Sarah J. Valle

Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for refractory malignant ascites in patients unsuitable for cytoreductive surgery.

INTRODUCTION Malignant ascites (MA) is the abnormal accumulation of fluid in the peritoneal cavity of patients with intraperitoneal dissemination of their disease and is associated with a short life expectancy. The most common clinical feature is a progressive increase of abdominal distention resulting in pain, discomfort, anorexia and dyspnoea. Currently, no treatment is established standard of care due to limited efficacy or considerable toxicity. The objective was to examine the efficacy of laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in the palliation of refractory MA in patients who were unsuitable for cytoreductive surgery. METHODS From May 2009 to June 2015, 12 patients with MA due to their peritoneal malignancy were treated with laparoscopic HIPEC. The time between operation and repeat paracentesis, in-hospital data, and the proportion of patients that did not require repeat paracentesis was analyzed. RESULTS One patient (8%) was admitted to ICU for 1 day. The mean operating time and hospital stay was 149.3 min (range 79-185) and 4.6 days (range 2-11) respectively. Neither high-grade morbidity nor mortality was observed. The median OS was 57 days. In our experience, a complete and definitive disappearance of MA was observed in 83% of patients. Two patients (17%) developed recurrent MA 124 days and 283 days post-HIPEC. CONCLUSION Laparoscopic HIPEC is a beneficial treatment for the management and palliation of refractory MA and results in an excellent clinical and radiological resolution in patients with a complete resolution observed in selected patients.

Synchronous liver resection with cytoreductive surgery for the treatment of liver and peritoneal metastases from colon cancer: results from an Australian centre

Treatment of peritoneal metastases (PM) and liver metastases (LM) from colon cancer remains controversial. LM has been viewed as exclusion criterion for cytoreductive surgery (CRS) on the basis that such spread represents systemic disease. CRS and intraperitoneal chemotherapy (IPC) has gained increasing recognition as a treatment modality for selected patients with colon cancer and PM. This study analyses results of CRS and IPC for colon cancer and synchronous resection for treatment of LM and PM.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined have been recognized as standard of care for treatment of a subset of patients with peritoneal carcinomatosis (PC). The aim of CRS is to eliminate all macroscopic disease through a series of visceral resections followed by targeting any residual microscopic disease with intraperitoneal chemotherapy, exposing the peritoneal surfaces to a high concentration of chemotherapy with a lower systemic toxicity. Different regimes of intraperitoneal chemotherapy include HIPEC, early postoperative intraperitoneal chemotherapy (EPIC) and bidirectional chemotherapy. The efficacy and modality of treatment with intraperitoneal chemotherapy is dependent on multiple factors including the chosen cytotoxic agent and its pharmacokinetics and pharmacodynamics. There is no standardized methodology for intraperitoneal chemotherapy administration. This review will discuss the pharmacological principles of the various intraperitoneal chemotherapy techniques.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: long-term results at St George Hospital, Australia.

Peritoneal carcinomatosis (PC) results from the secondary spread of many intraabdominal tumour types, such as colorectal malignancy (colorectal cancer, CRC), disseminated peritoneal adenomucinosis (DPAM), appendiceal cancer, ovarian carcinoma, sarcoma or from the occurrence of primary peritoneal disease such as peritoneal mesothelioma. The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has seen improvements in survival in selected cases of these cancers.

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

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

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

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.

Targeting MUC16 in Cancer Therapy

Over the recent decades, there has been a number of studies investigating the role of mucins in the pathogenesis of various cancers such as breast, lung, ovarian, gastrointestinal and pancreatic malignancies. Since then, it has been discovered that mucins play a critical role in tumorigenesis as they can mediate cell proliferation, metastasis and resistance to chemotherapy. Thus, mucins have been explored as a potential therapeutic target as well as a biomarker, as cancer cells often have an aberrant expression of mucins. MUC16 is a glycoprotein coded by one of the 21 mucin genes. CA125, the extracellular domain of MUC16, is a well-established biomarker for ovarian cancer, however there is no in depth literature review on MUC16 as a target for anti-cancer therapy. Thus, this review summarises the existing literature on MUC16, the current therapies targeting on MUC16 and highlights future avenues for targeting mucin-producing cancers.

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

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. There are two novel therapies – second‐look surgery and synchronous hyperthermic intraperitoneal chemotherapy – that are proposed to prophylactically treat or intervene early in the disease process to reduce the incidence and adverse outcomes associated with PM. These strategies are limited to patients at high risk of developing CRPM, including those that had synchronous PM or ovarian metastases resected at primary tumour removal, or a perforated primary tumour. The data on advanced primary tumour (T4) as a prognostic factor for PM after primary resection suggest that T4a tumours are prognostically worse than T4b. This literature review outlines the evidence, feasibility and safety regarding the pre‐emptive treatments, as well as the relevance of T4a tumours as a risk factor for metachronous CRPM.

The use of carbon dioxide insufflation to facilitate identification of intestinal injuries in patients undergoing cytoreductive surgery and intraperitoneal chemotherapy

Since Sugarbaker introduced the concept of cytoreduction (CRS) and intraperitoneal chemotherapy (IPC) in the mid 1990s, the approach to management of peritoneal metastases has drastically changed [1]. This has resulted in markedly improved outcomes for selected patients with peritoneal dissemination of many tumours including colorectal cancer and pseudomyxoma peritonei [2, 3]. The treatment necessitates radical surgical resection of macroscopically visible disease in the abdomen and pelvis and administration of intraperitoneal chemotherapy to eradicate remaining microscopic disease [4]. However, this surgical procedure harbours a level of complexity in that it combines long operative times, numerous and complex resections, peritoneal stripping and administration of heated intraperitoneal chemotherapy, all of which contribute to a degree of morbidity and mortality. Intestinal perforations, anastomotic leaks and their subsequent clinical sequelae (such as fistulae and abscesses) are amongst the most common complications associated with this radical therapy [5–7]. Reasons for this are multifactorial and involve a combination of patient, treatment and technical factors. Of particular concern are patients with extensive small and large bowel disease, requiring aggressive resection of the tumour from the bowel surface and often resulting in a mixture of serosal, seromuscular and full-thickness injuries to the bowel at multiple sites. These can be quite subtle, especially after administration of hyperthermic intraperitoneal chemotherapy (HIPEC) which results in discolouration and oedema of the intestine. Nonetheless, identification and repair of all defects contributes to reduction in bowel complications including perforations, anastomotic leaks, fistulae and abscess formation. The use of carbon dioxide (CO2) insufflation of the bowel as a method of detecting occult defects requiring repair is a novel approach. The technique was given the name ‘‘the sausage test’’ by the surgeon who pioneered its use, due to the gross appearance of bowel when insufflated and distended throughout. It is a simple, economical and effective technique which requires little more than a laparoscopic stack insufflator (our unit utilises the Olympus UHI-3 ), insufflation tubing and medical grade CO2 as would be used routinely for establishing pneumoperitoneum in a laparoscopic operation (supplementary video 1). The insufflator is set at a high flow rate with a pressure of 12–15 mmHg. The end of the tubing is fed a small way into the intestinal lumen through either the most distal or proximal enterotomy, colotomy or via the stoma if one is fashioned. A purse-string suture can be applied around the entry point of the insufflation tubing to create a seal; however, we generally find that application of gentle manual pressure at this site often suffices. The insufflation is applied to the bowel, and it is carefully and thoroughly run through its entire length and examined while distended. At sites of suspected otomy or anastomosis, the intestine distal and proximal is gently squeezed to give the CO2 a Electronic supplementary material The online version of this article (doi:10.1007/s10151-017-1644-6) contains supplementary material, which is available to authorized users.

Unusual Indications of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: A Review of Outcomes and Report of the Literature

The occurrence of peritoneal carcinomatosis (PC) is serious in all malignancies and usually results in a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an aggressive surgical approach combining visceral resections and peritonectomy procedures to remove macroscopic disease followed by HIPEC, targeting residual microscopic disease. CRS/HIPEC is the standard and potentially curative treatment for select patients with PC. This combined approach, however, has consistently demonstrated improved survival outcomes across a variety of disease types including appendiceal cancer, colorectal cancer, low-grade appendix mucinous neoplasm, peritoneal mesothelioma and ovarian cancer with peritoneal metastases [1–6], with randomised evidence demonstrating the superiority of CRS/HIPEC for colorectal cancer PC [2]. Although peritonectomy procedures are less likely to achieve disease control in selected patients with significant metastatic disease [7], CRS/HIPEC has been applied and reported in small series of patients with PC of unusual origin including tumours arising from sarcoma, desmoplastic small round cell tumour (DSRCT) and neuroendocrine tumours [8–10]. The role of CRS/HIPEC in these patients remains uncertain with limited data on the clinical efficacy of this treatment, as many reports outline specific outcomes in large heterogeneous groups. This goal of this manuscript was to review our single institution experience with CRS/HIPEC for patients with PC of unusual primaries followed by a literature review of studies that reported on greater than five patients of each unusual primary.