Risk factors, histopathological landscape, biomarkers, treatment patterns and survival of early-onset colorectal cancer: A narrative review.

Early-onset colorectal cancer (EOCRC) incidence has increased in most Western countries over the last decade, with Australia at the forefront. Recent literature has thus focused on characterizing EOCRC from later-onset colorectal cancer (LOCRC). Earlier exposure to modifiable risk factors resulting in gut dysbiosis has been linked with EOCRC development. EOCRCs have more aggressive histopathological features with somatic mutations resulting in pro-inflammatory tumor microenvironments. There is a tendency to treat EOCRCs with multimodal chemotherapeutic regimens and more extensive surgery than LOCRCs with conflicting postoperative outcomes and survival data. Current research is limited by a lack of Australasian studies, retrospective study designs, and heterogeneous definitions of EOCRC. Future research should address these and focus on investigating the role of immunotherapies, establishing minimally invasive diagnostic biomarkers and nomograms, and evaluating the survival and functional outcomes of EOCRC.

A patient-designed integrative oncology intervention for stage IV locally recurrent rectal cancer: A case report.

INTRODUCTION: Stage IV colorectal cancer is a highly challenging condition to treat, with 5-year survival rates of 13% in Australia, improving to 40% for those patients with locally recurrent rectal cancer who are suitable for total neoadjuvant therapy and pelvic exenterative surgery. This study reports a unique case of a patient with Stage IV locally recurrent rectal cancer (LRRC), who designed and implemented a holistic integrative oncology intervention. CASE PRESENTATION: The patient was 59-years-old when diagnosed with Stage IV locally recurrent rectal cancer, and referred to a highly specialised centre for colorectal cancer care at a tertiary teaching hospital in Sydney, Australia. Treatment included chemo/radiotherapy, liver resection and posterior pelvic exenteration surgery. The patient's background as a health researcher and clinician optimised her ability to design and implement an integrative oncology model of care, including yoga, mindfulness, Buddhist meditation and study, social connection, exercise, psychotherapeutic and nutritional support. This paper describes these mind-body practices and lifestyle modifications and outlines her experiences and outcomes at each stage of her extensive and radical treatment. CONCLUSION: This case provides a unique perspective into how the integration of mind-body practices and lifestyle modifications with conventional treatment can support those living with colorectal cancer.

Pelvic exenteration for locally advanced and recurrent prostate cancer.

Locally advanced or recurrent prostate cancer which invades adjacent pelvic organs, bone or other soft tissue structures is a rare situation. This study aimed to report the outcomes of ten consecutive patients who underwent total pelvic exenteration for prostate cancer at a high-volume specialist centre. Two patients had locally advanced primary tumours, while eight had locally recurrent prostate cancer. Median operating time, blood loss, ICU stay, and hospital stay was 12.2 h (range 9.6-13.8), 2500 ml (500-3000), 4.5 days (2-7) and 36 days (21-78), respectively. There was no inpatient, 30-day, or 90-day mortality. Six patients developed a Clavien-Dindo III complication. R0 resection was achieved in eight patients. Median follow up was 16 months (range 2-77). At last follow up, five patients were alive without disease. These findings suggest that pelvic exenteration for locally advanced and recurrent prostate cancer is safe and represents a potentially curative treatment option for highly selected patients.

The health-related quality of life of early-onset colorectal cancer patients: an Australian cross-sectional study.

AIM: Early-onset colorectal cancer (EOCRC) patients are more likely to have advanced disease and undergo more aggressive treatment modalities. However, current literature investigating the health-related quality of life (HRQoL) of EOCRC patients is scarce. This study aimed to determine the HRQoL of an Australian cohort of EOCRC patients including a subset who underwent pelvic exenteration (PE) or cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: A cross-sectional study of EOCRC patients treated at the Royal Prince Alfred Hospital, Sydney Australia was performed. Patients were divided into groups based on the time interval from their index operation: ≤2 years and >2 years. HRQoL was evaluated using the SF-36v2 questionnaire. RESULTS: A total of 50 patients were included. For patients ≤2 years from surgery, the median physical component summary (PCS) and mental health component summary (MCS) scores were 53.3 (36.4-58.9) and 47.3 (37.5-55.7). In the >2 years group, the median PCS and MCS scores were 50.6 (43.3-57.7) and 50.2 (39.04-56.2), respectively. Stage I (vs. stage II) disease and emergency (vs. elective) surgery conferred poorer PCS scores in patients ≤2 years from surgery. No other variables impacted PCS or MCS scores in EOCRC patients in either group. CONCLUSIONS: HRQoL of EOCRC patients was equivocal to the Australian population. Having an earlier stage of diagnosis and emergency index operation was associated with poorer levels of physical functioning in patients ≤2 years from surgery. However, because of the limitations of this study, these findings require validation in future large-scale prospective research.

Defining Benchmarks for Pelvic Exenteration Surgery: A Multicentre Analysis of Patients with Locally Advanced and Recurrent Rectal Cancer.

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

Patients' and carers' views on research priorities in prehabilitation for cancer surgery.

INTRODUCTION: The views of patients and carers are important for the development of research priorities. This study aimed to determine and compare the top research priorities of cancer patients and carers with those of multidisciplinary clinicians with expertise in prehabilitation. MATERIALS AND METHODS: This cross-sectional study surveyed patients recovering from cancer surgery at a major tertiary hospital in Sydney, Australia, and/or their carers between March and July 2023. Consenting patients and carers were provided a list of research priorities according to clinicians with expertise in prehabilitation, as determined in a recent International Delphi study. Participants were asked to rate the importance of each research priority using a 5-item Likert scale (ranging from 1 = very high research priority to 5 = very low research priority). RESULTS: A total of 101 patients and 50 carers participated in this study. Four areas were identified as research priorities, achieving consensus of highest importance (> 70% rated as "high" or "very high" priority) by patients, carers, and clinical experts. These were "optimal composition of prehabilitation programs" (77% vs. 82% vs. 88%), "effect of prehabilitation on surgical outcomes" (85% vs. 90% vs. 95%), "effect of prehabilitation on functional outcomes" (83% vs. 86% vs. 79%), and "effect of prehabilitation on patient reported outcomes" (78% vs. 84% vs. 79%). Priorities that did not reach consensus of high importance by patients despite reaching consensus of highest importance by experts included "identifying populations most likely to benefit from prehabilitation" (70% vs. 76% vs. 90%) and "defining prehabilitation core outcome measures" (66% vs. 74% vs. 87%). "Prehabilitation during neoadjuvant therapies" reached consensus of high importance by patients but not by experts or carers (81% vs. 68% vs. 69%). CONCLUSION: This study delineated the primary prehabilitation research priorities as determined by patients and carers, against those previously identified by clinicians with expertise in prehabilitation. It is recommended that subsequent high-quality research and resource allocation be directed towards these highlighted areas of importance.

Enhancing outpatient anxiety treatment with mobile technology: A quality improvement study.

INTRODUCTION: Mobile mental health applications are a novel treatment method with unique qualities and capabilities for enhancing existing psychiatric treatments. Outpatient settings such as Mile Square Health Clinic have identified a need to leverage this new technology into their routine care. BACKGROUND: In the U.S., over 40 million people suffer from an anxiety disorder, however, only 1 in 4 responds to pharmacological treatment. Preliminary research indicates mental health apps are acceptable, feasible, and can improve patient outcomes for those with anxiety. METHODS: Participants from two different outpatient psychiatric clinics locations with generalized anxiety disorder were identified and recruited by participating nurse practitioners. Participants were instructed on how to download and use IntelliCare by the Project Lead. The Project Lead administered a semi-structured interview to collect qualitative data at three weeks and six weeks follow-up. RESULTS AND CONCLUSIONS: Survey responses at three and six weeks showed relevant themes of increased journaling, increased feelings of connectedness, positive associations with gamification, and IntelliCare being most useful for a moderate to severe level of anxiety. RECOMMENDATIONS: The results of this QI project demonstrate the clinical utility of incorporating the IntelliCare app into regular outpatient practice. IntelliCare should be used with those with moderate to severe anxiety and journaling features should follow research developments to incorporate best-practice guidelines.

Influence of hospital-level and surgeon factors on the outcomes after ileo-anal pouch surgery for inflammatory bowel disease: systematic review.

BACKGROUND: Ileal pouch-anal anastomosis ('pouch surgery') provides a chance to avoid permanent ileostomy after proctocolectomy, but can be associated with poor outcomes. The relationship between hospital-level/surgeon factors (including volume) and outcomes after pouch surgery is of increasing interest given arguments for increasing centralization of these complex procedures. The aim of this systematic review was to appraise the literature describing the influence of hospital-level and surgeon factors on outcomes after pouch surgery for inflammatory bowel disease. METHODS: A systematic review was performed of studies reporting outcomes after pouch surgery for inflammatory bowel disease. The MEDLINE (Ovid), Embase (Ovid), and Cochrane CENTRAL databases were searched (1978-2022). Data on outcomes, including mortality, morbidity, readmission, operative approach, reconstruction, postoperative parameters, and pouch-specific outcomes (failure), were extracted. Associations between hospital-level/surgeon factors and these outcomes were summarized. This systematic review was prospectively registered in PROSPERO, the international prospective register of systematic reviews (CRD42022352851). RESULTS: A total of 29 studies, describing 41 344 patients who underwent a pouch procedure, were included; 3 studies demonstrated higher rates of pouch failure in lower-volume centres, 4 studies demonstrated higher reconstruction rates in higher-volume centres, 2 studies reported an inverse association between annual hospital pouch volume and readmission rates, and 4 studies reported a significant association between complication rates and surgeon experience. CONCLUSION: This review summarizes the growing body of evidence that supports centralization of pouch surgery to specialist high-volume inflammatory bowel disease units. Centralization of this technically demanding surgery that requires dedicated perioperative medical and nursing support should facilitate improved patient outcomes and help train the next generation of pouch surgeons.

Mental illness comorbidity significantly impacts surgical outcomes for emergency surgical patients.

BACKGROUND: Whilst both mental illness comorbidity and the delivery of emergency surgery are commonplace in Australia, there is little evidence investigating any link between them. As such, this study examines the emergency surgical outcomes for patients with mental illness compared to other surgical patients within the Australian public surgical system. METHODS: Retrospective cohort study involving adult emergency and elective surgical patients treated at three public hospitals in Sydney, Australia between 2018 and 2019. Patients were identified using ICD-10 diagnosis codes, and grouped by those with decompensated mental illness, chronic depression, or those without mental illness. Outcome measures included those within the emergency department (ED), along with in-hospital mortality and surgical outcomes. RESULTS: Of 48 338 total patients, 31 890 (66.0%) had elective and 16 448 (34.0%) had emergency surgery. For patients with decompensated mental illness, only 228 (0.7%) had elective whilst 425 (2.6%) had emergency surgery. Their outcomes for this surgery type included being triaged significantly higher (Cat 1 or 2, 34% vs. 15%) and longer ED stays (8.3 vs. 6.6 h). They also had significantly more post-operative complications (26% vs. 8%) and total days in hospital (33.8 vs. 8.5 days). There was no significant difference for in-hospital mortality. CONCLUSION: Patients with mental illness are significantly more likely to have emergency surgery including presenting to the ED with more acute physical illness and to experience worse surgical outcomes compared to other surgical patients for every measure analyzed except mortality. There is considerable opportunity to further investigate how these differences might be improved.

Complex Heart-Lung Ventilator Emergencies in the CICU.

This review aims to enhance the comprehension and management of cardiopulmonary interactions in critically ill patients with cardiovascular disease undergoing mechanical ventilation. Highlighting the significance of maintaining a delicate balance, this article emphasizes the crucial role of adjusting ventilation parameters based on both invasive and noninvasive monitoring. It provides recommendations for the induction and liberation from mechanical ventilation. Special attention is given to the identification of auto-PEEP (positive end-expiratory pressure) and other situations that may impact hemodynamics and patients' outcomes.

Anatomic Subtype Differences in Extramammary Paget Disease: A Meta-Analysis.

Importance: Extramammary Paget disease (EMPD) is a rare, highly recurrent cutaneous malignant neoplasm of unclear origin. EMPD arises most commonly on the vulvar and penoscrotal skin. It is not presently known how anatomic subtype of EMPD affects disease presentation and management. Objective: To compare demographic and tumor characteristics and treatment approaches for different EMPD subtypes. Recommendations for diagnosis and treatment are presented. Data Sources: MEDLINE, Embase, Web of Science Core Collection, and Cochrane Reviews CENTRAL from December 1, 1990, to October 24, 2022. Study Selection: Articles were excluded if they were not in English, reported fewer than 3 patients, did not specify information by anatomic subtype, or contained no case-level data. Metastatic cases on presentation were also excluded. Data Extraction and Synthesis: Abstracts of 1295 eligible articles were independently reviewed by 5 coauthors, and 135 articles retained. Reporting was in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The analysis was cunducted in August 2019 and updated in November 2022. Findings: Most vulvar EMPD cases were asymptomatic, and diagnosis was relatively delayed (mean, 25.1 months). Although most vulvar EMPD cases were intraepidermal (1247/1773 [70.3%]), radical surgeries were still performed in almost one-third of cases. Despite this aggressive surgical approach, 481 of 1423 (34%) recurred, commonly confined to the skin and mucosa (177/198 [89.4%]). By contrast, 152 of 1101 penoscrotal EMPD cases (14%) recurred, but more than one-third of these recurrences were regional or associated with distant metastases (54 of 152 [35.5%]). Perianal EMPD cases recurred in one-third of cases (74/218 [33.9%]), with one-third of these recurrences being regional or associated with distant metastasis (20 of 74 [27.0%]). Perianal EMPD also had the highest rate of invasive disease (50% of cases). Conclusions and Relevance: The diagnosis and treatment of EMPD should differ based on anatomic subtypes. Considerations for updated practice may include less morbid treatments for vulvar EMPD, which is primarily epidermal, and close surveillance for local recurrence in vulvar EMPD and metastatic recurrence in perianal EMPD. Recurrences in penoscrotal subtype were less common, and selective surveillance in this subtype may be considered. Limitations of this study include the lack of replication cohorts and the exclusion of studies that did not stratify outcomes by anatomic subtype.

Nanocavity-Mediated Purcell Enhancement of Er in TiO2 Thin Films Grown via Atomic Layer Deposition.

The use of trivalent erbium (Er3+), typically embedded as an atomic defect in the solid-state, has widespread adoption as a dopant in telecommunication devices and shows promise as a spin-based quantum memory for quantum communication. In particular, its natural telecom C-band optical transition and spin-photon interface make it an ideal candidate for integration into existing optical fiber networks without the need for quantum frequency conversion. However, successful scaling requires a host material with few intrinsic nuclear spins, compatibility with semiconductor foundry processes, and straightforward integration with silicon photonics. Here, we present Er-doped titanium dioxide (TiO2) thin film growth on silicon substrates using a foundry-scalable atomic layer deposition process with a wide range of doping controls over the Er concentration. Even though the as-grown films are amorphous after oxygen annealing, they exhibit relatively large crystalline grains, and the embedded Er ions exhibit the characteristic optical emission spectrum from anatase TiO2. Critically, this growth and annealing process maintains the low surface roughness required for nanophotonic integration. Finally, we interface Er ensembles with high quality factor Si nanophotonic cavities via evanescent coupling and demonstrate a large Purcell enhancement (≈300) of their optical lifetime. Our findings demonstrate a low-temperature, nondestructive, and substrate-independent process for integrating Er-doped materials with silicon photonics. At high doping densities this platform can enable integrated photonic components such as on-chip amplifiers and lasers, while dilute concentrations can realize single ion quantum memories.

Complexity of surgery and treatment burden in patients with peritoneal malignancy is not determined by addition of hyperthermic intraperitoneal chemotherapy.

BACKGROUND: This study describes surgical and quality of life outcomes in patients with peritoneal malignancy treated by cytoreductive surgery (CRS) alone compared with a subgroup treated with CRS and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Peritoneal malignancy patients undergoing surgery between 2017 and 2023 were included. The cohort was divided into patients treated by CRS and HIPEC and those treated by CRS without HIPEC (including CRS only or maximal tumour debulking (MTB)). Main outcomes included surgical outcomes, survival, and quality of life. Groups were compared using non-parametric tests and log-rank test was used to compare survival curves. RESULTS: 403 had CRS and HIPEC, 25 CRS only and 15 MTB. CRS and HIPEC patients had a lower peritoneal carcinomatosis index (12.0 vs. 17.0 vs. 35.0; P < 0.001) and longer surgical operative time (9.3 vs. 8.3 vs. 5.2 h; P < 0.001), when compared to CRS only and MTB, respectively. No other significant difference between groups was observed. CONCLUSIONS: The optimal management of selected patients with resectable peritoneal malignancy incorporates a combined strategy of CRS and HIPEC. When HIPEC is not utilized, due to significant residual disease or comorbidity precluding safe delivery, CRS alone is associated with good outcomes. Hospital stay and complications are acceptable but not significantly different to the CRS and HIPEC group. CRS alone is a complex intervention requiring comparable resources with good outcomes. In view of our findings 'intention to treat' with CRS and HIPEC should be the basis for resource allocation and funding.

High but decreasing rates of reconstruction after total proctocolectomy for ulcerative colitis, and evidence of a direct volume outcome relationship.

BACKGROUND: Total (procto)colectomy is indicated in 15%-20% of ulcerative colitis(UC) patients during their disease course. Reconstruction options to avoid a permanent ileostomy include an ileoanal pouch anastomosis (IPAA) or ileorectal anastomosis (IRA). This study aimed to investigate reconstruction rates using Australian-based population-level data, and factors influencing reconstruction. METHODS: A retrospective data linkage study of the NSW population over a 19-year period was performed. Patients with UC who underwent total (procto)colectomy with a minimum of 1-year follow up were included. The main outcome was reconstruction with either IPAA or IRA. The influence of hospital and patient factors on reconstruction rates was assessed by Cox regression. RESULTS: Overall, 1047 patients underwent a (procto)colectomy for UC (mean age 45.9 years [SD ± 18.3], 640 [61.1%] male). The 5-year reconstruction rate was 55% (IPAA 89%). Advanced age, emergent colectomy, higher comorbidity burden, and geographical remoteness were significantly associated with lower reconstruction rates. A lower reconstruction rate was also observed in the most recent time-period (2014-2019) (aHR 0.68[95% CI 0.54-0.86]), and where index (procto)colectomy was performed in low-volume (<1 pouch/year) pouch hospitals (aHR 0.60 [95% CI 0.43-0.82]). CONCLUSIONS: NSW Australia has the highest reported rate of reconstruction following UC (procto)colectomy globally. However, rates reduced in the most recent time-period. There was variation in reconstruction rates across centres, with primary and overall reconstruction rates proportionate to hospital pouch volume. Reconstruction rates were also lower for patients living outside major cities. To ensure equitable opportunities for reconstruction, patients being considered for IBD pouch surgery should be centralized to a limited number of specialist pouch centres.

Surgical and survival outcomes of early-onset colorectal cancer patients: a single-centre descriptive Australian study.

BACKGROUND: Early-onset colorectal cancer (EOCRC) incidence is increasing in Australia. However, no Australian studies have reported on EOCRC patients' surgical management and survival patterns. METHODS: A retrospective study of 111 EOCRC patients treated at the Royal Prince Alfred Hospital (RPAH), Sydney, Australia between January 2013 and December 2021 was performed. RPAH is a quaternary referral centre for pelvic exenteration (PE) and cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). RESULTS: Most patients had left-sided tumours (76.58%) and stage IV disease at the time of presentation (37.85%). 27.93% of patients underwent either CRS/HIPEC and PE and 72.07% of patients underwent other colorectal resections of which the most common was low anterior resection (19.82%). A stoma was fashioned in 50.54% of patients. Complications occurred in 54.95% of patients of which most were Clavien-Dindo grade II (47.54%). Absolute 1-, 3- and 5-year time intervals were 93.69%, 87.39% and 85.48%. Disease-free and overall survival were poorer in stage IV patients who had PE, followed by CRS/HIPEC then other colorectal resections (P < 0.001 and P = 0.003). CONCLUSIONS: Stoma formation, PE and CRS/HIPEC and minor postoperative complications were common in our EOCRC cohort. Despite this, the 5-year absolute survival rate was acceptable. Thus, an aggressive surgical approach in EOCRC patients at a quaternary referral centre may be feasible at the cost of greater postoperative morbidity. This information is imperative in the surgical consent and preoperative counselling of EOCRC patients and highlights the need for further research to assess the postoperative functional outcomes and quality of life of EOCRC patients.

Training Paradigms in Critical Care Cardiology: A Scoping Review of Current Literature.

Background: Over the past decade there has been increasing interest in critical care medicine (CCM) training for cardiovascular medicine (CV) physicians either in isolation (separate programs in either order [CV/CCM], integrated critical care cardiology [CCC] training) or hybrid training with interventional cardiology (IC)/heart failure/transplant (HF) with targeted CCC training. Objective: To review the contemporary landscape of CV/CCM, CCC, and hybrid training. Methods: We reviewed the literature from 2000-2022 for publications discussing training in any combination of internal medicine CV/CCM, CCC, and hybrid training. Information regarding training paradigms, scope of practice and training, duration, sequence, and milestones was collected. Results: Of the 2,236 unique citations, 20 articles were included. A majority were opinion/editorial articles whereas two were surveys. The training pathways were classified into - (i) specialty training in both CV (3 years) and CCM (1-2 years) leading to dual American Board of Internal Medicine (ABIM) board certification, or (ii) base specialty training in CV with competencies in IC, HF or CCC leading to a non-ABIM certificate. Total fellowship duration varied between 4-7 years after a three-year internal medicine residency. While multiple articles commented on the ability to integrate the fellowship training pathways into a holistic and seamless training curriculum, few have highlighted how this may be achieved to meet competencies and standards. Conclusions: In 20 articles describing CV/CCM, CCC, and hybrid training, there remains significant heterogeneity on the standardized training paradigms to meet training competencies and board certifications, highlighting an unmet need to define CCC competencies.