Local recurrences in western low rectal cancer patients treated with or without lateral lymph node dissection after neoadjuvant (chemo)radiotherapy: An international multi-centre comparative study

BackgroundIn the West, low rectal cancer patients with abnormal lateral lymph nodes (LLNs) are commonly treated with neoadjuvant (chemo)radiotherapy (nCRT) followed by total mesorectal excision (TME). Additionally, some perform a lateral lymph node dissection (LLND). To date, no comparative data (nCRT vs. nCRT + LLND) are available in Western patients.MethodsAn international multi-centre cohort study was conducted at six centres from the Netherlands, US and Australia. Patients with low rectal cancers from the Netherlands and Australia with abnormal LLNs (≥5 mm short-axis in the obturator, internal iliac, external iliac and/or common iliac basin) who underwent nCRT and TME (LLND-group) were compared to similarly staged patients from the US who underwent a LLND in addition to nCRT and TME (LLND + group).ResultsLLND + patients (n = 44) were younger with higher ASA-classifications and ypN-stages compared to LLND-patients (n = 115). LLND + patients had larger median LLNs short-axes and received more adjuvant chemotherapy (100 vs. 30%; p < 0.0001). Between groups, the local recurrence rate (LRR) was 3% for LLND + vs. 11% for LLND- (p = 0.13). Disease-free survival (DFS, p = 0.94) and overall survival (OS, p = 0.42) were similar. On multivariable analysis, LLND was an independent significant factor for local recurrences (p = 0.01). Sub-analysis of patients who underwent long-course nCRT and had adjuvant chemotherapy (LLND-n = 30, LLND + n = 44) demonstrated a lower LRR for LLND + patients (3% vs. 16% for LLND-; p = 0.04). DFS (p = 0.10) and OS (p = 0.11) were similar between groups.ConclusionA LLND in addition to nCRT may improve loco-regional control in Western patients with low rectal cancer and abnormal LLNs. Larger studies in Western patients are required to evaluate its contribution.     

Lateral lymph node dissection in rectal cancer: State of the art review

Half of the local regional recurrences from rectal cancer are nowadays located in the lateral compartments, most likely due to lateral lymph node (LLN) metastases. There is evidence that a lateral lymph node dissection (LLND) can lower the lateral local recurrence rate. An LLND without neoadjuvant (chemo)radiotherapy in patients with or without suspected LLN metastases has been the standard of care in the East, while Western surgeons believed LLN metastases to be cured by neoadjuvant treatment and total mesorectal excision (TME) only. An LLND in patients without enlarged LLNs might result in overtreatment with low rates of pathological LLNs, but in patients with enlarged LLNs who are treated with (C)RT and TME only, the risk of a lateral local recurrence significantly increases to 20%. Certain Eastern and Western centers are increasingly performing a selective LLND after neoadjuvant treatment in the presence of suspicious LLNs due to new scientific insights, but (inter)national consensus on the indication and surgical approach of LLND is lacking. An LLND is an anatomically challenging procedure with intraoperative risks such as bleeding and postoperative morbidity. It is therefore essential to carefully select the patients who will benefit from this procedure and where possible to perform the LLND in a minimally invasive manner to limit these risks. This review gives an overview of the current evidence of the assessment of LLNs, the indications for LLND, the surgical technique, pitfalls in performing this procedure and the future studies are discussed, aiming to contribute to more (inter)national consensus.     

Oncologic impact of lateral lymph node metastasis at the distal lateral compartment in locally advanced low rectal cancer after neoadjuvant (chemo)radiotherapy

IntroductionThe frequency and oncologic outcomes of lateral lymph node (LLN) metastasis at the most distal lateral compartment (DLC) among clinical stage II-III low rectal cancer patients treated with neoadjuvant (chemo)radiotherapy (nCRT) are poorly understood. The aim was to investigate the oncologic impact of LLN metastasis in the DLC versus the proximal lateral compartment (PLC).Materials and methodsConsecutive patients with low rectal cancer treated with nCRT followed by total mesorectal excision and selective LLN dissection including the DLC were analyzed retrospectively. DLC was defined as the area distal to the infra–piriformis foramen on axial MRI images. Size and location of LLN metastasis on MRI, and survival were retrospectively assessed.ResultsOf the 718 patients, 72 (10.0%) had pathological LLN metastasis. Thirty-two (44.4%) had metastasis in the DLC (DLC group), while 40 (55.6%) had metastasis in the PLC without metastasis in the DLC (PLC group). The proportion of ypN2 category tended to be lower in the DLC group (15.6% vs 35.0%, P = 0.105). The median number of metastatic LLN was similar (1 vs. 1, P = 0.691). The median short-axis size of metastatic LLN was smaller in the DLC group than in the PLC group on pre-treatment (P < 0.001) and re-staging (P = 0.004) MRI. By multivariable analysis, LLN metastasis in the DLC was predictive of better disease-free survival (HR, 0.412; 95% CI, 0.159–0.958, P = 0.039).ConclusionLLN metastasis in the DLC is frequent and has favorable oncologic outcomes after surgical dissection with nCRT.     

Lateral pelvic lymph node dissection in the management of locally advanced low rectal cancer: Summary of the current evidence

Lateral pelvic lymph nodes (LPLN) are a major site for local recurrence following curative resection for low locally advanced rectal cancer. Ongoing advances in imaging techniques have improved predicting LPLN metastasis (LPLNM) during pre-operative staging. However, there is ongoing debate on optimal management of this subgroup of patients with variation between guidance of different societies. In Japan, LPLNM is considered as local disease and addressed by lateral pelvic node dissection (LPLND) in addition to total mesorectal excision (TME). However, in the west, LPLNM is considered as metastatic disease and those patients are offered neoadjuvant chemoradiotherapy (nCRT) followed by TME surgery. The potential surgical risks and morbidity associated with LPLND as well as the uncertainty of the oncological outcome have raised the concern that patients with locally advanced low rectal cancer with LPLNM could be over or under-treated.A comprehensive review of literature was performed, summarizing the current evidence on available modalities for predicting LPLNM, the role of LPLND in the management of advanced low rectal cancer and the available surgical approaches with their impact on surgical and oncological outcomes.LPLND is associated with increased operative time, blood loss and post-operative morbidity. The potential benefits for local disease control and survival still awaits high quality studies. There has been increasing number of reports of the use minimally invasive approaches in LPLND in an attempt to reduce post-operative complications.There is need for high quality evidence to define the role of LPLND in management of patients with advanced low rectal cancer.     

Tumour-stroma ratio to predict pathological response to neo-adjuvant treatment in rectal cancer

IntroductionManagement of rectal cancer has advanced, with an increasing use of neoadjuvant chemoradiotherapy (nCRT). This opens options for organ preserving treatment for those with a major response to nCRT. However, the degree of clinical response, based on MRI and post-treatment biopsies, only poorly matches the degree of actual pathological response. In order to select patients with major pathological response without surgical resection, it is of importance to define tumour markers predicting the degree of pathological response to nCRT. The intra-tumoural tumour-stroma ratio (TSR) might be this marker.MethodsTSR in pre-treatment biopsies was estimated according to the method described by van Pelt et al. The degree of pathological response was assessed on the tumour resection according to tumour regression grading (TRG) by Mandard. The primary endpoint of this study was the difference in pathological response to nCRT between TSR-high and TSR-low groups.ResultsWe found that 26.2% of patients with major response was classified as TSR-high, while 73.8% of patients were classified as TSR-low. A high TSR in pre-treatment biopsies was associated with a lower chance of major-response to nCRT (OR = 0.37, 95%CI; 0.19–0.73), p = 0.004), independent of tumour stage and time between nCRT and surgery.ConclusionIn rectal cancer, TSR in pre-treatment biopsies predicts pathologic response to nCRT, with a high TSR bringing twice the risk of poor to no response compared to low TSR. In future, assessment of TSR may fulfil a role in a therapeutic algorithm identifying patients who will or will not respond to nCRT prior to treatment initiation.     

Association between factor of parotid lymph node and prognosis in parotid cancer

IntroductionSurvival significance of parotid lymph node (LN) factors in parotid cancer remains unclear, our goal was to assess the impact of number, size, and extranodal extension (ENE) of metastatic parotid LNs on prognosis in parotid cancer.Materials and methodsPatients with surgically treated parotid cancer were retrospectively enrolled. Primary outcome variable was recurrence-free survival (RFS) and overall survival (OS). The hazard ratios (HRs) of main predictive variables including the number, size, and ENE of positive parotid LNs on RFS and OS were analyzed using Cox model. The secondary outcome variable was ENE of metastatic parotid LN, its association with clinicopathologic variables were evaluated using Chi-square test.ResultsIn total, 453 patients (186 male and 267 female) were included. The 10-year RFS and OS rates were 73% (95%CI: 69%–77%) and 61% (95%CI: 55%–67%), respectively. In Cox model, compared none parotid LN metastasis, one metastatic parotid LN did not offer additional compromise of RFS (p = 0.224) or OS (p = 0.135), but two or more positive LNs decreased the control of RFS (HR: 2.017; 95%CI: 1.378–4.632) and OS (HR: 2.173; 95%CI: 1.367–4.275). When accounting for the number of metastatic LNs, LN size or ENE was no longer related to RFS or OS. ENE of parotid LN tended to develop if there was presence of T3/4 stage, lymphovascular invasion, high histologic grade, N2/3 stage, and three or more positive parotid LNs.ConclusionQuantitative parotid LN burden but not ENE or LN size is an important determinant of survival in patients with parotid cancer.     

Refraining from resection in patients with potentially curable gastric carcinoma

BackgroundSurgical resection is the cornerstone of curative treatment for gastric cancer. The aim of this study was to evaluate reasons for and patient- and tumor characteristics that are associated with refraining from surgical resection in patients with potentially curable gastric cancer.Materials and methodsBetween 2015 and 2017, all patients with potentially curable gastric adenocarcinoma (cT1-4a-x, cN0-3-x, cM0) were included from the Netherlands Cancer Registry (NCR). Patients were divided into a resection (RG) and a no-resection group (nRG). Reasons for not undergoing resection as registered by the NCR were evaluated. Using multivariable logistic regression analyses, patient and tumor characteristics associated with refraining from resection were assessed.ResultsOf the 1679 analyzed patients with potentially curable disease, 1127 patients (67%) underwent resection, and 552 patients (33%) did not. Most common registered reasons for refraining from surgery were patient refusal (25%), low performance status (23%), comorbidity and extent of disease (both 10%). Factors associated with not undergoing resection were: age ≥80 years (OR 4.77, [95%CI 2.27–10.06], p < 0.001), low Social-Economic-Status (SES) (OR 2.68 [95%CI 1.31–5.46], p = 0.007), WHO performance status 3–4 (OR 10.48 [95%CI 2.41–45.73], p = 0.002) with several accompanying comorbidities, unclassified Lauren classification (OR 3.93 [95%CI 1.61–9.56], p = 0.003) and overlapping/diffuse tumors (OR 3.51, [95%CI 1.54–8.05], p = 0.003).ConclusionA third of patients with potentially curable gastric cancer did not undergo resection. Most frequent registered reasons for refraining from surgery were patient refusal, performance status, comorbidity and extent of disease. Additionally, multivariable analyses identified higher age, lower SES, and poor tumor characteristics as associated factors.     

Tumour grade and stage are associated with specific body composition phenotypes with visceral obesity predisposing the host to a less aggressive tumour in colorectal cancer

BackgroundSarcopenia, myosteatosis and visceral obesity (VO) are known to negatively impact on outcomes from colorectal cancer (CRC). Little is known about tumour factors associated with these body composition (BC) phenotypes. We aimed to identify whether histopathological tumour characteristics were associated with various BC phenotypes.MethodsA prospectively collected database of patients undergoing surgery for primary CRC at a tertiary referral unit in the United Kingdom was analysed. Sarcopenia, myosteatosis and VO were identified on preoperative CT. Binary logistic regression modelling was performed to determine significant associations between tumour stage, grade and BC phenotype.ResultsFinal analysis included 795 patients; median age 69, 56% male, 65% were sarcopenic, 72% myosteatotic, 52% VO and 20% had sarcopenic obesity (SO). VO patients were significantly less likely to have advanced T Stage (T3-4) OR0.62(95%CI 0.44–0.86, p = 0.005); nodal metastases OR0.60(95%CI 0.44–0.82, p = 0.001); vascular invasion OR0.63(95%CI 0.46–0.88, p = 0.006) and poor tumour differentiation OR0.49(95%CI 0.28–0.86, p = 0.012). Myosteatotic patients were more likely to have metastatic disease OR2.31(95%CI 1.15–4.63, p = 0.018) but less likely to have poorly differentiated tumours OR0.48(95%CI 0.27–0.86, p = 0.013). SO patients were significantly more likely to have poorly differentiated tumours OR2.01(95%CI 1.04–3.87, p = 0.037).ConclusionVO predisposes to earlier stage tumours with a less aggressive tumour phenotype. The SO group have adverse tumour characteristics which may be explained by differences in fat distribution. Myosteatosis relates to increased likelihood of distant metastasis that may be related to a systemic inflammatory response, despite the association with better differentiated tumours.     

Development of a predictive score of axillary lymph node dissection based on targeted axillary dissection in patients with breast cancer diagnosis,affected lymph nodes,and neoadjuvant treatment

AimTo determine predictive factors of axillary lymph node dissection (ALND) results in breast cancer (BC) patients undergoing neoadjuvant chemotherapy (NACT), and subsequent staging using Targeted Axillary Dissection (TAD).Material and methodCase-control study between January 2016 and August 2019. Patients with BC, cN1 staging, marked with a metallic clip prior to NACT, and subsequently staged with TAD and ALND were included. They were divided into 2 groups: ALND patients with or without metastatic involvement (group 1 and group 2, respectively). We carried out a univariate analysis comparing clinical, radiological, surgical and pathological variables, and a logistic regression, (dependent variable: positive result of ALND; independent variables: number of suspicious lymph nodes in diagnostic ultrasound, positive hormone receptors, HER2 positive, complete clinical-radiological response to NACT, positive TAD, and biopsy of ≤2 nodes in TAD). A score for prediction of a metastatic ALND was proposed, with an internal validation study.Results60 patients were included: Group 1: 33 (55.0%); Group 2: 27 (45.0%). Tumor size (Odds Ratio (OR) = 1.67; 95%CI 1.02–2.74), number of suspected nodes in ultrasound (OR = 2.20; 95%CI 1.01–4, 77), HER2 positive (OR 0.04; 95%CI 0.003–0.54), clinical-radiological response to NACT (OR = 0.07; 95%CI 0.01–0.75), and positive TAD (OR 15.48; 95%CI 1.68–142.78) were independent predictors of a positive result in ALND. We developed a “positive ALND predictive score”, with good calibration (Hosmer-Lemeshow test: p = 0.65), and discrimination (AUC = 0.93; 95% CI 0, 87–0.99), with highest Youden index (0.7) at cut-off point of 17% risk of positive ALND (sensitivity = 100%; specificity = 70%).ConclusionTumor size, number of suspected nodes, positive HER2, response to NACT, and metastatic TAD are independent predictors of ALND. The predictive score for positive ALND would be a good indicator to safely omit ALND.     

Colonoscopy,imaging, and carcinoembryonic antigen: Comparison of guideline adherence to surveillance strategies in patients who underwent resection of colorectal cancer - A systematic review and meta-analysis

IntroductionAlmost one-third of patients with colorectal cancer (CRC) experience recurrence after resection. Adherence to surveillance guidelines largely dictates efficacy in early detection of recurrence. We sought to assess and compare adherence to postoperative surveillance guidelines for colonoscopy, imaging, and Carcinoembryonic Antigen (CEA).MethodsPubMed, Medline, Embase, Scopus, Cochrane, Web of Science, and CINAHL were systematically searched. Random-effects meta-analysis was performed and pooled adherence to each surveillance strategy was assessed for CEA, imaging, and colonoscopy.ResultsOverall 14 studies (55,895 patients) met the inclusion criteria. Adherence to colonoscopy guidelines was the highest (70%, 95%CI 67–73), followed by imaging (63%, 95%CI 47–80), and CEA (54%; 95%CI 42–66). Among 7 (50%) studies that examined adherence to the American Society of Clinical Oncology guidelines, compliance with colonoscopy was the highest (73%; 95% CI 70–76), followed by imaging (58%; 95% CI 37–78), and CEA (45%; 95%CI 37–52). Of note, guideline adherence to CEA testing was much lower than colonoscopy among patients with colon (OR 0.21; 95%CI 0.20–0.22) and rectal cancer (OR 0.25; 95%CI 0.23–0.28) (both p < 0.05). This was also noted when compared with imaging recommendations among older patients (OR = 0.62; 95%CI 0.42–0.93) and patients with stage II, (OR = 0.80; 95%CI 0.76–0.84) and stage III disease (OR = 0.88; 95%CI 0.82–0.94) (all p < 0.05).ConclusionWhile guideline adherence to postoperative surveillance with colonoscopy was high, adherence to CEA testing and imaging surveillance strategies was markedly lower following CRC resection. Future studies should investigate avenues to improve compliance with surveillance guidelines among health care providers and patients to optimize postoperative follow-up for CRC.     

Disparities in primary pancreatic adenocarcinoma survival by Medicaid-status: A national population-based risk analysis

BackgroundPancreatic adenocarcinoma (PAC) has one of the highest mortality rates among all malignancies. While previous research has analyzed socioeconomic factors’ effect on PAC survival, outcomes of Medicaid patients are understudied.MethodsUsing the SEER-Medicaid database, we studied non-elderly, adult patients with primary PAC diagnosed between 2006 and 2013. Five-year disease-specific survival analysis was performed using the Kaplan-Meier method and adjusted analysis using Cox proportional-hazards regression.ResultsAmong 15,549 patients (1799 Medicaid, 13,750 non-Medicaid), Medicaid patients were less likely to receive surgery (p < .001) and more likely to be non-White (p < .001). The 5-year survival of non-Medicaid patients (8.13%, 274 days [270–280]) was significantly higher than that of Medicaid patients (4.97%, 152 days, [151–182], p < .001). Among Medicaid patients, those in high poverty areas had significantly lower survival rates (152 days [122–154]) than those in medium poverty areas (182 days [157–213], p = .008). However, non-White (152 days [150–182]) and White Medicaid patients (152 days [150–182]) had similar survival (p = .812). On adjusted analysis, Medicaid patients were still associated with a significantly higher risk of mortality (aHR 1.33 [1.26–1.41], p < .0001) compared to non-Medicaid patients. Unmarried status and rurality were associated with a higher risk of mortality (p < .001).DiscussionMedicaid enrollment prior to PAC diagnosis was generally associated with a higher risk of disease-specific mortality. While there was no difference in the survival between White and non-White Medicaid patients, Medicaid patients living in high poverty areas were shown to be associated with poor survival.     

Neutrophil-to-lymphocyte ratio as a prognostic marker in locally advanced nasopharyngeal carcinoma: A pooled analysis of two randomised controlled trials

PurposeTo assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) in patients with International Union Against Cancer (UICC)–staged III/IVA,B nasopharyngeal carcinoma (NPC), who were enrolled into two randomised controlled trials of concurrent/adjuvant chemotherapy when added to radiotherapy (SQNP01), and induction chemotherapy when added to chemoradiotherapy (NCC0901).Material and methodsA post hoc analysis of pooled cohorts from SQNP01 (N = 221) and NCC0901 (N = 172) was performed. We employed a threshold of pre-treatment NLR = 3.0 (median) to stratify patients. Survival outcomes were compared using log-rank test. Multivariable Cox regression analyses were performed to assess association between NLR and overall survival (OS), disease-free survival (DFS), distant metastasis–free survival (DMFS), and locoregional recurrence–free survival (LRFS).ResultsHigh NLR (≥3.0) was associated with advanced T-status (p = 0.002), N-status (p = 0.002), overall UICC stage (p = 0.004), and high pre-treatment Epstein–Barr virus DNA titre (p = 0.001). High NLR was not associated with OS (0.94 [0.67–1.32], p = 0.7), DFS (0.98 [0.73–1.33], p = 0.9), DMFS (1.02 [0.66–1.57], p = 0.9), and LRFS (1.37 [0.84–2.22], p = 0.2) on univariable and multivariable analyses, while conventional clinical indices (T-status, N-status, and overall UICC stage) were prognostic of clinical outcomes. High NLR also did not predict for a treatment effect with the experimental arms in both trials.ConclusionOur pooled analyses that were confined to a homogenous patient population of locally advanced NPC do not suggest that NLR adds prognostic value to conventional clinical indices in identifying patients with unfavourable disease.     

Upfront primary tumour resection and survival in synchronous metastatic colorectal cancer according to primary tumour location and RAS status: Pooled analysis of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

IntroductionRetrospective studies and meta-analyses suggest that upfront primary tumour resection (UPTR) confers a survival benefit in patients with asymptomatic unresectable metastatic colorectal cancer (mCRC) undergoing chemotherapy, however a consensus of its role in routine clinical practice in the current era of targeted therapies is lacking. This retrospective study aimed to analyse the survival benefit of UPTR in terms of tumour location and mutational status, in patients with synchronous mCRC receiving chemotherapy and targeted therapy.Patients and methodsSurvival was analysed in a pooled cohort of synchronous mCRC patients treated with a first-line anti-VEGF or anti-EGFR inhibitor in seven trials of the Spanish TTD group, according to UPTR, tumour-sidedness and mutational profiling.ResultsOf 1334 eligible patients, 642 (48%) had undergone UPTR. UPTR was associated with significantly longer overall survival (OS; 25.0 vs 20.3 months; HR 1.30, 95%CI 1.15–1.48; p < 0.0001). UPTR was associated with significant OS benefit in both left-sided (HR 1.38, 95%CI 1.13–1.69; p = 0.002) and right-sided (HR 1.39, 95%CI 1.00–1.94; p = 0.049) tumours, RASwt (HR 1.29, 95%CI 1.05–1.60; p = 0.016) and BRAFwt (HR 1.49, 95%CI 1.21–1.84; p = 0.0002) tumours, and treatment with anti-EGFRs (HR 1.47, 95%CI 1.13–1.92; p = 0.004) and anti-VEGFs (HR 1.25, 95%CI 1.08–1.44; p = 0.003). Multivariate analysis identified number of metastatic sites, RAS status, primary tumour location and UPTR as independent prognostic factors for OS.ConclusionConsidering the selection bias inherent to this study, our results support UPTR before first-line anti-EGFR or anti-VEGF targeted therapy in right and left-sided asymptomatic unresectable synchronous mCRC patients. RAS/BRAF mutational status may also influence UPTR function.     

Surgical excision margins in primary cutaneous melanoma: A systematic review and meta-analysis

BackgroundThe main treatment of primary cutaneous melanoma is surgery. This review aims to assess the width of excision margin that minimises the risk of adverse outcome from surgery, locoregional recurrence, distant recurrence, and death.MethodsPRISMA guidelines were followed. MEDLINE, EMBASE, and four other databases were searched by using the term “melanoma”, “margin”, and limiting the search to randomised clinical trials (RCTs).ResultsSeven RCTs involving 4579 patients data were analysed. No statistically significant difference was found in locoregional recurrence RR 1.09 (95%CI 0.98–1.22, p = 0.12), local recurrence RR 1.20 (95%CI 0.66–2.21, p = 0.55), in-transit metastasis RR1.30 (95%CI 0.86–1.97, p = 0.21), regional nodal metastasis RR 1.04 (95%CI 0.91–1.18, p = 0.56), distant metastasis RR 0.95 (95%CI 0.72–1.24, p = 0.68), death RR 1.00 (95%CI 0.93–1.07, p = 0.97), death from melanoma RR 1.11 (95%CI 0.96–1.28, p = 0.16), wound infection RR 1.22 (95%CI 0.68–2.17, p = 0.50), and wound dehiscence RR 0.96 (95%CI 0.54–1.71, p = 0.88) when narrow (1–2 cm) versus wide (3–5 cm) excision margins were compared. In contrast, patients with narrow excision margins had a significant reduction in complex surgical reconstruction RR 0.30 (95%CI 0.19–0.49, p < 00001). When studies were excluded because of high risk of bias the only significant difference was death due to melanoma RR 1.25 (95%CI1.01–1.55, P = 0.04).ConclusionsNo significant difference between narrow and wide excision margins in locoregional or distant recurrence, metastasis, death, or death due to melanoma. Wide margins (2–5 cm) increased the need for surgical reconstruction. Further studies are needed to assess optimal excision margins with regards to Breslow thickness and other prognostic factors and are in progress.     

Impact of robotic learning curve on histopathology in rectal cancer: A pooled analysis

BackgroundA beneficial impact of robotic proctectomy on circumferential resection margin (CRM) is expected due to the robot's articulating instruments in the pelvis. There are however concerns about a negative impact on the quality of total mesorectal excision (TME) due to the lack of tactile feedback. The aim of this study was to assess whether surgeons' learning curve impacted CRM and TME quality.MethodsIn a multicenter study, individual patient data of robotic proctectomy for resectable rectal cancer were pooled. Patients were stratified into two phases of surgeons’ learning curve. Cumulative sum (CUSUM) analysis was used to determine the transition from learning phase (LP) to plateau phase (PP), which were compared. CRM was microscopically measured in mm by pathologists. TME quality was classified by pathologists as complete, nearly complete or incomplete. T-test and Chi-squared tests were used to compare continuous and categorical variables, respectively.Results235 patients underwent robotic proctectomy by five surgeons. 83 LP patients were comparable to 152 PP patients for age (p = 0.20), gender (67.5% vs. 65.1% males; p = 0.72), BMI (p = 0.82), cancer stage (p = 0.36), neoadjuvant chemoradiation (p = 0.13), distance of tumor from anal verge (5.8 ± 4.4 vs. 5.5 ± 3.3; p = 0.56). CRM did not differ (7.7 ± 11.4 mm vs. 8.4 ± 10.3 mm; p = 0.62). The rate of complete TME quality was significantly improved in PP patients as compared to LP patients (73.5% vs. 92.1%; p < 0.001).ConclusionWhile learning had no impact on circumferential resection margins, the quality of TME significantly improved during surgeons’ plateau phase as compared to their learning phase.     

Prognostic impact of sterilized lymph nodes in esophageal squamous cell carcinomas after neoadjuvant chemoradiotherapy

BackgroundThe prognostic importance of sterilized lymph nodes (SLN) remains unclear in patients with esophageal squamous cell carcinomas (ESCC) treated by neoadjuvant chemoradiotherapy (nCRT). This study aimed to determine whether SLN predicted disease-free survival (DFS) in ESCC.MethodsWe enrolled 246 eligible patients who were divided into SLN (+) and SLN (-) group according to the presence or absence of fibrosis, necrosis, calcifications and/or foreign body giant cell reactions in the negative lymph nodes specimens. The prognostic value of SLN was determined using univariate and multivariate analyses. The prognostic strength of counting SLN as positive lymph nodes was evaluated using the difference of Akaike information criterion (ΔAIC).ResultsA total of 61 SLN were identified in 38 (15.4%) patients. There was no significant difference in baseline characteristics between SLN (+) and SLN (-) group. The most frequently detected SLN in the thoracic cavity and abdominal cavity were those along bilateral recurrent laryngeal nerve (21/38,55.3%) and left gastric artery (13/24,60.9%), respectively. The univariate and multivariate analyses showed SLN was an independent prognostic factor for worse DFS in the whole cohort (HR = 2.05, 95%CI = 1.08–3.90, P = 0.029). The SLN (+) group additionally correlated with worse 5-year DFS than SLN (-) group in the ypT0, ypN0 and pCR subgroups. Counting SLN as positive lymph nodes showed better prognostic strength than ignoring them.ConclusionSLN was of prognostic significance for worse DFS in patients with ESCC, particularly in patients with good response to nCRT.     

Prevalence of extracapsular extension in metastatic sentinel lymph nodes in breast cancer

IntroductionAxillary lymph node involvement is recognized as a key prognostic factor for invasive breast cancer. Retrospective analyzes have shown that extracapsular extension (ECE) is correlated with negative prognostic factors in this neoplasia.Objectiveto evaluate the measurement of ECE and its relationship with the number of affected non-sentinel lymph nodes, as well as to investigate the association between ECE with other clinical and pathological prognostic factors.MethodsThis is a cross-sectional observational study carried out from January 2015 to June 2019, at the Breast Surgical Oncology service of Liga Contra o Cancer (LIGA), in Natal, Brazil. A total of 150 patients were included in the study and were divided into three groups: absence of ECE, ECE less than or equal to 2 mm and ECE greater than 2 mm.ResultsThe mean age was 58 years for the group with ECE and 57 years for the group without ECE. Most of the patients were mixed race (66.7%), had no family history of breast cancer (64%) and underwent quadrantectomy (64.5%). Regarding the characteristics of the disease, most presented a histological report compatible with Invasive Carcinoma of the non-special type (IC NST) (87.5%), histological grade II (52.7%), negative Lymphovascular invasion (LVI) (52.7%), Tumor Size T1 (<2.0 cm) (52%) and Luminal B molecular subtype (36.7%). Regarding sentinel lymph nodes: 103 patients (68.7%) had ECE and 1 positive sentinel lymph node was identified in most cases. There was a statistically significant association between the presence of ECE and of being mixed race (p = 0.03), between ECE and LVI (p = 0.05) and between ECE and a greater number of positive non-sentinel lymph nodes (p < 0.001).ConclusionOur study showed that ECE> 2 mm is associated with increased axillary nodal load compared to groups without ECE and ECE ≤ 2 mm in sentinel node biopsy in patients who met the Z0011 criteria.     

Treatment and outcome trends and predictors of overall survival of rectal melanoma: Analysis of the National Cancer Database

BackgroundWe aimed to assess characteristics, treatment, and outcomes of rectal melanoma (RM).MethodsThis retrospective cohort study looked at patients with RM from National Cancer Database (2004–2019) analyzed characteristics and outcomes of the entire cohort and across three time periods (2004–2009; 2010–2014; 2015–2019). Main outcome measures were change in treatment and survival trends across time periods and overall survival (OS).Results641 patients (58.5% female; mean age: 68.2 ± 13.6 years) were included. OS rate was 26%; median survival duration was 17.9 (IQR: 15.93–20.67) months. There was a significant decrease in the use of chemotherapy (17.3%–6.6%; p = 0.001) and surgery (62.9%–41.8%; p = 0.00004) but increased use of immunotherapy (11.9%–52%; p < 0.001) across time periods. OS was longer in the last time period than in the first two (21.8 vs 16.8 vs 16.5 months; p = 0.09). Surgical excision was an independent predictor of improved OS (HR = 0.266, 95%CI: 0.089–0.789, p = 0.017) whereas older age (HR = 1.039, 95%CI: 1.007–1.072, p = 0.016), positive resection margins (HR = 5.06, 95%CI: 1.902–13.48, p = 0.001) and metastasis (HR = 34.62, 95%CI: 3.973–301.6, p = 0.001) were predictors of poor survival.ConclusionsOver time, chemotherapy and surgery have been used less often in the treatment of RM while the use of immunotherapy increased by more than four-fold. Older age, surgical treatment, positive resection margins, and metastasis were predictive of survival of RM.     

Multicenter study to assess surgical treatments of 452 sinonasal intestinal-type adenocarcinomas: A REFCOR study

PurposeThe objective was to assess the local oncological outcomes of endoscopic versus external surgical treatment of sinonasal intestinal-type adenocarcinomas (ITAC) and the factors of recurrence.Methodsa retrospective non-randomized case-control multicenter study was carried out, including 452 untreated sinonasal ITACs recruited from 10 tertiary referral centers. The tumors were re-classified according to the UICC 2017 (pT). Survival curves were obtained using the Kaplan-Meier method. Univariate analysis was done with the log-rank test. Multivariate analysis was performed with a Cox model adjusted for age, T stage, and radiotherapy. A binary logistic regression compared surgical complications and performed two supplementary analyses on positive margins.ResultsWe compared 195 and 257 patients operated by the external and endoscopic approach, respectively. The mean follow-up was 59.2 ± 48.7 months. Post-operative margins were invaded in 30.6 versus 18.9% of patients, respectively (p = 0.007). The overall recurrence rate was 33.8 versus 24.6%, respectively (p = 0.034). There was a significant difference in favor of the endoscopic approach regarding local recurrence-free survival thanks to better surgical margins in univariate and multivariate analysis (Odd Ratio = 2.01 (1.2–3.36) p = 0.0087). The complication rate (Odds Ratio = 3.4 (1.79–6.32) p < 0.001) was significantly lower in the endoscopic group. The histological positivity of signet-ring cells shows a statistically significant difference in recurrence-free survival (p = 0.0028).Conclusionthe oncological control of ITAC is better through the endoscopic approach, with negative margins and the absence of signet-ring-cells, two independent factors of recurrence.