Resection Of Colorectal Carcinoma Research Articles

The Doppler Perfusion Index of the Liver and the Underlying Duplex Sonography of Visceral Vessels-A Systematic and Comprehensive Evaluation of Reproducibility.

Prior to the curative resection of colorectal carcinoma (CRC) or pancreatic ductal adenocarcinoma (PDAC), the exclusion of hepatic metastasis using cross-sectional imaging is mandatory. The Doppler perfusion index (DPI) of the liver is a promising method for detecting occult liver metastases, but the underlying visceral duplex sonography is critically viewed in terms of its reproducibility. The aim of this study was to investigate systematically the reproducibility of the measured variables, the calculated blood flow, and the DPI. Between February and September 2023, two examinations were performed on 80 subjects within a period of 0-30 days and at two previously defined quality levels, aligned to the German standards of the DEGUM. Correlation analyses were carried out using Pearson's correlation coefficient (PCC) and the intraclass correlation coefficient (ICC). The diameters, blood flow, and DPI showed a high degree of agreement (PCC of 0.9 and ICC of 0.9 for AHP). Provided that a precise standard of procedure is adhered to, the Doppler examination of AHC, AHP, and PV yields very reproducible blood flows and DPI, which is a prerequisite for a comprehensive investigation of its prognostic value for the prediction of metachronous hepatic metastasis in the context of curatively treated CRC or PDAC.

Treatment Decision for Locally Resected T1 Colorectal Carcinoma-Verification of the Japanese Guideline Criteria for Additional Surgery Based on Long-Term Clinical Outcomes.

To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009. We enrolled 4,719 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,259 patients with local resection alone [group A], 1,508 patients with additional surgery after local resection [group B], and 1,952 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively. Any of the risk factors were present in 3,801 patients. The LNM incidence was 10.3% (95% confidence interval 9.3-11.4) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.2) in those without risk factors ( P < 0.01). In group A, the incidence of recurrence was 3.4% in patients with risk factors, but it was only 0.1% in patients without risk factors ( P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.2%. Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM.

BRAFV600E immunohistochemistry can reliably substitute BRAF molecular testing in the Lynch syndrome screening algorithm in colorectal cancer.

The Lynch syndrome (LS) screening algorithm requires BRAF testing as a fundamental step to distinguish sporadic from LS-associated colorectal carcinomas (CRC). BRAF testing by immunohistochemistry (IHC) has shown variable results in the literature. Our aim was to analyse concordance between BRAFV600E IHC and BRAF molecular analysis in a large, mono-institutional CRC whole-slide, case series with laboratory validation. MisMatch repair (MMR) protein (hMLH1, hPMS2, hMSH2, and hMSH6) and BRAFV600E IHC were performed on all unselected cases of surgically resected CRCs (2018-2023). An in-house validation study for BRAFV600E IHC was performed in order to obtain optimal IHC stains. BRAFVV600E IHC was considered negative (score 0), positive (scores 2-3), and equivocal (score 1). Interobserver differences in BRAFV600E IHC scoring were noted in the first 150 cases prospectively collected. Nine-hundred and ninety CRCs cases (830 proficient (p)MMR/160 deficient (d)MMR) were included and all cases performed BRAFV600E IHC (BRAFV600E IHC-positive 13.5% of all series; 66.3% dMMR cases; 3.4% pMMR cases), while 333 also went to BRAF mutation analysis. Optimal agreement in IHC scoring between pathologists (P < 0.0001) was seen; concordance between BRAFV600E IHC and BRAF molecular analysis was extremely high (sensitivity 99.1%, specificity 99.5%; PPV 99.1%, and NPV 99.5%). Discordant cases were reevaluated; 1 score 3 + IHC/wildtype case was an interpretation error and one score 0 IHC/mutated case was related to heterogenous BRAFV600E IHC expression. Among the 12 IHC-equivocal score 1+ cases (which require BRAF molecular analysis), three were BRAF-mutated and nine BRAF-wildtype. BRAFV600E IHC can be used as a reliable surrogate of molecular testing after stringent in-house validation.

Combined robot-assisted radical prostatectomy and anterior resection for synchronous prostate and colorectal carcinoma: a case series

Combined robot-assisted radical prostatectomy and anterior resection for synchronous prostate and colorectal carcinoma: a case series

Application of MFI-5 in severe complications and unfavorable outcomes after radical resection of colorectal cancer

BackgroundFrailty is considered a characteristic manifestation of physiological decline in multiple organ systems, which significantly increases the vulnerability of elderly individuals with colorectal cancer (CRC) and is associated with a poor prognosis. While studies have demonstrated that the 11-factor Modified Frailty Index (mFI-11) can effectively predict adverse outcomes following radical resection of CRC, there is a lack of research on the applicability of the 5-factor Modified Frailty Index (mFI-5) within this patient population.MethodsIn this retrospective analysis, we examined a cohort of CRC patients aged 65 years and above who had undergone radical resection. For each patient, we calculated their mFI-5 score, considering a score of ≥ 2 as an indication of frailty. We conducted univariate and multivariate analyses to assess the association between the mFI-5 and adverse outcomes as well as postoperative complications.ResultsPatients with an mFI-5 score ≥ 2 exhibited a significantly higher incidence of serious postoperative complications (53% vs. 30%; P = 0.001) and experienced a longer hospital stay [19.00 (15.00–24.50) vs. 17.00 (14.00–20.00); P < 0.05]. Notably, an mFI-5 score greater than 2 emerged as an independent risk factor for severe postoperative complications (odds ratio: 2.297; 95% confidence interval: 1.216 to 4.339; P = 0.01). Furthermore, the mFI-5 score displayed predictive capabilities for severe postoperative complications with an area under the receiver operating characteristic (ROC) curve of 0.629 (95% confidence interval: 0.551 to 0.707; P < 0.05).ConclusionThe mFI-5 demonstrates a high level of sensitivity in predicting serious complications, prolonged hospital stays, and mortality following radical resection of colorectal carcinoma. As a practical clinical assessment tool, the mFI-5 enables the identification of high-risk patients and facilitates preoperative optimization.

Routine elastin staining improves venous invasion detection in colorectal carcinoma

BackgroundColorectal carcinoma is the second most common cause of cancer-related deaths in North America. Invasion of tumor cells into lymphatic and blood vessels is an imperative step in the metastatic progression of colorectal carcinoma. ObjectivesThis is a before-and-after study conducted by the Department of Pathology and Laboratory Medicine of Mount Sinai Medical Center of Florida to assess the impact on venous invasion (VI) detection by implementing routine elastin staining on all tumor-containing blocks per case, where feasible, in colorectal carcinoma (CRC) resection specimens. MethodsClinicopathological parameters of CRC specimens were collected from January until December 2021 (n = 93) for the pre-implementation cohort and from January until December 2022 (n = 61) for the post-implementation cohort. ResultsVI detection was significantly increased in the post-implementation cohort at a rate of 50.8 % compared to only 18.6 % in the pre-implementation cohort. The majority of VI identified in the pre-implementation cohort was extramural (61.5 %), whereas in the post-implementation cohort it was intramural (41.9 %). On univariate analysis, implementation of routine elastin stain was associated with strikingly increased VI detection rates (OR = 4.5, p-value < 0.001). On multivariate analysis, after adjusting for other clinicopathologic variables, elastin staining retained its independent statistically significant impact on VI detection (OR = 2.6, p-value = 0.034). Of note, there were no significant differences in the pre- and post-implementation cohorts in the frequency of nodal metastases, tumor extent, histologic grade, perineural invasion, T stage or M stage. ConclusionBased on our results and what has been published recently, we confirm an increase in the VI detection rate after implementing routine elastin staining on all tumor-containing blocks in CRC resection specimens.

Commentary.

Endoscopic full-thickness resection (EFTR) is increasingly used for local resection of suspected T1 colorectal carcinoma (CRC), completing scar excision after an R1/Rx resection of pT1 CRC, and for nonlifting residual or recurrent adenoma. The technique has some important advantages such as an en bloc resection for optimal histological evaluation, the high chance of obtaining an R0 resection especially at the vertical margin, and the technical ability to remove complex polyps by endoscopy, where more conventional techniques would likely fail. Recent publications including large cohorts have shown that the EFTR technique is both safe and effective in a large number of selected and deemed suitable cases.

Low PD-L1 expression in immune cells predicts the presence of nodal metastasis in early invasive (pT1) colorectal cancer: a novel tool to tailor surgical treatment.

The current criteria for surgical treatment after endoscopic resection of a pT1 colorectal carcinoma (CRC) are unsatisfactory because nodal involvement is rarely present. This study investigates the correlation between PD-L1 expression and nodal metastasis in pT1 CRCs to enable its use for tailoring surgical treatment after endoscopic removal. Histopathological features of 81 surgically resected pT1 CRC, 19 metastatic and 62 non-metastatic cases were assessed. PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and independently assessed by two pathologists using tumour proportion score (TPS), combined positive score (CPS) and immune cell score (ICS). The correlation between PD-L1 expression and nodal metastasis, the optimal cut-off values, interobserver agreement and impact upon patients' surgical management were determined. PD-L1 expression in termsof CPS and ICS independently correlated with lymph node metastasis (PD-L1CPS : OR = -2.5, 95% CI = -4.11 to -0.97, P = 0.008 and PD-L1ICS : OR = -1.85, 95% CI = -2.90 to -0.79, P = 0.004) and < 1.2 CPS and <1.3% ICS were identified as the optimal cut-off values to discriminate between metastatic and non-metastatic patients. In our cohort, the implementation of these cut-off values would have avoided a significant rate of unnecessary surgeries in pN0 patients (PD-L1CPS = 43.2; PD-L1ICS = 51.9%). Ultimately, PD-L1 evaluation showed good interpathologist concordance in absolute terms [PD-L1CPS interclass correlation coefficient (ICC) = 0.91; PD-L1ICS ICC = 0.793] and using the identified cut-off values (PD-L1CPS ICC = 0.848; PD-L1ICS ICC = 0.756). Our study shows that PD-L1 expression is an effective predictor of nodal status and could improve patient selection for surgery after endoscopic removal of pT1 CRCs.

Study of carcinoembryonic antigen tumor marker in gastrointestinal pathology

Background: Cancer mortality and morbidity has been increased in recent years, with gastrointestinal cancers comprising the majority of overall malignant conditions. All Indian cancer registries identify the digestive system as the most common cancer site in males. In women, breast cancer exhibits the highest occurrence, followed by cancers of the genital organs and the digestive system. Tumor markers are usually proteins or glycoproteins produced by the body in response to cancerous growth or by the cancer tissue that are possible to detect in serum, urine, or tissue samples. CEA assay is an inexpensive and easy to perform test; however, repeated measurements to monitor disease, follow up and the response to therapy contribute to higher costs and increase laboratory workload. Materials and Methods: The present study was carried out on 100 patients. Type of sample includes blood sample in plain vacutte received in tumor marker section of the pathology department. Objective: To make a comparative analysis of CEA in various gastrointestinal lesions.  Pre and post operative study of Serum CEA in known case of gastrointestinal carcinoma.  To study the factors affecting serum CEA concentrations. Results: The present study was conducted from June 2018 to December2020 in the Department of Pathology, at tertiary care hospital, 100 cases were studied. Preoperative and postoperative mean CEA value, Mean CEA value in inflammatory, Benign and Malignant lesions as well as in well, moderately and poorly differentiated carcinoma were measured.Conclusion: In general, this study showed that serum CEA levels are increased in people with habit of cigarette smoking and in benign and inflammatory lesions of GIT along with Malignant GI lesions. Carcinoembryonic antigen (CEA) usually normalizes after surgery. After curative resection of primary CRC (colorectal carcinoma), a large number of patients' CEA levels declined to normal values within 4-6 weeks. Amongst many contradictory results, the measurement of CEA is a useful method for screening, diagnosis, follow-up and treatment of CRC but Physiological influences that need to be considered in interpreting the results include effects of aging and smoking. Serum CEA values fails to decline in patients with distant metastasis and advanced disease even after complete surgical removal of the tumour. Serum concentrations of CEA tend to be higher in patients with well-differentiated tumors compared with those with poorly differentiated tumors.

Long-term outcomes after endoscopic versus surgical resection of T1 colorectal carcinoma.

The long-term outcomes of patients with T1 colorectal cancer (CRC) who undergo endoscopic and/or surgical treatment are not well understood. Invasive CRC confined to the colonic submucosa (T1 CRC) is challenging in terms of clinical decision-making. We compared the long-term outcomes of T1 CRC by treatment method. We examined 370 patients with pathological T1 CRC treated between 2000 and 2015 at Seoul St. Mary's Hospital. In total, 93 patients underwent endoscopic resection (ER) only, 82 underwent additional surgery after ER, and 175 underwent surgical resection only. Patients who did not meet the curative criteria were defined as "high-risk." High-risk patients were classified into three groups according to the treatment modalities: ER only (Group A: 35 patients), additional surgery after ER (Group B: 72 patients), and surgical resection only (Group C: 133 patients). The recurrence-free and overall survival (OS) rates, and factors associated with recurrence and mortality, were analyzed. Factors associated with lymph node metastasis (LNM) were subjected to multivariate analysis. Of the 370 patients, 7 experienced recurrence and 7 died. All recurrences occurred in the high-risk group and two deaths were in the low-risk group. In high-risk groups, there was no significant group difference in recurrence-free survival (P = 0.511) or OS (P =0.657). Poor histology (P =0.042) was associated with recurrence, and vascular invasion (P =0.044) with mortality. LNMs were observed in 30 of 277 patients who underwent surgery either initially or secondarily. Lymphatic invasion was significantly associated with the incidence of LNM (P < 0.001). ER prior to surgery did not affect the prognosis of high-risk T1 CRC patients, and did not worsen the clinical outcomes of patients who required additional surgery. Lymphatic invasion was the most important predictor of LNM.

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Discontinuous extramural tumour nodules (DTNs) are deposits of metastatic carcinoma in soft tissue not associated with lymph nodes. Although they are established as an adverse prognostic factor in colorectal carcinoma (CRC), under the AJCC eighth edition staging system their presence does not upstage patients who also have lymph node metastases. Counterintuitively, in some situations the presence of lymph node metastases may in effect downstage a patient with DTNs from pN1c to pN1a/b. Therefore, we sought to critically assess the significance of DTNs in a large unselected single institution cohort of patients undergoing surgical resection for CRC. Of 3822 CRC patients undergoing surgical resection from 2005 to 2021, DTNs were present in 686 (18.0%). In univariate (HR=2.687, 95CI 2.355-3.065; p<0.001) and multivariate analysis (HR=1.805, 95CI 1.529-2.132; p<0.001) in a model including age, gender, stage, grade, location, lymph node ratio and apical lymph node status, DTNs were associated with worse overall survival (OS). N1c patients (DTN present but no nodal metastasis) demonstrated worse OS compared to the current pN1a group (p<0.001) and were least different to the current pN2a group (p=0.571). Within the current N1a (p=0.013), N1b (p=0.004) and N2a (p=0.002) groups, patients who also had DTNs had worse OS. DTNs were associated with worse OS for all stage III CRCs combined (p<0.001), and for stage IIIB (p<0.001) and stage IIIC (p=0.007) individually. We conclude that DTNs are an independent adverse prognostic factor that should be considered in the staging system in a way that is additional to (rather than integrated with) the number of involved lymph nodes. We then assess a simple suggestion for how this could be achieved by increasing the overall stage by one group in the presence of DTNs (requiring the creation of a new stage IIID).

Influence of stathmin 1 (STMN1) expression on neoangiogenesis in colorectal adenocarcinoma

Stathmin1 is a microtubular regulatory protein. The expression disorders of this protein result in significant changes in cell migration, invasion, adhesion and colony formation in many malignant tumors. The aim of our research was to investigate the effects of Stathmin1 expression on neoangiogenesis in colorectal adenocarcinoma. Biopsy material that was obtained by the resection of colorectal carcinoma was used. The experimental group consisted of operative biopsies of colorectal cancer (n = 72), and the control group (n = 72) consisted of biopsies of adjacent non-tumor colon tissue. The biopsy material was taken from an operative preparation submitted to the Department of Pathology. After histopathological treatment, classical Hematoxylin- Eosin and immunohistochemical ABC methods with anti-Stathmin1, anti-VEGF and anti CD105 antibodies were applied on 4 µm thick sections. High expression of Stathmin1 is associated with severe (91.9%) and moderate (8.1%) expression of VEGF in a significantly high number of cases. This relation is defined by a highly significant correlation coefficient (r = 0.768; p = 0.000). High expression of Stathmin1 is associated with a high microvascular density index (mvdIDX) in a significant number of cases (73.0%) while low expression of Stathmin1 is in relation with low mvdIDX in a significant 73.7% of cases. This relationship is also defined by a highly significant correlation coefficient (r = 0.566; p = 0.000). ROC analysis showed that the sensitivity for Stathmin1 was 97.4% and the specificity was 91.4%. Based on Stathmin1 expression, it is possible to differentiate patients with increased risk for metastatic disease. The highly significant association of Stathmin1 expression with VEGF expression and microvascular density (MVD) suggests that Stathmin1 may be a serious candidate for therapeutic target.

Simultaneous Resection of Colorectal Carcinoma and Hepatic Metastases is Safe and Effective: Examining the Role of the Robotic Approach.

Up to 50% of patients with colorectal carcinoma (CRC) present with liver metastases (CLM) throughout their course. Complete resection of both sites provides the only chance for cure. Either a staged or simultaneous resection is feasible. The latter avoids delays in adjuvant systemic chemotherapy but may increase technical complexity and perioperative complications. We aim to evaluate our initial outcomes of simultaneous CRC and CLM resections with a focus on the robotic technique. With institutional review board approval, we followed 26 consecutive patients who underwent simultaneous/concomitant liver and colorectal resection. Major liver resection is defined as resection of ≥3 contiguous Couinaud segments. Data are presented as median (mean ± SD). Patients were 64 (63 ± 14.0) years old. Body mass index was 29 (29 ± 5.7) kg/m2. 54% of patients had prior abdominal operation(s). A majority of patients were >ASA class III (73%), underwent major liver resection (62%) with robotic approach (77%). In the robotic cohort, there were no unplanned conversions to open. Estimated blood loss was 150 (210 ± 181.8) ml. Total operative duration was 446 (463 ± 93.6) minutes. Negative margins (R0) were obtained in all patients. Postoperative complication of Clavien-Dindo≥3 occurred in three patients, including one requiring reoperation with end ileostomy for anastomotic leak. Length of stay was 5 (6 ± 3.5) days. Three patients were readmitted within 30days after discharge, none for reoperation. There was no 90-day mortality. Our cohort of concomitant CRC and CLM resection demonstrates safety and efficacy via both the open and robotic approach.

Financial Impact of Out-of-Pocket Costs Among Patients Undergoing Resection for Colorectal Carcinoma

IntroductionLittle is known about the societal burden of cancer surgical care in terms of out-of-pocket (OOP) costs. The current study sought to define OOP costs incurred by patients undergoing colorectal cancer resection.MethodsPrivately insured patients undergoing colorectal cancer resection between 2013 and 2017 were identified from the IBM MarketScan database. Total and OOP costs were calculated within 1 year prior to and 1 year post surgery. A multivariable linear regression model was used to estimate total OOP costs relative to patient demographic and clinical characteristics.ResultsAmong 10,935 patients, 7289 (66.7%) had primary colon cancer while 3643 (33.3%) had rectal cancer. Median total costs were US$93,967 (IQR US$51027–168,251). Median OOP costs were US$4417 (IQR US$2519–6943), or 4.5% (IQR 2.2–8.1%) of total costs. OOP costs varied over the course of patient care; specifically, median OOP costs in the preoperative period were US$432 (IQR US$130–1452) versus US$2146 (IQR US$851–3525) in the perioperative period and US$969 (IQR US$327–2239) in the postoperative period. On multivariable analysis, receipt of chemotherapy (+US$1368, 95%CI +US$1211 to +US$1525) or radiotherapy (+US$842, 95% CI +US$626 to +US$1059) was associated with higher total OOP costs. Patients with a health maintenance organization (HMO) (−US$2119, 95% CI −US$2550 to −US$1689) or a point-of-service plan (−US$938, 95% CI −US$1385 to −US$491) had lower total OOP costs than patients with comprehensive insurance. In contrast, patients with a consumer-driven or a high-deductible health plan had considerably higher total OOP costs than patients with comprehensive insurance (+US$1400, 95% CI +US$972 to +US$1827 and +US$3243, 95% CI +US$2767 to +US$3717, respectively).ConclusionsPrivately insured colorectal cancer patients undergoing surgical resection pay a median of US$4417 in OOP costs, or 4.5% of total costs. OOP costs varied with receipt of chemotherapy or radiotherapy, region of residence, and insurance plan type.Supplementary InformationThe online version contains supplementary material available at 10.1245/s10434-022-11755-2.

ASO Author Reflections: The Financial Impact of Out-of-Pocket Costs Among Patients Undergoing Resection for Colorectal Carcinoma.

ASO Author Reflections: The Financial Impact of Out-of-Pocket Costs Among Patients Undergoing Resection for Colorectal Carcinoma.

Impact of Neoadjuvant Chemotherapy on SATB2 Expression in Colorectal Carcinomas: SATB2 Positivity is Preserved in Most Cases, but Down-Expressed in Effective Cases of Chemotherapy.

Special AT-rich sequence-binding protein 2 (SATB2) is a novel, diagnostically useful, and highly sensitive immunohistochemical marker for both primary and metastatic colorectal or appendiceal tumors. In the present study, we aimed to assess the impact of neoadjuvant chemotherapy on SATB2 expression in primary colorectal carcinomas and their corresponding liver metastases. Forty-four patients with colorectal carcinomas who received neoadjuvant chemotherapy were included. SATB2 expression in specimens of biopsy, resected primary colorectal carcinomas, and resected metastatic foci were examined by immunohistochemistry and compared to caudal-type homeobox transcription factor 2 (CDX2). Using a modified H-score, expressions were scored semiquantitatively for both staining intensity and tumor cell proportion with nuclear staining. SATB2 was positive in 43/44 cases (98%) in biopsy specimens, 42/44 cases (96%) in resected colorectal carcinomas with neoadjuvant chemotherapy, and 9/9 cases (100%) with liver metastases. However, these expressions were variably decreased, and the H-score was lower in resected colorectal carcinomas (158 ± 69) than in biopsy specimens (174 ± 60) (p < 0.01). The proportion of SATB2-positive area of colorectal carcinoma was 93% in metastatic foci, while the CDX2-positive area was 78%. When categorized by histopathological tumor regression, the most effective tumors of chemotherapy showed the lowest H-score in resected colorectal carcinomas among the three groups (p < 0.01). SATB2 is a useful marker for both primary colorectal carcinoma and corresponding liver metastases, even with neoadjuvant chemotherapy. However, caution should be exercised when performing needle biopsy for metastatic foci with neoadjuvant therapy because expressions could be decreased, especially in chemotherapy-effective cases, and show immunohistochemically negative results.

Tumour budding in colorectal carcinoma: Association with other histopathological prognostic parameters

Colorectal carcinoma (CRC) is the third leading cancer in India. Pathologists play a crucial role in assessing stage, analyzing surgical margins and documenting the histopathologic prognostic parameters. Tumour budding is one such prognostic parameter, defined as single cells or small groups of tumour cells (up to 4 cell clusters) at the invasive front of the tumour. The aim of this study is to examine the association of tumour budding with other histopathological prognostic parameters in patients with colorectal carcinoma.TheHematoxylin &amp; Eosin (H &amp;E) stained slides of 52 histopathologically diagnosed CRC resection specimens were reviewed and tumour budding (BD) was assessed into four grades under 200x power. Other histopathological prognostic parameters like tumour size, site, grade, laterality, lymphovascular invasion, perineural invasion, T and N stage were analyzed using descriptive statistics and Chi-square test with Software SPSS version 23.A higher BD score is seen to be more often associated with grade 3 tumour morphology, presence of perineural invasion, tumour size of 5cm or more and tumours located in the sigmoid colon or rectum. No association of tumour budding is seen with TIL’s or tumour of size &amp;#60; 5cm.Tumour budding is a practical and significant histological index for identification of high malignant potential and poor outcome in CRC patients with rectal or sigmoid colon location, size more than 5cm, perineural invasion and higher histological grade. Tumour budding may help identify patients who need a more intensive postoperative follow up and the possibility of adjuvant therapy.

Switch/sucrose-non-fermentable (SWI/SNF) complex (SMARCA4, SMARCA2, INI1/SMARCB1)-deficient colorectal carcinomas are strongly associated with microsatellite instability: an incidence study in 4508 colorectal carcinomas.

Loss of expression of mammalian switch/sucrose-non-fermentable (SWI/SNF) [BRG1/BRM-associated factor (BAF)] complex subunits, including SMARCA4, SMARCA2 and INI1/SMARCB1 (termed SWI/SNF complex deficiency), has been reported in colorectal carcinomas (CRCs) but its frequency and clinical significance are uncertain. We performed immunohistochemistry for SMARCA4, SMARCA2 and SMARCB1 on 4508 consecutive resected CRCs. Loss of SMARCA4 expression was found in 13 cases (0.3%), loss of SMARCA2 expression was found in 59 cases (1.3%), and loss of SMARCB1 expression was found in 21 cases (0.4%). Some CRCs showed loss of expression of more than one subunit, so that 84 CRCs (1.7%) were deficient for at least one component. SWI/SNF complex deficiency was associated with higher grade, a right-sided location, mismatch repair deficiency, and BRAF V600E mutation (P < 0.05); 5.8% of mismatch repair-deficient (MMRd) cases and 5.4% of BRAF V600E-mutant cases were SWI/SNF complex-deficient, as compared with 0.9% and 0.4% of mismatch repair-proficient and BRAF-wild-type cases (P < 0.001). Any loss of SMARCB1 expression and global loss of SMARCA2 expression were associated with statistically significant worse overall survival, whereas SMARCA4-deficient cases showed a trend only towards poor overall survival (P = 0.121). In multivariate analysis, any loss of SMARCA4 expression and global loss of SMARCA2 expression were associated with worse survival [odds ratio (OR) 3.33, P = 0.019; and OR 3.39, P < 0.001]. Of particular note, among the subgroup of cases that were MMRd and BRAF V600E-mutated (otherwise considered to be a good prognostic group), loss of SMARCA4 expression was associated with much worse median survival (10.5 months versus 110.9 months; P = 0.003). SWI/SNF complex deficiency is rare in CRC but is enriched in MMRd cases. Identifying these cases has morphological associations and prognostic significance, and in the future may have potential therapeutic implications.

Universal tumor screening in a population with MSH6- and PMS2-associated Lynch syndrome

PurposeUniversal screening for Lynch syndrome (LS) on resected colorectal carcinomas (CRCs) and endometrial carcinomas (ECs) was implemented in Iceland in 2017 using immunohistochemistry (IHC) for mismatch repair (MMR) proteins. We examined the efficacy of the universal screening algorithm to detect LS and the diagnostic accuracy of MMR IHC by comparing results with a population-based genotype database. MethodsAll patients diagnosed with CRC or EC per the Icelandic Cancer Registry from 2017 to 2019 who had tumor MMR IHC performed were included. Pathology reports and patient charts were reviewed. MMR IHC stains were crossmatched with genotyping results obtained from the deCODE database. ResultsIHC staining was done on 404 patients with CRC and 74 patients with EC. A total of 61 (15.1%) patients with CRC and 15 (20.3%) patients with EC were MMR-deficient. MMR IHC had 88.9% sensitivity in identifying patients with LS and a positive predictive value of 10.7%. Only 50% of individuals were appropriately referred for genetic testing, leading to underdiagnosis of LS. ConclusionUniversal screening for LS using MMR protein IHC in CRC and EC accurately identified patients appropriate for genetic testing in a population with MSH6 and PMS2 LS predominance. Because of lack of referral to genetic counseling, only 50% of patients with LS were identified through the screening algorithm.

Surgical Strategy for Primary Colorectal Carcinoma and Synchronous Pulmonary Metastasis Resection.

BackgroundThe surgical strategy for single-stage resection of primary colorectal cancer (CRC) and synchronous pulmonary metastases remains a matter of debate.MethodsPerioperative data of patients who underwent single-stage resection of primary CRC and synchronous pulmonary metastases were compared to those of patients who underwent 2-stage resections. The demographic data, number of metastases, type of pulmonary and colorectal resections, operation time, blood loss, postoperative complications, morbidities, mortality, medical costs, and length of hospital stay were analyzed.ResultsTwenty-two patients underwent single-stage resection of primary CRC and pulmonary metastases, while 27 patients underwent 2-stage resection. Tumor size and the number of pulmonary metastases were not significantly different between the 2 groups. The extent of pulmonary metastasectomy and abdominal procedures were similar in both groups, as was the thoracic surgical approach (video-assisted thoracic surgery vs. thoracotomy). However, open laparotomy was performed more frequently in the 2-stage group than in the single-stage group (p=0.045), which also had a longer total anesthetic time (p=0.013). The operation time, medical costs, estimated blood loss, complication rates, and severity were similar in both groups, but the length of hospital stay was shorter in the single-stage group (p<0.001).ConclusionSingle-stage colorectal and pulmonary resection shortened the overall hospital stay, with no significant changes in operation time, medical costs, hospital mortality, and morbidity. Therefore, single-stage resection could be a good surgical strategy in selected patients.