Accuracy of deep neural learning models in the imaging prediction of pathological complete response after neoadjuvant chemoradiotherapy for locally advanced rectal cancer: a systematic review.

PURPOSE: Up to 15-27% of patients achieve pathologic complete response (pCR) following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). Deep neural learning (DL) algorithms have been suggested to be a useful adjunct to allow accurate prediction of pCR and to identify patients who could potentially avoid surgery. This systematic review aims to interrogate the accuracy of DL algorithms at predicting pCR. METHODS: Embase (PubMed, MEDLINE) databases and Google Scholar were searched to identify eligible English-language studies, with the search concluding in July 2022. Studies reporting on the accuracy of DL models in predicting pCR were selected for review and information pertaining to study characteristics and diagnostic measures was extracted from relevant studies. Risk of bias was evaluated using the Newcastle-Ottawa scale (NOS). RESULTS: Our search yielded 85 potential publications. Nineteen full texts were reviewed, and a total of 12 articles were included in this systematic review. There were six retrospective and six prospective cohort studies. The most common DL algorithm used was the Convolutional Neural Network (CNN). Performance comparison was carried out via single modality comparison. The median performance for each best-performing algorithm was an AUC of 0.845 (range 0.71-0.99) and Accuracy of 0.85 (0.83-0.98). CONCLUSIONS: There is a promising role for DL models in the prediction of pCR following neoadjuvant-CRT for LARC. Further studies are needed to provide a standardised comparison in order to allow for large-scale clinical application. PROPERO REGISTRATION: PROSPERO 2021 CRD42021269904 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021269904 .

The management of clinically suspicious para-aortic lymph node metastasis in colorectal cancer: A systematic review.

Approximately 1%-2% of patients with colorectal cancer (CRC) develop para-aortic lymph node (PALN) metastases, which are typically considered markers of systemic disease, and are associated with a poor prognosis. The utility of PALN dissection (PALND) in patients with CRC is of ongoing debate and only small-scale retrospective studies have been published on this topic to date. This systematic review aimed to determine the utility of resecting PALN metastases with the primary outcome measure being the difference in survival outcomes following either surgical resection or non-resection of these metastases. A comprehensive systematic search was undertaken to identify all English-language papers on PALND in the PubMed, Medline, and Google Scholar databases. The search results identified a total of 12 eligible studies for analysis. All studies were either retrospective cohort studies or case series. In this systematic review, PALND was found to be associated with a survival benefit when compared to non-resection. Metachronous PALND was found to be associated with better overall survival as compared to synchronous PALND, and the number of PALN metastases (2 or fewer) and a pre-operative carcinoembryonic antigen level of <5 was found to be associated with a better prognosis. No PALND-specific complications were identified in this review. A large-scale prospective study needs to be conducted to definitively determine the utility of PALND. For the present, PALND should be considered within a multidisciplinary approach for patients with CRC, in conjunction with already established treatment regimens.

The utility of ctDNA in colorectal cancer with peritoneal metastases.

BACKGROUND: The development of peritoneal metastases (PM) in patients with colorectal cancer (CRC) connotates a poor prognosis. Circulating tumour (ctDNA) is a promising tumour biomarker in the management CRC. This systematic review aimed to summarize the role of ctDNA in patients with CRC and PM. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic review of the literature until June 2022 was performed. Studies reporting on the utility of ctDNA in colorectal PM were included. A total of eight eligible studies were identified including a total of 167 patients. RESULTS: The findings from this review suggest an evolving role for ctDNA in CRC with PM. ctDNA can be isolated from both plasma and peritoneal fluid, with peritoneal fluid preferred as the liquid biopsy of choice with higher mutation detection rates. Concordance rates between tissue and plasma/peritoneal ctDNA mutation detection can vary, but is generally high. ctDNA has a potential role in monitoring anti-EGFR treatment response and resistance, as well as in predicting future prognosis and recurrence. The detection of ctDNA in plasma of patients with isolated PM is also possibly suggestive of occult systemic disease, and patients exhibiting such ctDNA positivity may benefit from systemic treatment. Limitations to ctDNA mutation detection may include the size of peritoneal lesions, as well as the fact that PM poorly shed ctDNA. CONCLUSION: While these findings are promising, further large-scale studies are needed to better evaluate the utility of ctDNA in this subset of patients.

The complication profile of low Hartmann's in rectal cancer: a systematic review and meta-analysis.

BACKGROUND: Non-restorative options for low rectal cancer not invading the sphincter includes low Hartmann's procedure (LH) and inter-sphincteric abdominoperineal resection (ISAPR). There is currently little comparative data to differentiate these options. OBJECTIVES: The aim of this review was to assess the peri-operative morbidity of LH, and then to compare it to that of ISAPR. DATA SOURCES: An up-to-date systematic review was performed on the available literature between 2000-2020 on PubMed, EMBASE, Medline, and Cochrane Library databases. STUDY SELECTION: All studies reporting on non-restorative surgeries for rectal cancer were analysed. Outcomes were firstly analysed between LH and non-LH groups, with further sub-analysis comparing the LH and ISAPR groups. MAIN OUTCOME MEASURE: The main outcome measures were the rates of pelvic sepsis, rates of overall post-operative complication rates, oncological outcomes, and survival. RESULTS: A total of 12 observational studies were included. There were 3526 patients (61.1%) in the LH group, and 2238 patients (38.9%) in the non-LH group, which included 461 patients who underwent ISAPR. The LH group had a higher rate of pelvic sepsis as compared to the non-LH group (OR: 1.79, 95% CI: 1.39-2.29, P < 0.001). The difference is more marked in the sub-analysis comparing LH and ISAPR alone (OR: 3.94, 95% CI: 1.88-7.84, P < 0.01) corresponding to a higher rate of unplanned re-intervention. LH was associated with a higher rate of short-term post-operative mortality as compared to the non-LH group. CONCLUSION: ISAPR is the preferred option for non-restorative rectal surgery, with a more favourable peri-operative morbidity and short-term mortality profile as compared to LH.

Preoperative serum calcitonin may improve initial surgery for medullary thyroid cancer in patients with indeterminate cytology.

BACKGROUND: Medullary thyroid cancer (MTC) is rare, with poorer outcomes than differentiated thyroid cancer. We aimed to identify areas for improvement in the pre-operative evaluation of patients with possible MTC in a high-volume endocrine surgery unit in accordance with current practice guidelines. We hypothesised that the selective use of serum calcitonin (sCT) as a biomarker for possible MTC could guide the extent of initial surgical management. METHODS: We recruited MTC patients between 2000 and 2020 from the Monash University Endocrine Surgery Unit database. Demographics, tumour characteristics, pre-operative evaluation, operative management, and outcomes were analysed. RESULTS: Of 1454 thyroid cancer patients, 43 (3%) had MTC. Pre-operatively, 36 (84%) patients with MTC confirmed on cytology (28, 65%), elevated sCT (6, 14%) or RET mutation (2, 4%). Of these 36 patients, 31 (86%) had optimal extent of thyroidectomy and lymph node dissection (LND). Five (14%) had less than total thyroidectomy due to nerve injury. Thirty-four patients had compartmental LND. In the 12 (27%) patients with indeterminate or non-diagnostic cytology, 5 had elevated sCT and were managed as above. None of the remaining seven had LND, thus potentially suboptimal surgery. CONCLUSION: Our findings reflect the rarity of MTC, and the challenges of pre-operative diagnosis. The addition of sCT may improve surgical planning in patients with indeterminate cytology.

Latest evidence on the management of early-stage and locally advanced rectal cancer: a narrative review.

Rectal cancer is a challenging disease process to manage, with a rising incidence in young adults. Several clinical advances have been made in the past decade with regards to optimal treatment strategies in early-stage (T1-2, node negative tumours) and locally advanced cancers (T3-4 and/or nodal positivity) utilizing a multimodal approach of surgery, neoadjuvant chemoradiotherapy, and adjuvant chemotherapy, all aiming to optimize oncological outcomes, while minimizing associated morbidity. This narrative review aimed to summarize trial level evidence apropos the management of early and locally advanced rectal cancer. All relevant prospective clinical trials were identified through a computer-assisted search of PubMed, EMBASE, Medline databases between 1990 and 30 June 2021. With regards to early rectal cancer, there is limited trial-level evidence in the literature. Total mesorectal excision (TME) is the current standard of care, but local excision could be considered in select patients with pT1 tumours, or patients with near or complete clinical response to neoadjuvant CRT. As for locally advanced rectal cancer, the current standard of care consists of long-course chemotheradiotherapy or short-course radiotherapy, followed by TME. However, the role of total neoadjuvant therapy is promising, with respect to both oncological outcomes, as well as in reducing toxicity. Both induction and consolidation chemotherapy treatment approaches have been described in literature, with encouraging early results. The optimal management of rectal cancer is constantly evolving. More research is needed to investigate the long-term oncological and functional outcomes following new multimodal therapies in the management of early-stage and locally advanced rectal cancer.

Anastomotic Leak in Colorectal Surgery: Predictive Factors and Survival.

<br><b>Introduction:</b> Anastomotic leak (AL) is a serious complication following colorectal surgery.</br> <br><b>Aim:</b> The aim of this study was to identify factors associated with the development of AL and to analyze its impact on survival.</br> <br><b>Materials and methods:</b> All consecutive adult colorectal cancer resections performed between 2007 and 2020 with curative intent and anastomosis formation were included from a prospectively maintained database. The primary outcome measure was the rate of AL. The secondary outcome measure was 5-year overall survival (OS).</br> <br><b>Results:</b> There were 6837 eligible patients. The rate of AL was 2.2% and 4.0% in patients with colon and rectal cancer, respectively. AL was a significant independent predictor of reduced 5-year OS in patients who underwent curative surgery for rectal cancer (odds ratio 2.293, p = 0.009). Emergency surgery (p = 0.015), surgery at a public hospital (p = 0.002), and an open surgical approach (p = 0.021) were all associated with a significantly higher risk of AL in patients with colon cancer, with higher rates of AL noted in left colectomies as compared to right hemicolectomies (4.4% <i>vs.</i> 1.3%, p < 0.001). In rectal cancer patients, AL was associated with neoadjuvant chemoradiotherapy (p = 0.038) and male gender (p = 0.002). The anastomosis formation technique (hand-sewn <i>vs.</i> stapled) did not impact the rate of AL (p = 0.116 and p = 0.198 with colon and rectal cancer, respectively).</br> <br><b>Discussion:</b> Clinicians should be cognizant of the predictive factors for AL and should consider early intervention for at-risk patients.</br>.

Comparison of colorectal cancer outcomes in young adults and octogenarians.

BACKGROUND: This study aimed to characterise the outcomes associated with colorectal cancer (CRC), comparing young adults (<50 years), patients of screening age (50-79 years), and octogenarians (>80 years). METHODS: All consecutive CRC resections with curative intent were recruited into this study from a prospectively maintained CRC database at a tertiary academic centre. RESULTS: A total of 745 eligible cases were identified. Five-year survival in young adults was poorer than that of patients of screening age. Young adults had the highest incidence of rectal cancer resections, and presented with the most advanced tumour stages. Independent associations for poorer survival in young adults were increased nodal stage, the presence of distal metastases, and loss of MLH1/PMS2 staining on immunohistochemistry. Young adults had similar survival to octogenarians, when comparing patients treated with curative intent, regardless of oncological treatment.

Predictive Factors for Anastomotic Leak in Colorectal Surgery: A Bi-National Database Study.

IntroductionAnastomotic leak (AL) is a serious complication following colorectal surgery. This study aimed to identify factors associated with the development of AL and analyze its impact on survival.Materials and MethodsAll consecutive adult colorectal cancer resections with curative intent and anastomosis formation were included from a prospectively maintained bi-national database between 2007 and 2020. The primary outcome measure was the rate of AL. The secondary outcome measure was 5-year overall survival (OS).ResultsThere were 7566 eligible patients. The rate of AL was 2.3% and 4.4% in patients with colon and rectal cancer respectively. AL was a significant independent predictor of reduced 5-year OS in patients who underwent curative surgery for rectal cancer (Odds ratio 1.999, p = 0.017). Emergency surgery (p = 0.013), surgery at a public hospital (p < 0.01), and an open surgical approach (p = 0.002) were all significantly associated with a higher risk of AL in patients with colon cancer, with higher rates of AL noted in left colectomies as compared to right hemicolectomies (6.8% vs 1.6%, p < 0.05). In rectal cancer patients, ultra-low anterior resections had the highest risk of AL (4.6%), and associations were found with neoadjuvant chemotherapy (p = 0.011), surgery in a public hospital (p = 0.019), and an open approach (p = 0.035). Anastomosis formation technique (hand-sewn vs stapled) did not impact on rate of AL.DiscussionClinicians should be cognizant of the predictive factors for AL and consider early intervention for patients at risk of this.

Predictive factors for distant recurrence of colorectal cancer in patients after curative resection for stage I-III colorectal cancer in Australia.

PURPOSE: Distant recurrence is a devastating occurrence after colorectal cancer resection. This study aimed to identify the risk factors for distant recurrence following surgery. METHODS: All consecutive colorectal cancer resections with curative intent were included from a prospectively maintained colorectal cancer database. The primary outcome was to identify predictive factors for distant recurrence of colorectal cancer. RESULTS: A total of 670 eligible cases were identified with 88 (13.1%) developing distant recurrence during the follow-up period. The median time to distant recurrence was 1.2 years with the most common sites of distant recurrence being the lung (44.3%) and liver (44.3%). Predictive factors for distant recurrence in colon cancer included a high tumor, nodal, and overall stage of the primary cancer (p < 0.001 for all). Surgical complications (p = 0.007), including anastomotic leak (p = 0.023), were associated with a higher risk of developing distant recurrence in rectal cancer patients. Independent variables associated with distant recurrence included tumor stage (OR 1.61, p = 0.011), nodal stage (OR 2.18, p < 0.001), and both KRAS (OR 11.04, p < 0.001) and MLH/PMS2 (OR 0.20, p = 0.035) genetic mutations. Among patients with distant recurrence, treatment with surgery conferred the best survival, with patients < 50 years of age having the best overall 5-year survival. CONCLUSION: Predictive factors for distant recurrence include advanced tumor and nodal stages, and the presence of KRAS and MLH/PSM2 mutations. Clinicians should be cognizant of these risk factors, and instate close surveillance plans for patients exhibiting these features.

The impact of the COVID-19 pandemic on colorectal cancer diagnosis and management: a Binational Colorectal Cancer Audit study.

BACKGROUND: The COVID-19 pandemic has resulted in global disruptions to the delivery of healthcare. The national responses of Australia and New Zealand has resulted in unprecedented changes to the care of colorectal cancer patients, amongst others. This paper aims to determine the impact of COVID-19 on colorectal cancer diagnosis and management in Australia and New Zealand. METHODS: This is a multicentre retrospective cohort study using the prospectively maintained Binational Colorectal Cancer Audit (BCCA) registry. Data is contributed by over 200 surgeons in Australia and New Zealand. Patients receiving colorectal cancer surgery during the pandemic were compared to averages from the same period over the preceding 3 years. RESULTS: There were fewer operations in 2020 than the historical average. During April to June, patients were younger, more likely to have operations in public hospitals and more likely to have urgent or emergency operations. By October to December, proportionally less patients had Stage I disease, proportionally more had Stage II or III disease and there was no difference in Stage IV disease. Patients were less likely to have rectal cancer, were increasingly likely to have urgent or emergency surgery and more likely to have a stoma created. CONCLUSION: This study shows that the response to COVID-19 has had measurably negative effects on the diagnosis and management of colorectal cancer in two countries that have had significantly fewer COVID-19 cases than many other countries. The long-term effects on survival and recurrence are yet to be known, but could be significant.

Comparing functional outcomes between transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME) for rectal cancer: a systematic review and meta-analysis.

BACKGROUND: There is concern that transanal total mesorectal excision (TaTME) may result in poorer functional outcomes as compared to laparoscopic TME (LaTME). These concerns arise from the fact that TaTME entails both a low anastomosis and prolonged dilatation of the anal sphincter from the transanal platform. OBJECTIVES: This paper aimed to assess the comparative functional outcomes following TaTME and LaTME, with a focus on anorectal and genitourinary outcomes. DATA SOURCES: A meta-analysis and systematic review was performed on available literature between 2000 and 2020 from the PubMed, EMBASE, Medline, and Cochrane Library databases. STUDY SELECTION: All comparative studies assessing the functional outcomes following taTME versus LaTME in adults were included. MAIN OUTCOME MEASURE: Functional anorectal and genitourinary outcomes were evaluated using validated scoring systems. RESULTS: A total of seven studies were included, consisting of one randomised controlled trial and six non-randomised studies. There were 242 (52.0%) and 233 (48.0%) patients in the TaTME and LaTME groups respectively. Anorectal functional outcomes were similar in both groups with regard to LARS scores (30.6 in the TaTME group and 28.3 in the LaTME group), Jorge-Wexner incontinence scores, and EORTC QLQ C30/29 scores. Genitourinary function was similar in both groups with IPSS scores of 5.5 to 8.0 in the TaTME group, and 3.5 to 10.1 in the LaTME group. (p = 0.835). CONCLUSION: This review corroborates findings from previous studies in showing that the transanal approach is not associated with increased anal sphincter damage. Further prospective clinical trials are needed in this field of research.

Oncological reasons for performing a complete mesocolic excision: a systematic review and meta-analysis.

BACKGROUND: While complete mesocolic excision (CME) has been shown to have an oncological benefit as compared to conventional colonic surgery for colon surgery, this benefit must be weighed up against the risk of major intra-abdominal complications. This paper aimed to assess the comparative oncological benefits of CME. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic review of the literature until May 2020 was performed. Comparative studies assessing CME versus conventional colonic surgery for colon cancer were compared, and outcomes were pooled. RESULTS: A total of 700 publications were identified, of which 19 were found to meet the inclusion criteria. A total of 25 886 patients were compared, with 14 431 patients in the CME arm. CME was associated with a significantly higher rate of vascular injury (odds ratio 3, P < 0.001). Rates of local and distant recurrence were lower in the CME group (odds ratio 0.66 and 0.73, respectively, both P < 0.001). CME patients had a significantly higher lymph node yield (P < 0.001). While no significant differences were noted between the two groups in terms of pooled 3- or 5-year disease-free survival, pooled 5-year overall survival was significantly higher in the CME group (relative risk 0.82, P < 0.001). CONCLUSION: Based on the available evidence, CME is associated with improved oncologic outcomes at the expense of higher complication rates, including vascular injury. The oncological benefits need to weighed up against a multitude of factors including the level of hospital support, surgeon experience, patient age, and associated comorbidities.

Predictors of Surgical Difficulty in Laparoscopic Total Mesorectal Excision.

Concerns have been raised regarding the oncological safety of laparoscopic total mesorectal excision (TME) as compared to an open approach. This study aimed to identify risk factors for surgically difficult laparoscopic TME. All consecutive laparoscopic rectal cancer cases were included from a prospectively maintained colorectal cancer database. The primary outcome was to identify risk factors for surgically difficult TME. A Surgical Difficulty Risk Score (SDRS) between 0 and 6 was calculated for each case with cases achieving an SDRS of 2 or greater being deemed as surgically difficult. A total of 2795 consecutive cases of laparoscopic TME were identified, with 464 (16.6%) surgically difficult cases. Univariate analysis found that operating in the male pelvis, performing abdomino-perineal resections, Hartmann's procedures, and proctocolectomies were all significantly associated with higher operative difficulty (P < 0.001). A higher nodal stage of cancer (P = 0.046), and the resection of another organ (P = 0.003) were significantly associated with higher surgical difficulty. On multivariate analysis, a female pelvis was associated with a favorable laparoscopic resection (Odds ratio [OR] 0.54, 95% CI 0.43-0.67, P < 0.001), whereas patients who had another organ resection (OR 2.6, 95% CI 1.53-4.42, P < 0.001), nodal positivity (OR 1.37, 95% CI 1.11-1.69, P = 0.003), and high ASA scores had more difficult surgeries. Predictive factors for surgically difficult laparoscopic TME include male gender, high ASA scores, mid and low rectal cancer, positive nodal stage, and resection of another organ at time of surgery.

Utility of intra-operative flexible sigmoidoscopy to assess colorectal anastomosis: a systematic review and meta-analysis.

BACKGROUND: Anastomotic leak (AL) after colorectal resection leads to increased oncological and non-oncological, morbidity and mortality. Intra-operative assessment of a colorectal anastomosis with intra-operative flexible sigmoidoscopy (IOFS) has become increasingly prevalent and is an alternative to conventional air leak test. It is thought that intra-operative identification of an AL or anastomotic bleeding (AB) allows for immediate reparative intervention at the time of anastomosis formation itself. We aim to assess the available evidence for the use of IOFS to prevent complications following colorectal resection. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, a systematic review of the literature between January 1980 and June 2020 was performed. Comparative studies assessing IOFS versus conventional air leak test were compared, and outcomes were pooled. RESULTS: A total of 4512 articles were assessed, of which eight were found to meet the inclusion criteria. A total of 1792 patients were compared; 884 in the IOFS arm and 908 in the control arm. IOFS was associated with an increase in the rate of positive leak test (odds ratio (OR) 5.21, P > 0.001), a decrease in AL (OR 0.45, P = 0.006) and a decrease in post-operative AB requiring intervention (OR 0.40, P = 0.037). CONCLUSION: In a non-randomized meta-analysis, IOFS increases the likelihood of identifying an anastomotic defect or bleeding intra-operatively. This allows for immediate intervention that decreases the rate of AL and AB. This adds impetus for performing routine IOFS after a left-sided colorectal resection with anastomosis and highlights the need for randomized controlled trial to confirm the finding.