Evolution of surgical approach to rectal cancer resection: A multinational registry assessment.

PURPOSE: Surgical approach to rectal cancer has evolved in recent decades, with introduction of minimally invasive surgery (MIS) techniques and local excision. Since implementation might differ internationally, this study is aimed at evaluating trends in surgical approach to rectal cancer across different countries over the last 10 years and to gain insight into patient, tumour and treatment characteristics. METHODS: Pseudo-anonymised data of patients undergoing resection for rectal cancer between 2010 and 2019 were extracted from clinical audits in the Netherlands (NL), Sweden (SE), England-Wales (EW) and Australia-New Zealand (AZ). RESULTS: Ninety-nine thousand five hundred ninety-seven patients were included (38,413 open, 55,155 MIS and 5416 local excision). An overall increase in MIS was observed from 29.9% in 2010 to 72.1% in 2019, with decreasing conversion rates (17.5-9.0%). The MIS proportion was highly variable between countries in the period 2010-2014 (54.4% NL, 45.3% EW, 39.8% AZ, 14.1% SE, P < 0.001), but variation reduced over time (2015-2019 78.8% NL, 66.3% EW, 64.3% AZ, 53.2% SE, P < 0.001). The proportion of local excision for the two periods was highly variable between countries: 4.7% and 11.8% in NL, 3.9% and 7.4% in EW, 4.7% and 4.6% in AZ, 6.0% and 2.9% in SE. CONCLUSIONS: Application and speed of implementation of MIS were highly variable between countries, but each registry demonstrated a significant increase over time. Local excision revealed inconsistent trends over time.

Lateral Pelvic Sidewall Nodes.

CASE SUMMARY: A 68-year-old woman presented with rectal bleeding, urgency, and tenesmus. A digital rectal examination confirmed a craggy mass infiltrating into the sphincter complex. Follow-up colonoscopy noted a low-rectal tumor (3 cm from the dentate), and histopathology confirmed a moderately differentiated adenocarcinoma. Subsequent staging with MRI confirmed a 5-cm circumferential low-rectal neoplasm with extramural vascular invasion and threatened circumferential resection margin. The neoplasm abutted the posterior vaginal wall and was invading the internal sphincter complex. Four enlarged mesorectal nodes (>7 mm) and several enlarged right pelvic sidewall nodes (largest at 17 mm) were also observed. There was no evidence of distant disease. The patient underwent long-course neoadjuvant chemoradiotherapy. Restaging showed a good treatment response with some regression and no involvement/encroachment of the vagina. All the mesorectal nodes had reduced in size (~4 mm), and all but one of the right pelvic sidewall nodes had also decreased in size. However, 1 pelvic sidewall node (obturator fossa) still remained at 10 mm. After the tumor board discussion, a decision to proceed to abdominoperineal resection with right sidewall clearance was made. Final histopathology confirmed a moderately differentiated adenocarcinoma with no mesorectal nodal involvement (19 nodes sampled), and 1 of 7 sidewall nodes had evidence of metastatic adenocarcinoma.

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.

Robotic versus laparoscopic proctectomy: a comparative study of short-term economic and clinical outcomes.

BACKGROUND: Although several studies compare the clinical outcomes and costs of laparoscopic and robotic proctectomy, most of them reflect the outcomes of the utilisation of older generation robotic platforms. The aim of this study is to compare the financial and clinical outcomes of robotic and laparoscopic proctectomy within a public healthcare system, utilising a multi-quadrant platform. METHODS: Consecutive patients undergoing laparoscopic and robotic proctectomy between January 2017 and June 2020 in a public quaternary centre were included. Demographic characteristics, baseline clinical, tumour and operative variables, perioperative, histopathological outcomes and costs were compared between the laparoscopic and robotic groups. Simple linear regression and generalised linear model analyses with gamma distribution and log-link function were used to determine the impact of the surgical approach on overall costs. RESULTS: During the study period, 113 patients underwent minimally invasive proctectomy. Of these, 81 (71.7%) underwent a robotic proctectomy. A robotic approach was associated with a lower conversion rate (2.5% versus 21.8%;P = 0.002) at the expense of longer operating times (284 ± 83.4 versus 243 ± 89.8 min;P = 0.025). Regarding financial outcomes, robotic surgery was associated with increased theatre costs (A$23,019 ± 8235 versus A$15,525 ± 6382; P < 0.001) and overall costs (A$34,350 ± 14,770 versus A$26,083 ± 12,647; P = 0.003). Hospitalisation costs were similar between both approaches. An ASA ≥ 3, non-metastatic disease, low rectal cancer, neoadjuvant therapy, non-restorative resection, extended resection, and a robotic approach were identified as drivers of overall costs in the univariate analysis. However, after performing a multivariate analysis, a robotic approach was not identified as an independent driver of overall costs during the inpatient episode (P = 0.1). CONCLUSION: Robotic proctectomy was associated with increased theatre costs but not with increased overall inpatient costs within a public healthcare setting. Conversion was less common for robotic proctectomy at the expense of increased operating time. Larger studies will be needed to confirm these findings and examine the cost-effectiveness of robotic proctectomy to further justify its penetration in the public healthcare system.

Impact of the approach on conversion to open surgery during minimally invasive restorative total mesorectal excision for rectal cancer.

BACKGROUND: The aim of this study is to explore the impact of the approach on conversion in patients undergoing minimally invasive restorative total mesorectal excision within a single unit. METHODS: A retrospective cohort study was conducted. Patients with rectal cancer undergoing minimally invasive restorative total mesorectal excision between January 2006 and June 2020 were included. Subjects were classified according to the presence or absence of conversion. Baseline variables and short-term outcomes were compared. Regression analyses were conducted to assess the relationship between the approach and conversion. RESULTS: During the study period, 318 patients underwent a restorative proctectomy. Of these, 240 met the inclusion criteria. Robotic and laparoscopic approaches were undertaken in 147 (61.3%) and 93 (38.8%) cases, respectively. A transanal approach was utilised in 62 (25.8%) cases (58.1% in combination with a robotic transabdominal approach). Conversion to open surgery occurred in 30 cases (12.5%). Conversion was associated with an increased overall complication rate (P = 0.003), surgical complications (P = 0.009), superficial surgical site infections (P = 0.02) and an increased length of hospital stay (P = 0.006). Robotic and transanal approaches were both associated with decreased conversion rates. The multiple logistic regression analysis, however, showed that only a transanal approach was independently associated with a lower risk of conversion (OR 0.147, 0.023-0.532; P = 0.01), whilst obesity was an independent risk factor for conversion (OR 4.388, 1.852-10.56; P < 0.00). CONCLUSIONS: A transanal component is associated with a reduced conversion rate in minimally invasive restorative total mesorectal excision, regardless of the transabdominal approach utilised. Larger studies will be required to confirm these findings and define which subgroup of patients could benefit from transanal component when a robotic approach is undertaken.

Use of patient-derived explants as a preclinical model for precision medicine in colorectal cancer: A scoping review.

PURPOSE: Whilst the treatment paradigm for colorectal cancer has evolved significantly over time, there is still a lack of reliable biomarkers of treatment response. Treatment decisions are based on high-risk features such as advanced TNM stage and histology. The role of the tumour microenvironment, which can influence tumour progression and treatment response, has generated considerable interest. Patient-derived explant cultures allow preservation of native tissue architecture and tumour microenvironment. The aim of the scoping review is to evaluate the utility of patient-derived explant cultures as a preclinical model in colorectal cancer. METHODS: A search was conducted using Ovid MEDLINE, EMBASE, Web of Science, and Cochrane databases from start of database records to September 1, 2022. We included all peer-reviewed human studies in English language which used patient-derived explants as a preclinical model in primary colorectal cancer. Eligible studies were grouped into the following categories: assessing model feasibility; exploring tumour microenvironment; assessing ex vivo drug responses; discovering and validating biomarkers. RESULTS: A total of 60 studies were eligible. Fourteen studies demonstrated feasibility of using patient-derived explants as a preclinical model. Ten studies explored the tumour microenvironment. Thirty-eight studies assessed ex vivo drug responses of chemotherapy agents and targeted therapies. Twenty-four studies identified potential biomarkers of treatment response. CONCLUSIONS: Given the preservation of tumour microenvironment and tumour heterogeneity, patient-derived explants has the potential to identify reliable biomarkers, treatment resistance mechanisms, and novel therapeutic agents. Further validation studies are required to characterise, refine and standardise this preclinical model before it can become a part of precision medicine in colorectal cancer.

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.

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

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

Functional outcomes after lateral pelvic lymph node dissection for rectal cancer: a systematic review and meta-analysis.

PURPOSE: Lateral pelvic lymph node dissection (LPLND) may improve oncological outcomes for select patients with rectal cancer, though functional outcomes may be adversely impacted. The aim of this study is to assess the functional outcomes associated with LPLND for rectal cancer and compare these outcomes with standard surgical resection. METHODS: A systematic search was undertaken to identify relevant studies reporting on urinary dysfunction (UD), sexual dysfunction (SD), and defecatory dysfunction (DD) for patients who underwent LPLND for rectal cancer. Studies comparing functional outcomes in patients who underwent surgery with and without LPLND were assessed. In addition, a comparison of functional outcomes in patients who underwent LPLND before and after the year 2000 was performed. RESULTS: Twenty-one studies of predominantly non-randomised observational data were included. Ten were comparative studies. Male SD was worse in patients who underwent LPLND compared with those who did not (RR 1.68 (95% CI 1.41-1.99, P < 0.001)). No difference was observed for the rate of UD between treatment groups. The rates of UD and male SD in patients who underwent LPLND after the year 2000 were significantly lower than those who underwent LPLND before the year 2000 ((UD) RR = 4.5, p value = 0.0034; male SD RR = 28.7, p value < 0.001). CONCLUSION: Lateral pelvic lymph node dissection is associated with worse male sexual dysfunction compared to standard surgical resection. However, the rates of urine dysfunction and male sexual dysfunction are better in contemporary cohorts which may reflect improved surgical technique and autonomic nerve preservation.

Robotic beyond total mesorectal excision surgery for primary and recurrent pelvic malignancy: Feasibility and short-term outcomes.

AIM: To explore the feasibility and safety of robotic beyond total mesorectal excision (TME) surgery for primary and recurrent pelvic malignancy. METHODS: Patients undergoing robotic beyond TME resections for primary or recurrent pelvic malignancy between July 2015 and July 2021 in a public quaternary and a private tertiary centre were included. Demographic and clinical data were recorded and outcomes analysed. RESULTS: Twenty-four patients (50% males) were included, with a median age of 58 (45-70.8) years, and a BMI of 26 (24.3-28.1) kg/m2 . Indication for surgery was rectal adenocarcinoma in nineteen, leiomyosarcoma in two, anal squamous cell carcinoma in one and combined rectal and prostatic adenocarcinoma in two patients. All patients required resection of at least one adjacent pelvic organ including genitourinary structures (n = 23), internal iliac vessels (n = 3) and/or bone (n = 2). Eleven patients had a restorative procedure. Of the 13 nonrestorative cases, nine needed perineal reconstruction with a flap. There was one conversion due to bleeding. The mean operating time was 370 (285-424) min, and the median blood loss was 400 (200-2,000) ml. The median length of stay was 16 (9.3-23.8) days. Fourteen patients (58.3%) had postoperative complications; eight of them (33.3%) were Clavien-Dindo III or more complication. Twenty-three (95.8%) patients had an R0 resection. During a median follow-up of 10 (7-23.5) months, five patients (20.8%) had systemic recurrences. No local recurrences were identified during the study period. CONCLUSION: Implementation of robotic beyond TME surgery for primary and recurrent pelvic malignancy is feasible within a highly specialised setting.

Robotic complete mesocolic excision versus conventional robotic right colectomy for right-sided colon cancer: a comparative study of perioperative outcomes.

AIM: This study aims to compare the short-term outcomes of robotic complete mesocolic excision (RCME) versus conventional robotic right colectomy (RRC) for right-sided colon cancer. METHODS: Consecutive patients who underwent robotic surgery for right-sided colon cancer in a public quaternary and a private tertiary healthcare centre between November 2018 and June 2020 were included. Clinical, perioperative and histopathological variables were collected and analysed. RESULTS: Fifty-one patients were included; 25 (49%) of them had an RCME. The groups were evenly distributed in terms of demographic characteristics and tumour location. Operative time was similar between both groups, and no patients required conversion to open surgery. There were no differences in overall complications (16% in RCME vs. 26.9% in RRC; p = 0.499) or their profile between groups. There were no anastomotic leaks recorded, and the reoperation rates were similar (0% for RCME versus 3.8% for RRC; p = 1). In addition, the median length of hospital stay was similar in between the RCME and the RRC groups (4 [4-6] days versus 5 [3-8.5] days, respectively; p = 0.891). Whilst there were no differences in the TNM staging, the mean number of lymph nodes harvested with RCME was 37.7 (±12.9) compared to 21.8 (±7.5) with RCC (p < 0.001). CONCLUSION: In our series, RCME was associated with a higher lymph node harvest and a similar morbidity profile compared to RCC. Further studies are required to validate these results and provide long-term oncologic outcomes.

Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer: A Systematic Review and Metaanalysis of Oncological and Operative Outcomes.

BACKGROUND: Total neoadjuvant therapy in rectal cancer refers to the administration of chemoradiotherapy plus chemotherapy before surgery. Recent studies have shown improved pathological complete response and disease-free survival with this approach. However, survival benefits remain unproven. Our objective is to present a metaanalysis of oncological outcomes of total neoadjuvant therapy in locally advanced rectal cancer. PATIENTS AND METHODS: A comprehensive search was performed on PubMed, Medline, and Google Scholars. Studies comparing total neoadjuvant therapy with standard neoadjuvant chemoradiotherapy were included. Data extracted from the individual studies were pooled and a metaanalysis performed. The outcomes of interest are the rate of complete pathological response, nodal response, resection margin, anal preservation, anastomotic leak, local recurrence, distant recurrence, disease-free survival, and overall survival. RESULTS: There were 15 comparative studies with 2437 patients in the neoadjuvant chemoradiotherapy group and 2284 in the total neoadjuvant therapy group. The pooled complete pathological response was 22.3% in the total neoadjuvant therapy group, compared with 14.2% in the standard neoadjuvant chemoradiotherapy group (p < 0.001). Even though there was no difference in local recurrence rate, there was a significantly lower rate of distant recurrence (OR 0.81, p = 0.02), and better 3-year disease-free survival (70.6% vs. 65.3%, respectively, p < 0.001) and overall survival (84.9% vs. 82.3%, respectively, p = 0.006), favoring the total neoadjuvant therapy group. Due to significant heterogeneity in the study protocols, there remains uncertainty on the ideal chemotherapy/radiotherapy sequence. CONCLUSIONS: This study provides supporting evidence on the favorable immediate and intermediate oncological outcomes with the use of total neoadjuvant therapy for locally advanced rectal cancer.

Preemptive Femoral-Femoral Crossover Grafting of Artery and Vein Before Pelvic Exenterative Surgery for Locally Advanced and Recurrent Pelvic Malignancy Involving the Aortoiliac Axis.

INTRODUCTION: Achieving a negative resection through a pelvic exenteration for a recurrent or an advanced pelvic malignancy offers the potential for cure. Exenterative surgical units have expanded the boundaries and redefined what constitutes resectable disease through improved surgical technique. In selected cases, contiguous tumor involvement of the aortoiliac axis requires en bloc resection and subsequent vessel reconstruction. However, vascular reconstruction can be challenging in a contaminated field during an extended radical resection. TECHNIQUE: The aim of this Technical Note is to describe a novel method in the management of patients with recurrent or advanced pelvic malignancy involving the aortoiliac axis by performing preemptive femoral-femoral arterial and venous crossover grafts, with adjunctive arteriovenous loop fistula formation before undergoing an extended radical pelvic resection 4 weeks later. RESULTS: Four patients have undergone preemptive femoral-femoral arterial and venous crossover grafts at our institution (median age = 60 y (range, 47-66 y); 2 women). There were no early complications, and all of the patients subsequently underwent extended radical pelvic resections for a pelvic malignancy. CONCLUSIONS: Preemptive vascular reconstruction before major pelvic surgery reduces the risk of graft infection because this method avoids the wounds being contaminated by GI or genitourinary organisms. Other advantages to this technique include a reduction in the overall operating time for the pelvic exenteration, a significant reduction in the ischemia time to the lower limbs, and ensuring that the grafts are patent before embarking on major intra-abdominal surgery.

Synchronous Liver Resection, Cytoreductive Surgery, and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Liver and Peritoneal Metastases: A Systematic Review and Meta-analysis.

BACKGROUND: Synchronous liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases have traditionally been contraindicated. More recent clinical practice has begun to promote this aggressive treatment in select patients. OBJECTIVE: This study aimed to investigate the perioperative and oncological outcomes of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, with and without liver resection, in the management of metastatic colorectal cancer. DATA SOURCES: Medline, Embase, and Cochrane Library databases were searched up to July 2020. STUDY SELECTION: Cohort studies comparing outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with and without liver resection for metastatic colorectal cancer were reviewed. No randomized controlled trials were available. INTERVENTION: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with or without synchronous liver resection were compared. MAIN OUTCOME MEASURES: The primary outcome measures were perioperative mortality and major morbidity. Secondary outcomes included 3- and 5-year overall survival and 1- and 3-year disease-free survival. RESULTS: Fourteen studies fitted the inclusion criteria, with 8 studies included in the meta-analysis. On pooled analysis, there was no significant difference in perioperative morbidity and mortality between the two groups. Patients that underwent concomitant liver resection had worse 1- and 3-year disease-free survival and 3- and 5-year overall survival. LIMITATIONS: Only a limited number of studies were available, with a moderate degree of heterogeneity. CONCLUSIONS: The addition of synchronous liver resection to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of resectable metastatic colorectal cancer was not associated with increased perioperative major morbidity and mortality in comparison with cytoreduction and hyperthermic intraperitoneal chemotherapy alone. However, the presence of liver metastases was associated with inferior disease-free and overall survival. These data support the continued practice of liver resection, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy in the management of select patients with such stage IV disease.

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.

Developing clinical indicators for oncology: the inaugural cancer care indicator set for the Australian Council on Healthcare Standards.

INTRODUCTION: The Australian Council on Healthcare Standards (ACHS) sponsored an expert-led, consensus-driven, four-stage process, based on a modified Delphi methodology, to determine a set of clinical indicators as quality measures of cancer service provision in Australia. This was done in response to requests from institutional health care providers seeking accreditation, which were additional and complementary to the existing radiation oncology set. The steering group members comprised multidisciplinary key opinion leaders and a consumer representative. Five additional participants constituted the stakeholder group, who deliberated on the final indicator set. METHODS AND RECOMMENDATIONS: An initial meeting of the steering group scoped the high level nature of the desired set. In stage 2, 65 candidate indicators were identified by a literature review and a search of international metrics. These were ranked by survey, based on ease of data accessibility and collectability and clinical relevance. The top 27 candidates were debated by the stakeholder group and culled to a final set of 16 indicators. A user manual was created with indicators mapped to clinical codes. The indicator set was ratified by the Clinical Oncology Society of Australia and is now available for use by health care organisations participating in the ACHS Clinical Indicator Program. This inaugural cancer clinical indicator set covers high level assessment of various critical processes in cancer service provision in Australia. Regular reviews and updates will ensure usability. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This is the inaugural indicator set for cancer care for use across Australia and internationally under the ACHS Clinical Indicator Program. Multidisciplinary involvement through a modified Delphi process selected indicators representing both generic and specific aspects of care across the cancer journey pathway and will provide a functional tool to compare health care delivery across multiple settings. It is anticipated that this will drive continual improvement in cancer care provision.

Beyond transanal total mesorectal excision: short-term outcomes of transanal total mesorectal excision in locally advanced rectal cancer requiring resection beyond total mesorectal excision.

AIM: The aim of this work was to define the role of transanal total mesorectal excision (taTME) in locally advanced rectal cancer (LARC) requiring resection beyond the mesorectal plane. METHOD: We performed a retrospective review of the outcomes of a case series of patients undergoing taTME for rectal cancer with mesorectal fascia or adjacent organ involvement. RESULTS: Eleven patients (six men) underwent taTME for LARC requiring resection beyond total mesorectal excision (TME). All had a restorative procedure. The transabdominal approach was open in five and minimally invasive in six cases. All patients required the resection of at least one adjacent structure, including presacral fascia, internal iliac vessels, nerve roots, uterus, vagina or seminal vesicles. Four patients required a pelvic side-wall lymph node dissection and four had intraoperative radiotherapy. In all cases, the transanal approach was useful to disconnect the rectum distally, resect adjacent organs or control the R1 risk-point. Three patients had a complication of Clavien-Dindo grade III or above (one mechanical bowel obstruction, one pelvic collection and one urine sepsis). There were no anastomotic complications. Ten patients had an R0 resection. During a median follow-up of 11 (8.6-16) months there were no local recurrences, but two patients had distant metastases. During the study period, eight patients underwent closure of their stoma whilst the remaining three have had normal anastomotic assessments and will be closed in the future. CONCLUSION: This early series shows that implementation of taTME for resections beyond TME may be feasible and safe in a highly selected setting.

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.

Whither Anal Cancer?

Improving outcomes for uncommon tumours such as anal cancer can be challenging. Evolution of care tends to be incremental rather than transformative and identifying the specific factors facilitating improvement can be difficult. Outcome from specialist units may be better than that demonstrated in trials, posing challenges for development of future trials.