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Respiratory diseases such as cystic fibrosis, COPD, and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Earlier studies have shown success with BromAc as a mucolytic agent. Hence, we tested the formulation on two gelatinous airway representative sputa models, to determine whether similar efficacy exist. Sputum lodged in an endotracheal tube was treated to aerosol N-acetylcysteine, bromelain, or their combination (BromAc). After measuring the particle size of aerosolized BromAc, the apparent viscosity was measured using a capillary tube method, whilst the sputum flow was assessed using a 0.5 mL pipette. Further, the concentration of the agents in the sputa after treatment were quantified using chromogenic assays. The interaction index of the different formulations was also determined. Results indicated that the mean particle size of BromAc was suitable for aerosol delivery. Bromelain and N-acetylcysteine affected both the viscosities and pipette flow in the two sputa models. BromAc showed a greater rheological effect on both the sputa models compared to individual agents. Further, a correlation was found between the rheological effects and the concentration of agents in the sputa. The combination index using viscosity measurements showed synergy only with 250 µg/mL bromelain + 20 mg/mL NAC whilst flow speed showed synergy for both combinations of bromelain (125 and 250 µg/mL) with 20 mg/mL NAC. Hence, this study indicates that BromAc may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretions.

Background No universally accepted guidelines exist for treatment of patients with colorectal cancer peritoneal metastases (CRPM) undergoing cytoreductive surgery and intraperitoneal chemotherapy (CRS/IPC). Several uncertainties remain concerning almost every aspect of this treatment modality, resulting in marked variability in patient management and likely outcomes. This survey aimed to define variations and trends in clinician decision making more clearly. Methods A 41-question web-based survey was distributed electronically via the Peritoneal Surface Oncology Group International (PSOGI), the International Society for the Study of Pleura and Peritoneum (ISSPP) as well as via social media (particularly Twitter). The survey sought to address and record clinician responses regarding patient workup/assessment, selection for preoperative systemic therapy, preoperative and intraoperative selection for CRS/IPC, and consideration of prognosis and complications. Results Complete responses were received from 60 clinicians from 45 centres in 22 countries. Upon assessment of survey responses, several interesting trends were noted in each section of the survey. Significant variability in surgeon practice and opinion were identified concerning almost every aspect of the treatment modality. Conclusion This international survey provides the most comprehensive insight into clinician decision-making trends regarding patient assessment, selection and management. This should allow areas of variability to be more clearly defined and could potentially prompt development of initiatives for achieving consensus and standardisation of care in the future.

The management of patients with extensive appendiceal mucinous neoplasms and mesothelioma is controversial. Our aims were to analyze overall survival (OS), disease-free survival (DFS) and independent prognostic factors associated with high peritoneal cancer index (PCI) status in patients who underwent cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC).A prospectively-maintained database for patients with appendiceal neoplasms and mesothelioma undergoing CRS/PIC from year 1996 to 2018 was retrospectively analyzed. Patients who achieved complete cytoreduction were stratified into limited (PCI30) and extensive (PCI ≥ 30) disease groups.260 female and 235 male patients were identified. The 5-year survival for low-grade appendiceal mucinous neoplasms (LAMN) was significantly higher in the low PCI group (96.2% vs. 63.5%,Long-term survivals following CRS/PIC are achievable with acceptable mortality and higher morbidity rates in extensive appendiceal mucinous neoplasms and mesothelioma. High PCI status does not preclude treatment with CRS/PIC.

Objectives Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has enabled better prognosis for patients with peritoneal surface malignancies. However, in older age groups, short -and long-term outcomes are still perceived as poor. We evaluated patients aged 70 and over and determine if age is a predictor of morbidity, mortality and overall survival (OS). Methods A retrospective cohort analysis was performed on CRS/HIPEC patients and categorised by age. The primary outcome was overall survival. Secondary outcomes included morbidity, mortality, hospital and incentive care unit (ICU) stay and early postoperative intraperitoneal chemotherapy (EPIC). Results A total of 1,129 patients were identified with 134 aged 70+ and 935 under 70. There was no difference in OS (p=0.175) or major morbidity (p=0.051). Advanced age was associated with higher mortality (4.48 vs. 1.11 %, p=0.010), longer ICU stay (p Conclusions In patients undergoing CRS/HIPEC, age of 70 and above does not impact OS or major morbidity but is associated with increased mortality. Age alone should not be a limiting factor in selecting CRS/HIPEC patients. Careful multi-disciplinary approach is needed when considering those of advanced age.

PDF file - 2503K, Influence of minocycline on inducible NF-кB activation.

PDF file - 1507K, Effect of minocycline on constitutive and TNF-α-induce NF-кB activation in HUVEC and HOSE cells.

Substantial evidence supports the critical role of NF-κB in ovarian cancer. Minocycline, a tetracycline, has been shown to exhibit beneficial effects in this malignancy through regulation of a cohort of genes that overlap significantly with the NF-κB transcriptome. Here, it was examined whether or not the molecular mechanism could be attributed to modulation of NF-κB signaling using a combination of in vitro and in vivo models. Minocycline suppressed constitutive NF-κB activation in OVCAR-3 and SKOV-3 ovarian carcinoma cells and was correlated with attenuation of IκBα kinase (IKK) activation, IκBα phosphorylation and degradation, and p65 phosphorylation and nuclear translocation. The inhibition of IKK was found to be associated with suppression of TGF-β-activated-kinase-1 (TAK1) activation and its dissociation from TAK1-binding-protein-1 (TAB1), an indispensable functional mediator between TGF-β and TAK1. Further studies demonstrated that minocycline downregulated TGF-β1 expression. Enforced TGF-β1 expression induced NF-κB activity, and minocycline rescued this effect. Consistent with this finding, TGF-β1 knockdown suppressed NF-κB activation and abrogated the inhibitory effect of minocycline on this transcription factor. These results suggest that the minocycline-induced suppression of NF-κB activity is mediated, in part, through inhibition of TGF-β1. Furthermore, the influence of minocycline on NF-κB pathway activation was examined in female nude mice harboring intraperitoneal OVCAR-3 tumors. Both acute and chronic administration of minocycline led to suppression of p65 phosphorylation and nuclear translocation accompanied by downregulation of NF-κB activity and endogenous protein levels of its target gene products. These data reveal the therapeutic potential of minocycline as an agent targeting the pro-oncogenic TGF-β—NF-κB axis in ovarian cancer.Implications: This preclinical study lends support to the notion that ovarian cancer management would benefit from administration of minocycline. Mol Cancer Res; 11(10); 1279–91. ©2013 AACR.

Interparietal hernias are rare and occur most commonly in the long-term postoperative setting following abdominopelvic surgery. This case report describes the development of a strangulated interparietal hernia through a defect in the posterior rectus sheath 4 days post-lower segment caesarean section (LSCS) in a 36-year-old female. Whilst she had an acute abdomen, she did not have a palpable incisional hernia. Her interparietal hernia was identified via a computed tomography scan of her abdomen and pelvis. She underwent a midline laparotomy where ischaemic small bowel was found within her hernia. This was resected and she had an unremarkable recovery. This case is the first of its kind and highlights the diagnostic challenge of interparietal hernias in acute postoperative patients as well as the importance of having a low threshold for suspicion for complicated interparietal hernias in patients with an acute abdomen following LSCS.

Formation of stoma during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) is often performed to reduce the risk of anastomotic leak. Subsequent stoma reversal provides a unique opportunity for second-look surgery to detect early peritoneal recurrence. Current surveillance methods often fail to detect disease early, including imaging and biochemical markers. In our study, we examined the safety and efficacy of second-look surgery for detection and treatment of disease recurrence.We performed a retrospective analysis of prospectively collected data from 35 patients undergoing stoma reversal from 2015 to 2019 with negative pre-operative imaging.A total of 37% of cases had disease recurrence, with a median peritoneal cancer index of 4. Complete cytoreduction was achieved in all patients. The majority of patients (77%) suffered minor complications only. Median length of hospital stay was 12 days.Second-look surgery detects early disease recurrence and is a safe alternative to conventional screening methods post primary CRS/HIPEC for PC. Long-term, routine second-look surgery can improve survival.

Purpose Low-grade intermediate-risk nonmuscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumor under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to transurethral resection of bladder tumor for patients with LG IR NMIBC. Materials and methods This prospective, phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary end point was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. Results A total of 63 patients (38 males and 25 females 33-96 years old) enrolled and received ≥1 instillation of UGN-102. Among the patients 41 (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%) and 25 (61%) remained disease-free at 6, 9 and 12 months after treatment initiation, respectively. A total of 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection and fatigue. Conclusions Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.

Background/Aim: Up to a third of patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) of appendiceal or colorectal origin receive a stoma during primary surgery. Stoma reversal provides an opportunity for second-look surgery. Patients and Methods: We performed a retrospective analysis of prospectively collected data of patients with colorectal cancer (CRC) or high-grade appendiceal cancer (AC) from 2006 to 2021 from our database. A total of 34 consecutive stoma closure patients with no evidence of preoperative disease recurrence (tumor markers and CT scans) were compared with 141 consecutive re-do CRS/HIPEC patients with known recurrence. Results: Eleven patients (32.4%) were identified to have peritoneal recurrence at stoma closure. Time between first and second CRS was 12 months (4 to 64.2) in the stoma closure group vs. 24.6 months (5.8 to 119.8) in the re-do group, while median peritoneal cancer index (PCI) was 4 (3 to 6) vs. 8 (1 to 39), respectively (p=0.0143). Conclusion: Second-look laparotomy during stoma closure identified unexpected PC in 32.4% of our patients with significantly lower PCI than planned re-do operations.

Objectives There are currently scarce data exploring ureteric reimplantation (UR) during cytoreductive surgery (CRS). Methods We identified patients undergoing CRS for peritoneal surface malignancies (PSM) of any origin at a single high-volume unit. UR was defined as ureteroureterostomy, transureterouretostomy, ureteroneocystostomy, ureterosigmoidostomy or ileal conduit performed during CRS. Peri-operative outcomes, long-term survival and risk factors for requiring UR were analysed. Results Seven hundred and sixty-seven CRSs were identified. Twenty-three (3.0%) procedures involved UR. Bladder resection and colorectal cancer (CRC) were associated with increased risk of UR (bladder resection: OR 12.90, 95% CI 4.91–33.90, p Conclusions UR during CRS does not increase major morbidity or mortality for carefully selected patients, and is associated with low rates of urologic complications. Whilst decreased survival was apparent in patients with HAMN undergoing UR, it is unclear whether this relationship is causal.

Introduction: The PRODIGE 7-trial investigated the additional value of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to cytoreductive surgery (CRS) for patients with colorectal peritoneal metastases (CPM). The results of PRODIGE 7 were presented at the 2018 ASCO meeting showing that 30 min oxaliplatin-based HIPEC did not improve overall survival. The current study investigated the impact of PRODIGE 7 on the worldwide practice of CRS and HIPEC. Materials and methods: CRS-HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning the current CRS-HIPEC practice in their hospital and country, and were asked to appraise the effect of PRODIGE 7. Results: The survey was completed by 18/19 experts. Although their personal opinions of CRS-HIPEC were barely influenced by PRODIGE 7, they reported a substantial impact on daily practice. This included a switch towards Mitomycin-C based HIPEC-regimens and prolongation of HIPEC perfusion time, a reduction in the number of referrals from non-HIPEC centers, a reduction in national consensus, the removal of HIPEC from national guidelines, and a reduced reimbursement rate. Conclusion: The PRODIGE 7 has had a major impact on the practice of CRS-HIPEC for CPM worldwide. HIPEC remains an attractive option with potential for control and eradication of disease and further studies into the optimal HIPEC-regimen are urgently needed. Meanwhile, given the complexity of the treatment of patients with CPM, and the proven benefits of optimal CRS, referral of patients with potentially resectable CPM to expert centers is recommended whilst the precise role of HIPEC is further evaluated. (c) 2021 Published by Elsevier Ltd.

Background/aim While controversial, cytoreductive surgery (CRS) with heated intra-peritoneal chemotherapy (HIPEC) and early postoperative intra-peritoneal chemotherapy (EPIC) remains the mainstay of treatment for low grade appendiceal neoplasm with pseudomyxoma peritonei (PMP). Our study aimed to investigate the difference in survival when administering HIPEC alone vs. HIPEC + EPIC. Additionally, we examined whether the duration of EPIC affects survival. Patients and methods We compared the difference in survival in 238 patients who underwent CRS + HIPEC alone vs. CRS + HIPEC/EPIC combination for low grade appendiceal cancer. We also compared short course (1-2 days) vs. long course (3-5 days) of EPIC. Results HIPEC/EPIC combination group (n=179) showed a significantly better 5-year survival of 95% compared to 71% in HIPEC alone (n=59). There was no statistically significant difference in 5-year survival between short course (n=22) and long course of EPIC (n=157). Conclusion Combined use of HIPEC and EPIC improves 5-year survival in low-grade appendiceal neoplasm. Two days of EPIC are sufficient.

The COVID-19 crisis has highlighted the difficulties that might occur when attempting to oxygenate patients who have suffered a severe pulmonary insult, including in the development of acute respiratory distress syndrome (ARDS). Traditional mechanical ventilation (MV) is effective; however, in severe cases of hypoxia, the use of rescue therapy, such as extracorporeal membrane oxygenation (ECMO), may be required but is also associated with significant complexity and complications. In this review, we describe peritoneal oxygenation; a method of oxygenation that exploits the peritoneum’s gas exchange properties in a fashion that is similar to peritoneal dialysis and has shown considerable promise in animal models. We have conducted a review of the available literature and techniques, including intraperitoneal perfluorocarbons, intraperitoneal jet ventilation, a continuous low-pressure oxygen system (PEROX) and the use of phospholipid-coated oxygen microbubbles (OMBs) through peritoneal microbubble oxygenation (PMO). We conclude that peritoneal oxygenation is a promising technique that warrants further investigation and might be used in clinical settings in the future.

The prognosis of pancreatic cancer is poor with the overall 5-year survival rate of less than 5% changing minimally over the past decades and future projections predicting it developing into the second leading cause of cancer related mortality within the next decade. Investigations into the mechanisms of pancreatic cancer development, progression and acquired chemoresistance have been constant for the past few decades, thus resulting in the identification of human nucleoside transporters and factors affecting cytotoxic uptake via said transporters. This review summaries the aberrant expression and role of human nucleoside transports in pancreatic cancer, more specifically human equilibrative nucleoside transporter 1/2 (hENT1, hENT2), and human concentrative nucleoside transporter 1/3 (hCNT1, hCNT3), while briefly discussing the connection and importance between these nucleoside transporters and mucins that have also been identified as being aberrantly expressed in pancreatic cancer. The review also discusses the incidence, current diagnostic techniques as well as the current therapeutic treatments for pancreatic cancer. Furthermore, we address the importance of chemoresistance in nucleoside analogue drugs, in particular, gemcitabine and we discuss prospective therapeutic treatments and strategies for overcoming acquired chemoresistance in pancreatic cancer by the enhancement of human nucleoside transporters as well as the potential targeting of mucins using a combination of mucolytic compounds with cytotoxic agents.

Fear-of-missing-out, or FoMO, is the experience of believing that other people are having an enjoyable experience from which one is absent. FoMO has been identified in previous research as a person...

Intraperitoneal administration of BromAc (bromelain + acetylcysteine) is currently undergoing a phase 1 clinical trial for pseudomyxoma peritonei at our institution. This study reports on analysis of routine blood parameters before and after treatment for a series of 25 patients in this trial. Blood parameters assessed included full blood count, electrolytes, urea, and creatinine, liver function tests, coagulation studies, as well as inflammatory markers (CRP). Certain parameters such as CRP, and white cell count, were significantly elevated after treatment whilst serum albumin level was reduced indicating an inflammatory reaction. However, liver enzymes, coagulation studies, and other parameters were not affected. Therefore, there are no additional safety signals evident upon analysis of routine blood parameter testing.

The prevalence and severity of SLE have been found to vary across populations of different ancestries. This review explores whether these differences can be explained by the genetic aetiology of the condition. Large genetic studies suggest that populations of different ancestry share the same risk loci but individual risk alleles are more common in some, leading to a higher prevalence and severity and an earlier onset of the condition. Despite many of the loci being shared across populations, some have been found to be ancestry specific and these are hypothesized to have undergone differential selective pressure in recent human history. Additionally, the effectiveness of some of the drugs used in SLE has been found to vary across ancestries, which might affect progression of the disease, but it is unclear whether these differences are pharmacogenetic. We concluded that to understand the full role of genetics in the risk, presentation and response to treatment of SLE, larger studies including individuals from a wider representation of ancestries will be required.

Gallbladder cancer is a rare cancer, associated with an extremely poor prognosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is not commonly performed in gallbladder cancer; however, case series have shown prolonged survival time with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gallbladder cancer and no increase in morbidity compared to cytoreductive surgery without hyperthermic intraperitoneal chemotherapy. We present a case of gallbladder cancer with peritoneal metastases in a 60-year-old male who was successfully treated with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and survived for 4 years following diagnosis.

Background Higher Peritoneal Cancer Index (PCI) requires more extensive surgery and maybe associated with more limited outcomes. The aim of this study in a high-volume centre in Australia was to analyse the outcomes in PCI 39 patients regarding short and long term outcomes in appendiceal tumours. Methods A retrospective analysis of prospectively maintained database of patients that underwent primary cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) with PCI 39 at St George Hospital, Sydney from 1996 to 2018. Patients with appendiceal tumours (inclusive of high and low grade) were analysed. Factors contributing to high grade (III/IV Clavien-Dindo) morbidity and mortality were assessed. Results Of the 1201 patients in the database, 58 patients had a PCI 39 from appendix tumours at their first operation. The overall survival rate at 1, 3 and 5 year was 91.2%, 79.5% and 62.9% respectively. The median survival was 87.2 months (96% CI 51.8-NR). The rate of major morbidity was 71%. The postoperative mortality incidence was 1.7%. The median hospital length of stay was 34 days (IQR:27–54 days). Conclusions In an experienced centre CRS + HIPEC is safe in selected patients with PCI 39. Despite the high morbidity, the overall survival for appendiceal tumours appear considerably better than debulking surgery.

Pseudomyxoma peritonei (PMP) is a rare mucinous disease most commonly arising from the appendix. Pleural involvement arising from established PMP is seen in a small number of cases. Combined cytoreductive surgery and hyperthermic intrathoracic chemotherapy is the treatment of choice when managing intra-thoracic PMP. In cases of recurrence, surgical intervention may be technically challenging and carry higher rates of complications, morbidity, and mortality. Bromelain and acetylcysteine (BromAc®) is a novel treatment modality that has demonstrated mucolytic properties. When injected directly into mucinous disease, it facilitates tumour dissolution and allows it to be aspirated. It has recently been tested in the treatment of inoperable peritoneal mucinous disease, with an acceptable safety profile and positive objective response. Here we describe the first two cases of BromAc® administered directly into pleural adenomucinosis, with striking differences in response between the two patients likely due to differences in tumour hardness.

Autologous reconstruction for major facial defects is primarily considered for patient's lifetime care. There are situations, however, when autologous reconstruction is not ideal or feasible, and prosthetic reconstruction is necessary to reconstruct missing anatomy or to complement surgical reconstruction. The history of facial prosthetic reconstruction can be traced for millennia. At our craniofacial center, craniomaxillofacial prosthetic rehabilitation has been incorporated in the care provided to our patients since the center's inception, more than 70 years ago.The purpose of this review is to present the evolution of our current thinking based on our long experience since the implementation of computer-assistive technologies over 15 years ago, to further improve our patients' overall rehabilitation.These applications include all stages of prosthetic care from planning, design through device delivery, and for lifetime maintenance. The collaboration among surgeons and anaplastologists is fundamental to achieving optimal patient outcomes and in the success of our technology-based practice. Such collaboration starts with the patient's decision to proceed with prosthetic rehabilitation and continues with postoperative care and lifetime management of the patient's prosthetic device and prosthesis-bearing soft tissue.Although computer-assistive techniques often represent a substantial financial investment, the benefits of using them demonstrate clear advantages to both the clinician and patient. These benefits include: Improved predictability of outcomes, surgeon preparedness, reduction in operating room time, reduction in overall treatment times, improved precision and anatomical accuracy, improved treatment efficiencies, and overall treatment experience, particularly for those patients traveling great distances for access to care.Representative examples will be presented.

Background/aim Cisplatin increases the risk of acute kidney injury (AKI) during systemic chemotherapy. However, little is known about its risk of inducing AKI when used during intraperitoneal chemotherapy. This study aimed to determine the incidence of AKI in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) with cisplatin. Patients and methods A retrospective analysis of patients who received cisplatin-based HIPEC from November 2008 to March 2018 was undertaken to determine the incidence of AKI. Results A total of 111 patients were identified. The incidence of AKI was 15.3% (17/111). Univariate analysis showed increased peritoneal cancer index (PCI), low intraoperative and post-operative urine output were significantly associated with the development of AKI. Multivariate analyses did not identify any significant predictors factors for AKI. Conclusion Cisplatin-based HIPEC is associated with AKI. At our centre, the incidence of AKI was 15.3%. Risk factors that may influence its development include high PCI and low perioperative diuresis.

The proportion of patients with liver metastases in patients with appendiceal versus colorectal adenocarcinomas was 3.1 percent and 24 percent, respectively, in our peritonectomy centre. From our internal analyses, carcinoembryonic antigen (CEA) was potentially involved. A hypothesis was proposed regarding the natural progression of appendiceal adenocarcinoma. To support this, a systematic review and meta-analysis were performed to examine whether there was a difference in the proportion of patients with an elevated CEA in appendiceal versus colorectal adenocarcinoma patients in the current literature.Medline (PubMed), EMBASE (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature, Clinicaltrials.gov, Web of Science, and Google Scholar were searched. All studies involving patients with appendiceal and/or colorectal adenocarcinoma were eligible. Data were analysed by grouping appendiceal and colorectal adenocarcinoma in separate meta-analyses, and then comparing their weighted proportions of elevated CEA. Principal summary measures were weighted proportions of patients with elevated CEA.From the initial identification of 1,928 articles, 136 articles were included in the final synthesis. Ninety-two articles were included in the meta-analysis. Proportions of appendiceal and colorectal adenocarcinoma with elevated CEA were 56% (95%CI=47-65%) and 42% (95%CI=38-46%), respectively (p=0.0001).Patients with appendiceal adenocarcinoma had a higher proportion of CEA than those with colorectal adenocarcinoma. Future studies should focus on the several aspects of CEA presented in patients with appendiceal adenocarcinoma. This could provide treatments for patients with colorectal adenocarcinoma by preventing the development of liver metastases.

Background: Iterative cytoreduction (iCRS) and hyperthermic intraperitoneal chemotherapy is a treatment for recurrence of peritoneal carcinomatosis. There are considerable upfront costs for this approach for which the cost-effectiveness has not been evaluated. Patients and Methods: We used a prospectively maintained database of patients having undergone primary and iterative cytoreduction at St. George Hospital between January 1, 2014, and December 31, 2017, which was linked with financial data. Cost effectiveness and survival outcomes were used to compare primary cytoreduction (pCRS) and iterative cytoreduction (iCRS) in addition to comparison with other treatment modalities. Results: The average cost per patient in Australian dollars was $69,295 ($14,691-$696,002) and the average cost per life-year was $15,842. There was no difference in cost-effectiveness between those who had undergone pCRS and those who had undergone iCRS. The overall survival was 52.5 months (95% confidence interval=49.7-55.2 months) with no difference in survival between pCRS and iCRS groups. The median length of hospital stay was significantly longer for patients in the pCRS treatment group (25.51 days) when compared to the iCRS treatment group (21.15 days, p=0.034). Conclusion: iCRS is a cost-effective treatment in the management of recurrent peritoneal carcinomatosis.

Background Bromelain (Brom) and Acetylcysteine (Ac) have synergistic activity resulting in dissolution of tumour-produced mucin both in vitro and in vivo. The aim of this study was to determine whether treatment of mucinous peritoneal tumour with BromAc can be performed with an acceptable safety profile and to conduct a preliminary assessment of efficacy in a clinical setting. Methods Under radiological guidance, a drain was inserted into the tumour mass or intraperitoneally. Each patient could have more than one tumour site treated. Brom 20–60 mg and Ac 1·5-2 g was administered in 5% glucose. At 24 h, the patient was assessed for symptoms including treatment-related adverse events (AEs) and the drain was aspirated. The volume of tumour removed was measured. A repeat dose via the drain was given in most patients. All patients that received at least one dose of BromAc were included in the safety and response analysis. Findings Between March 2018 and July 2019, 20 patients with mucinous tumours were treated with BromAc. Seventeen (85%) of patients had at least one treatment-emergent AE. The most frequent treatment-related AEs were CRP rise (n = 16, 80%), WCC rise (n = 11, 55%), fever (n = 7, 35%, grade I) and pain (n = 6, 30%, grade II/III). Serious treatment-related AEs accounted for 12·5% of all AEs. There were no anaphylactic reactions. There were no deaths due to treatment-related AEs. An objective response to treatment was seen in 73·2% of treated sites. Conclusion Based on these preliminary results and our preclinical data, injection of BromAc into mucinous tumours had a manageable safety profile. Considerable mucolytic activity was seen by volume of mucin extracted and radiological appearance. These results support further investigation of BromAC for patients with inoperable mucinous tumours and may provide a new and minimally invasive treatment for these patients.

Peritoneal mesothelioma (PM) is a rare and aggressive primary peritoneal malignancy characterized by widespread multiple metastatic tumour nodules originating from the peritoneum. The conventional classification distinguishes diffuse malignant peritoneal mesothelioma (DMPM) and border-line forms: multicystic peritoneal mesothelioma (MCPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM). Despite the novel achievements in the management of PM, there is difficulty in conducting randomized trials due to its rarity and aggressive biology in many cases. As there is, a necessity to standardize diagnosis and management of PM, the Peritoneal Surface Oncology Group International (PSOGI) commissioned a steering committee to elaborate clinical guidelines.

Background Colorectal cancer (CRC) treatment in patients with peritoneal metastases is complex. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are under debate. The aim of this study was to assess the consensus among international experts for decision-making regarding CRS/HIPEC in CRC patients. Materials and methods Twelve of 15 experts provided their decision algorithms for CRS/HIPEC for patients with or at high risk for peritoneal metastases from CRC. Based on the objective consensus methodology, the results were transformed into decision trees, which then provided information on the consensus and discordance. Results There was only one scenario in which the consensus on performing HIPEC reached 100%, which was when treating young patients with complete cytoreduction and a peritoneal carcinomatosis index (PCI) of less than 16 in the presence of certain risk factors (RFs). Five major decision criteria were identified and displayed: age, PCI, completeness of cytoreduction (CC), extent of extraperitoneal metastases (EoM) and, in the case of nonverified extraperitoneal metastases, further RFs. There was consensus to refrain from using HIPEC in older patients with a high PCI, and the consensus further increased when addressing incomplete cytoreduction and extensive EoM. Conclusion A definite consensus concerning the use of HIPEC was only determined for very selected scenarios. These findings can be used for general guidance, but due to the heterogeneity of each individual situation and the impracticality to present this information through decision trees, as well as the unclear future of the role of HIPEC in the adjuvant setting, a one-on-one transfer to daily clinical practice cannot be achieved.

Background The incidence of underlying malignancy in appendicitis ranges between 0.5% and 1.7%. We sought to identify the subset of patients with appendicitis who are at increased risk of appendiceal malignancy. Methods Using the Eastern Association for the Surgery of Trauma Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous database, we included all patients from 28 centers undergoing immediate, delayed, or interval appendectomy between 2017 and 2018. Univariate then multivariable analyses were performed to compare patients with and without malignancy and to identify independent demographic, clinical, laboratory, and/or radiological predictors of malignancy. Akaike information criteria for regression models were used to evaluate goodness of fit. Results A total of 3,293 patients were included. The median age was 38 (27–53) years, and 46.5% were female patients. On pathology, 48 (1.5%) had an underlying malignancy (adenocarcinoma [60.4%], neuroendocrine [37.5%], and lymphoma [2.1%]). Patients with malignancy were older (56 [34.5–67] vs 37 [27–52] years, P 40 years with an appendiceal diameter >10 mm on computed tomography was 2.95% compared with 0.97% in patients ≤40 years old with appendiceal diameter ≤10 mm. The corresponding risk ratio for that population was 3.03 (95% confidence interval: 1.24–7.42; P = .02). Conclusion The combination of age >40 and an appendiceal diameter >10 mm is associated with a greater than 3-fold increased risk of malignancy in patients presenting with appendicitis.

Background Cytoreductive surgery (CRS) for the management of peritoneal carcinomatosis (PC) can involve significant blood loss which necessitates the transfusion of blood products. This poses a particular challenge in the Jehovah's Witnesses population whose beliefs do not permit the transfusion of blood products or blood-related derivatives. This report describes the experience of one institution performing CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) for PC in Jehovah's Witnesses and perioperative management strategies employed to avoid blood transfusion. Methods A review of literature and prospectively collated data of Jehovah's Witnesses patients who underwent extensive CRS for PC and HIPEC for PC. Results Four patients had CRS and HIPEC for PC. The median PC index score was 11 and complete cytoreduction was achieved in all cases. Primary tumours were ovarian (n = 1), colorectal (n = 2) and neuroendocrine tumour of gastrointestinal origin (n = 1). The median difference between preoperative and postoperative haemoglobin was 38 g/L (23-43 g/L). Strategies included acute normovolumaeic haemodilution and autotransfusion within a closed circuit, autotransfusion from cell salvage and provisions for possible use of a haemoglobin based oxygen carrier. Ancillary measures identified and implemented to minimize transfusion dependence included, but were not limited to, preoperative iron infusion, perioperative acute haemodilution and cell salvage, administration of tranexamic acid, prothrombinex and use of paediatric tubes for venepuncture. Conclusion The review suggests CRS and HIPEC for extensive PC can be done safely in circumstances where transfusion of allogenic blood products is not permitted.

Objectives To assess the impact of short and long term outcomes of diaphragm resection and repair in cyto-reductive surgery (CRS) and intra-peritoneal chemotherapy (IPC). Methods 1230 consecutive CRS/IPC procedures were performed between 1996 and 2018 in Sydney, Australia. Among these, 652 underwent diaphragmatic intervention. The analysis was preformed according to histological subtype. First diaphragm interventions were compared to non-diaphragmatic CRS. Secondly, diaphragm resection was compared to diaphragm stripping. Overall survival and recurrence free survival was assessed based on histological diagnosis. Results There were no differences between the resection and stripping groups for the colorectal cohort. For mesothelioma, increased incidences of pleural effusions in the resection group were noted (63% vs.28%, p = 0.017). In HAMNs, the resection group was associated with increased reoperations (42% vs. 15%, p = 0.03) and in hospital death (16.7% vs. 0.6%, p = 0.012). Resection in LAMNs were linked with increased transfusion requirements (9 vs. 6, p = 0.01), reoperation (39% vs. 23%, p = 0.05) and prolonged length of stay (34 days vs. 25 days, p = 0.02). There were no differences in overall survival and recurrence free survival in colorectal cancer. Median overall survival was decreased in mesothelioma by 20 months. In LAMNs the median survival was significantly decreased for the resection group. Similarly, the resection group had a 4-month earlier recurrence. Conclusion We conclude that diaphragm interventions are an essential part of CRS. They are associated with increased perioperative morbidity. This morbidity is not attributable to whether the patient underwent diaphragm stripping or resection. However in mesothelioma and LAMNs, requiring diaphragm resection is likely to be an indicator for tumor aggression.

Background/Aims Rituximab is widely used to treat rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) but clinical response varies. Efficacy is determined by the efficiency of depletion, which may depend on a variety of Fc gamma receptor (FcγR)-dependent mechanisms. Previous research was limited by complexity of the FCGR locus, not integrating copy number variation with functional SNP, and small sample size. Here, we aimed to assess the effect of the full range of FcγRs variants on depletion, clinical response and functional effect on NK-cell-mediated killing in two rheumatic diseases with a view to personalised B-cell depleting therapies. Methods A prospective longitudinal study was conducted in 873 patients (RA = 611; SLE=262) from four cohorts (BSRBR-RA, BILAG-BR, Leeds RA and Leeds SLE Biologics). For RA, the outcome measures were 3C-DAS28CRP and 2C-DAS28CRP at 6 (+/-3) months post-rituximab (adjusted for baseline DAS28). For SLE, major clinical response (MCR) was defined as improvement of active BILAG-2004 domains to grade C/better at 6 months. B-cell depletion was evaluated by highly-sensitive flow cytometry. Qualitative and quantitative polymorphisms for five major FcγRs were measured using a commercial multiplex ligation-dependent probe amplification. Median NK cell FcγRIIIa expression (CD3-CD56+CD16+) and NK-cell degranulation (CD107a) in the presence of rituximab-coated Daudi/Raji B-cell lines were assessed using flow cytometry. Results In RA, for FCGR3A, carriage of V allele (coefficient -0.25 [SE 0.11]; p = 0.02) and increased copies of V allele (-0.20 [0.09]; p = 0.02) were associated with better 2C-DAS28 response. Irrespective of FCGR3A genotype, increased gene copies were associated with a better response. In SLE, 177/262 (67.6%) achieved BILAG response (MCR=34.4%; Partial=33.2%). MCR was associated with increased copies of FCGR3A-158V allele, OR 1.64 (95% CI 1.12-2.41) and FCGR2C-ORF allele 1.93 (1.09-3.40). Of patients with B-cells data in the combined cohort, 236/413 (57%) achieved complete depletion post-rituximab. Only homozygosity for V allele and higher copies of FCGR3A V allele were associated with increased odds of depletion. Patients with complete depletion had higher NK cell FcγRIIIa expression at rituximab initiation than those with incomplete depletion (p = 0.04) and this higher expression was associated with improved EULAR response in RA. Moreover, for FCGR3A, degranulation activity was increased in V allele carriers vs FF genotype in the combined cohort; p = 0.02. Conclusion FcγRIIIa is the major low affinity FcγR and increased copies of the FCGR3A-158V allele, encoding the allotype with a higher affinity for IgG1, was associated with clinical and biological responses to rituximab in two autoimmune diseases. This was supported by functional data on NK cell-mediated cytotoxicity. In SLE, increased copies of the FCGR2C-ORF allele was also associated with improved response. Our findings indicate that enhancing FcγR-effector functions could improve the next generation of CD20-depleting therapies and genotyping could stratify patients for optimal treatment protocols. Disclosure M. Md Yusof: None. J. Robinson: None. V. Davies: None. D. Wild: None. M. Morgan: None. J. Taylor: None. Y. El-Sherbiny: None. D. Morris: None. L. Liu: None. A. Rawstron: None. M. Buch: None. D. Plant: None. H. Cordell: None. J. Isaacs: None. I. Bruce: None. P. Emery: Grants/research support; PE has received consultancy fees and funding for research from Roche within the last 3 years. A. Barton: None. T. Vyse: None. J. Barrett: None. E. Vital: Grants/research support; EMV has received consultancy fees and funding for research from Roche within the last 3 years. A. Morgan: None.

The aim of the study was to determine outcomes and overall survival (OS) in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for malignant peritoneal mesothelioma (MPM).This was a retrospective cohort study from a prospectively maintained database of patients that underwent CRS/HIPEC for MPM from April 1999 to December 2021.A total of 81 patients were identified with MPM. Median OS was 53 months with a 1-, 3- and 5-year OS of 76%, 55% and 49% respectively. Multivariate analysis identified lymph node status, PCI and CC score as statistically significant prognostic factors that impact survival. Median OS for PCI 0-20 was 103 months vs. 33 months for PCI 21-39 (p=0.005). Median OS for CC0, CC1 and CC2 were 104, 30 and 2.7 months respectively (p0.001). Hazard ratio for node-positive disease over node-negative was 2.14 (95% CI=1.07-4.31, p0.033). Grade III/IV complication rate was 43.2% and mortality 4.9%.CRS/HIPEC remains the gold standard for treating patients with MPM with excellent patient OS. Lymph node status, PCI and CC score were independent prognostic factors that affect OS.

Objectives Cisplatin is commonly used during intraperitoneal chemotherapy however has well-established nephrotoxic side-effects. Sodium thiosulfate is often added to cisplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) protocols to mitigate this, however evidence regarding risk of hypernatraemia is scarce as of yet. Methods We retrospectively identified patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies of any origin at a single high-volume unit between April 2018 and December 2020. Patients were included if they received cisplatin-based HIPEC with intravenous sodium thiosulfate. Blood tests were collected pre-surgery and then daily during admission. Hypernatraemia was defined as serum sodium >145 mmol/L. Renal impairment was defined using the RIFLE criteria. Results Eleven CRSs met inclusion criteria, the majority of which were indicated for ovarian cancer (72.7%). One (9.1%) patient with mesothelioma received mitomycin C as an additional chemotherapy agent. The incidence of hypernatraemia was 100% but all cases were transient, with no clinical sequelae observed. The rate of AKI was 36.4%, with three (27.3%) patients classified as risk and one (9.1%) instance of failure. No long-term renal impairment was observed. Conclusions Despite biochemical evidence of mild hypernatraemia but with the absence of clinical sequelae, sodium thiosulfate appears to be safe when used in adjunct to cisplatin-based HIPEC during CRS. These findings should be evaluated with further comparative studies. When describing renal impairment, it is important that standardisation in reporting occurs, with the RIFLE and Acute Kidney Injury Network criteria now the preferred consensus definitions.

Respiratory diseases such as cystic fibrosis, COPD, bronchiectasis asthma and COVID-19 are difficult to treat owing to viscous secretions in the airways that evade mucocilliary clearance. Since earlier studies have shown success with BromAc® as mucolytic agent for treating a rare disease known as pseudomyxoma peritonei (PMP), we tested the formulation on two gelatinous airway representative sputa models, in order to determine whether similar efficacy exist.The sputum (1.5 ml) lodged in an endotracheal tube was treated to aerosolised N-acetylcysteine, bromelain, or their combination (BromAc®) using a nebuliser with 6.0 ml of the agents in phosphate buffer saline, over 25 min. Controls received phosphate buffer saline. The dynamic viscosity was measured before and after treatment using a capillary tube method, whilst the sputum flow (ml/sec) was assessed using a 0.5 ml pipette. Finally, the sequestered agents (concentration) in the sputa after treatment were quantified using standard bromelain and N-acetylcysteine chromogenic assays.Results indicated that bromelain and N-acetylcysteine affected both the dynamic viscosities and pipette flow in the two sputa models, with changes in the former parameter having immense effect on the latter. BromAc® showed a greater rheological effect on both the sputa models compared to individual agents. Further, correlation was found between the rheological effects and the concentration of agents in the sputa.Hence, this study indicates that BromAc® may be used as a successful mucolytic for clearing airway congestion caused by thick mucinous immobile secretion, however further studies with patient sputum samples using aerosol BromAc® is warranted.