Surgical Margin Status Research Articles

The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy: Involvement of Single Versus Multiple Sextant Sites.

Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1-3), pT (GG1-2/GG1-3/GG2/GG3), surgical margin status (GG1-3/GG3/GG5), or tumor volume (GG1-2/GG1-3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1-2 versus 3-6/1-3 versus 4-6/1-4 versus 5-6), RP GG (1-3 versus 4-6/1-4 versus 5-6), pT (1-2 versus 3-6/1-3 versus 4-6), pN (1-3 versus 4-6), or tumor volume (1-2 versus 3-6/1-4 versus 5-6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1-2/GG1-3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1-3 cancer.

Laparoscopic vs open liver resection for metastatic colorectal cancer: analysis of surgical margin status and survival.

Liver resection represents the curative treatment of choice for patients with colorectal liver metastases (CRLM). Laparoscopic hepatectomy in CRLM is considered a safe approach. However, the information on their oncological results in the different series is deficient. This study aimed to compare the surgical margin, overall survival (OS), and disease-free survival (DFS) in patients with oncological resections of CRLM according to the type of surgical approach performed. Between April 2007 and June 2017, 263 patients with CRLM underwent hepatic resection. Inclusion criteria were initial resectability, tumor size ≤ 50mm, 3 or less metastases, no bilobar involvement, and absence of extrahepatic disease. A propensity score was performed to adjust the indication bias. Eighty-two patients were included (56 open and 26 laparoscopic). Twenty-eight (50%) patients had synchronous presentation in the open approach and 6 (23%) in the laparoscopic approach (p = 0.021), with more frequent simultaneous open resections (p = 0.037). The resection margin was positive (R1) in 5 patients with an open approach and 2 with a laparoscopic approach (8.9% and 7.6% respectively; p = 0.852). Nine patients (16%) with conventional approach and 2 (7.7%) with laparoscopic approach had local complications (p = 0.3). There was one death in the open group and none in the laparoscopic. There were no significant differences in OS and DFS rate between both groups (1-3years, OS: 92-77% and 96-75% respectively; 1-3years, DFS: 63-20% and 73-36% respectively). There were no significant differences in terms of surgical margin, OS rate, and DFS rate between the laparoscopic and open approach in patients with CRLM.

Comparison of Recurrence Rate Between Re-Excision With Radiotherapy and Radiotherapy-Only Groups in Surgical Margin Involvement of In Situ Carcinoma.

PurposeSurgical margin status is a surrogate marker for residual tumors after breast-conserving surgery (BCS). A comparison of ipsilateral breast tumor recurrence (IBTR) rates between re-excision combined with radiotherapy (excision with RTx) and RTx alone, following the confirmation of ductal carcinoma in situ (DCIS) in the resection margin after BCS, has not been reported previously. Therefore, in the present study, the clinical characteristics of DCIS involvement in the surgical resection margin between excision with RTx and RTx alone were investigated, and the IBTR rate was compared.MethodsWe analyzed 8,473 patients treated with BCS followed by RTx between January 2013 and December 2019. Patients were divided into 2 groups based on surgical resection margin status in permanent pathology, and superficial and deep margins were excluded. Patients who underwent re-excision with DCIS confirmed in the resection margin were identified and the IBTR rate was examined.ResultsAmong 8,473 patients treated with BCS, 494 (5.8%) had positive surgical resection margins. The median follow-up period was 47 months. Among the 494 patients with a positive resection margin, 368 (74.5%) had residual DCIS at the surgical resection margin in the final pathology. Among those with confirmed DCIS at the resection margin, 24 patients (6.5%) were re-excised, and 344 patients (93.5%) underwent RTx after observation. The IBTR rates were 4.2% and 1.2% in the re-excision and observation groups, respectively. IBTR-free survival analysis revealed no significant difference between the excision with RTx and RTx-only groups (p = 0.262).ConclusionThe IBTR rate did not differ between the excision with RTx and RTx-only groups when DCIS was confirmed at the resection margins. This suggests that RTx and close observation without re-excision could be an option, even in cases where minimal involvement of DCIS is confirmed on surgical resection.

The Impact of Positive Resection Margin in Perihilar Cholangiocarcinoma, Ductal Margin vs Radial Margin

Introduction: Resection margin status is the most important prognostic factor in resected perihilar cholangiocarcinoma (pCCA). Although the impact of ductal margin (DM) was reported in many studies, the influence of radial margin (RM) is unclear. This study aims to investigate the incidence and the effect of positive RM on survival. Methods: Patients with pCCA who underwent curative resection between October 2013 to December 2018 were retrospectively reviewed. Resection margin status were divided into negative resection margin (R0) and positive resection margin (R1); positive RM alone (RM+) and positive DM with or without positive RM (DM+). Results: Of the 170 pCCA patients, 63 (37%) had R1 margin. Among 63 R1 patients; 18 (28.6%) had positive DM alone, 20 (31.7%) had positive RM alone and 25 (39.7%) had both positive DM and RM. The R1 patients had a significantly greater number of LN metastasis and advanced tumor staging than R0 patients, however there was no difference between the RM+ and DM+ patients. The median survival time of patients with RM+ was significantly poorer than R0 patients (13.8 vs 24.7 months; p<0.001, respectively) and similar to the DM+ patients (9.1 months, p=0.561). In multivariable analysis, positive resection margin and lymph node metastasis were independently prognostic factors. Conclusion: Positive resection margin remains the most important prognostic factors and positive RM is common in these patients. Positive RM also had a comparable effect on survival as positive DM. As a result, in pCCA, surgical resection should target both RM and DM. Tabled 1EP03A-039CharacteristicsUnivariableMultivariableNMST (months)p-valueHR95%CIp-valueBismuth type0.0441.3770.838-2.2620.207 1-314416.8 42310.6Portal vein invasion0.0291.0920.212-5.6130.916 Absence8418.4 Present6714.8Hepatic artery invasion0.0410.8560.465-1.5780.619 Absence10018.4 Present5114.2pT stage (AJCC 8th)0.0190.9970.211-4.7090.997 pT 1-29818.4 pT 3-46914.2pN stage (AJCC 8th)<0.0012.2931.437-3.6620.001 pN09025.7 pN1/2778.0Staging (AJCC 8th)<0.0011.3630.729-2.5490.332 Stage 1-24930.7 Stage 3-411810.6Surgical margin status<0.001 R010524.711.613-4.180<0.001 DM+429.12.5971.231-3.8510.008 RM+2013.82.177Surgical margin status<0.001 R010524.70.3850.239-0.620<0.001 DM+429.110.463-1.5190.561 RM+2013.80.838 Open table in a new tab

MRI-Based Radiomic Models to Predict the Surgical Margin Status and Infer the Tumor Immune Microenvironment in Breast Cancer Patients With Breast-Conserving Surgery: A Multicenter Validation Study

MRI-Based Radiomic Models to Predict the Surgical Margin Status and Infer the Tumor Immune Microenvironment in Breast Cancer Patients With Breast-Conserving Surgery: A Multicenter Validation Study

Long-term functional outcomes of vesicourethral anastomosis with bladder neck preservation and distal urethral length preservation after videolaparoscopic radical prostatectomy.

IntroductionRadical prostatectomy (RP) is the standard surgical treatment for localized prostate cancer (PCa), with excellent oncologic outcomes; however, complications such as post-prostatectomy incontinence could significantly affect quality of life.AimTo provide data on long-term urinary functional outcomes of bladder neck preservation (BNP) combined with distal urethral length preservation (DULP) in patients treated with videolaparoscopic prostatectomy.Material and methodsIn this retrospective study, data were analysed from 619 consecutive patients who underwent laparoscopic radical prostatectomy (LRP) due to localized prostate cancer between November 2014 and December 2018 in a single tertiary care centre in Poland. Of these patients, 227 had BNP and DULP during the procedure. Urinary continence status was assessed in patients at 3, 6, 12, and 18 months after LRP. Cancer resection was assessed by surgical margin status.ResultsIn the group with BNP and DULP, urinary continence recurred earlier than it did in the control group up to 3 months after surgery: 204 (89.8%) patients in this group were fully continent compared with 283 (72.2%) in the control group (p < 0.001). The difference was also significant after 6 months (95.1% vs. 80.6%, respectively; p < 0.001). Despite these early promising results, there was no difference in urinary continence recovery after 12 and 18 months. There was also no difference between the 2 groups regarding surgical margin status of the resected tissue.ConclusionsOur study showed that BNP combined with DULP is a safe procedure that helps to improve early urinary continence rates after surgery without altering the risk of positive surgical margin.

Evaluation of the Surgical Margin Threshold for Avoiding Recurrence after Partial Nephrectomy in Patients with Renal Cell Carcinoma.

PurposeAn adequate minimal surgical margin for partial nephrectomy (PN) has not yet been conclusively established. Therefore, we aimed to compare PN recurrence rates according to surgical margin status and to establish an adequate minimal surgical margin.Materials and MethodsWe retrospectively studied patients with clinically localized renal cell carcinoma who underwent PN between 2005 and 2014. Surgical margin width (SMW) was assessed for all surgical tissues and divided into three groups: SMW <1 mm, SMW ≥1 mm, and positive surgical margin (PSM). The data were analyzed using the Kaplan-Meier method with log-rank tests and multivariate Cox regression models.ResultsOf 748 patients (median age, 55 years; interquartile range, 46–64 years; 220 female), 704 (94.2%) and 44 (5.8%) patients had negative and PSMs, respectively. Recurrence-free survival was significantly lower in patients with PSMs (p<0.001) and was not significantly different between SMW ≥1 mm and <1 mm groups (p=0.604). PSM was a significant predictor of recurrence (hazard ratio: 8.03, 95% confidence interval: 2.74–23.56, p<0.001), in contrast to SMW <1 mm (p=0.680).ConclusionA PSM after PN significantly increases the risk of recurrence. We discovered that even a submillimeter safety surgical margin may be enough to prevent recurrence. To maximize normal renal parenchyma preservation and to avoid cancer recurrence in renal parenchymal tumor patients, PN may be a safe treatment, except for those with a PSM in the final pathology.

Surgical Margins Status and Prognosis after Resection of Oral Cavity Squamous Cell Carcinoma: Results from a Taiwanese Nationwide Registry-Based Study.

Simple SummaryWhile the prognostic role of surgical margins in oral cavity squamous cell carcinoma is well-established, the optimal cutoff values for margin status remain controversial. This study addressed this issue in a large sample of 13,768 patients included in a nationwide registry in Taiwan. The identification of the most suitable cutoff value for surgical margins was conducted using 5-year local control as the outcome of interest. On analyzing the margin status—categorized as 0, 0.1–4 and > 4 mm—the 5-year outcomes were as follows: local control, 87, 89 and 92%; disease-specific survival, 57, 76 and 81%; overall survival, 47, 67 and 74%, respectively. Collectively, these data indicate that a margin status >4 mm can be considered as adequate.(1) Background: The optimal cutoff value that maximizes the prognostic value of surgical margins in patients with resected oral cavity squamous cell carcinoma has not yet been identified. (2) Methods: Data for this study were retrieved from the Taiwan Cancer Registry Database. A total of 13,768 Taiwanese patients with oral cavity squamous cell carcinoma were identified and stratified according to different margin statuses (0, 0.1–4 and > 4 mm). The five-year local control, disease-specific survival and overall survival rates were the main outcome measures. (3) Results: The 5-year local control, disease-specific survival and overall survival rates of patients with close margins (0 and 0.1–4 mm) were significantly lower than those observed in patients with clear margins (> 4 mm; all p values < 0.001). In multivariate analysis, margin status, depth of invasion and extra-nodal extension were identified as independent adverse prognostic factors for 5-year local control. (4) Conclusions: A thorough assessment of surgical margins can provide a reliable prognostic prediction in patients with OCSCC. This has potential implications for treatment approaches tailored to the individual level. The achievement of clear margins (>4 mm) should be considered a key surgical goal to improve outcomes in this patient group.

A Comparison of Clinicopathologic Outcomes Across Neoadjuvant and Adjuvant Treatment Modalities in Resectable Gastric Cancer

Treatment of resectable gastric cancer (RGC) uses a multimodal approach, including surgical treatment and chemotherapy with or without radiation therapy, and the optimal treatment strategy and timing of each of these modalities is unknown. To investigate the association of various neoadjuvant and adjuvant treatment modalities with pathologic complete response (pCR), surgical margin status (SMS), and overall survival (OS) in RGC. For this comparative effectiveness study, the National Cancer Database was interrogated to identify patients with RGC diagnosed from 2004 to 2015. Patients with gastric adenocarcinoma that was cT2-T4b, any N, and M0 and who underwent definitive surgical treatment were included. The association of 9 treatment groups (ie, neoadjuvant chemoradiation only [nCRT], neoadjuvant chemotherapy only, adjuvant chemotherapy only [aCT], adjuvant chemoradiation only [aCRT], neoadjuvant chemotherapy and adjuvant radiation, chemotherapy with timing unknown [CTTU], chemoradiation therapy with timing unknown, radiation therapy with timing unknown (RTTU), and no perioperative therapy [NT]) with 3 end points (ie, pCR, SMS, and OS) was analyzed. The analysis was done using logistic regression and Cox proportional hazards models with adjustment for baseline characteristics. Data were analyzed from September 2019 through February 2020. Among 183 204 patients with RGC who were screened, 3064 patients were included in the analysis (median [IQR] age, 68 [57-77] years; 1764 [57.6%] men). There were 1584 tumors (51.7%) located in the antrum and 1539 stage 2 tumors (50.2%). On multivariable analyses among 1939 patients (owing to 137 patients with missing data for pCR and the exclusion of 988 patients with aCT and aCRT from pCR analysis), nCRT was associated with increased odds of pCR compared with NT, with the greatest odds ratio (OR) among all treatments (OR, 59.55; 95% CI, 10.63-333.56; P < .001). RTTU had the next highest OR (29.96; 95% CI, 2.92-307.53; P = .004). In multivariable analysis for OS among 3061 patients (owing to missing data for OS), CTTU was associated with decreased risk of death compared with NT (hazard ratio, [HR], 0.41; 95% CI, 0.35-0.48; P < .001), with the lowest HR, as was nCRT (HR, 0.48; 95% CI, 0.35-0.66; P < .001), with the next lowest HR. Median OS was greatest among patients treated with CTTU (53.9 months; 95% CI, 44.5-61.0 months), followed by nCRT (39.1 months; 95% CI, 26.9 months-not applicable) and aCT (36.1 months; 95% CI, 28.88-49.18 months), while 2-year OS rates were 65.6% (95% CI, 61.3%-69.5%) for CTTU, 63.6% (95% CI, 52.3%-73.0%) for nCRT, and 59.7% (95% CI, 54.2%-64.7%) for aCT. This study found that nCRT was associated with the highest pCR rate, while CTTU (ie, neoadjuvant or adjuvant therapy) was associated with the greatest OS.

Frozen Section Analysis and Real-Time Magnetic Resonance Imaging of Surgical Specimen Oriented on 3D Printed Tongue Model to Assess Surgical Margins in Oral Tongue Carcinoma: Preliminary Results.

BackgroundA surgical margin is the apparently healthy tissue around a tumor which has been removed. In oral cavity carcinoma, a negative margin is considered ≥ 5 mm, a close margin between 1 and 5 mm, and a positive margin ≤ 1 mm. Currently, the intraoperative surgical margin status is based on the visual inspection and tissue palpation by the surgeon and intraoperative histopathological assessment of the resection margins by frozen section analysis (FSA). FSA technique is limited and susceptible to sampling errors. Definitive information on the deep resection margins requires postoperative histopathological analysis.MethodsWe described a novel approach for the assessment of intraoperative surgical margins by examining a surgical specimen oriented through a 3D-printed specific patient tongue with real-time Magnetic Resonance Imaging (MRI). We reported the preliminary results of a case series of 10 patients, prospectively enrolled, with oral tongue carcinoma who underwent surgery between February 2020 and April 2021. Two radiologists with 5 and 10 years of experience, respectively, in Head and Neck radiology in consensus evaluated specimen MRI and measured the distance between the tumor and the specimen surface. We performed intraoperative bedside FSA. To compare the performance of bedside FSA and MRI in predicting definitive margin status we computed the weighted sensitivity (SE), specificity (SP), accuracy (ACC), area under the ROC curve (AUC), F1-score, Positive Predictive Value (PPV), and Negative Predictive Value (NPV). To express the concordance between FSA and ex-vivo MRI we reported the jaccard index.ResultsIntraoperative bedside FSA showed SE of 90%, SP of 100%, F1 of 95%, ACC of 0.9%, PPV of 100%, NPV (not a number), and jaccard of 90%, and ex-vivo MRI showed SE of 100%, SP of 100%, F1 of 100%, ACC of 100%, PPV of 100%, NPV of 100%, and jaccard of 100%. These results needed to be validated in a larger sample size of 21- 44 patients.ConclusionThe presented method allows a more accurate evaluation of surgical margin status, and the first clinical experiences underline the high potential of integrating FSA with ex-vivo MRI of the fresh surgical specimen.

Evaluation of Surgical Margin Status in Patients With Salivary Gland Cancer

Salivary gland cancer comprises a diverse group of histologic types with different biological behavior. Owing to this heterogeneity, the association of margin status and postoperative adjuvant radiotherapy has been poorly studied. To examine the association between surgical margin status and oncologic outcomes and the subsequent outcome of adjuvant radiotherapy in patients with salivary gland carcinomas. This cohort study analyzed data from institutional records at Memorial Sloan Kettering Cancer Center from 1985 to 2015. Statistical analysis was completed on October 31, 2020. After exclusions, 837 patients with surgically treated salivary gland carcinoma were identified. Surgical margins and histologic characteristics identified from pathology reports were recorded, with margins classified as negative, close, and positive, and individual histologic types classified into 3 risk groups: low, intermediate, and high. The outcome of adjuvant radiotherapy was determined in patients with close margins with low- and intermediate-risk histologic type and overall pathologic stage I/II disease. Disease-specific survival (DSS) and local recurrence-free survival (LRFS) outcomes were calculated using the Kaplan-Meier method. Multivariable analysis was performed using the Cox proportional hazards regression model. A planned subgroup analysis of patients with close margins was conducted. Among the 837 patients identified, 438 were women (52.3%); median age at surgery was 58 years (range, 6-98). A total of 399 tumors (47.7%) originated from major salivary glands, and 438 (52.3%) from minor salivary glands. Margin positivity rates were not different between minor and major salivary gland tumors. Positive surgical margins were identified in 252 patients (30.1%), with nasal cavity/paranasal sinuses and trachea/larynx subsites as the most common sites. Close margins were recorded in 203 patients (24.3%). Adjuvant radiotherapy was administered in 80.5% (103 of 128) of patients with major salivary gland cancer with positive margins, 58.8% (60 of 102) with close margins, and 30.7% (52 of 169) with negative margins and in 70.2% (87 of 124), 36.6% (37 of 101) , and 19.7% (42 of 213) patients with minor salivary gland cancer. With median follow up time of 57 months (range, 1-363 months), patients with positive margins had poorer DSS and LRFS. However, after controlling for overall stage, histologic risk group, and adjuvant radiotherapy, margin status was not a factor associated with poorer DSS or LRFS. In patients with close margins, low-risk and intermediate-risk histologic type, and overall pathologic stage I/II, patients who did not have adjuvant radiotherapy had comparable local control with those who received adjuvant radiotherapy. The findings of this cohort study suggest that patients with salivary gland cancer who have either close or positive surgical margins are at increased risk for poorer local control and survival. After controlling for tumor stage, histologic risk group, and the use of adjuvant radiotherapy, margin status was not an independent factor associated with poorer outcome. Subgroup analyses showed that care for patients with close margins with low-risk or intermediate-risk histologic type who have stage I/II cancers might be managed safely without adjuvant radiotherapy.

Treatment at a high-volume academic research program mitigates racial disparities in pancreatic adenocarcinoma.

Racial disparities have long been a subject of concern between patients afflicted with pancreatic cancer in the United States. We believe that, in addition to a high-volume center, treatment at an academic research program (ARP) will mitigate racial outcome disparities. A total of 12,950 patients diagnosed with stage I-III pancreatic adenocarcinoma from 2003-2011 and at ACS Commission on Cancer (COC) accredited facilities [e.g., high-volume (≥12 cases/year) ARPs] were evaluated from the National Cancer Data Base (NCDB). Sociodemographic, clinicopathological, and treatment variables were compared between Black (N=1,127) and White (N=11,823) patients. The Kaplan-Meier Estimator and Cox Proportional Hazards Model were used for survival analysis. P value ≤0.05 was considered significant. Black patients had a significantly higher overall survival (OS) than White patients, despite having a significantly lower household income, lower education level, more stage III disease, more Medicaid recipients, and higher comorbidity index (P<0.05). The 5-year unadjusted OS (28.6% versus 23.9%, a median survival time (months) was (25.2 versus 23.7 months for Black and White patients, respectively (P<0.05). There was no significant difference in surgical margin status or receipt of chemoradiation between the two cohorts. After adjusting for covariates, race was no longer a significant predictor of OS (P=0.096). Treatment at a high volume, ARP can mitigate racial disparities in pancreatic cancer.

Factors influencing recurrence after complete remission in children with hepatoblastoma: A 14-year retrospective study in China.

ObjectiveAfter a complete remission to treatment for hepatoblastoma, some children still have recurrence. We identified and explored the factors that influence recurrence after complete remission in a retrospective study.MethodsOf 197 children with hepatoblastoma, 140 (71.1%) achieved initial complete remission and were enrolled in factor analysis. Variables consisted of age, sex, PRE-Treatment EXTent of tumor (PRETEXT) stage, pathologic type, metastatic disease, serum alpha-fetoprotein level, vascular involvement, and surgical margin status. We employed univariate and multivariate analyses to assess the relationship between each factor and tumor recurrence.ResultsOf 140 children who achieved initial complete remission, 42 (30%) had recurrent hepatoblastoma. The 5-year overall survival rates for the non-recurrence and recurrence group were 99.0% and 78.6%, respectively. The overall 1-year, 3-year, and 5-year recurrence-free survival (RFS) rates were 77.8%, 69.8%, and 69.8%, respectively. All recurrences occurred within 2 years from complete remission. The RFS rate was significantly higher in children younger than 3 years and in those with mixed pathological type, PRETEXT II and III, without metastatic disease, without vascular involvement, and microscopic negative margin than in that of children older than 3 years, with epithelial pathological type, PRETEXT IV, metastatic disease, vascular involvement, and macroscopic positive margin (P < 0.001, = 0.020, < 0.001, = 0.004, = 0.002, and < 0.001, respectively). The independent risk factors for recurrence after complete remission were age ≥3 years, PRETEXT IV, and metastatic disease (P < 0.05).ConclusionAge, PRETEXT stage, metastatic disease, vascular involvement, pathologic type, and surgical margin status might be associated with recurrent hepatoblastoma after complete remission; meanwhile, age ≥3 years, PRETEXT IV, and metastatic disease are independent risk factors of recurrence. Further research is needed on the causes of tumor recurrence, which may improve the long-term outcomes of children with hepatoblastoma.

Impact of Pathology Review in Adverse Histological Characteristics and pT Stages of Upper Tract Urothelial Cancer in a Multicenter Study.

PurposePathology reviews for upper urinary tract cancer (UTUC) remained scarce in the literature. Here, we reported the interobserver variation among the review and local pathologies of featured histologic characteristics for UTUC.MethodsPatients who underwent definitive surgical treatments for UTUC were retrospectively reviewed for eligibility of pathology review. In the Taiwan UTUC Collaboration cohort, 212 cases were reviewed, of which 154 cases were eligible for pathology review. Agreement between original pathology and review pathology was measured by the total percentage of agreement and by simple kappa statistics. The prognostic impact was analyzed by the Cox regression model with the estimation of hazard ratios (HR) and 95% confidence intervals.ResultsThere were 80 women and 74 men enrolled in this study, and the median age at treatment was 71.7 years. The agreement is moderate agreement for surgical margin status (87.7%; κ = 0.61), tumor grade (82.5%; κ = 0.43), tumor invasiveness (76.6%; κ = 0.45), lymphovascular invasion (70.8%; κ = 0.42) and T stage (67.5%; κ = 0.52). The interobserver agreements for perineural invasion and variant histology identification were slight. Kaplan–Meier analysis for disease-free survival revealed comparable results in local and review pathology for localized (Tis, Ta, T1–2) or advanced T stage (T3–4).ConclusionsPathology review of UTUC had minimal impact on clinical practice based on current available disease treatment guidelines. However, significant interobserver variations were observed in featured adverse histopathological characters.

Pretreatment tumor sampling and prognostic factors in patients with soft-tissue sarcoma of the head and neck.

BackgroundInsufficient preoperative work-up and consequent intralesional or marginal resection of soft-tissue sarcomas of the head and neck (STSHNs) is common.MethodsThis retrospective cohort study comprised 63 patients with STSHN treated at the Helsinki University Hospital between 2005 and 2017. We assessed the effect of pretreatment tumor sampling on surgical margin status and need for supplemental surgery, as well as prognostic factors and survival.ResultsThe lack of representative pretreatment biopsy specimen was associated with unfavorable margin status. Primary surgery at a non-academic center was associated with need for supplemental surgery. The 3-year overall survival (OS) was 68%, disease-specific survival (DSS) 71%, and recurrence-free survival (RFS) 61%. Higher tumor grade and primary tumor size over 5 cm were associated with reduced DSS.ConclusionsDiagnosis and management of STSHNs should be centralized to experienced academic centers. Decision-making between needle biopsy, open biopsy, or upfront radical surgery depends on tumor location and size.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00405-021-07162-0.

Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases.

There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer. Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models. In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001). Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

Prostatic Ductal Adenocarcinoma Controlled for Tumor Grade, Stage, and Margin Status Does Not Independently Influence the Likelihood of Biochemical Recurrence in Localized Prostate Cancer After Radical Prostatectomy.

Prostatic ductal adenocarcinoma (PDA) has historically been considered to be an aggressive subtype of prostate cancer. To investigate if PDA is independently associated with worse biochemical recurrence (BCR)-free survival after radical prostatectomy. A review of 1584 radical prostatectomies was performed to grade, stage, and assess margin status in each tumor nodule. Radical prostatectomies with localized PDA (ie, those lacking metastasis) in the tumor nodule with the highest grade and stage and worst margin status were matched with prostatic acinar adenocarcinoma according to grade, stage, and margin status. The effect of PDA on BCR was assessed by multivariable Cox regression and Kaplan-Meier analyses. Prostatic ductal adenocarcinoma was present in 171 cases. We excluded 24 cases because of lymph node metastasis (n = 13), PDA not in the highest-grade tumor nodule (n = 9), and positive surgical margin in a lower-grade tumor nodule (n = 2). The remaining 147 cases included 26 Grade Group (GG) 2, 44 GG3, 6 GG4, and 71 GG5 cancers. Seventy-six cases had extraprostatic extension, 33 had seminal vesicle invasion, and 65 had positive margins. Follow-up was available for 113 PDA and 109 prostatic acinar adenocarcinoma cases. Prostate-specific antigen density (odds ratio, 3.7; P = .001), cancer grade (odds ratio, 3.3-4.3; P = .02), positive surgical margin (odds ratio, 1.7; P = .02), and tumor volume (odds ratio, 1.3; P = .02) were associated with BCR in multivariable analysis. Prostatic ductal adenocarcinoma, its percentage, intraductal carcinoma, and cribriform Gleason pattern 4 were not significant independent predictors of BCR. Advanced locoregional stage, higher tumor grade, and positive surgical margin status rather than the mere presence of PDA are more predictive of worse BCR-free survival outcomes following radical prostatectomy in men with a component of PDA.

Molecular margin status after radical prostatectomy using glutathione S‐transferase P1 (GSTP1) promoter hypermethylation

To assess the potential for molecular staging in biopsies of the prostatic fossa after radical prostatectomy (RP) by searching for occult tumour cells through analysis of glutathione S-transferase P1 (GSTP1) methylation status. We analysed 2446 biopsies: 2286 biopsies from a group of 254 patients with clinically organ-confined prostate cancer who underwent RP and 160 biopsies from a control group of 32 patients. After prostate gland excision, biopsies were obtained from defined areas of the prostatic fossa and bisected for histopathological and molecular genetics analyses. Results were related to clinicopathological data including tumour stage, lymph node status, resection status, tumour grading, initial PSA level, and biochemical recurrence. In total, 34 patients (13.4%) had at least one core positive for the GSTP1 promoter hypermethylation, six of whom (17.6%) were characterised as having a clinically localised tumour stage (pT2, pN0) and 28 (82.4%) as an advanced tumour stage (≥pT3 and/or pN1). GSTP1 promoter hypermethylation significantly correlated with tumour stage (P < 0.001), International Society of Urological Pathology grading (P = 0.001), lymph node status (P < 0.001), surgical marginstatus (P < 0.001), and biochemical recurrence (P = 0.001). Furthermore, in 46 patients (18.1%) further analysis led to a down- or upgrading of conventional surgical margin status. Classical R-status (margins of the specimen) issignificantly superior to histological sampling from the fossa (P = 0.006) but not to GSTP1 analysis from the fossa (P = 0.227). For the detection of residual tumour in the fossa after RP in order to better predict recurrence, molecular GSTP1 promoter hypermethylation has some value; however, the classical R-status (margins of the specimen) is simpler and more widely applicable with similar results.

Neither Surgical Margin Status nor Somatic Mutation Predicts Local Recurrence After R0-intent Resection for Colorectal Liver Metastases

BackgroundWe evaluated the associations of surgical margin status and somatic mutations with the incidence of local recurrence (LR) and oncologic outcomes in patients undergoing R0-intent (microscopically negative margin) resection of colorectal liver metastases (CLM). MethodsPatients with CLM who underwent initial R0-intent resection and analysis of tumor tissue using next-generation sequencing during 2001–2018 were analyzed. Recurrences were classified as LR (at the resection margin), other intrahepatic recurrence, or extrahepatic recurrence. Predictors and survival effect of LR were evaluated using univariate and multivariate analysis. ResultsOf 552 patients analyzed, 415 (75%) had R0 resection (margin width ≥ 1.0 mm), and 38 (7%) had LR. LR incidence was not affected by surgical margin width. RAS/TP53 co-mutation was associated with increased risk of intrahepatic recurrence (67% vs. 49%; p < 0.001) and overall recurrence (p < 0.001). However, incidence of LR did not differ significantly by RAS/TP53, BRAF, SMAD4, or FBXW7 mutation. Extrahepatic disease (hazard ratio [HR], 1.47; p = 0.034), > 8 cycles of preoperative chemotherapy (HR, 1.98; p = 0.033), tumor viability ≥ 50% (HR, 1.55; p = 0.007), RAS/TP53 co-mutation (HR, 1.69; p = 0.001), and SMAD4 mutation (HR, 2.44; p < 0.001) were independently associated with poor overall survival, but surgical margin status was not. ConclusionsAlthough somatic mutations were associated with overall recurrence, neither surgical margin width nor somatic mutations affected LR risk after R0-intent hepatectomy for CLM. LR and prognosis were likely driven by individual tumor biology rather than surgical margins.

Comedonecrosis Gleason pattern 5 is associated with worse clinical outcome in operated prostate cancer patients

Individual growth patterns and cribriform architecture are increasingly considered in risk stratification and clinical decision-making in men with prostate cancer. Our objective was to establish the prognostic value of individual Gleason 5 patterns in a radical prostatectomy (RP) cohort. We reviewed 1064 RPs and recorded Grade Group (GG), pT-stage, surgical margin status, Gleason 4 and 5 growth patterns as well as intraductal carcinoma. The clinical endpoints were biochemical recurrence and post-operative distant metastasis. Gleason pattern 5 was present in 339 (31.9%) RPs, of which 47 (4.4%) presented as primary, 166 (15.6%) as secondary, and 126 (11.8%) as tertiary pattern. Single cells/cords were present in 321 (94.7%) tumors with Gleason pattern 5, solid fields in 90 (26.5%), and comedonecrosis in invasive carcinoma in 32 (9.4%) tumors. Solid fields demonstrated either a small nested morphology (n = 50, 14.7%) or medium to large solid fields (n = 61, 18.0%). Cribriform architecture was present in 568 (53.4%) RPs. Medium to large solid fields and comedonecrosis coincided with cribriform architecture in all specimens, and were not observed in cribriform-negative cases. In multivariable analysis adjusted for Prostate-Specific Antigen, pT-stage, GG, surgical margin status and lymph node metastases, cribriform architecture (Hazard Ratio (HR) 9.9; 95% Confidence Interval (CI) 3.9–25.5, P < 0.001) and comedonecrosis (HR 2.1, 95% CI 1.2–3.7, P = 0.01) were independent predictors for metastasis-free survival, while single cells/cords (HR 1.2; 95% CI 0.7–1.8, P = 0.55) and medium to large solid fields (HR 1.6, 95% CI 0.9–2.7, P = 0.09) were not. In conclusion, comedonecrosis in invasive carcinoma is an independent prognostic Gleason 5 pattern for metastasis-free survival after RP. These data support the current recommendations to routinely include cribriform pattern in pathology reports and indicate that comedonecrosis should also be commented on.