Tissue morphometric measurements do not predict survival following colorectal cancer surgery.

BACKGROUND: Ex vivo tissue morphometric (TM) measurements have been proposed as a quality marker for colorectal cancer (CRC) surgery. However, their survival associations require clarification. This study aimed to evaluate the feasibility of capturing TM measurements based on ex vivo fresh specimen images and explore the association between these TM measurements and survival outcomes. METHODS: A prospective cohort study at Concord Hospital, Sydney was conducted with Stage I to III CRC patients (2009-2019) who underwent an anterior resection (AR) or right hemicolectomy (RH). Using high-resolution digital photographs of fresh CRC specimens, ex vivo tissue morphometric (TM) measurements-resected mesentery area (TM A), distances from high vascular tie to tumour (TM B) and bowel wall (TM C), and bowel length (TM D)-were recorded using Image J. Overall survival (OS) and disease-free survival (DFS) estimates and their associations to clinicopathological variables were investigated with Kaplan-Meier and Cox regression analyses. Linear regression models tested association between TM measurements and lymph node (LN) yield. RESULTS: Of the 1,425 patients who underwent CRC surgery, TM measurements were performed on 312 patients, with an average age of 69.4 years (SD 12.3), of whom 52.9% were male. The majority had an AR (57.8%). Among AR patients, a 5-year OS rate of 77.4% and a DFS rate of 70.1% were observed, with TM measurements bearing no relationship to survival outcomes. Similarly, RH patients exhibited a 5-year OS rate of 67.2% and a DFS rate of 63.1%, with TM measurements again showing no association with survival. Only TM D (P = 0.02) measurements were associated with the number of LNs examined. CONCLUSION: This study successfully demonstrates the feasibility of measuring TM measurements on photographs of ex vivo fresh specimens following CRC surgery. The lack of association with survival outcomes questions the utility of TM measurements as a quality metric of CRC surgery.

Validation of the German classification system for quality assessment of right-sided colon cancer specimens.

AIM: The German classification system of the completeness of mesocolic excision aims to assess the quality of right-sided colonic cancer surgery by review of photographs. We aimed to validate the reliability of the classification in a clinical context. METHOD: The study was based on a cohort of patients undergoing resection for right-sided colon cancer in two university hospitals served by the same group of pathologists. Prospectively collected photographs of the specimens were assessed twice by six colorectal surgeons to determine the intra-rater and inter-rater accuracy of the German classification and a modification assessing extended right-sided resections. RESULTS: Specimens from 613 resections for right-sided colon cancer were reviewed. Twenty-one specimens were found to be non-assessable, leaving 436 right hemicolectomies, 139 extended right hemicolectomies and 17 right-sided subtotal colectomies. Intra-rater reliability was 0.57-0.74 and weighted kappa coefficients 0.58-0.74, without differences between subgroups. The percentage of agreement between all six participants was 20.3% for all specimens, 21.1% for right hemicolectomy specimens and 18.1% for extended hemicolectomy and right-sided subtotal colectomy specimens. For the right hemicolectomy specimens, the model-based kappa coefficient for agreement was 0.27 (95% CI 0.24-0.30) and for association 0.45 (95% CI 0.41-0.49). CONCLUSION: The German classification of right hemicolectomy specimens showed low intra-rater reliability and inter-rater agreement and association. The use of this classification for scientific purposes appeared not to be reliable.

What factors determine specimen quality in colon cancer surgery? A cohort study.

PURPOSE: Tenets of 'good quality' colon cancer surgery include mesocolic plane dissection to preserve an intact mesocolic fascia/peritoneum, and excision of sufficient mesocolon for adequate lymphadenectomy. However, it remains controversial what clinicopathological factors determine 'good quality' surgery, and whether quality of surgery influences morbidity/mortality. This study documents the quality of colon cancer surgery at a quaternary referral centre and identifies factors that influence quality of surgery and post-operative outcomes. METHODS: Consecutive patients who underwent resection for colon adenocarcinoma at St. James's University Hospital, Leeds, UK (2015-2017), were included. Primary outcome measures included (i) plane of mesocolic dissection, prospectively assessed; and (ii) tissue morphometry (area of mesentery and vascular pedicle length). Other histopathological data were extracted from a prospective database. Clinical data were obtained from the National Bowel Cancer Audit and individual records. RESULTS: Four hundred five patients were included (mean 69.6 years). The majority (67.4%) of specimens were mesocolic plane dissections. Median area of mesentery excised was 12,085.4 mm2. Median vascular pedicle length was 89.3 mm. Post-operative complication was recorded in one-third of patients. Mesocolic plane excision was associated with open surgery (OR 1.80, 95% CI 1.05-3.09), especially in emergency colectomy. Open resections also had a greater mesentery excised (P = 0.002), but incurred more post-operative complication (OR 2.11, 95% CI 1.12-3.99). Post-operative complication was not associated with plane of excision or tissue morphometry. CONCLUSION: Majority of resections were 'optimal' mesocolic plane dissections. Open resections yielded better quality specimens, but incurred more morbidity. There is room for improvement in the quality of laparoscopic colon cancer surgery, particularly those performed as emergency.

Oncological adequacy of laparoscopic rectal cancer resection: An audit in Indian perspective.

BACKGROUND: Laparoscopic resection for rectal cancer (LRR) has gained popularity because of better short-term outcomes and less post-operative morbidity. However, LRR is still not endorsed as a standard of care mainly due to concerns centred on oncological safety in comparison with open approach. Moreover, two recent randomised trials (Australian Laparoscopic Cancer of the Rectum [ALaCaRT] and the American College of Surgeons Oncology Group [ACOSOG] Z6051) have failed to prove that LRR is non-inferior to open resection. Studies on oncological adequacy of LRR in the Indian population in terms of quality of mesorectal excision are scarce. In this article, we aim to audit the oncological adequacy of LRR in our centre and thereby critically analyse the reliability of extrapolation of results of ALaCaRT and ACOSOG trials to the Indian population. METHODS: We retrospectively analysed the oncological adequacy of LRR in terms of completeness of total mesorectal excision (TME), distal and circumferential resection margin (CRM) status and nodal harvest in patients with rectal cancer who underwent LRR between January 2016 and June 2018 at our centre. RESULTS: Of 157 patients included in this study, a complete TME was achieved in 148 (94.26%) patients and nearly complete in 7 (4.46%) patients. A safe CRM (≥1 mm) was obtained in 151 (96.18%) patients. Distal margin results were negative in 155 (98.73%) patients. Average nodal harvest was 19.86 ± 9.28. Overall surgical success, calculated as a composite measure of negative distal margin and negative CRM and complete TME was 95.54%. CONCLUSION: Good quality rectal cancer resection can be achieved by experienced laparoscopic surgeons without compromising oncological safety.

The effect of a multidisciplinary regional educational programme on the quality of colon cancer resection.

AIM: Mesocolic plane surgery with central vascular ligation produces an oncologically superior specimen following colon cancer resection and appears to be related to optimal outcomes. We aimed to assess whether a regional educational programme in optimal mesocolic surgery led to an improvement in the quality of specimens. METHOD: Following an educational programme in the Capital and Zealand areas of Denmark, 686 cases of primary colon cancer resected across six hospitals were assessed by grading the plane of surgery and undertaking tissue morphometry. These were compared to 263 specimens resected prior to the educational programme. RESULTS: Across the region, the mesocolic plane rate improved from 58% to 77% (P < 0.001). One hospital had previously implemented optimal surgery as standard prior to the educational programme and continued to produce a high rate of mesocolic plane specimens (68%) with a greater distance between the tumour and the high tie (median for all fresh cases: 113 vs 82 mm) and lymph node yield (33 vs 18) compared to the other hospitals. Three of the other hospitals showed a significant improvement in the plane of surgical resection. CONCLUSION: A multidisciplinary regional educational programme in optimal mesocolic surgery improved the oncological quality of colon cancer specimens as assessed by mesocolic planes; however, there was no significant effect on the amount of tissue resected centrally. Surgeons who attempt central vascular ligation continue to produce more radical specimens suggesting that such educational programmes alone are not sufficient to increase the amount of tissue resected around the tumour.

Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study.

OBJECTIVES: To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

Short, full-dose adjuvant chemotherapy (CT) in high-risk adult soft tissue sarcomas (STS): long-term follow-up of a randomized clinical trial from the Italian Sarcoma Group and the Spanish Sarcoma Group.

BACKGROUND: To report on long-term results of a phase 3 trial comparing three versus five cycles of adjuvant chemotherapy (CT) with full-dose epirubicin+ifosfamide in high-risk soft tissue sarcomas (STS). METHODS: Patients (pts) were randomized to receive three preoperative cycles of epirubicin 120 mg/m2 and ifosfamide 9 g/m2 (Arm A) or to receive the same three preoperative cycles plus two postoperative cycles (Arm B). Radiotherapy could be either delivered in the preoperative or in the postoperative setting. Non-inferiority of the primary end point, OS, was assessed by the confidence interval of the hazard ratio (HR; Arm A/Arm B) derived from Cox model. RESULTS: Between January 2002 and April 2007, 164 pts were assigned to arm A and 164 to arm B. At a median follow-up (FU) of 117 months (IQ range 103-135 months), 123 deaths were recorded: 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients: 64% in Arm A and 59% in Arm B. The intention-to-treat analysis confirmed that three cycles were not inferior to five cycles (one-sided 95% upper confidence limit was 1.24). A per protocol analysis was consistent with these results. Pts with leiomyosarcoma and undifferentiated pleomorphic sarcoma (UPS) had the lowest, and the highest response rates, respectively. Consistently, Leiomyosarcoma and UPS had the worse and the best prognosis, respectively. CONCLUSIONS: At a longer FU, the non-inferiority of three cycles of a full-dose conventional CT in comparison to five is confirmed. Response to therapy is also confirmed to be associated with better survival. This regimen is currently tested within an ongoing international trial against three cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176).

The mode of circumferential margin involvement in rectal cancer determines its impact on outcomes: A population-based study.

BACKGROUND: The clinical value of different modes of CRM involvement in rectal cancer patients is unclear. This study aims to determine the clinical impact of different modes of circumferential resection margin (CRM) involvement in patients with a locally advanced rectal carcinoma. PATIENTS AND METHODS: A cohort of patients who were diagnosed with stage III rectal cancer between June 2014 and June 2020 was selected from the prospective Dutch nationwide pathology databank (PALGA). Histopathological and clinical data were analyzed according to the nature of CRM involvement (via primary tumor invasion, lymph node metastasis, tumor deposit, multiple factors) and analyses on recurrence and overall survival (OS) were performed. RESULTS: 3020 patients were included, of whom 12.4 % had a positive CRM. The majority of these patients (63.2 %) had CRM involvement by primary tumor invasion and in 9 % of patients multiple factors caused the positive CRM. The rates of local recurrence and distant metastasis were related to the nature of the CRM involvement, with lowest rate for lymph node metastasis and highest rate for multiple factors. On multivariate analysis, CRM involvement by primary tumor invasion, tumor deposits and multiple factors, but not by lymph node metastasis, were associated with poor OS. CONCLUSION: This nationwide population based study highlights the clinical importance of reporting the nature of CRM involvement in rectal cancer patients. Lymph node metastasis involving the CRM does not bear the same risks for local recurrence, distant metastases and OS as CRM involvement by primary tumor invasion or CRM involvement by multiple factors.

Macroscopic Evaluation of Colon Cancer Resection Specimens.

Colon cancer is a common disease internationally. Outcomes have not improved to the same degree as in rectal cancer, where the focus on total mesorectal excision and pathological feedback has significantly contributed to improved survival and reduced local recurrence. Colon cancer surgery shows significant variation around the world, with differences in mesocolic integrity, height of the vascular ligation and length of the bowel resected. This leads to variation in well-recognised quality measures like lymph node yield. Pathologists are able to assess all of these variables and are ideally placed to provide feedback to surgeons and the wider multidisciplinary team to improve surgical quality over time. With a move towards complete mesocolic excision with central vascular ligation to remove the primary tumour and all mechanisms of spread within an intact package, pathological feedback will be central to improving outcomes for patients with operable colon cancer. This review focusses on the key quality measures and the evidence that underpins them.

Institution-Level Evolution of Lung Cancer Resection Quality With Implementation of a Lymph Node Specimen Collection Kit.

INTRODUCTION: Lung cancer surgery with a lymph node kit improves patient-level outcomes, but institution-level impact is unproven. METHODS: Using an institutional stepped-wedge implementation study design, we compared lung cancer resection quality between institutions in preimplementation and postimplementation phases of kit deployment and, within implementing institutions, resections without versus with the kit. Benchmarks included rates of nonexamination of lymph nodes, nonexamination of mediastinal lymph nodes, and attainment of American College of Surgeons Operative Standard 5.8. We report institution-level adjusted ORs (aORs) for attaining quality benchmarks. RESULTS: From 2009 to 2020, three preimplementing hospitals had 953 resections; 11 implementing hospitals had 4013 resections, 58% without and 42% with the kit. Quality was better in implementing institutions and with kit cases. Compared with preimplementing institutions, the aOR for nonexamination of lymph nodes was 0.62 (0.49-0.8, p = 0.002), nonexamination of mediastinal lymph nodes was 0.56 (0.47-0.68, p < 0.0001), and attainment of Operative Standard 5.8 was 7.3 (5.6-9.4, p < 0.0001); aORs for kit cases were 0.01 (0.001-0.06), 0.08 (0.06-0.11), and 11.6 (9.9-13.7), respectively (p < 0.0001 for all). Surgical quality was persistently poor in preimplementing institutions but sequentially improved in implementing institutions in parallel with kit adoption. In implementing institutions, resections with the kit had a uniformly high level of quality, whereas nonkit cases had a low level of quality, approximating that of preimplementing institutions. Within implementing institutions, 5-year overall survival was 61% versus 51% after surgery with versus without the kit (p < 0.001). CONCLUSIONS: Surgery with a lymph node specimen collection kit improved institution-level quality of curative-intent lung cancer resection.

Reducing recurrence in non-muscle-invasive bladder cancer by systematically implementing guideline-based recommendations: effect of a prospective intervention in primary bladder cancer patients.

Objective: In non-muscle-invasive bladder cancer (NMIBC), local recurrence after transurethral resection of the bladder (TURB) is common. Outcomes vary between urological centres, partly due to the sub-optimal surgical technique and insufficient application of measures recommended in the guidelines. This study evaluated early recurrence rates after primary TURB for NMIBC before and after introducing a standardized treatment protocol. Methods: Medical records of all patients undergoing primary TURB for NMIBC in 2010 at Skåne University Hospital, Malmö, Sweden, were reviewed. A new treatment protocol for NMIBC was defined and introduced in 2013, and results documented during the first year thereafter were compared with those recorded in 2010 prior to the intervention. The primary endpoint was early recurrence at first control cystoscopy. Comparisons were made by Chi-square analysis and Fisher's exact test. Recurrence-free survival (RFS) in the two cohorts was also investigated. Results: TURB was performed on 116 and 159 patients before and after the intervention, respectively. The early recurrence rate decreased from 22% to 9.6% (p = 0.005) at the first control cystoscopy after treatment. Residual/Recurrent tumour at the first control cystoscopy after the primary TURB (i.e. at second-look resection or first control cystoscopy) decreased from 31% to 20% (p = 0.038). The proportion of specimens containing muscle in T1 tumours increased from 55% to 94% (p < 0.001). RFS was improved in the intervention group (HR = 0.65, CI = 0.43-1.0; p = 0.05). Conclusions: Introduction of a standardized protocol and reducing the number of surgeons for primary treatment of NMIBC decreased the early recurrence rate from 22% to 9.6% and lowered the recurrence incidence by 35%.

Different quality of treatment in retroperitoneal sarcomas (RPS) according to hospital-case volume and surgeon-case volume: a retrospective regional analysis in Italy.

BACKGROUND: Retroperitoneal sarcomas (RPS) should be surgically managed in specialized sarcoma centers. However, it is not clearly demonstrated if clinical outcome is more influenced by Center Case Volume (CCV) or by Surgeon Case Volume (SCV). The aim of this study is to retrospectively explore the relationship between CCV and SCV and the quality of surgery in a wide region of Northern Italy. METHODS: We retrospectively collected data about patients M0 surgically treated for RPSs in 22 different hospitals from 2006 to 2011, dividing them in two hospital groups according to sarcoma clinical activity volume (HCV, high case volume or LCV, low case volume hospitals). The HCV group (> 100 sarcomas observed per year) included a Comprehensive Cancer Center (HVCCC) with a high sarcoma SCV (> 20 cases/year), and a Tertiary Academic Hospital (HVTCA) with multiple surgeon teams and a low sarcoma SCV (≤ 5 cases/year for each involved surgeon). All other hospitals were included in the LCV group (< 100 sarcomas observed per year). RESULTS: Data regarding 138 patients were collected. Patients coming from LCV hospitals (66) were excluded from the analysis as prognostic data were frequently not available. Among the 72 remaining cases of HCV hospitals 60% of cases had R0/R1 margins, with a more favorable distribution of R0/R1 versus R2 in HVCCC compared to HVTCA. CONCLUSIONS: In HCV hospitals, sarcoma SCV may significantly influence RPS treatment quality. In low-volume centers surgical reports can often miss important prognostic issues and surgical quality is generally poor.

Surgeon has a major impact on long-term recurrence risk in patients with non-muscle invasive bladder cancer.

INTRODUCTION: One of the factors responsible for the risk of recurrence after complete transurethral resection of the bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) is the quality of surgery that may vary between individual surgeons. The aim of the study was to evaluate the impact of the surgeon on recurrence-free survival in patients with NMIBC. MATERIAL AND METHODS: The long-term results of a series of consecutive TURBTs performed by five staff urologists at a single institution were retrospectively analyzed. A total of 949 cases of organ-preserving treatment in 784 patients with NMIBC were included in the analysis. RESULTS: With the median follow-up of 64.3 months (3-124 months), the 5-year recurrence-free survival rates according to the surgeon were 62.9% (95% CI 56.2-69.7%), 53.6% (95% CI 47.4-59.9%), 51.0% (95% CI 39.6-62.4%), 46.2% (95% CI 36.4-56.0%), and 44.2% (95% CI 36.8-51.7%), respectively (p <0.0001). In the multivariate analysis including all potential risk factors, the individual surgeon was associated with a risk of recurrence with a high degree of statistical significance (p = 0.0013). The between-surgeon differences in the recurrence risk were not that pronounced in less extensive tumors. CONCLUSIONS: A surgeon has a significant impact on the risk of recurrence after curative treatment of patients with NMIBC. This effect was observed despite the relatively extensive experience in bladder endoscopic surgery of all of the surgeons and practicing in a setting of one specialized center. These findings should be taken into account while performing and evaluating the results of comparative studies.

Pathological evaluation and quality of surgery in radical cystectomy in New South Wales, Australia.

BACKGROUND: Australian bladder cancer patients especially women are thought to have worse outcomes when compared to the other international series. The objective of this study was to assess the pathological pattern of primary bladder cancer at the time of radical cystectomy as well as assessing the quality of resection in New South Wales. METHOD: Pathology reports of radical cystectomy performed for primary bladder cancer were reviewed for a period of 10 years in a single major pathology centre servicing the state of New South Wales. RESULTS: Two hundred one specimens reviewed over 10 years. The tumour stage at the time of cystectomy was: CIS 29 (14%), Tx,a 5 (2%), T1 24 (12%), T2 49 (24%), T3 57 (28%) and T4 37 (18%). Lymphovascular invasion was seen in 94 (47%). Soft tissue margins were positive in 31 (15%), pelvic lymph node dissection was not performed in 64 (32%) of patients and only 32 (16%) of the patients had 10 or more lymph nodes harvested. No significant differences between men and women were noted in tumour stages, soft tissue positive margin rates and performance of pelvic lymph node dissection. Improving trends were noted in rates of negative soft tissue margins and the lymph node count during this period. CONCLUSION: Pattern of disease at the time of cystectomy was similar to the North American and European cohorts. Higher main specimen margin rates as well as lower lymph nodes retrieval rates were observed. No sex discrimination was observed. Further study is recommended to investigate the survival impact of this finding.