Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.

Generation and assessment of cytokine-induced killer cells for the treatment of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Cytokine-induced killer (CIK) cells are an adoptive immunotherapy reported to have strong anti-tumour activity across a range of cancers. They are a heterogeneous mix of lymphoid cells generated by culturing human peripheral blood mononuclear cells with cytokines and monoclonal antibodies in vitro. In this study, we investigated the yield and function of CIK cells generated from patients with CRC liver metastases. We first showed that CIK cells generated in serum free medium X-VIVO 15 were comparable to those from RPMI medium with 10% FBS in terms of the number and percentages of the main subsets of cells in the CIK culture, and the intracellular levels of granzyme B and perforin, and the pro-inflammatory cytokines IL-2, IFN-γ and TNF-α. The CIK cells were cytotoxic to CRC cell lines grown in 2D cultures or as spheroids, and against autologous patient-derived tumour organoids. Donor attributes such as age, sex, or prior chemotherapy exposure had no significant impact on CIK cell numbers or function. These results suggest that functional CIK cells can be generated from patients with CRC liver metastatic disease, and support further investigations into the therapeutic application of autologous CIK cells in the management of patients with CRC liver metastases.

Intraoperative complications of robotic-assisted extended totally extraperitoneal (eTEP) ventral hernia retromuscular repairs with mesh: a systematic literature review and narrative synthesis.

Minimally invasive extended totally extraperitoneal (eTEP) technique is revolutionising ventral hernia repairs. Robotic-assisted eTEP has been gaining popularity due to better visual clarity and greater dexterity provided by the robotic systems, compared to laparoscopy. Despite growing number of papers being published each year, so far, no study has explored intraoperative complications in robotic-assisted eTEP. The aim was to perform a systematic literature review on the incidence of intraoperative complications in robotic-assisted eTEP ventral hernia repairs. The study protocol was preregistered with PROSPERO, registration number CRD42023450072. Twelve categories of intraoperative complications were defined by the authors. A search of PubMed and Embase was conducted on 16/08/2023, for articles pertaining to robotic-assisted eTEP operations in ventral hernias in adults. Articles were critically appraised and data were extracted using predefined extraction templates. No data were suitable for statistical analysis and a narrative synthesis was performed instead. Ten studies fulfilled the inclusion criteria, of which four studies reported intraoperative complications. Of the 12 categories of intraoperative complications, only 5 were reported. Three studies encountered adherent bowel inside the hernia sac. One reported linea alba injury with subsequent anterior layer dehiscence. There was one case of unrecognised intraoperative retromuscular bleeding and one case of insufflation injury with subcutaneous emphysema. There is a paucity of literature on the incidence of intraoperative complications in robotic-assisted eTEP ventral hernia repairs. Available studies suggest complication rates are low. More robust studies using prospective data from hernia registries are required before further conclusions can be drawn.

Achieving equity: patient demographics and outcomes after surgical and non-surgical procedures in South Australia, 2022.

BACKGROUND: Although modern Australian healthcare systems provide patient-centred care, the ability to predict and prevent suboptimal post-procedural outcomes based on patient demographics at admission may improve health equity. This study aimed to identify patient demographic characteristics that might predict disparities in mortality, readmission, and discharge outcomes after either an operative or non-operative procedural hospital admission. METHODS: This retrospective cohort study included all surgical and non-surgical procedural admissions at three of the four major metropolitan public hospitals in South Australia in 2022. Multivariable logistic regression, with backwards selection, evaluated association between patient demographic characteristics and outcomes up to 90 days post-procedurally. RESULTS: 40 882 admissions were included. Increased likelihood of all-cause, post-procedure mortality in-hospital, at 30 days, and 90 days, were significantly associated with increased age (P < 0.001), increased comorbidity burden (P < 0.001), an emergency admission (P < 0.001), and male sex (P = 0.046, P = 0.03, P < 0.001, respectively). Identification as ATSI (P < 0.001) and being born in Australia (P = 0.03, P = 0.001, respectively) were associated with an increased likelihood of 30-day hospital readmission and decreased likelihood of discharge directly home, as was increased comorbidity burden (P < 0.001) and emergency admission (P < 0.001). Being married (P < 0.001) and male sex (P = 0.003) were predictive of an increased likelihood of discharging directly home; in contrast to increased age (P < 0.001) which was predictive of decreased likelihood of this occurring. CONCLUSIONS: This study characterized several associations between patient demographic factors present on admission and outcomes after surgical and non-surgical procedures, that can be integrated within patient flow pathways through the Australian healthcare system to improve healthcare equity.

Clinical application of cytokine-induced killer (CIK) cell therapy in colorectal cancer: Current strategies and future challenges.

Colorectal cancer (CRC) remains a significant global health burden and is the second leading cause of cancer-related death. Cytokine induced killer (CIK) cell therapy is an immunotherapy which has the potential to meet this need. Clinical trials of CIK cell therapy for the management of CRC have reported improved clinical outcomes. However, production and delivery protocols varied significantly, and many studies were reported only in Chinese language journals. Here we present the most comprehensive review of the clinical CIK cell therapy trials for CRC management to date. We accessed both English and Chinese language clinical studies, and summarise how CIK cell therapy has been implemented, from manufacturing to patient delivery. We discuss current challenges that impede wider adoption of CIK cell therapy in CRC management.

Reoperation for post hepatectomy complications.

BACKGROUND: Reoperation for post hepatectomy complications is associated with high rates of morbidity and mortality. We aim to describe the frequency, indications, and risk factors for reoperation after liver resection in a single centre. METHODS: Perioperative data of 464 patients, who underwent elective hepatectomy from 2001 to 2020 at The Queen Elizabeth Hospital in South Australia, were retrospectively analysed. The frequency and indications for reoperation for post hepatectomy complications were recorded. Binary logistic regression analysis was performed to determine variables associated with reoperation. RESULTS: A total of seven patients (1.5%) underwent reoperation post hepatectomy. The most common indications for reoperation were intra-abdominal abscess, post-operative haemorrhage, bile leak, and ischaemic bowel. Three out of the seven patients died. Patients were more likely to require reoperation if an additional major non-hepatic procedure was performed. CONCLUSION: Reoperation post hepatectomy is associated with morbidity and mortality and is more likely to occur in patients who have undergone a non-hepatic procedure at the same time as the primary hepatic resection. Surgeons should ensure these patients are appropriately monitored and be selective about performing complex, multiple procedures. When possible, procedures should be staged.

Surgery's Rosetta Stone: Natural language processing to predict discharge and readmission after general surgery.

BACKGROUND: This study aimed to examine the accuracy with which multiple natural language processing artificial intelligence models could predict discharge and readmissions after general surgery. METHODS: Natural language processing models were derived and validated to predict discharge within the next 48 hours and 7 days and readmission within 30 days (based on daily ward round notes and discharge summaries, respectively) for general surgery inpatients at 2 South Australian hospitals. Natural language processing models included logistic regression, artificial neural networks, and Bidirectional Encoder Representations from Transformers. RESULTS: For discharge prediction analyses, 14,690 admissions were included. For readmission prediction analyses, 12,457 patients were included. For prediction of discharge within 48 hours, derivation and validation data set area under the receiver operator characteristic curves were, respectively: 0.86 and 0.86 for Bidirectional Encoder Representations from Transformers, 0.82 and 0.81 for logistic regression, and 0.82 and 0.81 for artificial neural networks. For prediction of discharge within 7 days, derivation and validation data set area under the receiver operator characteristic curves were, respectively: 0.82 and 0.81 for Bidirectional Encoder Representations from Transformers, 0.75 and 0.72 for logistic regression, and 0.68 and 0.67 for artificial neural networks. For readmission prediction within 30 days, derivation and validation data set area under the receiver operator characteristic curves were, respectively: 0.55 and 0.59 for Bidirectional Encoder Representations from Transformers and 0.77 and 0.62 for logistic regression. CONCLUSION: Modern natural language processing models, particularly Bidirectional Encoder Representations from Transformers, can effectively and accurately identify general surgery patients who will be discharged in the next 48 hours. However, these approaches are less capable of identifying general surgery patients who will be discharged within the next 7 days or who will experience readmission within 30 days of discharge.

Opioid prescribing, pain, and hospital stay of general surgery patients with oxycodone allergies in South Australia.

BACKGROUND: The frequency of oxycodone adverse reactions, subsequent opioid prescription, effect on pain and patient care in general surgery patients are not well known. This study aimed to determine prevalence of documented oxycodone allergy and intolerances (independent variables) in a general surgical cohort, and association with prescribing other analgesics (particularly opioids), subjective pain scores, and length of hospital stay (dependent variables). METHODS: This retrospective cohort study included general surgery patients from two South Australian hospitals between April 2020 and March 2022. Multivariable logistic regression evaluated associations between previous oxycodone allergies and intolerances, prescription records, subjective pain scores, and length of hospital stay. RESULTS: Of 12 846 patients, 216 (1.7%) had oxycodone allergies, and 84 (0.7%) oxycodone intolerances. The 216 oxycodone allergy patients had lower odds of receiving oxycodone (OR 0.17, P < 0.001), higher odds of tramadol (OR 3.01, P < 0.001) and tapentadol (OR 2.87, P = 0.001), but 91 (42.3%) still received oxycodone and 19 (8.8%) morphine. The 84 with oxycodone intolerance patients had lower odds of receiving oxycodone (OR 0.23, P < 0.001), higher odds of fentanyl (OR 3.6, P < 0.001) and tramadol (OR 3.35, P < 0.001), but 42 (50%) still received oxycodone. Patients with oxycodone allergies and intolerances had higher odds of elevated subjective pain (OR 1.60, P = 0.013; OR 2.36, P = 0.002, respectively) and longer length of stay (OR 1.36, P = 0.038; OR 2.24, P = 0.002, respectively) than patients without these. CONCLUSIONS: General surgery patients with oxycodone allergies and intolerances are at greater risk of worse postoperative pain and longer length of stay, compared to patients without. Many still receive oxycodone, and other opioids that could cause cross-reactivity.

Incidence of occult appendiceal neoplasm in patients over 40 years with acute appendicitis: A single-institution review.

OBJECTIVE: To investigate the incidence of occult appendiceal neoplasm in patients aged 40 years and over who underwent appendicectomy for appendicitis. METHODS: The clinical coding electronic database was used to identify patients aged 40 years and over who were diagnosed with appendicitis from September 2010 to September 2022. Patients were included if they were managed operatively. DESIGN: Retrospective cohort study. SETTING: Modified Monash category 3 (large rural town). PARTICIPANTS: Patients aged 40 years and over undergoing appendicectomy for appendicitis. MAIN OUTCOME MEASURES: Incidence of appendiceal neoplasm within appendicectomy specimen. RESULTS: A total of 279 patients aged 40 years and over underwent appendicectomy, with a median age of 53 years (range 40-95). Nineteen patients (7%) were found to have a primary neoplastic lesion within the appendix: seven neuroendocrine neoplasms (37%), six sessile serrated lesions (32%), two colonic-type adenocarcinoma (11%), two goblet cell adenocarcinoma (11%) and two appendiceal mucinous neoplasms (11%). Additionally, one patient had a metastatic adenocarcinoma of pancreaticobiliary aetiology. CONCLUSIONS: Occult appendiceal neoplasm was higher than reported in the literature in our cohort. This would support appendicectomy as the treatment of choice for patients aged 40 years and over with acute appendicitis and caution against nonoperative management in this demographic.

Evolving challenges of leadership in surgery to improve inclusivity, representation, and well-being.

BACKGROUND: Leadership is a complex and demanding process crucial to maintaining quality in surgical systems of care. Once an autocratic practice, modern-day surgical leaders must demonstrate inclusivity, flexibility, emotional competence, team-building, and a multidisciplinary approach. The complex healthcare environment challenges those in leadership positions. The aim of this narrative review was to consolidate the major challenges facing surgeons today and to suggest evidence-based strategies to support surgical leaders. METHODS: Google Scholar, PubMed, MEDLINE, and Ovid databases were searched to review literature on the challenges faced by surgical leaders. The commonly identified areas that compromise inclusivity and productive leadership practices were consolidated into 10 main subheadings. Further research was conducted using the aforementioned databases to outline the importance of addressing such challenges, and to consolidate evidence-based strategies to resolve them. RESULTS: The importance of increasing representation of marginalized groups in leadership positions, including women, ethnic groups, the queer community, and ageing professionals, has been identified by surgical colleges in many countries. Leaders must create a collegial environment with proactive, honest communication and robust reporting pathways for victims of workplace harassment. The retention of diverse, empowering, and educating leaders relies on equitable opportunities, salaries, recognition, and support. Thus, it is important to implement formal training and mentorship, burnout prevention, conflict management, and well-being advocacy. CONCLUSION: There are two aspects to addressing challenges facing surgical leadership; improving advocacy by and for leaders. Systems must be designed to support surgical leaders through formal education and training, meaningful mentorship programmes, and well-being advocacy, thus enabling them to proactively and productively advocate and care for their patients, colleagues, and professional communities.

Sociocultural and Demographic Factors Predict Readmissions for General Surgery Patients.

INTRODUCTION: Readmission is a poor outcome for both patients and healthcare systems. The association of certain sociocultural and demographic characteristics with likelihood of readmission is uncertain in general surgical patients. METHOD: A multi-centre retrospective cohort study of consecutive unique individuals who survived to discharge during general surgical admissions was conducted. Sociocultural and demographic variables were evaluated alongside clinical parameters (considered both as raw values and their proportion of change in the 1-2 days prior to admission) for their association with 7 and 30 days readmission using logistic regression. RESULTS: There were 12,701 individuals included, with 304 (2.4%) individuals readmitted within 7 days, and 921 (7.3%) readmitted within 30 days. When incorporating absolute values of clinical parameters in the model, age was the only variable significantly associated with 7-day readmission, and primary language and presence of religion were the only variables significantly associated with 30-day readmission. When incorporating change in clinical parameters between the 1-2 days prior to discharge, primary language and religion were predictive of 30-day readmission. When controlling for changes in clinical parameters, only higher comorbidity burden (represented by higher Charlson comorbidity index score) was associated with increased likelihood of 30-day readmission. CONCLUSIONS: Sociocultural and demographic patient factors such as primary language, presence of religion, age, and comorbidity burden predict the likelihood of 7 and 30-day hospital readmission after general surgery. These findings support early implementation a postoperative care model that integrates all biopsychosocial domains across multiple disciplines of healthcare.

Colorectal adenomatous and serrated polyps in rural South Australia: who, why, what and where?

BACKGROUNDS: The adenoma-carcinoma and serrated pathways offer a window of opportunity for the removal of pre-malignant polyps and prevention of colorectal cancer (CRC) through the use of colonoscopy. The aim of this study was to investigate variation in polyp incidence in different age groups, gender and indications for undertaking colonoscopy. We also address histological types of polyps found and where in the bowel they are located. METHODS: This study is based on the colonoscopy data collected prospectively over a one-year period in multiple South Australian rural centres, 24 general surgeons contributed to this study. All histopathology results were subsequently entered into the dataset. RESULTS: A total of 3497 colonoscopies were performed, with a total of 2221 adenomatous and serrated polyps removed. Both serrated and adenomatous polyps were more common in the distal colon. Patients of male gender, aged 70 years and over and with an indication of polyp surveillance had higher adenoma and serrated polyp detection rates (ADR and SPDR). Patients aged 40-49 years old who underwent colonoscopy for positive faecal occult blood had an ADR and SPDR of 25.0% and 6.3%, respectively. CONCLUSIONS: This study has shown variation in ADR and SPDR depending on age, gender and indication for colonoscopy. This variation will help further develop key performance indicators in colonoscopy. The high ADR and SPDR in patients aged 40-49 years old whom underwent colonoscopy for positive faecal occult blood may support lowering the age of commencement of CRC screening in Australia.