Development and Validation of Micro-Azocasein Assay for Quantifying Bromelain.

The proteolytic activity of enzymes may be evaluated by a colorimetric method with azocasein. Hence, we developed a micro-assay to quantify bromelain using azocasein. A total of 250 µL of 1.

Taming the SARS-CoV-2-mediated proinflammatory response with BromAc.

Introduction: In the present study, the impact of BromAc®, a specific combination of bromelain and acetylcysteine, on the SARS-CoV-2-specific inflammatory response was evaluated.

Methods: An in vitro stimulation system was standardized using blood samples from 9 healthy donors, luminex assays and flow cytometry were performed.

Results And Discussion: BromAc® demonstrated robust anti-inflammatory activity in human peripheral blood cells upon SARS-CoV-2 viral stimuli, reducing the cytokine storm, composed of chemokines, growth factors, and proinflammatory and regulatory cytokines produced after short-term in vitro culture with the inactivated virus (iSARS-CoV-2).

Long-Term Treatment of Unresectable Pseudomyxoma Peritonei with Multiple Treatments of Intratumoural Bromelain and Acetylcysteine (BromAc): A Case Report.

Pseudomyxoma peritonei is a rare peritoneal malignancy characterized by the progressive accumulation of mucinous material and tumour within the abdomen and pelvis. Percutaneous drainage of mucin may be a non-surgical option for relief of symptoms; however, it remains difficult due to the high viscosity of mucin, with numerous case reports reporting difficulty removing material through medium-bore catheters alone. BromAc is a therapy currently undergoing development which dissolves mucinous tumour masses and allows for extraction.

Intraperitoneal BromAc Does Not Interfere with the Healing of Colon Anastomosis.

A combination of bromelain and acetylcysteine, BromAc, is an efficient intraperitoneal mucolytic for thick mucus secreted in pseudomyxoma peritonei (PMP). Patients with PMP quite often undergo colon anastomosis. Hence, we investigated the effect of the intraperitoneal delivery of BromAc on colon-anastomosis healing in a rat model.

Bromelain and acetylcysteine (BromAc): a novel approach to the treatment of mucinous tumours.

Mucins are a significant extracellular component of neoplastic entities such as pseudomyxoma peritonei and several gastrointestinal adenocarcinomas. Mucinous tumours present a challenge for systemic treatments due to poor drug penetrance and increased resistance. Therefore, the development of an effective mucolytic therapy has significant therapeutic implications for these tumour types.

Physical and chemical factors affecting the loading and release of bromelain from DC beads.

Doxorubicin loaded DC beads (microspheres) has been used for treating un-resectable tumours by transarterial chemoembolization (TACE). We have shown that bromelain, an enzyme from the pineapple plant, enhances the cytotoxic effect of a number of chemotherapeutic drugs and in an earlier study we have demonstrated that it can be loaded into DC beads. Therefore, in the current study we have investigated how certain physical and chemical parameters affect its loading and release for future development of DC beads in cancer therapy.

Ex-vivo mucolytic and anti-inflammatory activity of BromAc in tracheal aspirates from COVID-19.

Unlabelled: COVID-19 is a lethal disease caused by the pandemic SARS-CoV-2, which continues to be a public health threat. COVID-19 is principally a respiratory disease and is often associated with sputum retention and cytokine storm, for which there are limited therapeutic options. In this regard, we evaluated the use of BromAc®, a combination of Bromelain and Acetylcysteine (NAC).

The effect of intraperitoneal administration of BromAc on blood parameters: phase 1 study.

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).

Bromelain and acetylcysteine (BromAc) alone and in combination with gemcitabine inhibit subcutaneous deposits of pancreatic cancer after intraperitoneal injection.

Gemcitabine (GEM) is commonly chosen for treating pancreatic cancer. However, its use is limited by toxicity. Earlier studies with GEM in combination with Bromelain (Brom) and Acetylcysteine (Ac) indicated a substantial reduction in IC.

Addition of bromelain and acetylcysteine to gemcitabine potentiates tumor inhibition in human colon cancer cell line LS174T.

The combinations of Bromelain and Acetylcysteine (BromAc) with cytotoxics such as Gemcitabine, 5-Fluorouracil or Oxaliplatin have shown a dramatic reduction in IC50 values in a variety of cancers, including colon cancer, suggesting the possibility of effective treatment without undesired side effects. In the current study, we investigated whether a similar effect is present using the colorectal cell line LS174T. Animals after acclimatization were randomized and allocated equally in the groups for the different studies (safety, dose-escalation, and efficacy).

Novel Use of Bromelain and Acetylcysteine (BromAc®) for Pleural Involvement in Pseudomyxoma Peritonei.

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.

The Combination of Bromelain and Acetylcysteine (BromAc) Synergistically Inactivates SARS-CoV-2.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is the cause of a worldwide pandemic, currently with limited therapeutic options. The spike glycoprotein and envelope protein of SARS-CoV-2, containing disulfide bridges for stabilization, represent an attractive target as they are essential for binding to the ACE2 receptor in host cells present in the nasal mucosa. Bromelain and Acetylcysteine (BromAc) has synergistic action against glycoproteins by breakage of glycosidic linkages and disulfide bonds.

Intraoperative packed red blood cell transfusion (iPRBT) and PCI-normalised iPRBT rates (iPRBT/PCI ratio) negatively affect short- and long-term outcomes of patients undergoing cytoreductive surgery and intraperitoneal chemotherapy - An analysis of 880 patients.

Background: Most studies on the effects of intraoperative packed red blood cell transfusions (iPRBT) on patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown deleterious outcomes. It is unclear if this is a result of the transfusion itself or because iPRBTs serve as a surrogate of more advanced disease.

Methods: A retrospective analysis of 880 patients treated from 1996 to 2017.

Long-term survival outcomes of cytoreductive surgery and perioperative intraperitoneal chemotherapy: Single-institutional experience with 1225 cases.

Background And Objectives: To review long-term survival outcomes of patients with Peritoneal metastasis (PM) who underwent colorectal cancer (CRS) and intraperitoneal chemotherapy (PIC).

Methods: Patients that underwent CRS, with or without PIC, from January 1996 to March 2018 at the Peritonectomy Unit of St. George Hospital, Sydney were retrospectively analyzed from a prospectively maintained database.

The effect of intraoperative fluid administration on outcomes of patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Background: Determine the effect of intraoperative fluids (IOFs) administered during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on postoperative patient outcomes.

Methods: Retrospective cohort study of patients that underwent CRS/HIPEC from February 2010 to June 2017.

Results: A total of 335 patients formed the cohort study.

The volume-time index (VTI) is prognostic in patients with colorectal cancer peritoneal metastases undergoing cytoreductive surgery and intraperitoneal chemotherapy.

Background: Peritoneal cancer index (PCI) is an important prognostic factor in colorectal cancer peritoneal metastases (CRPM), however it fails to consider the time period over which disease burden develops. The volume-time index (VTI) is the ratio between PCI and time from primary tumour resection.

Methods: A retrospective cohort study of 182 patients managed from 1996 to 2017 was performed.

Intraoperative macroscopic tumour consistency is associated with overall survival after cytoreductive surgery and intraperitoneal chemotherapy for appendiceal adenocarcinoma with peritoneal metastases: A retrospective observational study.

Background: This study examines the impact of intraoperative macroscopic tumour consistency on short-term and long-term outcomes after cytoreductive surgery (CRS) with intraperitoneal chemotherapy (IPC) for appendiceal adenocarcinoma with peritoneal metastases.

Methods: Macroscopic intraoperative tumour consistency was classified in three groups as soft (jelly-like geltatinous tumours), hard (hard tumour nodules without gelatinous features) and intermediate (both soft and hard features). In-hospital mortality, major morbidity, intensive care unit (ICU), high dependency unit (HDU) and total hospital stay, disease-free survival (DFS) and overall survival (OS) were compared.

Iterative cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A multi-institutional experience.

Background And Objectives: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival.

Methods: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases.

Results: The study comprised of 231 patients, including 126 females (54.

Prevention of peritoneal recurrence in high-risk colorectal cancer and evidence of T4 status as a potential risk factor.

Peritoneal metastasis (PM) following primary resection of colorectal cancer is common. The combined use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has significantly improved the survival outcome of patients with colorectal PM (CRPM). Diagnosing and treating early PM is essential as its extent is correlated with poorer outcomes.

CEA to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with colorectal cancer peritoneal carcinomatosis undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

Background And Objectives: Serum tumor markers are prognostic in patients with colorectal cancer peritoneal carcinomatosis (CRPC) undergoing cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC). Assessment of the ratio of tumor marker to volume, as depicted by peritoneal carcinomatosis index (PCI), and how this may affect overall (OS) and recurrence free survival (RFS) has not been reported.

Methods: Survival effect of this ratio was analyzed in patients with CRPC managed from 1996 to 2016 with CRS and IPC.

CA 19-9 to peritoneal carcinomatosis index (PCI) ratio is prognostic in patients with epithelial appendiceal mucinous neoplasms and peritoneal dissemination undergoing cytoreduction surgery and intraperitoneal chemotherapy: A retrospective cohort study.

Background: Serum tumour levels have been shown to be prognostic in patients with epithelial appendiceal mucinous neoplasms with peritoneal dissemination (pseudomyxoma peritonei (PMP)). A singular index which incorporates both tumour activity (as depicted by serum tumour marker levels) and tumour volume (as depicted by peritoneal carcinomatosis index (PCI)), may give a more precise surrogate of tumour biological behaviour. The prognostic implication of this index has not yet been reported.

Recurrence and Survival Outcomes After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Small Bowel Adenocarcinoma.

Background: Peritoneal dissemination of small bowel adenocarcinoma (SBA) is rare but is associated with a dismal prognosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a promising treatment option. We evaluated our experience of CRS-HIPEC for the treatment of SBA.

Allogenic Blood Transfusion Is an Independent Predictor of Poorer Peri-operative Outcomes and Reduced Long-Term Survival after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: a Review of 936 Cases.

Introduction: There is a paucity of data on the impact of allogenic blood transfusion (ABT) on morbidity and survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).

Methods: Nine hundred and thirty-five consecutive CRS/HIPEC procedures were performed between 1996 and 2016 at a high-volume institution in Sydney, Australia. Of these, 337(36%) patients required massive ABT (MABT) (≥5 units).

Limited synchronous hepatic resection does not compromise peri-operative outcomes or survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Introduction: There is uncertainty about whether hepatic resection (HR) combined with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is effective.

Methods: Nine hundred and thirty-five consecutive CRS/HIPEC procedures were performed between 1996 and 2016 of which 132(14%) involved concomitant HR. Peri-operative complications were graded according to the Clavien-Dindo Classification.