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.

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.

The Impact of Neoadjuvant Chemotherapy on the Surgical Management of Colorectal Peritoneal Metastases: A Systematic Review and Meta-Analysis.

BACKGROUND: Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognised treatment option for the management of colorectal peritoneal metastases (CRPM). However, incorporating the routine use of neoadjuvant chemotherapy (NAC) into this management plan is controversial. METHODS: A systematic review and meta-analysis were conducted to evaluate the impact of neoadjuvant chemotherapy on perioperative morbidity and mortality, and long-term survival of patients with CRPM undergoing CRS and HIPEC. RESULTS: Twelve studies met the inclusion criteria (n = 2,463 patients). Ten were retrospective cohort, one was prospective cohort, and one was a prospective randomised by design. Patients who received NAC followed by CRS and HIPEC experienced no difference in major perioperative morbidity and mortality compared with patients who underwent surgery first (SF). There was no difference in overall survival at 3 years, but at 5 years NAC patients had superior survival (relative risk [RR] 1.31; 95% confidence interval [CI] 1.11-1.54, P < 0.001). There were no differences in 1- and 3-year, disease-free survival (DFS) between groups. Study heterogeneity was generally high across all outcome measures. CONCLUSIONS: Patients who received neoadjuvant chemotherapy did not experience any increase in perioperative morbidity or mortality. The potential improvement in 5-year overall survival in patients receiving NAC is based on limited confidence due to several limitations in the data, but not sufficiently enough to curtail its use. The practice of NAC in this setting will remain heterogeneous and guided by retrospective evidence until prospective, randomised data are reported.

Diagnostic performance of positron emission tomography in the staging of pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical entity, commonly derived from a mucin-producing tumour of the appendix. International consensus is unclear on the role of positron emission tomography (PET) in preoperative staging. This study aimed to assess the ability of preoperative PET in predicting the histological grade of PMP. METHODS: All patients scheduled for cytoreductive surgery (CRS) +/- hyperthermic intraperitoneal chemotherapy (HIPEC) for PMP who underwent preoperative PET at a single centre between June 2007 and June 2020 were included. A nuclear medicine physician, blinded to patient outcomes, retrospectively reviewed imaging studies to assess for maximum tumour standardised uptake value (SUV) to mean liver SUV ratio (SUVTLR) and maximum porta hepatis SUV to mean liver SUV ratio (SUVPLR). RESULTS: Between April 2007 and December 2020, a total of 204 patients underwent surgical intervention for PMP. Of these, 124 (60.8%) met the inclusion criteria. Median peritoneal carcinomatosis index for the entire cohort was 9 and complete cytoreduction (CC0/1) was achieved in 109 (88%) patients. Patients with high-grade PMP were more likely to have diffuse peritoneal disease (p < 0.001) and higher SUVTLR (p<0.001). The area under the ROC curve (AUC) of SUVTLR in predicting high-grade pathology was 71% (p = 0.003). Patients with a SUVTLR ≤ 0.78 had improved disease-free survival (p = 0.042). CONCLUSION: Preoperative PET showed positive correlation with high-grade PMP and acceptable sensitivity and specificity as a diagnostic tool. PET should be considered a useful adjunct to standard imaging for predicting histological grade in the staging of patients with PMP.

Is neoadjuvant therapy an alternative strategy to immediate surgery in locally perforated colon cancer?

BACKGROUND: Perforations are a rare but serious complication of colorectal cancer. The current standard of treatment is emergent surgery followed by adjuvant chemotherapy. The concern with this approach is not only the uncertainty of achieving a R0 resection but also potential injury to adjacent vessels, nerves and ureters due to inflamed tissue planes. A subset of this patient population with a contained perforation who are clinically stable may have superior oncological outcomes with local sepsis control, neoadjuvant therapy followed by radical resection. The aim of this study is to report on the pre-operative safety profile for neoadjuvant therapy in the setting of an abscess from colon cancer perforation and the short-term oncological surgical quality outcomes. METHODS: In this retrospective observational study, all consecutive perforated colon cancer receiving neoadjuvant therapy from Jan 2010 to Dec 2019 were included. RESULTS: There were 21 patients that met the inclusion criteria. The most common symptom at presentation was abdominal pain (71.4%) and most common site of perforation was sigmoid colon (61.9%). Local sepsis control was achieved with a combination of radiological or surgical drainage, diverting ostomy and/or intravenous antibiotics. Thirteen patients had long-course chemoradiation and eight patients had neoadjuvant chemotherapy. Of these, 13 (61.9%) had tumour regression, with one patient having a pathological complete response. All patients achieved a R0 resection. CONCLUSIONS: In a small subset of patients with colon cancer perforation, this study has demonstrated the potential safe usage of neoadjuvant therapy first before radical surgery to achieve a clear resection margin.

Appendiceal pseudomyxoma peritonei: predictors of recurrence and iterative surgery.

AIM: Appendiceal pseudomyxoma peritonei (PMP) is a rare entity, with recurrence rates up to 26% despite optimal cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Evidence specific to PMP originating from non-infiltrative appendiceal mucinous neoplasms (low grade - LAMN and high grade - HAMN) is lacking. The aim of this study was to identify patterns of recurrence and predictive factors for patients appropriate for iterative surgery. METHOD: A bi-institutional retrospective analysis was performed on patients undergoing complete cytoreduction and HIPEC for PMP derived from perforated LAMN or HAMN. Multivariate logistic regression was performed to identify independent predictors for re-do CRS. Five-year overall survival (OS) was stratified according to surgical intervention, and 5-year disease-free survival (DFS) was stratified according to histological PMP grade. Cox regression analysis was performed to identify independent predictors for OS and DFS. RESULTS: Sixty of 239 (25.1%) patients developed peritoneal recurrence between 2007 and 2020. The median time to recurrence was 20.7 months. The risk of disease recurrence was highest with high-grade PMP (P <0.001) and increasing PCI (P <0.001). Patients with high-grade histology from their index procedure and aged over 60 years were less likely to be offered iterative surgery on multivariate analysis. Patients who underwent iterative CRS and HIPEC had a 5-year survival of 100%. CONCLUSION: Iterative CRS and HIPEC is feasible in selected patients with recurrent PMP, displaying good oncological outcomes. Age, index histology and level of abdominal quadrant involvement are predictive of proceeding to re-do surgery.

Neoadjuvant chemotherapy in locally advanced colon cancer: a systematic review and meta-analysis.

BACKGROUND: There is increasing evidence to support the use of neoadjuvant chemotherapy (NAC) in locally advanced colon cancer (LACC). However, its safety, efficacy and side effect profile is yet to be completely elucidated. This review aims to assess NAC regimens, duration, compare completion rates, intra-operative and post-operative complication profiles and oncological outcomes, in order to provide guidance for clinical practice and further research. METHODS: PubMed, EMBASE and MEDLINE were searched for a systematic review of the literature from 2000 to 2020. Eight eligible studies were included, with a total of 1213 patients, 752 (62%) of whom received NAC. Of the eight studies analysed, two were randomised controlled trials comparing neoadjuvant chemotherapy followed by oncological resection to upfront surgery and adjuvant chemotherapy, three were prospective single-arm phase II trials analysing neoadjuvant chemotherapy followed by surgery only, one was a retrospective study comparing neoadjuvant chemotherapy followed by surgery versus surgery first followed by adjuvant chemotherapy and the remaining two were single-arm retrospective studies of neoadjuvant chemotherapy followed by surgery. RESULTS: All cases of LACC were determined and staged by computed tomography; majority of the studies defined LACC as T3 with extramural depth of 5 mm or more, T4 and/or nodal positivity. NAC administered was either folinic acid, fluorouracil and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (XELOX) with the exception of one study which utilised 5-fluorouracil and mitomycin. Most studies had NAC completion rates of above 83% with two notable exceptions being Zhou et al. and The Colorectal Cancer Chemotherapy Study Group of Japan who both recorded a completion rate of 52%. Time to surgery from completion of NAC ranged on average from 16 to 31 days. The anastomotic leak rate in the NAC group ranged from 0 to 4.5%, with no cases of postoperative mortality. The R0 resection rate in the NAC group was 96.1%. Meta-analysis of both RCTs included in this study showed that neoadjuvant chemotherapy increased the likelihood of a negative resection margin T3/4 advanced colon cancer (pooled relative risk of 0.47 with a 95% confidence interval) with no increase in adverse consequence of anastomotic leak, wound infection or return to theatre. CONCLUSIONS: Our systematic review and meta-analysis show that NAC is safe with an acceptable side effect profile in the management of LACC. The current data supports an oncological benefit for tumour downstaging and increased in R0 resection rate.

Robotic colorectal surgery in Australia: evolution over a decade.

BACKGROUND: Despite reports of increasing adoption of robotics in colorectal surgery worldwide, data regarding its uptake in Australasia are lacking. This study examines the trends of robotic colorectal surgery in Australia during the last 10 years. METHODS: Data from patients undergoing robotic colorectal surgery with the da Vinci robotic platform between 2010 and 2019 were obtained. Overall, numbers of specific colorectal procedures across Australia were obtained from the Medicare Benefit Schedule data over the same period. Pearson's correlation analysis was used to determine the statistical trends of overall and specific robotic colorectal procedures over time. RESULTS: A total of 6110 robotic general surgery procedures were performed across Australia during the study period. Of these, 3522 (57.6%) were robotic colorectal procedures. An increasing trend of overall robotic colorectal procedures was seen over 10 years (Pearson's coefficient of 0.875; P = 0.001). While this applied to both the public and private sectors, 90.7% of the procedures were undertaken in the private sector. Restorative rectal resections, rectopexies, and right hemicolectomies accounted for 82.6% of the robotic colorectal procedures performed during this period with an increasing trend seen over time for each intervention. Moreover, a robotic approach was utilized in 12.5%, 41.0% and 9.0% of all restorative rectal resections, rectopexies and right hemicolectomies undertaken in Australia during 2019, respectively. CONCLUSION: Robotic colorectal surgery has increased dramatically in Australia over the last 10 years, especially in the private sector. Penetration of robotic colorectal surgery in the public healthcare system will require focussed cost-benefit evaluations and governmental investment.

Treatment of peritoneal carcinomatosis with hyperthermic intraperitoneal chemotherapy in colorectal cancer.

The peritoneum is the second most common site of metastasis after the liver and the only site of metastatic disease in approximately 25% of patients with colorectal cancer (CRC). In the past, peritoneal carcinomatosis in CRC was thought to be equivalent to distant metastasis; however, the transcoelomic spread of malignant cells is an acknowledged alternative pathway. Metastasectomy with curative intent is well accepted in patients with liver metastasis in CRC despite the paucity of randomized trials. Therefore, there is rationale for local treatment with peritonectomy to eliminate macroscopic disease, followed by hyperthermic intraperitoneal chemotherapy to destroy any residual free tumour cells within the peritoneal cavity. The aim of this paper is to summarize the current evidence for cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis in CRC.

Colonic transit: what is the impact of a diverting loop ileostomy?

BACKGROUND: Diverting loop ileostomy (DLI) is used following low anterior resections (LAR) or ultra-low anterior resections (ULAR) to reduce anastomotic leak (AL). Preoperative mechanical bowel preparation (MBP) is traditionally used with DLI. However, clearance of the left colon can be achieved with a fleet enema without the physiological compromise of MBP. We aimed to assess colonic transit following DLI in this context. METHODS: A prospective, observational study was performed with patients with rectal cancer undergoing LAR or ULAR in a tertiary colorectal unit with preoperative fleet enema. Radiopaque markers were inserted into the caecum following rectal resection and formation of a DLI with placement confirmed by image intensifier and endoscopy. X-rays were performed at days 1, 3, 5 and 14 post-operation with data collected prospectively. RESULTS: Ten patients (mean age 57, nine males) were enrolled. Mean time to functioning stoma was 1.9 days (range 1-3). There was no movement in the majority of markers in all patients at Day 5 post-operation. In all seven patients with Day 14 X-rays, the majority of markers remained in the right colon. Two patients had delayed AL, with markers found within the pelvis in both of these patients. CONCLUSIONS: This is the first study to assess colonic transit following DLI using fleet enema only, with results suggesting colonic motility is abolished in this setting. The use of a fleet enema without MBP may be sufficient prior to rectal resection surgery when DLI is employed. AL may actually increase colonic transit. Further research is warranted.