right, and anterior-posterior planes. In all, 10 of the 16 (63%) patients with EPE and five of the nine patients with positive margins had three-dimensional concordance between their pathology and their local recurrence. In quantitative assessment, 17 of the 24 patients, had local recurrences that correlated with the location of their original tumour in the craniocaudal plane. CONCLUSION: Local recurrence is highly concordant with the position of the tumour within the prostate. Predicting the location of local recurrence using the location of the EPE and positive margins is less helpful. Further investigation into this field, could impact surgical technique and salvage radiotherapy clinical target volume.

Macrocystic ductal adenocarcinoma, a good outcome for a rare cancer in an elderly comorbid patient.

Ductal adenocarcinoma is an aggressive prostate cancer often presenting late due to low serum PSA. A variant presentation of ductal adenocarcinoma occurs with formation of large cystic structures in the prostate, often associated with lower urinary tract symptoms. We present a case illustrating investigation and successful management of a macrocytic ductal carcinoma in a 90 year old patient.

Tumors alter life history traits in the freshwater cnidarian, Hydra oligactis.

Although tumors can occur during the lifetime of most multicellular organisms and have the potential to influence health, how they alter life-history traits in tumor-bearing individuals remains poorly documented. This question was explored using the freshwater cnidarian Hydra oligactis, a species sometimes affected by vertically transmitted tumors. We found that tumorous polyps have a reduced survival compared to healthy ones. However, they also displayed higher asexual reproductive effort, by producing more often multiple buds than healthy ones. A similar acceleration is observed for the sexual reproduction (estimated through gamete production). Because tumoral cells are not transmitted through this reproductive mode, this finding suggests that hosts may adaptively respond to tumors, compensating the expected fitness losses by increasing their immediate reproductive effort. This study supports the hypothesis that tumorigenesis has the potential to influence the biology, ecology, and evolution of multicellular species, and thus should be considered more by evolutionary ecologists.

The role of a urine dipstick in the diagnosis of the acute scrotum.

Objective: To evaluate the role of a urine dipstick in the assessment of acute scrotal pain emergency department presentations. Methods: A single institution, prospective case series, from February 2020 to February 2021. All patients who received a bedside review by a urology doctor for acute scrotal pain were included. Urine dipstick results were pre-defined as having had an impact on the emergency clinician's diagnosis if it showed pyuria and/or nitrituria and the final diagnosis was epididymitis-orchitis or haematuria and the final diagnosis was ureterolithiasis. Results: 139 patients presented to the emergency department with a complaint of acute scrotal pain. 85 (61%) were referred for bedside urology review. Median age of 17 years (P25 12 yrs, P75 31 yrs). 2.3% (n = 2) had proven testicular torsion, 28.5% (n = 24) had epididymitis-orchitis and 8.2% (n = 7) had ureterolithiasis. 68 (80%) of patients received a primary diagnosis of testicular torsion by the emergency department clinician. Following review by a urology unit doctor, 14 proceeded to scrotal exploration for concern of testicular torsion. 7 patients were diagnosed with ureterolithiasis, all of whom had haematuria on their urine dipsticks (100%, 95% CI: 59-100%), 100% of these urine dipsticks were initiated by the urology unit doctor following bedside review. 22 patients were diagnosed with epididymitis-orchitis. 8 of these had pyuria, nitrituria and/or haematuria on their urine dipstick (36%, 95% CI: 17-59%) and only one urine dipstick was completed prior to referral. 20.6% of patients perceived to have testicular torsion by the emergency department had a positive urine dipstick that aligned with their final alternative diagnosis (95% CI: 12-32%). Conclusion: A collection of clinical findings is required to diagnose the aetiology of acute scrotal pain. Information that can be easily, quickly, cheaply, and reliably collected, such as a urine dipstick, can assist in clinical decision making.

Intraoperative indocyanine green fluorescence navigation in a robot-assisted partial nephrectomy for a large renal cell carcinoma in a horseshoe kidney.

A man in his 60s was referred to the urology department with an incidental finding of large 75 mm mass within a horseshoe kidney. CT imaging highlighted the well-known aberrant arterial anatomy seen in horseshoe kidney which often causes significant surgical challenges.After careful preoperative planning, the mass was resected successfully during a robot-assisted partial nephrectomy. Intraoperatively, indocyanine green fluorescence navigation helped to confirm arteries supplying area of resection were appropriately clamped, allowing for safe resection of the mass. Histology revealed a chromophobe renal cell carcinoma with clear margins. The patient was discharged on day 4 postoperatively and continues to be cancer free on routine surveillance imaging.

Case report: Recurrent urethral polyps, an atypical presentation of ductal prostate adenocarcinoma.

Prostate ductal adenocarcinoma is a rare subtype of prostate adenocarcinoma which can show aggressive features and have poor response to conventional treatment. Early diagnosis aids in shared patient decision making. We report an atypical presentation of this rare condition where a recurrent urethral polyp which showed pagetoid spread was diagnosed as ductal adenocarcinoma of the prostate, with emphasis on review of prior available histology.

Transmissible Cancer Evolution: The Under-Estimated Role of Environmental Factors in the "Perfect Storm" Theory.

Although the true prevalence of transmissible cancers is not known, these atypical malignancies are likely rare in the wild. The reasons behind this rarity are only partially understood, but the "Perfect Storm hypothesis" suggests that transmissible cancers are infrequent because a precise confluence of tumor and host traits is required for their emergence. This explanation is plausible as transmissible cancers, like all emerging pathogens, will need specific biotic and abiotic conditions to be able to not only emerge, but to spread to detectable levels. Because those conditions would be rarely met, transmissible cancers would rarely spread, and thus most of the time disappear, even though they would regularly appear. Thus, further research is needed to identify the most important factors that can facilitate or block the emergence of transmissible cancers and influence their evolution. Such investigations are particularly relevant given that human activities are increasingly encroaching into wild areas, altering ecosystems and their processes, which can influence the conditions needed for the emergence and spread of transmissible cell lines.

Case report: Challenging adult case of erosive coronal sulcus hair thread tourniquet.

Hair thread tourniquet syndrome has been well described in the literature, with one of the rare presentations including resultant tourniquet of the penis. We describe an unusual case in an adult resulting in erosion of the urethra as well as the reconstructive and social challenges faced in an attempt to preserve the glans. SECTION HEADING: Trauma and Reconstruction.

Optimizing surgical training in the time of COVID-19-Victorian regional teaching hospital experience.

BACKGROUND: Reductions in elective surgery due to the COVID-19 pandemic led to a paralleled reduction in patient based surgical training opportunities. METHODS: To quantify the impact of COVID-19 on surgical training, we completed a retrospective audit of the Urology Department activity during Victorian pandemic waves in 2020 at our large regional teaching hospital. Corresponding weeks in the year prior were used as the control. Interviews with department members illustrated the adaptive approach to surgical training used at our institution. RESULTS: A State of Disaster Surgical Triage Team was assembled and surgical operations were split between one public and two private hospitals. A pandemic triaging protocol was established and 335 Category-2 patients were re-triaged. The first wave saw a 13.8% reduction in clinic reviews, with the second wave having an overall increase of 8.8% with 56% being telehealth. The second wave saw an 11.0% reduction in overall operating, with reduced emergency operating in both the first and second wave of 17.4% and 45.5%, respectively. Reductions impacted surgical technical skill training, resulting in surgical education provided through technology platforms including webinars, podcasts and pre-recorded operative videos. The unique challenges trainees were faced with due to the pandemic encouraged development of non-technical RACS competencies. CONCLUSION: The COVID-19 pandemic presented significant challenges for service delivery and training. Reduced direct patient contact and procedures, but opportunities to develop the non-technical skills required to respond to the pandemic. The use of variable educational opportunities and tools ensured our trainees continued to progress through their training.

The evolution and ecology of benign tumors.

Tumors are usually classified into two main categories - benign or malignant, with much more attention being devoted to the second category given that they are usually associated with more severe health issues (i.e., metastatic cancers). Here, we argue that the mechanistic distinction between benign and malignant tumors has narrowed our understanding of neoplastic processes. This review provides the first comprehensive discussion of benign tumors in the context of their evolution and ecology as well as interactions with their hosts. We compare the genetic and epigenetic profiles, cellular activities, and the involvement of viruses in benign and malignant tumors. We also address the impact of intra-tumoral cell composition and its relationship with the tumoral microenvironment. Lastly, we explore the differences in the distribution of benign and malignant neoplasia across the tree of life and provide examples on how benign tumors can also affect individual fitness and consequently the evolutionary trajectories of populations and species. Overall, our goal is to bring attention to the non-cancerous manifestations of tumors, at different scales, and to stimulate research on the evolutionary ecology of host-tumor interactions on a broader scale. Ultimately, we suggest that a better appreciation of the differences and similarities between benign and malignant tumors is fundamental to our understanding of malignancy both at mechanistic and evolutionary levels.

On the need for integrating cancer into the One Health perspective.

Recent pandemics have highlighted the urgency to connect disciplines studying animal, human, and environment health, that is, the "One Health" concept. The One Health approach takes a holistic view of health, but it has largely focused on zoonotic diseases while not addressing oncogenic processes. We argue that cancers should be an additional key focus in the One Health approach based on three factors that add to the well-documented impact of humans on the natural environment and its implications on cancer emergence. First, human activities are oncogenic to other animals, exacerbating the dynamics of oncogenesis, causing immunosuppressive disorders in wildlife with effects on host-pathogen interactions, and eventually facilitating pathogen spillovers. Second, the emergence of transmissible cancers in animal species (including humans) has the potential to accelerate biodiversity loss across ecosystems and to become pandemic. It is crucial to understand why, how, and when transmissible cancers emerge and spread. Third, translating knowledge of tumor suppressor mechanisms found across the Animal Kingdom to human health offers novel insights into cancer prevention and treatment strategies.

Ecological and Evolutionary Consequences of Anticancer Adaptations.

Cellular cheating leading to cancers exists in all branches of multicellular life, favoring the evolution of adaptations to avoid or suppress malignant progression, and/or to alleviate its fitness consequences. Ecologists have until recently largely neglected the importance of cancer cells for animal ecology, presumably because they did not consider either the potential ecological or evolutionary consequences of anticancer adaptations. Here, we review the diverse ways in which the evolution of anticancer adaptations has significantly constrained several aspects of the evolutionary ecology of multicellular organisms at the cell, individual, population, species, and ecosystem levels and suggest some avenues for future research.