Prospective and multi-reader evaluation of deep learning reconstruction-based accelerated rectal MRI: image quality, diagnostic performance, and reading time.

OBJECTIVES: To evaluate deep learning reconstruction (DLR)-based accelerated rectal magnetic resonance imaging (MRI) compared with standard MRI. MATERIALS AND METHODS: Patients with biopsy-confirmed rectal adenocarcinoma between November/2022 and May/2023 in a single centre were prospectively enrolled for an intra-individual comparison between standard fast spin-echo (FSEstandard) and DLR-based FSE (FSEDL) sequences. Quantitative and qualitative image quality metrics of the pre-therapeutic MRIs were evaluated in all patients; diagnostic performance and evaluating time for T-staging, N-staging, extramural vascular invasion (EMVI), and mesorectal fascia (MRF) status was further analysed in patients undergoing curative surgery, with histopathologic results as the diagnostic gold standard. RESULTS: A total of 117 patients were enrolled, with 60 patients undergoing curative surgery. FSEDL reduced the acquisition time by 65% than FSEstandard. FSEDL exhibited higher signal-to-noise ratios, contrast-to-noise ratio, and subjective scores (noise, tumour margin clarity, visualisation of bowel wall layering and MRF, overall image quality, and diagnostic confidence) than FSEstandard (p < 0.001). Reduced artefacts were observed in FSEDL for patients without spasmolytics (p < 0.05). FSEDL provided higher T-staging accuracy by junior readers than FSEstandard (reader 1, 58.33% vs 70.00%, p = 0.016; reader 3, 60.00% vs 76.67%, p = 0.021), with similar N-staging, EMVI, and MRF performance. No significant difference was observed for senior readers. FSEDL exhibited shorter diagnostic time in all readers' T-staging and overall evaluation, and junior readers' EMVI and MRF (p < 0.05). CONCLUSION: FSEDL provided improved image quality, reading time, and junior radiologists' T-staging accuracy than FSEstandard, while reducing the acquisition time by 65%. CLINICAL RELEVANCE STATEMENT: DLR is clinically applicable for rectal MRI, providing improved image quality with shorter scanning time, which may ease the examination burden. It is beneficial for diagnostic optimisation in improving junior radiologists' T-staging accuracy and reading time. KEY POINTS: The rising incidence of rectal cancer has demanded enhanced efficiency and quality in imaging examinations. FSEDL demonstrated superior image quality and had a 65% reduced acquisition time. FSEDL can improve the diagnostic accuracy of T-staging and reduce the reading time for assessing rectal cancer.

Impact of neoadjuvant therapy on nodal harvest in clinical stage III rectal cancer: Establishing optimum cut-offs by disease response.

INTRODUCTION: A minimum lymph node harvest (LNH) of 12 is the current standard for appropriate nodal staging in resectable rectal cancer. However, the rise of neoadjuvant chemoradiation (NCRT) and total neoadjuvant therapy (TNT) has been associated with decreasing number of LNH. We hypothesize that as tumor response to neoadjuvant therapy increases, the optimum for LNH to achieve appropriate nodal staging should decrease. METHODS: Patients with clinical stage III rectal adenocarcinoma who underwent NCRT/TNT followed by resection were identified from the National Cancer Database. A JoinPoint regression analysis was used to determine the LNH for each tumor regression grade (TRG) category beyond which the rate of positive nodes does not significantly change. RESULTS: Thirteen thousand four hundred and twenty-six patients met inclusion criteria. Of these, 2406 (17.9%) achieved TRG 0 or ypT0 and 8210 (61.2%) achieved ypN0. Collectively, 2043 patients (15.2%) were reported to have a pathologic complete response (ypT0 ypN0). Positive pathologic nodes were found in 15%, 23%, 31%, 54%, and 53% as ypT stage increased from ypT0 to ypT4, respectively. Similarly, ypN+ rates were 15%, 36%, 41%, and 55% in TRG 0-3. No JoinPoint was identified for TRG 0, whereas inflection points were found at 6-10 nodes for TRG1 (p = 0.002) and TRG 2 (p = 0.016), and at 11-15 nodes for TRG 3. CONCLUSION: The benchmark of retrieving 12 nodes in resectable stage III rectal cancer is not consistently achieved after NCRT/TNT. We demonstrate that the LNH requirement to establish accurate pathologic nodal staging can vary depending on the tumor response to neoadjuvant therapies.

Measurement of the distance between tumor micro-foci and gross tumor in rectal cancer pathological specimens: implication on margin distance of clinical target volume treated with high-dose radiotherapy for rectal cancer.

PURPOSE: To measure the micro-foci distance away from gross tumor and to provide reference to create the clinical target volume (CTV) margin for boost radiotherapy in rectal adenocarcinoma. METHODS: Twenty-eight rectal cancer surgical specimens of only total mesorectal excision were collected. The pathological specimens were retrospectively measured, and the nearest distance between the tumor micro-foci and gross tumor was microscopically measured. The "in vivo-in vitro" retraction factor was calculated as the ratio of the deepest thickness laterally and the vertical height superior/inferiorly of the rectal tumor measured in MRI and those measured in immediate pathological specimens. The retraction factor during pathological specimen processing was calculated as the distance ratio before and after dehydration in the lateral, superior, and inferior sides by the "knot marking method." The distances of tumor micro-foci were individually corrected with these two retraction factors. RESULTS: The mean "in vivo-in vitro" tumor retraction factors were 0.913 peripherally and 0.920 superior/inferiorly. The mean tumor specimen processing retraction factors were 0.804 peripherally, 0.815 inferiorly, and 0.789 superiorly. Of 28 patients, 14 cases (50.0%) had 24 lateral micro-foci, 8 cases (28.6%) had 13 inferior micro-foci, and 7 cases (25.0%) had 19 superior micro-foci. The 95th percentiles of the micro-foci distance for 28 patients were 6.44 mm (peripheral), 5.54 mm (inferior), and 5.42 mm (superior) after retraction correction. CONCLUSION: The micro-foci distances of 95% of rectal adenocarcinoma patients examined were within 6.44 mm peripherally, 5.54 mm inferiorly, and 5.42 mm superiorly. These findings provide reference to set the boost radiotherapy CTV margin for rectal cancer.

Predicting the Feasibility of Curative Resection in Low Rectal Cancer: Insights from a Prospective Observational Study on Preoperative Magnetic Resonance Imaging Accuracy.

Background and Objectives: A positive pathological circumferential resection margin is a key prognostic factor in rectal cancer surgery. The point of this prospective study was to see how well different MRI parameters could predict a positive pathological circumferential resection margin (pCRM) in people who had been diagnosed with rectal adenocarcinoma, either on their own or when used together. Materials and Methods: Between November 2019 and February 2023, a total of 112 patients were enrolled in this prospective study and followed up for a 36-month period. MRI predictors such as circumferential resection margin (mCRM), presence of extramural venous invasion (mrEMVI), tumor location, and the distance between the tumor and anal verge, taken individually or combined, were evaluated with univariate and sensitivity analyses. Survival estimates in relation to a pCRM status were also determined using Kaplan-Meier analysis. Results: When individually evaluated, the best MRI predictor for the detection of a pCRM in the postsurgical histopathological examination is mrEMVI, which achieved a sensitivity (Se) of 77.78%, a specificity (Sp) of 87.38%, a negative predictive value (NPV) of 97.83%, and an accuracy of 86.61%. Also, the best predictive performance was achieved by a model that comprised all MRI predictors (mCRM+ mrEMVI+ anterior location+ < 4 cm from the anal verge), with an Se of 66.67%, an Sp of 88.46%, an NPV of 96.84%, and an accuracy of 86.73%. The survival rates were significantly higher in the pCRM-negative group (p < 0.001). Conclusions: The use of selective individual imaging predictors or combined models could be useful for the prediction of positive pCRM and risk stratification for local recurrence or distant metastasis.

Management of lateral pelvic lymph nodes in rectal cancer.

Lateral pelvic lymph node (LPLN) involvement occurs in 10%-25% of rectal cancer cases. Total mesorectal excision (TME) with routine LPLN dissection (LPLND) is predominantly applied in Japan whereas TME with neoadjuvant treatment are used in the West. LPLND is a morbid procedure and minimally invasive techniques may help reduce its morbidity. Selective lateral pelvic node dissection with TME following neoadjuvant treatment achieves acceptable disease-free and overall survival.

An optimised liver-first strategy for synchronous metastatic rectal cancer leads to higher protocol completion and lower surgical morbidity.

INTRODUCTION: The optimal management of rectal cancer with synchronous liver metastases remains debatable. Thus, we propose an optimised liver-first (OLF) strategy that combines concomitant pelvic irradiation with hepatic management. This study aimed to evaluate the feasibility and oncological quality of the OLF strategy. MATERIALS AND METHODS: Patients underwent systemic neoadjuvant chemotherapy followed by preoperative radiotherapy. Liver resection was performed in one step (between radiotherapy and rectal surgery) or in two steps (before and after radiotherapy). The data were collected prospectively and analysed retrospectively as intent to treat. RESULTS: Between 2008 and 2018, 24 patients underwent the OLF strategy. The rate of treatment completion was 87.5%. Three patients (12.5%) did not proceed to the planned second-stage liver and rectal surgery because of progressive disease. The postoperative mortality rate was 0%, and the overall morbidity rates after liver and rectal surgeries were 21% and 28.6%, respectively. Only two patients developed severe complications. Liver and rectal complete resection was performed in 100% and 84.6%, respectively. A rectal-sparing strategy was performed in 6 patients who underwent local excision (n = 4) or a watch and wait strategy (n = 2). Among patients who completed treatment, the median overall and disease-free survivals were 60 months (range 12-139 months) and 40 months (range 10-139 months), respectively. Eleven patients (47.6%) developed recurrence, among whom five underwent further treatment with curative intent. CONCLUSION: The OLF approach is feasible, relevant, and safe. Organ preservation was feasible for a quarter of patients and may be associated with reduced morbidity.

Carbonic Anhydrase IX Expression and Treatment Response Measured in Rectal Adenocarcinoma Following Neoadjuvant Chemo-Radiotherapy.

The overexpression of the pH regulator carbonic anhydrase IX (CAIX) due to hypoxic/metabolic stress was reported in various tumors as an adverse prognostic feature. Our retrospective study aimed to investigate the general pattern and dynamics of CAIX expression in rectal adenocarcinoma following preoperative neoadjuvant therapy (NAT) in matched initial biopsy and surgical resection samples. A total of 40/55 (72.72%) of the post-treatment samples showed partial CAIX expression, frequently in the proximity of hypoxic tumor areas. CAIX expression showed a significant increase in post-treatment tumors (mean% 21.8 ± 24.9 SD vs. 39.4 ± 29.4 SD, p < 0.0001), that was not obvious in untreated tumors (mean% 15.0 ± 21.3 SD vs. 20 ± 23.02, p = 0.073). CAIXhigh phenotype was associated with mutant KRAS status and lack of pathological regression (WHO Tumor Regression Grade 4 and 5). However, the adverse effect of CAIX on overall or progression-free survival could not be statistically confirmed. In conclusion, the dynamic upregulation of CAIX expression is a general feature of rectal adenocarcinoma following neoadjuvant chemo-radiotherapy indicating therapy-induced metabolic reprogramming and cellular adaptation. A synergism of the CAIX-associated regulatory pathways and the mutant KRAS oncogenic signaling most likely contributes to therapy resistance and survival of residual cancer.

Patient management after primary rectal cancer diagnosis. Special focus on surgical treatment for non-metastatic disease.

Background: Rectal cancer is a public health priority. Primary objectives of this study were to evaluate the quality of care for non-metastatic rectal cancer using process and outcome indicators. Delay of management, length of stay and readmission rate, sphincter preservation, morbidity, number of examined lymph nodes, mortality, overall and disease-free survivals were evaluated. Secondary objectives were to estimate the relationship between possible predictive parameters for (1) anastomotic leakage (logistic regression), (2) overall or disease-free survivals (cox regression).Methods: We performed a retrospective study on 312 consecutive patients diagnosed with primary rectal cancer between 2016 and 2019. We focused on the 163 patients treated by surgery for non-metastatic cancer.Results: The treatment began within 33 days (range 0-264) after incidence, resection rate was 67%. Digestive continuity rate in lower, middle and upper rectum was 30%, 87% and 96%. Median of 14 lymph nodes (range 1-46) was analyzed. Length of stay and readmission rate were 11 days (range 3-56) and 4%, respectively. Within 90 postoperative days, clinical anastomotic leakage occurred in 9.2% of cases, major morbidity rate was 17%, mortality 1.2%. Multivariate analysis revealed that stoma decreased the risk of anastomotic leakage [hazard ratio: 0.16; 95% confidence intervals: 0.04-0.63; p = 0.008]. The 5-year overall survival after surgery was 85 ± 4%, disease-free survival 83 ± 4%. Patients with major complications, male gender and R1/R2 resection margin had a poorer prognosis.Conclusion: This work showed encouraging results in rectal cancer treatment in our institution, our results were in line with recommendations at the time.

Deep-learning model for predicting the survival of rectal adenocarcinoma patients based on a surveillance, epidemiology, and end results analysis.

BACKGROUND: We collected information on patients with rectal adenocarcinoma in the United States from the Surveillance, Epidemiology, and EndResults (SEER) database. We used this information to establish a model that combined deep learning with a multilayer neural network (the DeepSurv model) for predicting the survival rate of patients with rectal adenocarcinoma. METHODS: We collected patients with rectal adenocarcinoma in the United States and older than 20 yearswho had been added to the SEER database from 2004 to 2015. We divided these patients into training and test cohortsat a ratio of 7:3. The training cohort was used to develop a seven-layer neural network based on the analysis method established by Katzman and colleagues to construct a DeepSurv prediction model. We then used the C-index and calibration plots to evaluate the prediction performance of the DeepSurv model. RESULTS: The 49,275 patients with rectal adenocarcinoma included in the study were randomly divided into the training cohort (70%, n = 34,492) and the test cohort (30%, n = 14,783). There were no statistically significant differences in clinical characteristics between the two cohorts (p > 0.05). We applied Cox proportional-hazards regression to the data in the training cohort, which showed that age, sex, marital status, tumor grade, surgery status, and chemotherapy status were significant factors influencing survival (p < 0.05). Using the training cohort to construct the DeepSurv model resulted in a C-index of the model of 0.824, while using the test cohort to verify the DeepSurv model yielded a C-index of 0.821. Thesevalues show that the prediction effect of the DeepSurv model for the test-cohort patients was highly consistent with the prediction resultsfor the training-cohort patients. CONCLUSION: The DeepSurv prediction model of the seven-layer neural network that we have established can accurately predict the survival rateand time of rectal adenocarcinoma patients.

A Nomogram of Combining IVIM-DWI and MRI Radiomics From the Primary Lesion of Rectal Adenocarcinoma to Assess Nonenlarged Lymph Node Metastasis Preoperatively.

BACKGROUND: Lymph node (LN) staging plays an important role in treatment decision-making. Current problem is that preoperative detection of LN involvement is always highly challenging for radiologists. PURPOSE: To explore the value of the nomogram model combining intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and radiomics features from the primary lesion of rectal adenocarcinoma in assessing the non-enlarged lymph node metastasis (N-LNM) preoperatively. STUDY TYPE: Retrospective. POPULATION: A total of 126 patients (43% female) comprising a training group (n = 87) and a validation group (n = 39) with pathologically confirmed rectal adenocarcinoma. FIELD STRENGTH/SEQUENCE: A 3.0 Tesla (T); T2 -weighted imaging (T2 WI) with fast spin-echo (FSE) sequence; IVIM-DWI spin-echo echo-planar imaging sequence. ASSESSMENT: Based on pathological analysis of the surgical specimen, patients were classified into negative LN (LN-) and positive LN (LN+) groups. Apparent diffusion coefficient (ADC), diffusion coefficient (D), pseudo diffusion coefficient (D*) and microvascular volume fraction (f) values of primary lesion of rectal adenocarcinoma were measured. Three-dimensional (3D) radiomics features were measured on T2 WI and IVIM-DWI. A nomogram model including IVIM-DWI and radiomics features was developed. STATISTICAL TESTS: General_univariate_analysis and multivariate logistic regression were used for radiomics features selection. The performance of the nomogram was assessed by the receiver operating characteristic (ROC) curve, calibration, and decision curve analysis (DCA). RESULTS: The LN+ group had a significantly lower D* value ([13.20 ± 13.66 vs. 23.25 ± 18.71] × 10-3  mm2 /sec) and a higher f value (0.43 ± 0.12 vs. 0.34 ± 0.10) than the LN- group in the training cohort. The nomogram model combined D*, f, and radiomics features had a better evaluated performance (AUC = 0.864) than any other model in the training cohort. DATE CONCLUSION: The nomogram model including IVIM-DWI and MRI radiomics features in the primary lesion of rectal adenocarcinoma was associated with the N-LNM. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Neoadjuvant rectal score is prognostic for survival: A population-based propensity-matched analysis.

INTRODUCTION: Neoadjuvant rectal (NAR) score may serve as a surrogate short-term endpoint for overall survival (OS) in clinical trials. This study aims to test the NAR score using a large, national cancer registry. METHODS: National Cancer Database patients with clinical stage II/III rectal adenocarcinoma (RAC) treated with neoadjuvant chemoradiation (CRT) followed by surgery were selected and divided into low-, intermediate-, and high-NAR subgroups. OS outcomes were analyzed using Kaplan-Meier and logistic regression models. RESULTS: A total of 12 452 patients were selected, of which 5071 (40.7%) were in clinical stage II and 7381 (59.3%) were in clinical stage III; 15.2% had pathologic complete response. The mean NAR score was 10.01 ± 10.61. Six thousand nine hundred and forty-one (55.7%) did not receive adjuvant chemotherapy (AC) and were propensity-matched across NAR subgroups (966 in each group). A significant difference in 5-year OS between low-, intermediate-, and high-NAR groups was observed (85% vs. 76% vs. 68%; p < 0.001). Five thousand five hundred and eleven (44.3%) received AC and 1045 triplets were propensity-matched per NAR groups. A significant difference was again observed for 5-year OS (93% vs. 88% vs. 75%; p < 0.001). Logistic regression confirmed NAR strata as a significant predictor of 5-year OS. CONCLUSION: NAR score, as a neoadjuvant response measure, is a strong predictor of 5-year OS, regardless of AC receipt in a heterogenous population of locally advanced RAC patients.

Nomogram to predict cause-specific mortality of patients with rectal adenocarcinoma undergoing surgery: a competing risk analysis.

BACKGROUND: Rectal adenocarcinoma is one of major public health problems, severely threatening people's health and life. Cox proportional hazard models have been applied in previous studies widely to analyze survival data. However, such models ignore competing risks and treat them as censored, resulting in excessive statistical errors. Therefore, a competing-risk model was applied with the aim of decreasing risk of bias and thereby obtaining more-accurate results and establishing a competing-risk nomogram for better guiding clinical practice. METHODS: A total of 22,879 rectal adenocarcinoma cases who underwent primary-site surgical resection were collected from the SEER (Surveillance, Epidemiology, and End Results) database. Death due to rectal adenocarcinoma (DRA) and death due to other causes (DOC) were two competing endpoint events in the competing-risk regression analysis. The cumulative incidence function for DRA and DOC at each time point was calculated. Gray's test was applied in the univariate analysis and Gray's proportional subdistribution hazard model was adopted in the multivariable analysis to recognize significant differences among groups and obtain significant factors that could affect patients' prognosis. Next, A competing-risk nomogram was established predicting the cause-specific outcome of rectal adenocarcinoma cases. Finally, we plotted calibration curve and calculated concordance indexes (c-index) to evaluate the model performance. RESULTS: 22,879 patients were included finally. The results showed that age, race, marital status, chemotherapy, AJCC stage, tumor size, and number of metastasis lymph nodes were significant prognostic factors for postoperative rectal adenocarcinoma patients. We further successfully constructed a competing-risk nomogram to predict the 1-year, 3-year, and 5-year cause-specific mortality of rectal adenocarcinoma patients. The calibration curve and C-index indicated that the competing-risk nomogram model had satisfactory prognostic ability. CONCLUSION: Competing-risk analysis could help us obtain more-accurate results for rectal adenocarcinoma patients who had undergone surgery, which could definitely help clinicians obtain accurate prediction of the prognosis of patients and make better clinical decisions.

Can transrectal ultrasonography distinguish anorectal malignant melanoma from low rectal adenocarcinoma? A retrospective paired study for ten years.

BACKGROUND: Anorectal malignant melanoma (ARMM) and low rectal adenocarcinoma (LRAC) have some similarities in clinical behaviors, histopathological characteristics and ultrasonographic findings, diagnostic errors are common. By comparing the transrectally ultrasonographic features between the two tumors, we propose to provide more possibilities in differentiating them. METHODS: The data of 9 ARMMs and 27 age- and gender-matched LRACs (the lower margin below the peritoneal reflection) in West China Hospital Sichuan University between April 2008 and July 2019 were retrospectively reviewed. The ultrasonic features between the two groups were compared. RESULTS: Transrectal ultrasonography (TRUS) showed that the length of ARMM was shorter than that of LRAC (28.22 ± 12.29 mm vs. 40.22 ± 15.16 mm), and ARMM had a lower position than that of LRAC (the distance to anal verge was 50.78 ± 11.70 vs. 63.81 ± 18.73 mm). Unlike LRAC, the majority of ARMM in our study was confined to the intestinal mucosa/submucosa (66.67/25.93%) (P < 0.05). CONCLUSIONS: Based on the data of our study, several ultrasonographic findings (length, invasion depth, and position) of ARMM were significantly different from LRAC. Accordingly, more attention should be paid to masses at anorectal junction with lower position, shorter length, and shallower infiltration depth. Instead of the most common tumor, LRAC, ARMM should be taken into account to avoid a misdiagnosis, which will result in a poorer prognosis.

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.

Prognosis of anal canal adenocarcinoma versus lower rectal adenocarcinoma in Japan: a propensity score matching study.

PURPOSE: Anal canal adenocarcinoma (AC) is rare and its surgical outcomes and prognostic factors (PFs) are not well understood. The aim of this retrospective study was to identify the characteristics and PFs of AC, using population-based data in Japan. METHODS: Patients with AC (n = 390) or lower rectal adenocarcinoma (LR) (n = 12,477) diagnosed between1991 and 2006 were enrolled in this study. We compared the clinical- and patient-related factors of the two diseases and then examined propensity score matching, overall survival (OS), and PFs. RESULTS: AC tended to develop more often in women and in patients of advanced age. Macroscopically, AC was of an unclassified type and microscopically, it was of high-grade histological types such as mucinous adenocarcinoma, poorly differentiated adenocarcinoma (por), or signet-ring cell carcinoma (sig), with a high frequency of inguinal node metastasis (P < 0.05). The 5 year OS rates were 56.9% for AC and 67.9% for LR (P = 0.002). The PFs of AC were a high-grade histological type (por/sig), T, N, and M. CONCLUSIONS: AC has a significantly worse prognosis than LR. Moreover, the AC lymph node metastatic sites for AC, especially the inguinal nodes, are different from those for LR.

Case control study investigating the clinical utility of NPWT in the perineal region following abdominoperineal resection for rectal adenocarcinoma: a single center study.

BACKGROUND: Perineal wound complications are common after abdominoperineal resection (APR) for rectal adenocarcinoma. Delayed wound healing may postpone postoperative adjuvant therapy and, therefore, lead to a worse survival rate. Negative-pressure wound therapy (NPWT) has been suggested to improve healing, but research on this subject is limited. METHODS: The aim of this study was to assess whether NPWT reduces surgical site infections (SSI) after APR for rectal adenocarcinoma when the closure is performed with a biological mesh and a local flap. A total of 21 consecutive patients had an NPWT device (Avelle, Convatec™) applied to the perineal wound. The study patients were compared to a historical cohort in a case-control setting in relation to age, body mass index, tumor stage, and length of neoadjuvant radiotherapy. The primary outcome was the surgical site infection rate. The secondary outcomes were the wound complication rate, the severity of wound complications measured by the Clavien-Dindo classification, length of hospital stay, and surgical revision rate. RESULTS: The SSI rate was 33% (7/21) in the NPWT group and 48% (10/21) in the control group, p = 0.55. The overall wound complication rate was 62% (13/21) in NPWT patients and 67% (14/21) in the control group, p > 0.90. The length of hospital stay was 15 days in the NPWT group and 13 in the control group, p = 0.34. The wound severity according to the Clavien-Dindo classification was 3b in 29% (6/21) of the NPWT group and in 38% (8/21) of the control group. A surgical revision had to be performed in 29% (6/21) of the cases in the NPWT group and 38% (8/21) in the control group, p = 0.73. CONCLUSION: NPWT did not statistically decrease surgical site infections or reduce wound complication severity in perineal wounds after APR in this case-control study. The results may be explained by technical difficulties in applying NPWT in the perineum, especially in female patients. NPWT devices should be further developed to suit the perineal anatomy before their full effect can be assessed. Trial registration The study was registered as a prospective registry study (266/2018, registered 15th of November 2018).

Combined histopathological risk score using TP53 protein expression, CD8+ T cell density and intratumoral budding is an independent predictor of neoadjuvant therapy response in rectal adenocarcinoma.

AIMS: Neoadjuvant therapy is the recommended treatment for locally advanced rectal adenocarcinoma; however, there remains significant variability in response to therapy. Tumour protein 53 (TP53) has been associated with therapy response and prognosis with conflicting data. Recently, we demonstrated that immune cell density and intratumoral budding (ITB) are predictive factors in rectal cancer. We investigated the predictive value of TP53 immunohistochemistry with CD8+ T cell density and ITB on pretreatment biopsies of rectal adenocarcinoma for response to neoadjuvant therapy. METHODS AND RESULTS: Pretreatment biopsies of rectal adenocarcinoma from 117 patients with neoadjuvant therapy were analysed for TP53 expression by immunohistochemistry, ITB, CD8+ T cell density and mismatch repair protein (MMR) status. Most rectal adenocarcinomas displayed aberrant TP53 expression (86 of 117, 74%). Compared to wild-type TP53, aberrant TP53 expression was associated with proficient MMR status (P = 0.003) and low CD8+ T cell density (P = 0.001). Aberrant TP53 was significantly associated with a partial to poor response to neoadjuvant therapy [odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.04-5.62, P = 0.04]. A combined histopathological risk score (HRS) was created using CD8+ T cell density, ITB and TP53 expression. Patients were separated into low (none to one factor) and high (two to three factors) HRS categories. In the multivariable model, patients with a high HRS were 3.25-fold more likely to have a partial or poor response to neoadjuvant therapy (95% CI = 1.48-7.11, P = 0.003). CONCLUSIONS: Our study demonstrates that aberrant TP53 expression, high ITB and low CD8+ T cell density in pretreatment biopsies can help predict response to neoadjuvant therapy. These biomarkers may be helpful in identifying patients at risk for therapy resistance.

Ten-year survival after pathologic complete response in rectal adenocarcinoma.

BACKGROUND: Multimodal treatment is the standard of care for rectal adenocarcinoma, with a subset of patients achieving a pathologic complete response (pCR). While pCR is associated with improved overall survival (OS), long-term data on patients with pCR is limited. METHODS: This is a single institution retrospective cohort study of all patients with clinical stages II/III rectal adenocarcinoma who underwent neoadjuvant chemoradiation therapy and operative resection (January 1, 2004-December 31, 2017). PCR was defined as no tumor identified in the rectum or associated lymph nodes by final pathology. RESULTS: Of 370 patients in this cohort, 50 had a pCR (13.5%). For pCR patients, 5-year disease-free survival (DFS) was 92%, 5-year OS was 95%. Twenty-six patients had surgery > 10 years before the study end date, of which 20 had an OS > 10 years (77%) with median OS 12.1 years and 95% alive to date (19/20). Of the 50 pCR patients, there was a single recurrence in the lung at 44.3 months after proctectomy which was surgically resected. CONCLUSION: For patients with rectal adenocarcinoma that undergo neoadjuvant chemoradiation and surgical resection, pCR is associated with excellent long-term DFS and OS. Many patients live greater than 10 years with no evidence of disease recurrence.

Meta-analysis of direct-to-surgery lateral pelvic lymph node dissection for rectal cancer.

AIM: Direct-to-surgery rectal resection with lateral pelvic lymph node dissection (LPLND) is a treatment strategy commonly employed in Japan to improve oncological outcomes for rectal cancer. The aim of this study was to assess oncological outcomes in the literature for patients with low rectal cancer who underwent direct-to-surgery resection and LPLND compared with those who underwent total mesorectal excision (TME) alone. METHOD: A literature search of Medline, Embase and PubMed databases was performed to identify relevant studies published between 1989 and 2020. The primary outcomes were 5-year overall survival (OS) and 5-year disease-free survival (DFS). The secondary outcomes were cancer recurrence (local, distant and total) and operative burden (operative time and blood loss). Pooled relative risk (RR) of oncological outcomes was performed using the DerSimonian-Laird method random-effect model. RESULTS: Twenty-one studies fulfilled inclusion criteria, including 19 nonrandomized studies of interventions and two studies from one randomized controlled trial. No differences were observed in 5-year OS or 5-year DFS. Local recurrence in nonrandomized studies was worse in patients who underwent LPLND [RR 1.41 (95% CI 1.21-1.64, p < 0.001)], as was total recurrence [RR 1.44 (95% CI 1.25-1.67, p < 0.001)]. No differences were observed for distant recurrence. CONCLUSION: In the published literature, direct-to-surgery resection with LPLND was associated with worse local and total recurrence. These predominantly nonrandomized data suggest that a nonselective approach to LPLND does not provide optimal management in radiotherapy-naïve patients with low rectal cancer. Further prospective randomized studies with a focus on patient selection are required.

Outcomes of exenteration in cT4 and fixed cT3 stage primary rectal adenocarcinoma: a subgroup analysis of consolidation chemotherapy following neoadjuvant concurrent chemoradiotherapy.

PURPOSE: The aim was to evaluate the oncological outcomes and the prognostic factors following pelvic exenteration (PE) in cT4 and fixed cT3 stage primary rectal adenocarcinoma and to study the impact of consolidation chemotherapy following neoadjuvant concurrent chemoradiotherapy (NACRT). METHODS: A retrospective analysis of a prospectively maintained database of PE from 2013 to 2018. RESULTS: Out of 2900 colorectal resections, there were 131 pelvic exenterations that were performed, and 100 of these patients had undergone exenteration for primary rectal adenocarcinoma. Of these 100 patients, there were 81 patients who had received NACRT followed by surgery, 50 of whom who had received consolidation chemotherapy and 31 who had undergone surgery without consolidation chemotherapy. R0 resection was achieved in 90% cases. At a median follow-up of 32 months, 2-year disease free survival was 61.8% and estimated 5-year overall survival was 62%. The incidence of distant metastases was 44% vs. 19% (p = 0.023), and the 2-year distant recurrence-free survival was 58% vs. 89% (p = 0.025), respectively, in the 'consolidation chemotherapy group' and the 'no chemotherapy group'. The poorly differentiated grade of tumours, presence of lympho-vascular-invasion, consolidation chemotherapy, and disease recurrence were all found to affect the survival. CONCLUSION: PE with R0 resection achieves excellent survival rates in cT4 and fixed cT3 stage primary rectal adenocarcinoma. The distant recurrence rate may not be altered by consolidation chemotherapy in the subset of high-risk patients. However, further research on consolidation chemotherapy following NACRT in cT4 and fixed cT3 stage primary rectal adenocarcinoma will give a definite answer in the future.