Predicting Positive Radial Margin on Restaging MRI of Patients with Low Rectal Cancer: Can We Do Better?

Objective The aim of this study was to characterize the tissue involving the margin and study if this information will affect margin prediction on restaging magnetic resonance imaging (MRI) in low rectal adenocarcinoma (LRC) patients treated with neoadjuvant long-course chemoradiotherapy (LCCRT). Methods In this retrospective study of nonmetastatic LRC (distal margin <5 cm from the anal verge) treated with LCCRT followed by surgery, a radiologist blinded to outcome reread the restaging MRI and documented if the radial margin was involved by tumor, fibrosis, or mucin reaction using T2 high-resolution (HR) and diffusion-weighted imaging (DWI). The diagnostic performance of tumor-involving margin on restaging MRI was assessed using surgical histopathology as a reference. Interobserver agreement between three independent radiologists was assessed in a subset. Results We included 133 patients (80 males and 53 females) with a mean (range) age of 44.7 (21-86) years and 82% of them had well or moderately differentiated adenocarcinoma. Baseline MRI showed T3 ( n = 58) or T4 ( n = 60) disease in 89% of the patients. The pathological margin was positive in 21% ( n = 28) cases. In restaging MRI, the circumferential resection margin (CRM) ≤1 mm in 75.1% ( n = 100) cases and MRI predicted tumor, fibrosis, and mucin reaction at the margin in 60, 34, and 6%, respectively, and histopathology showed tumor cells in 33, 14.7, and 16.6% of them, respectively. LRC with tumor-involving margin and bad response (MR tumor regression grade [mr-TRG] 3-5) on restaging MRI had fourfold increased risk of positive pathological circumferential resection margin (pCRM). There was moderate and fair inter-reader agreement for the tissue type involving the CRM ( κ = 0.471) and mr-TRG ( κ = 0.266), p < 0.05. The use of both distance criteria and tumor-involving margins improved the diagnostic accuracy for margin prediction from 39 to 66% on restaging MRI. Conclusions Margin prediction on restaging MRI can be improved by characterizing the tissue type involving the margin in low rectal cancer patients. The inter-reader agreement was moderate for determining the tissue type.

Primary adenocarcinoma of colon: A clinicopathological study with the prevalence and correlation of CDX2 biomarker expression - A tertiary care center experience.

BACKGROUND: Colorectal cancer is one of the alarming health problems worldwide. Prognostic biomarkers are the key for risk stratification in patients with colon cancer and the decision to recommend adjuvant chemotherapy. It has been difficult to identify a single prognostic biomarker for colon cancer. Currently, tumor stage, tumor grade, and microsatellite instability remain the most important prognostic variables that aid in the treatment of patients with colon cancer. Some studies highlighted that CDX2 immunohistochemistry negativity is an independent prognostic factor and indicates a worse survival rate. Our aim was to study the prevalence of CDX2 biomarker expression in patients diagnosed with primary adenocarcinoma and to correlate this with the clinical profile and pathological features. METHODS: Endoscopic mucosal biopsies and resection specimens of 148 patients diagnosed with colonic adenocarcinoma were analyzed. CDX2 immunohistochemistry was performed, and the result was correlated with clinicopathological features. The results were presented as mean, frequencies, and percentages. Pearson's Chi-square test was used to assess the associations between clinicopathological parameters and CDX2 immunohistochemistry negativity. RESULTS: The prevalence of CDX2 expression by immunohistochemistry in colon cancer was found to be 92%. CDX2 biomarker negativity was found to be higher in left-sided colon cancers, poorly differentiated adenocarcinoma, mucinous carcinoma, and higher TNM stages. CONCLUSION: CDX2-negative tumors are often associated with several adverse prognostic variables (e.g., advanced stage, poor differentiation, and metastasis). Thus, sub-classification of colon cancer based on the CDX2 biomarker aids to separate them into prognostically relevant categories.

Total Neoadjuvant Therapy (TNT) with Full Dose Concurrent Chemotherapy in Locally Advanced Rectal Adenocarcinoma Including Signet Ring and Mucinous Cancers.

PURPOSE: Total neoadjuvant therapy (TNT) with pre-operative chemotherapy and chemoradiotherapy results in improved survival and is becoming the new standard of care in locally advanced rectal cancer (LARC). We describe our experience with TNT consisting of induction chemotherapy followed by chemoradiotherapy using full dose 5FU without oxaliplatin. METHODS: Adults with biopsy-proven, newly diagnosed LARC with high-risk characteristics on pelvic MRI (T4a or T4b, extramural vascular invasion, N2, mesorectal fascia involvement, enlargement/tumor deposits on lateral lymph nodes) were included. The TNT protocol comprised of six biweekly courses of modified FOLFOX6 followed by pelvic RT with four concurrent cycles of biweekly 5-FU 2600 mg/m2 + LV 200 mg/m2 without oxaliplatin to complete 20 uninterrupted weeks of full dose 5FU. Surgery was planned 11-13 weeks after completing chemoradiotherapy. RESULTS: Eighty-four LARC patients, including 26% with signet-ring cell carcinoma, with high-risk MRI characteristics were treated with the TNT protocol with a 96% completion rate. Significant (> grade 3) toxicities included neutropenia (23.8%), diarrhea (14.2%) anemia (10.7%), and two deaths. The median DFS at 2 years was 22.5 months with better survival noted for those who underwent surgery or had cCR (with NOM) compared to those who did not undergo surgery (due to progression, inadequate regression, or patient preference despite residual disease) -mDFS 27.7 months versus 11.4 months, p = < 0.0001 and mOS 29.2 months versus 15 months p = < 0.0001. CONCLUSION: The hybrid TNT regimen was administered without significant dose delays or interruptions. Toxicity was manageable but with two treatment-related deaths. Ability to undergo surgery after TNT predicted for improved DFS and OS.

MDT stage migration in MRI of significant rectal polyps and early rectal cancers.

PURPOSE: To audit the diagnostic accuracy of MRI for staging early and polyp rectal cancers with the purpose of identifying scope for service improvement. METHODS: This is an IRB approved retrospective study of patients who underwent staging MRI for rectal growths followed by upfront TME type surgery or local excision without neoadjuvant therapy between 2018 and 2021. MR-T-stage was compared with surgical histopathology. The degree of stage migration in the multidisciplinary team meetings (MDT) was assessed and training needs were identified. RESULTS: 53 patients (32 males) with a mean (SD) age of 56.7 (13.6) years with 54 rectal lesions and underwent trans-anal excision (n = 18) or upfront surgery (n = 35) were included. Pathology showed < / = pT1 stage in n = 18 and > / = pT2 stage in n = 36. Radio-pathological concordance rate was 38.9% and 74.1%, respectively, for primary reports and MDT reads, respectively, and during MDT, the rates improved by 44.5% and 30.5% for < / = pT1 and > / = pT2 stages ,respectively. The overall T-stage migration rate at MDT was 44.6% (25/54) and the migration rate was higher (61.1%) for < / = pT1 stage lesions. The best sensitivity, specificity, PPV, NPV and accuracy of MRI for T-staging was 83.3%, 91.6%, 83.3%, 91.6% and 88.8%, respectively. CONCLUSION: Radio-pathological correlation for MRI T-stage is excellent for MDT reads by experienced radiologists. MDT reads lead to significant down-staging of T-stage in polyp and early rectal cancer thereby improving radio-path correlation.

Comparison of primary follicular lymphoma of gastrointestinal tract and secondary involvement: A study from South India.

Primary follicular lymphoma of the gut (PFL-GI) is a rare entity. This study aims to compare the clinicopathologic features of PFL-GI with cases of gastrointestinal involvement by disseminated nodal follicular lymphoma. This is a retrospective study with 6 cases of primary follicular lymphoma and 8 cases of secondary involvement of the gut, over a period of 9 years. The slides and blocks were retrieved and reviewed. Clinical data was obtained from hospital records. Clinicopathologic features were compared. PFL-GI cases had a slightly higher median age group (p value 0.23) and no gender predilection when compared to cases with secondary involvement which showed a female preponderance. Para-aortic lymphadenopathy was seen in all secondary cases whereas none of the primary cases showed significant lymphadenopathy. The only microscopic feature that was different was the presence of hollowed out pattern of immunostaining for follicular dendritic cells seen in all cases of PFL-GI but in none of the secondary cases.

Prognostic significance of MR identified EMVI, tumour deposits, mesorectal nodes and pelvic side wall disease in locally advanced rectal cancer.

AIM: To study the prognostic significance of MRI identified tumour deposits (TD), extramural vascular invasion (EMVI), lymph node metastases (LNM) and pelvic sidewall (PSW) disease in rectal cancer. METHODS: This IRB approved study was conducted on patients with stage IIA-IIIC rectal adenocarcinoma treated with neoadjuvant long course chemoradiotherapy (LCCRT) and total mesorectal excision (TME) type of surgery between 2012-2018. A radiologist blinded to outcome reviewed staging and restaging magnetic resonance imaging (MRI) for TD, EMVI, LNM and PSW. The agreement between four radiologists was studied and we obtained outcome data from a prospectively maintained database. The prognostic significance of imaging findings was assessed. RESULTS: A total of 297 (186 males) patients with a mean age of 47.3 (SD14.4) years were included in the study. The majority had T3 (n = 206) or T4 (n = 59) stage disease. The mean duration of follow-up was 49.3 ± 25 months (6.6-101 months). 5-year overall (OS) and disease-free survival (DFS) was 84% and 74%, respectively. Staging and restaging MRI had EMVI in 49.5% and 31.3%; TD in 47.5% and 31.6%; LNM in 61.1% and 38.1% and PSW in 11.4% and 6.1%. OS was adversely affected by EMVI, TD and PSW with the adjusted HR (aHR) of 3.32, 3.31, 3.27 for staging MRI and 2.99, 3.1, 2.81 for restaging MRI, respectively, p < 0.05. DFS was affected by EMVI (aHR = 1.85, 2.33) and TD (aHR = 1.83, 2.19), p < 0.05. Persistence of these findings after LCCRT led to worst outcome. Intra- and interobserver agreement for EMVI, TD and LN was 0.789, 0.734, 0.406 and 0.449, 0.354, 0.376, respectively, p < 0.001. CONCLUSIONS: MRI identified that TD, EMVI and PSW disease are independent poor prognostic indicators in rectal cancer patients. Interobserver agreement for these findings was moderate to fair.

Docetaxel, Oxaliplatin and Capecitabine (TEX) triplet regimen as adjuvant chemotherapy in resected gastric adenocarcinoma.

BACKGROUND: Adjuvant chemotherapy after surgery for gastric cancer improves survival but is difficult to administer due to poor tolerance. Combination chemotherapy with Docetaxel (Taxotere), Oxaliplatin (Eloxatin) and Capecitabine (Xeloda) (TEX) is used in the treatment of advanced gastric cancer. The efficacy and tolerability of this regimen (TEX) post resection of gastric cancer have not been studied. MATERIALS AND METHODS: Patients diagnosed with gastric adenocarcinoma, post resection without any prior chemotherapy between July 2007 and May 2011 and treated with TEX regimen administered as T 35 mg/m2 and E 50 mg/m2 on days (d) 1, 8 and X 625 mg/m2 bid (twice daily) on d 1-14 every 21 days were included in this retrospective analysis. Patient's electronic medical records were studied and data on tolerance, progression­free survival (PFS) and overall survival (OS) was collected. RESULTS: Fifty-eight patients were treated with adjuvant TEX chemotherapy, majority 40 (68%) had distal gastric cancer. All patients underwent a D1 gastrectomy, and resection was performed for 44 (75%). Only 14 (24%) patients had more than 15 nodes studied in the resected specimen. Distribution for stages I, II and III is 14 (24%), 30 (52%) and 14 (24%), respectively. After a median follow-up of 40 months, the 3-year relapse free survival was 58% (95% CI: 42-68), and estimated median OS was 71 months (95% CI: 19-123 months). Twenty-three (40%) required dose reduction due to toxicity. Grade 3 or 4 toxicity was recorded for 22 (37%). Half (52%) of patients completed all planned chemotherapy of six cycles. CONCLUSION: Post resection of gastric adenocarcinoma adjuvant triplet TEX chemotherapy is a feasible and effective outpatient regimen. Diarrhoea, neutropenia and neuropathy were the common dose limiting toxicity. Post-surgery only half the numbers of patients are able to complete all planned cycles.

Diffusion weighted imaging improves diagnostic ability of MRI for determining complete response to neoadjuvant therapy in locally advanced rectal cancer.

PURPOSE: To assess the diagnostic performance, interobserver agreement and confidence level for determining response to neoadjuvant chemoradiotherapy (NACRT) using morphology based MR-tumour regression grade (MR TRG), diffusion weighted imaging (DWI) patterns and their combination in patients with locally advanced rectal cancer. METHODS: This was a retrospective study including patients with locally advanced rectal cancer treated with NACRT and subsequent surgery. Two independent radiologists blinded to the histopathology reviewed staging and restaging MRI. Diagnostic performance of morphology based MR-TRG, DWI patterns and their combination for determining complete (CR) and incomplete (IR) response was assessed with pathological response as the reference. Likert's scale was used to assess the radiologist's level of confidence. Interobserver agreement was determined using Kappa statistics. RESULTS: The study included 251 patients (mean age of 47.9+/-14 (range 19-86) years, M:F = 164:87). Rate of pathological CR was 14.7 % (n = 37). Pattern based interpretation of DWI and combined approach (DWI + T2-HR) had superior diagnostic performance than morphology based assessment alone with area under curve (AUC) for T2HR, DWI and their combination being 0.531, 0.887, 0.874 respectively for observer 1 and 0.558, 0.653, 0.678 respectively for observer 2, p < 0.001. Interobserver agreement was substantial (k = 0.688) for combined approach, moderate (k = 0.402) for DWI patterns and fair (k = 0.265) for T2 HR MRI with both observers exhibiting highest level of confidence for determining response with the combined approach. CONCLUSION: Complete response to neoadjuvant chemoradiotherapy can be determined with excellent accuracy, substantial interobserver agreement and high level of confidence by combined interpretation of DWI and T2 high resolution MRI.

Microsatellite instability in young patients with mucinous colorectal cancers - characterization using molecular testing, immunohistochemistry, and histological features.

CONTEXT: The incidence of colorectal cancers (CRCs) in young Indian patients is higher than the international average. CRCs in young patients are commonly of mucinous type and show microsatellite instability (MSI). AIMS: To ascertain the MSI status of mucinous CRCs in patients ≤40 years of age by molecular testing and to correlate this with immunohistochemical (IHC) analysis and tumor histology. SUBJECTS AND METHODS: Archived formalin-fixed paraffin embedded tissue blocks of 30 young mucinous CRC patients were retrieved. MSI testing was done using two mononucleotide markers - BAT26 and NR24. IHC analysis was done using MLH1, MSH2, and MSH6. Histological features of all cases were studied. Data were analyzed using the SPSS software and the Pearson's chi-square test and Fisher's exact test. RESULTS: Eight out of 30 cases (26.7%) showed MSI by molecular testing. IHC identified seven of these cases. Histological features showing a statistically significant association with MSI were the presence of a well-differentiated adenocarcinoma component (P = 0.003), peritumoral lymphocytes (P = 0.002) and tumor budding (P = 0.021). CONCLUSION: The detection of defective mismatch repair (MMR) proteins using IHC for MLH1, MSH2, and MSH6 and molecular testing using BAT26 and NR24 appears to be a good protocol to detect CRCs with MSI. Histology could be useful in identifying cases that require screening for presence of MMR protein defects.

Not all colonic growths are malignant.

We present the case of a 34-year-old woman who was diagnosed to have adenocarcinoma of the caecum based on the clinical, radiological, histopathological and intraoperative findings. However, postoperative histopathology showed only features of xanthogranulomatous inflammation without any evidence of malignancy. This benign chronic inflammatory condition could present as a histological surprise. It is important for both surgeons and pathologists alike to be aware of this.

A Rare Case of Gastric Metastasis in Ewing's Sarcoma of the Femur.

The stomach is a very unusual site of metastasis. Published reports on metastatic lesion in the stomach is generally limited to single case reports and case series. Gastric metastasis in an Ewing's sarcoma is extremely rare and has been reported in English literature but once to our knowledge. We present a case report of Ewing's sarcoma of the right proximal femur metastasizing to the stomach. A young female treated for Ewing's sarcoma of the femur in 2012 presented with gastric metastasis after four years of disease-free interval. She was treated with irinotecan-based chemotherapy followed by total gastrectomy with esophagojejunal anastomosis and radiation therapy. At one-year follow-up, she was disease free.

Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report.

Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols.

Best MRI predictors of complete response to neoadjuvant chemoradiation in locally advanced rectal cancer.

OBJECTIVE: To identify the MRI parameters which best predict complete response (CR) to neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (LARC) and to assess their diagnostic performance. METHODS: This was a prospective study of pre- and post-CRT MRI and diffusion-weighted imaging (DWI) of 64 patients with LARC who underwent neoadjuvant CRT and subsequent surgery. Histopathological tumour regression grade was the reference standard. Multivariate regression analysis was performed to identify the best MRI predictors of CR to neoadjuvant CRT, and their diagnostic performance was assessed. RESULTS: The study cohort comprised 48 males and 16 females (n = 64), with mean age of 49.48 ± 14.3 years, range of 23-74 years. 11 patients had pathological complete response. The following factors predicted CR on univariate analysis: low initial (pre-CRT) tumour volume on T2 weighted high-resolution (HR) images and DWI, tumour volume-reduction rate (TVRR) of >95% on DWI and CR on post-CRT DWI (ydwiT0) as assessed by the radiologist. However, the best MRI predictors of CR on multivariate regression analysis were CR on post-CRT DWI (ydwiT0) as assessed by the radiologist and TVRR of >95% on DWI, and these parameters had an area under the curve (95% confidence interval) of 0.881 (0.74-1.0) and 0.843 (0.7-0.98), respectively. The sensitivity, specificity, positive-predictive value, negative-predictive value and accuracy of DWI in predicting CR was 81.8%, 94.3%, 75%, 96.1% and 76%; the sensitivity, specificity and accuracy of TVRR of >95% as a predictor of CR was 80%, 84.1% and 64.1%, respectively; however, this difference was not statistically significant. The interobserver agreement was substantial for ydwiT0. CONCLUSION: Visual assessment of CR on post-CRT DWI and TVRR of >95% on DWI were the best predictors of CR after neoadjuvant CRT in patients with LARC, and the former being more practical can be used in daily practice. ADVANCES IN KNOWLEDGE: In rectal cancer, ydwiT0 as assessed by the radiologist was the best and most practical imaging predictor of CR and scores over standard T2W HR images.

Infraorbital nerve schwannoma: a rare cause of upper jaw swelling.

INTRODUCTION: Schwannoma of the infraorbital nerve is a rare entity, with lesser than a dozen cases reported in literature and only one from India. REPORT: This article reports a 23-year-old male presenting with a painless swelling in the cheek, which was eventually diagnosed as infraorbital nerve schwannoma. He underwent a complete excision of the tumor via a Caldwell Luc approach and continues to be disease free on 3 year follow-up. CONCLUSION: Despite its rarity, infraorbital nerve schwannomas should be considered in the differential diagnosis, of upper jaw swelling. We recommend the Caldwell Luc approach as safe, effective and cosmetically acceptable, for anteriorly based infraorbital schwannomas, and review literature on this unusual entity.

A retroperitoneal enteric duplication cyst communicating with the right upper ureter in an infant.

We report an extremely rare case of isolated retroperitoneal enteric duplication cyst with gastric mucosa causing haematuria and dysuria by communicating with the urinary system. A 9-month-old male child was admitted to our hospital with persistent haematuria, dysuria and anaemia. Investigations revealed a retroperitoneal cyst abutting the hydronephrotic non-functioning right kidney. At surgery an isolated retroperitoneal cyst communicating with the right pelviureteric junction was found. The kidney and associated cyst were excised. Histology of the cystic lesion revealed an enteric duplication cyst lined by ectopic gastric mucosa. Isolated retroperitoneal enteric duplication cyst communicating with the urinary tract has not been previously reported in the English literature. We propose that acid secretion into the right renal system was the cause of the haematuria-dysuria syndrome which promptly resolved postoperatively.