A systematic review of minimally invasive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal malignancy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is traditionally a maximally invasive operation with a large abdominal incision and multi-visceral resections. However, to minimize abdominal wall morbidity and improve functional recovery, some centres have adopted a minimally invasive (MI) approach in select cases. The primary aim of this systematic review and meta-analysis was to assess the evidence for safety and patient selection for minimally invasive approaches to CRS and HIPEC with curative intent. METHODS: A PRISMA-compliant systematic review was performed using three electronic databases: Ovid MEDLINE, EMBASE and Web of Science. Data regarding postoperative morbidity was meta-analysed. RESULTS: Thirteen studies met the inclusion criteria (N = 462 MI patients), all of which were retrospective in design. Six studies included an open comparison group. Pseudomyxoma peritonei, mesothelioma and ovarian carcinoma made up the majority of cases (>90%), with a PCI < 10 listed as a prerequisite to selection across all studies. On pooled analysis there was no difference in major morbidity between MI and open groups (OR 0.52 95% CI 0.18-1.46, P = 0.33). There was one perioperative death reported in the MI group. Length of stay appeared shorter in the MI group (median range MI: 4-11 v Open: 7-13 days). Short-term recurrence and overall survival between both groups also appeared no different. CONCLUSION: Minimally invasive CRS and HIPEC appears feasible and safe in appropriately selected patients. Clear histological stratification and longer term follow up is required to determine oncological safety, particularly in more aggressive tumours such as colorectal peritoneal metastases.

The rise of robotic colorectal surgery: better for patients and better for surgeons.

Robotic colorectal surgery represents a major technological advancement in the treatment of patients with colorectal disease. Several recent randomized controlled trials comparing robotic colorectal surgery with laparoscopic surgery have demonstrated improved short-term patient outcomes in the robotic group. Whilst the primary focus of research in robotic surgery has been on patient outcomes, the robotic platform also provides unparalleled benefits for the surgeon, including improved ergonomics and surgeon comfort, with the potential to reduce occupational injuries and prolong career longevity. It is becoming clear that robotic surgical systems improve patient outcomes and may provide significant benefits to the surgical workforce.

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.

Impact of neoadjuvant systemic chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for appendiceal adenocarcinoma.

AIM: Peritoneal dissemination of infiltrative appendiceal tumors is a rare and poorly understood phenomenon. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a well-recognized treatment option for selected patients. Neoadjuvant systemic chemotherapy (NAC) has been shown to be associated with improved overall survival (OS) in colorectal peritoneal metastases but little is known of the impact of this from an appendiceal adenocarcinoma perspective. METHOD: A prospective database of 294 patients with advanced appendiceal primary tumors undergoing CRS ± HIPEC between June 2009 and December 2020 was reviewed. Baseline characteristics and long-term outcomes were compared between patients with adenocarcinoma who received neoadjuvant chemotherapy or upfront surgery. RESULTS: Eighty-six (29%) patients were histologically diagnosed with an appendiceal cancer. These included intestinal-type adenocarcinoma (11.6%), mucinous adenocarcinoma (43%), and goblet cell adenocarcinoma (GCA) or signet ring cell adenocarcinoma (SRCA) (45.4%). Twenty-five (29%) of these underwent NAC, of which eight (32%) exhibited some degree of radiological response. There was no statistical difference in OS at 3 years between the NAC and upfront surgery groups (47.3% vs. 75.8%, p = 0.372). Appendiceal histology subtypes, particularly GCA and SRCA (p = 0.039) and peritoneal carcinomatosis index >10 (p = 0.009), were factors independently associated with worse OS. CONCLUSION: Administration of NAC did not appear to prolong OS in the operative management of disseminated appendiceal adenocarcinomas. GCA and SRCA subtypes display a more aggressive biological phenotype.

Robotic natural orifice specimen extraction surgery (NOSES) for anterior resection.

Minimally invasive colorectal surgery is currently well-accepted, with open techniques being reserved for very difficult cases. Laparoscopic colectomy has been proven to have lower mortality, complication, and ostomy rates; a shorter median length of stay; and lower overall costs when compared to its open counterpart. This trend is seen in both benign and malignant indications. Natural orifice specimen extraction surgery (NOSES) in colorectal surgery was first described in the early 1990s. Three recent meta-analyses comparing transabdominal extraction against NOSES concluded that NOSES was superior in terms of overall postoperative complications, recovery of gastrointestinal function, postoperative pain, aesthetics, and hospital stay. However, NOSES was associated with a longer operative time. Herein, we present our technique of robotic NOSES anterior resection using the da Vinci Xi platform in diverticular disease and sigmoid colon cancers.

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.

Redo Pelvic Surgery and Combined Metastectomy for Locally Recurrent Rectal Cancer with Known Oligometastatic Disease: A Multicentre Review.

INTRODUCTION: Historically, surgical resection for patients with locally recurrent rectal cancer (LRRC) had been reserved for those without metastatic disease. 'Selective' patients with limited oligometastatic disease (OMD) (involving the liver and/or lung) are now increasingly being considered for resection, with favourable five-year survival rates. METHODS: A retrospective analysis of consecutive patients undergoing multi-visceral pelvic resection of LRRC with their oligometastatic disease between 1 January 2015 and 31 August 2021 across four centres worldwide was performed. The data collected included disease characteristics, neoadjuvant therapy details, perioperative and oncological outcomes. RESULTS: Fourteen participants with a mean age of 59 years were included. There was a female preponderance (n = 9). Nine patients had liver metastases, four had lung metastases and one had both lung and liver disease. The mean number of metastatic tumours was 1.5 +/- 0.85. R0 margins were obtained in 71.4% (n = 10) and 100% (n = 14) of pelvic exenteration and oligometastatic disease surgeries, respectively. Mean lymph node yield was 11.6 +/- 6.9 nodes, with positive nodes being found in 28.6% (n = 4) of cases. A single major morbidity was reported, with no perioperative deaths. At follow-up, the median disease-free survival and overall survival were 12.3 months (IQR 4.5-17.5 months) and 25.9 months (IQR 6.2-39.7 months), respectively. CONCLUSIONS: Performing radical multi-visceral surgery for LRRC and distant oligometastatic disease appears to be feasible in appropriately selected patients that underwent good perioperative counselling.

Risk-Directed Ambulatory Thromboprophylaxis in Lung and Gastrointestinal Cancers: The TARGET-TP Randomized Clinical Trial.

Importance: Thromboprophylaxis for individuals receiving systemic anticancer therapies has proven to be effective. Potential to maximize benefits relies on improved risk-directed strategies, but existing risk models underperform in cohorts with lung and gastrointestinal cancers. Objective: To assess clinical benefits and safety of biomarker-driven thromboprophylaxis and to externally validate a biomarker thrombosis risk assessment model for individuals with lung and gastrointestinal cancers. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial (Targeted Thromboprophylaxis in Ambulatory Patients Receiving Anticancer Therapies [TARGET-TP]) conducted from June 2018 to July 2021 (with 6-month primary follow-up) included adults aged 18 years or older commencing systemic anticancer therapies for lung or gastrointestinal cancers at 1 metropolitan and 4 regional hospitals in Australia. Thromboembolism risk assessment based on fibrinogen and d-dimer levels stratified individuals into low-risk (observation) and high-risk (randomized) cohorts. Interventions: High-risk patients were randomized 1:1 to receive enoxaparin, 40 mg, subcutaneously daily for 90 days (extending up to 180 days according to ongoing risk) or no thromboprophylaxis (control). Main Outcomes and Measures: The primary outcome was objectively confirmed thromboembolism at 180 days. Key secondary outcomes included bleeding, survival, and risk model validation. Results: Of 782 eligible adults, 328 (42%) were enrolled in the trial (median age, 65 years [range, 30-88 years]; 176 male [54%]). Of these participants, 201 (61%) had gastrointestinal cancer, 127 (39%) had lung cancer, and 132 (40%) had metastatic disease; 200 (61%) were high risk (100 in each group), and 128 (39%) were low risk. In the high-risk cohort, thromboembolism occurred in 8 individuals randomized to enoxaparin (8%) and 23 control individuals (23%) (hazard ratio [HR], 0.31; 95% CI, 0.15-0.70; P = .005; number needed to treat, 6.7). Thromboembolism occurred in 10 low-risk individuals (8%) (high-risk control vs low risk: HR, 3.33; 95% CI, 1.58-6.99; P = .002). Risk model sensitivity was 70%, and specificity was 61%. The rate of major bleeding was low, occurring in 1 participant randomized to enoxaparin (1%), 2 in the high-risk control group (2%), and 3 in the low-risk group (2%) (P = .88). Six-month mortality was 13% in the enoxaparin group vs 26% in the high-risk control group (HR, 0.48; 95% CI, 0.24-0.93; P = .03) and 7% in the low-risk group (vs high-risk control: HR, 4.71; 95% CI, 2.13-10.42; P < .001). Conclusions and Relevance: In this randomized clinical trial of individuals with lung and gastrointestinal cancers who were stratified by risk score according to thrombosis risk, risk-directed thromboprophylaxis reduced thromboembolism with a desirable number needed to treat, without safety concerns, and with reduced mortality. Individuals at low risk avoided unnecessary intervention. The findings suggest that biomarker-driven, risk-directed primary thromboprophylaxis is an appropriate approach in this population. Trial Registration: ANZCTR Identifier: ACTRN12618000811202.

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.

Immune mediated colitis: a surgical perspective.

BACKGROUND: This study aims to review and summarize the current up to date literature that explore the current treatment approaches to immune mediated colitis and the role of surgical specialties in the landscape of management. METHODS: A narrative review of papers was performed following a literature search through Medline, EMBASE and Cochrane Central databases pertaining to immune mediated colitis as an adverse event of cancer immunotherapy. RESULTS: Current guidelines for the diagnosis and treatment of immune mediated colitis mirror the approach to the workup of inflammatory bowel disease and guided by treating oncology and gastroenterology specialties. Immune mediated colitis however relies on surgical specific skills as a consequence of obtaining a diagnosis as well as in the management of complications that may arise. CONCLUSION: Immune mediate colitis management has largely been under the purview of medical specialties. This review explores the current landscape of managing immune mediated colitis from a surgical perspective and highlights key areas in which surgeons can engage in the multidisciplinary care of this condition. To facilitate prompt diagnosis and management of immune-mediated colitis, there is an increasing necessity for surgeons to become familiar with the latest multidisciplinary approaches and recommendations.

Perioperative nutritional assessment and interventions in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): A systematic review.

BACKGROUND: Peritoneal carcinomatosis is a catabolic state and cytoreductive surgery (CRS) is a high morbidity operation. Optimising perioperative nutrition is crucial to improve outcomes. This systematic review sought to examine literature describing clinical outcomes related to preoperative nutrition status and nutrition interventions in patients undergoing CRS with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A systematic review was registered with PROSPERO (300326). A search of eight electronic databases was undertaken on 8th May 2022 and reported according to the PRISMA statement. Studies reporting nutrition status through use of screening and assessment tools, nutrition interventions or nutrition-related clinical outcomes for patients undergoing CRS with HIPEC were included. RESULTS: Of 276 screened studies, 25 studies were included for review. Commonly used nutrition assessment tools for CRS-HIPEC patients included Subjective Global Assessment (SGA), sarcopenia assessment with computed tomography, preoperative albumin, and body mass index (BMI). Three retrospective studies compared SGA with postoperative outcomes. Malnourished patients were more likely to have postoperative infectious complications (p = 0.042 SGA-B, p = 0.025 SGA-C). Malnutrition was significantly associated with increased hospital length of stay (LOS) in two studies (p = 0.006, p = 0.02), and with overall survival in another study (p = 0.006). Eight studies analysing preoperative albumin levels reported conflicting associations with postoperative outcomes. BMI in five studies was not associated with morbidity. One study did not support routine nasogastric tube (NGT) feeding. CONCLUSIONS: Preoperative nutritional assessment tools, including SGA and objective sarcopaenia measures, have a role in predicting nutritional status for CRS-HIPEC patients. Optimisation of nutrition is important for preventing complications.

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.

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.

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.