A systematic review of minimally invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal malignancy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is traditionally a maximally invasive operation with a large abdominal incision and multi-visceral resections. However, to minimize abdominal wall morbidity and improve functional recovery, some centres have adopted a minimally invasive (MI) approach in select cases. The primary aim of this systematic review and meta-analysis was to assess the evidence for safety and patient selection for minimally invasive approaches to CRS and HIPEC with curative intent. METHODS: A PRISMA-compliant systematic review was performed using three electronic databases: Ovid MEDLINE, EMBASE and Web of Science. Data regarding postoperative morbidity was meta-analysed. RESULTS: Thirteen studies met the inclusion criteria (N = 462 MI patients), all of which were retrospective in design. Six studies included an open comparison group. Pseudomyxoma peritonei, mesothelioma and ovarian carcinoma made up the majority of cases (>90%), with a PCI < 10 listed as a prerequisite to selection across all studies. On pooled analysis there was no difference in major morbidity between MI and open groups (OR 0.52 95% CI 0.18-1.46, P = 0.33). There was one perioperative death reported in the MI group. Length of stay appeared shorter in the MI group (median range MI: 4-11 v Open: 7-13 days). Short-term recurrence and overall survival between both groups also appeared no different. CONCLUSION: Minimally invasive CRS and HIPEC appears feasible and safe in appropriately selected patients. Clear histological stratification and longer term follow up is required to determine oncological safety, particularly in more aggressive tumours such as colorectal peritoneal metastases.

Pornography exposure and access among young Australians: a cross-sectional study.

OBJECTIVE: This article aims to explore the extent and nature of Australian young people's pornography exposure and access. METHODS: Cross-sectional online survey of 1,985 young Australians aged 15-20 years, nationally representative of a range of demographics. RESULTS: Exposure to pornography was reported by 86% of male and 69% of female participants. Most exposure occurred when participants were alone and at home, regardless of gender. Young men were more likely than young women to seek pornography out and to view it frequently, with over half (54%) of male participants reporting weekly use compared with 14% of female participants. On average, boys and young men saw pornography 3.2 years before their first partnered sexual experience, and girls and young women saw it 2.0 years before theirs. CONCLUSIONS: It is common for young people to see pornography years before their first partnered sexual experience. IMPLICATIONS FOR PUBLIC HEALTH: Unintentional and deliberate exposure to pornography is common and frequent among young people. Public health strategies among young people are necessary to address the potential harms associated with pornography use, including gender-based violence and risky sexual practices.

Impact of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal adenocarcinoma.

AIM: Peritoneal dissemination of infiltrative appendiceal tumors is a rare and poorly understood phenomenon. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognized treatment option for selected patients. Neoadjuvant systemic chemotherapy (NAC) has been shown to be associated with improved overall survival (OS) in colorectal peritoneal metastases but little is known of the impact of this from an appendiceal adenocarcinoma perspective. METHOD: A prospective database of 294 patients with advanced appendiceal primary tumors undergoing CRS ± HIPEC between June 2009 and December 2020 was reviewed. Baseline characteristics and long-term outcomes were compared between patients with adenocarcinoma who received neoadjuvant chemotherapy or upfront surgery. RESULTS: Eighty-six (29%) patients were histologically diagnosed with an appendiceal cancer. These included intestinal-type adenocarcinoma (11.6%), mucinous adenocarcinoma (43%), and goblet cell adenocarcinoma (GCA) or signet ring cell adenocarcinoma (SRCA) (45.4%). Twenty-five (29%) of these underwent NAC, of which eight (32%) exhibited some degree of radiological response. There was no statistical difference in OS at 3 years between the NAC and upfront surgery groups (47.3% vs. 75.8%, p = 0.372). Appendiceal histology subtypes, particularly GCA and SRCA (p = 0.039) and peritoneal carcinomatosis index >10 (p = 0.009), were factors independently associated with worse OS. CONCLUSION: Administration of NAC did not appear to prolong OS in the operative management of disseminated appendiceal adenocarcinomas. GCA and SRCA subtypes display a more aggressive biological phenotype.

Redo Pelvic Surgery and Combined Metastectomy for Locally Recurrent Rectal Cancer with Known Oligometastatic Disease: A Multicentre Review.

INTRODUCTION: Historically, surgical resection for patients with locally recurrent rectal cancer (LRRC) had been reserved for those without metastatic disease. 'Selective' patients with limited oligometastatic disease (OMD) (involving the liver and/or lung) are now increasingly being considered for resection, with favourable five-year survival rates. METHODS: A retrospective analysis of consecutive patients undergoing multi-visceral pelvic resection of LRRC with their oligometastatic disease between 1 January 2015 and 31 August 2021 across four centres worldwide was performed. The data collected included disease characteristics, neoadjuvant therapy details, perioperative and oncological outcomes. RESULTS: Fourteen participants with a mean age of 59 years were included. There was a female preponderance (n = 9). Nine patients had liver metastases, four had lung metastases and one had both lung and liver disease. The mean number of metastatic tumours was 1.5 +/- 0.85. R0 margins were obtained in 71.4% (n = 10) and 100% (n = 14) of pelvic exenteration and oligometastatic disease surgeries, respectively. Mean lymph node yield was 11.6 +/- 6.9 nodes, with positive nodes being found in 28.6% (n = 4) of cases. A single major morbidity was reported, with no perioperative deaths. At follow-up, the median disease-free survival and overall survival were 12.3 months (IQR 4.5-17.5 months) and 25.9 months (IQR 6.2-39.7 months), respectively. CONCLUSIONS: Performing radical multi-visceral surgery for LRRC and distant oligometastatic disease appears to be feasible in appropriately selected patients that underwent good perioperative counselling.

Technological advances define shifting pathway signaling from normal to primary and metastatic colorectal cancer.

Adoption of organoid/tumoroid propagation of normal and malignant intestinal epithelia has provided unparalleled opportunities to compare cell growth factor and signaling dependencies. These 3D structures recapitulate tumours in terms of gene expression regarding the tumor cells but also allow deeper insights into the contribution of the tumour microenvironment (TME). Elements of the TME can be manipulated or added back in the form of infiltrating cytotoxic lymphocytes and/or cancer associated fibroblasts. The effectiveness of chemo-, radio- and immunotherapies can be explored within weeks of deriving these patient-derived tumour avatars informing treatment of these exact patients in a timely manner. Entrenched paths to colorectal cancer (CRC) from the earliest steps of conventional adenoma or serrated lesion formation, and the recognition of further sub-categorisations embodied by consensus-molecular-subtypes (CMS), provide genetic maps allowing a molecular form of pathologic taxonomy. Recent advances in organoid propagation and scRNAseq are reshaping our understanding of CMS and CRC.

Perioperative outcomes of cytoreductive surgery for tumours of colorectal or appendiceal origin with ovarian involvement.

BACKGROUND AND OBJECTIVES: Ovarian metastases (OM) are a common site for metastases in gastrointestinal tumours with peritoneal disease. This study aimed to evaluate perioperative complications between patients with and without OM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for appendiceal/colorectal cancer. METHODS: Female patients undergoing CRS ± HIPEC for appendiceal/colorectal tumours at a single centre from 2009 to 2020 were analysed. Patients were grouped according to presence or absence of OM at the time of CRS. RESULTS: The study included 318 patients, 72 (22.6%) had OM. Operation duration was longer for patients with OM (332 vs. 276 min, p < 0.0001). Patients with OM achieved higher rates of complete cytoreduction (93% vs. 79%, p = 0.006) despite a higher peritoneal carcinomatosis index (13 vs. 7, p < 0.001) and were more likely to require a blood transfusion (32% vs. 19%, p = 0.024) and a stoma (24% vs.10%, p = 0.005). Increasing age and presence of abdominal symptoms were independent predictors of major and all-cause morbidity, respectively. The presence of abdominal symptoms was independently associated with all-cause morbidity in the OM group. CONCLUSION: These results may assist with preoperative counselling. Prospective multicentre datasets are needed to evaluate morbidity in one- versus two-stage approaches for those with abdominal symptoms and OM.

Radiographic considerations for pediatric supracondylar humerus fractures.

Although supracondylar humerus fractures are common pediatric injuries, guidelines for postoperative imaging remain unclear. This study's purpose was to evaluate decision-making at various points in the postoperative period. The secondary objective was to compare the use of mini C arm fluoroscopy and flat plate X-rays at the first postoperative visit. A retrospective, cohort study was performed at one level I trauma center. Patients ages 1 to 14 with extension Gartland type II-IV supracondylar fractures sustained between January 2013 and May 2020 and treated with closed or open reduction and percutaneous fixation were included. Data collected included demographics, fracture characteristics, and imaging information. Of 553 patients who underwent surgery, 375 (67.8%) received intraoperative images after casting; none resulted in an intraoperative intervention. Of 463 patients with imaging at first follow-up, nine (1.9%) had a management modification, including seven for loss of reduction, all determined by the original operating surgeon. The method of imaging, did not differ significantly with respect to revision surgery. Twenty-six (4.0%) of 532 patients with imaging at pin removal received additional casting after pin removal, but no patients had their pins retained. This retrospective study examined the efficacy of imaging in pediatric supracondylar fractures. Intraoperative, postcasting images did not change management and should be discontinued. Imaging at first follow-up can be useful in identifying patients with loss of reduction and mini C arm serves as a viable alternative to standard X-rays. Finally, imaging at pin removal resulted in additional casting only in type III fractures. Level of evidence: Level III-retrospective, cohort study.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in small bowel adenocarcinoma with peritoneal metastasis: a systematic review.

Objectives: Small bowel adenocarcinoma (SBA) with peritoneal metastasis (PM) is rare and despite treatment with systemic chemotherapy, the prognosis is poor. However, there is emerging evidence that cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) may offer a survival benefit over systemic therapy alone. This systematic review will assess the effectiveness of CRS-HIPEC for SBA-PM. Content: Three databases were searched from inception to 11/10/21. Clinical outcomes were extracted and analysed. Summary: A total of 164 cases of SBA-PM undergoing CRS-HIPEC were identified in 12 studies. The majority of patients had neoadjuvant chemotherapy (87/164, 53%) and complete cytoreduction (143/164, 87%) prior to HIPEC. The median overall survival was 9-32 months and 5-year survival ranged from 25 to 40%. Clavien-Dindo grade III/IV morbidity ranged between 19.1 and 50%, while overall mortality was low with only 3 treatment-related deaths. Outlook: CRS-HIPEC has the potential to improve the overall survival in a highly selected group of SBA-PM patients, with 5-year survival rates comparable to those reported in colorectal peritoneal metastases. However, the expected survival benefits need to be balanced against the intrinsic risk of morbidity and mortality associated with the procedure. Further multicentre studies are required to assess the safety and feasibility of CRS-HIPEC in SBA-PM to guide best practice management for this rare disease.

Depression rates among African American inflammatory bowel disease patients at a large safety net hospital.

AIM: Major depressive disorder is a prominent psychiatric illness in the United States. It has been found to be higher among patients with inflammatory bowel disease. However, few studies have focused on depression among minority populations with inflammatory bowel disease. Our study determined the prevalence of depression in minority patients with inflammatory bowel disease at our safety-net hospital, which serves a predominantly African American patient population. METHODS: We conducted a single centre retrospective cohort study at a large, urban outpatient centre. We retrieved the electronic medical records of patients with inflammatory bowel disease who were seen in the gastroenterology clinic from December 2018-December 2019. Data on the severity of depression within the minority population, using the nine-question Patient Health Questionnaire, was obtained. The effects of age, sex, inflammatory bowel disease diagnosis, and comorbidities were analysed. A p-value <0.05 was considered statistically significant. RESULTS: A total of IBD patients were included in the study, of which 46.7% were female and 53.3% were male. Mean age was 44 years. With regard to race, 88.4% were African American, 5.3% Asian, 2.1% Hispanic, 1.1% American Indian/Alaskan Native, and 3.2% multiracial. A total of 71.6% had Crohn's disease and 28.4% had ulcerative colitis. Overall prevalence of major depressive disorder was 25.3%; 45.8% had minimal, 8.3% mild, 33.3% moderate, and 12.5% severe depression. A total of 34.7% of patients were never screened for depression, and 13.8% had other psychiatric conditions. There was a difference in depression rates based on psychiatric conditions (p = 0.00), but no difference based on sex (p = 0.37), IBD subtype (p = 0.34), or medical conditions (p = 0.84). CONCLUSIONS: Rates of depression among minority patients, predominantly African American, with inflammatory bowel disease were higher than previously reported for all patients with inflammatory bowel disease. Over 40% experienced moderate to severe depression. There was a low screening rate for depression. This data will be used to improve depression screening, especially among minorities.

Effect of Surgical Humidification on Inflammation and Peritoneal Trauma in Colorectal Cancer Surgery: A Randomized Controlled Trial.

BACKGROUND: Pre-clinical studies indicate that dry-cold-carbon-dioxide (DC-CO2) insufflation leads to more peritoneal damage, inflammation and hypothermia compared with humidified-warm-CO2 (HW-CO2). Peritoneum and core temperature in patients undergoing colorectal cancer (CRC) surgery were compared. METHODS: Sixty-six patients were randomized into laparoscopic groups; those insufflated with DC-CO2 or HW-CO2. A separate group of nineteen patients undergoing laparotomy were randomised to conventional surgery or with the insertion of a device delivering HW-CO2. Temperatures were monitored and peritoneal biopsies and bloods were taken at the start of surgery, at 1 and 3 h. Further bloods were taken depending upon hospital length-of-stay (LOS). Peritoneal samples were subjected to scanning electron microscopy to evaluate mesothelial damage. RESULTS: Laparoscopic cases experienced a temperature drop despite Bair-HuggerTM use. HW-CO2 restored normothermia (≥ 36.5 °C) by 3 h, DC-CO2 did not. LOS was shorter for colon compared with rectal cancer cases and if insufflated with HW-CO2 compared with DC-CO2; 5.0 vs 7.2 days, colon and 11.6 vs 15.4 days rectum, respectively. Unexpectedly, one third of patients had pre-existing damage. Damage increased at 1 and 3 h to a greater extent in the DC-CO2 compared with the HW-CO2 laparoscopic cohort. C-reactive protein levels were higher in open than laparoscopic cases and lower in both matched HW-CO2 groups. CONCLUSIONS: This prospective RCT is in accord with animal studies while highlighting pre-existing damage in some patients. Peritoneal mesothelium protection, reduced inflammation and restoration of core-body temperature data suggest benefit with the use of HW-CO2 in patients undergoing CRC surgery.

New insights into the unique nature of colorectal cancer peritoneal metastases-rethinking HIPEC.

Colorectal peritoneal metastases (CRPM) can be resistant to the chemotherapy agent (oxaliplatin) most employed, up until recently, as hyperthermic intraperitoneal chemotherapy (HIPEC). Glutathione-mediated inactivation of oxaliplatin can be substantially reduced by genomic deletion of the gene or pharmacological inhibition of glutamate-cysteine ligase in CRPM tumouroids. These discoveries may rekindle the enthusiasm for HIPEC in concert with cytoreductive surgery, which has been employed to manage patients with this once-nihilistic form of stage-IV disease.

The impact of molecular and mismatch repair status on the survival outcomes of surgically treated patients with colorectal peritoneal metastases.

BACKGROUND: Stratification of patients with colorectal peritoneal metastases (CRPM) using RAS/BRAF mutational status may refine patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This study aimed to analyse the association of RAS/BRAF status and their variants, with clinicopathological variables and survival outcomes in patients who have undergone CRS ± HIPEC. METHODS: A single centre, peritonectomy database was interrogated for patients with CRPM who underwent peritonectomy procedures between 2010 and 2020. RESULTS: During the study period, 174 patients were included. Molecular status was obtained on 169 patients, with 68 (40.5%) KRAS, 25 (14.8%) BRAF and 6 (3.6%) NRAS mutations detected. Patients with BRAF mutations were more likely to be mismatch repair deficient (dMMR) (BRAF 20%, KRAS 4.4%, wild type 8.6%, p = 0.015). Most common BRAF and KRAS variants were, V600E (80%) and G12D (39.7%), respectively. BRAF V600E was independently associated with worse overall (median: 28 months, multivariate: HR 2.29, p = 0.026) and disease-free survival (median: 8 months, multivariate: HR 1.8, p = 0.047). KRAS G12V was a strong prognostic factor associated with disease-free survival (median: 9 months, HR 2.63, p = 0.016). dMMR patients (14/161, 8.7%) exhibited worse median overall survival compared to those with proficient MMR (dMMR 27 months, pMMR 29 months p = 0.025). CONCLUSION: This study highlights the importance of molecular analysis in CRPM stratification. BRAF V600E mutations predict poor outcomes post CRS and HIPEC and may help refine patient selection for this procedure. Molecular analysis should be performed preoperatively to characterise prognosis and guide perioperative therapeutic options.

Perforation of the Knee Joint Following Antegrade Intramedullary Nailing of a Comminuted Femoral Diaphyseal Fracture: A Case Report.

A 63-year-old man with a comminuted spiral femoral shaft fracture was treated with closed reduction and internal fixation with a cephalomedullary nail. Two weeks postoperatively, one of the two static distal interlocking bolts began backing out and was removed. The nail ultimately migrated distally and perforated the knee joint at four months postoperatively. The patient was successfully treated with an exchange nail and percutaneous bone graft to the fracture site. A single static distal interlocking bolt may be inadequate to maintain length in a healing comminuted spiral femur shaft. Multiple distal interlocking bolts should be in place until the completion of fracture healing.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases in an elderly population: outcomes from a single centre.

BACKGROUND: The prevalence of elderly patients with resectable colorectal peritoneal metastases (CRPM) is increasing. This study aimed to compare short and long-term outcomes of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for CRPM in patients above and below 70 years of age. METHODS: This was a retrospective, 10-year analysis of 90-day major morbidity and mortality, and long-term survival. RESULTS: Thirty-two (21.3%) of 150 consecutive patients who underwent CRS and HIPEC during the study period were aged 70 and older. PCI (P = 0.04), perioperative chemotherapy use (P < 0.01) and organ resections (rectum P = 0.04, diaphragm P = 0.03) were less in the over 70 group. There was no significant differences in major morbidity (P = 0.19) and mortality (P = 0.32). There was also no difference in 5-year overall survival (OS) (≥70: 26% vs. <70: 39%; P = 0.68) and disease-free survival (DFS) (≥70: 25% vs. <70: 14%; P = 0.22). Age above 70 was not independently associated with worse OS (HR 1.55, P = 0.20) and DFS (HR 1.07, P = 0.81). CONCLUSION: The surgical management of CRPM appears safe and feasible in this elderly population. Appropriate selection of elderly patients for such radical intervention is reinforced by the comparable survival with those under 70.