Can Endorectal Ultrasound, MRI, and Mucosa Integrity Accurately Predict the Complete Response for Mid-Low Rectal Cancer After Preoperative Chemoradiation? A Prospective Observational Study from a Single Medical Center.

BACKGROUND: Patients with locally advanced rectal cancer could be managed by a watch-and-wait approach if they achieve clinical complete response after preoperative chemoradiotherapy. Mucosal integrity, endorectal ultrasound, and rectal MRI are used to evaluate clinical complete response; however, the accuracy remains questionable. Clinical practice based on those assessment methods needs more data and discussion. OBJECTIVE: The aim of this prospective study was to evaluate the accuracy of mucosal integrity, endorectal ultrasound, and rectal MRI to predict clinical complete response after chemoradiotherapy. DESIGN: Endorectal ultrasound and rectal MRI were undertaken 6 to 7 weeks after preoperative chemoradiation therapy. Patients then received radical surgery based on the principles of total mesorectal excision. Preoperative tumor staging achieved by endorectal ultrasound and rectal MRI was compared with postoperative staging by pathologic examination. Sensitivity, specificity, and accuracy of each evaluation method were calculated. SETTINGS: The study was conducted at a single tertiary care center. PATIENTS: Patients diagnosed with mid-low rectal cancer by biopsy between May 2014 and December 2016 were enrolled in this study. RESULTS: A total of 124 patients were enrolled in this study, and postoperative pathology revealed that 20 patients (16.13%) achieved complete response (ypT0N0). The sensitivity of mucosal integrity, endorectal ultrasound, and MRI to predict clinical complete response was 25%. The specificity of mucosal integrity, endorectal ultrasound, and MRI was 94.23%, 93.90%, and 93.27%. The combination of each 2 or all 3 methods did not improve accuracy. Regression analysis showed that none of these methods could predict postoperative ypT0. LIMITATIONS: The sample size is small, and we did not focus on the follow-up data and cannot compare prognosis data with previous research studies. CONCLUSIONS: Both single-method and combined mucosal integrity, endorectal ultrasound, and rectal MRI have poor correlation with postoperative pathologic examination. A watch-and-wait approach based on these methods might not be a proper strategy compared with radical surgery after neoadjuvant therapy. See Video Abstract at http://links.lww.com/DCR/A693.

[Effects of tumor distance from anal verge and types of operations on survival outcomes for low rectal cancer after neoadjuvant chemoradiotherapy].

OBJECTIVE: To assess the effects of neoadjuvant chemoradiotherapy on survival outcomes of low rectal cancer after sphincter-preserving or removing surgery. METHODS: A total of 135 patients with rectal cancer within 10 cm from anal verge after neoadjuvant chemoradiotherapy were enrolled into this retrospective study from 2005 to 2012 at a single institute. There were 79 males and 56 females with a mean age of (58 ± 12) years and an average distance of (5.2 ± 2.1) cm from anal verge. The effects of gender, age, distance of tumor from anal verge, surgical procedure, T-stage downstaging, lateral resection margin and post-treatment lymphatic node status on 3-year disease-free survival (DFS) were examined. RESULTS: The overall 3-year DFS was 85.2% (115/135). Among 95 sphincter-preserving operations, there were anterior resection (n = 79), anterior perineal plane for ultra low anterior resection (APPEAR) technique (n = 12), Hartmann procedure (n = 3) and Parks procedure (n = 1). Among 40 sphincter-removing operations, there were abdominoperineal resection (APR) procedure (n = 39) and intersphincteric resection(ISR) (n = 1). The survival of patients undergoing sphincter-preserving or removing procedures did not differ in 3-year DFS (85.3% (81/95) vs 85.0% (34/40) , χ(2) = 0.000, P = 0.985) . Lateral resection margin and post-treatment lymphatic node status significantly affected DFS. The differential level from anal verge showed a trend of close relationship to 3-year DFS (81.5% (22/27) for 2-3 cm, 82.5% (47/57) for 4-5 cm vs 95.1% (39/41) for 6-7 cm), but without statistic significance (χ(2) = 3.111, 3.522; P = 0.078, 0.061). The survival rate for patients with sphincter-preserving at 6-7 cm from anal verge was significantly higher than that at 4-5 cm (95.0% (38/40) vs 79.5% (31/39) ,χ(2) = 4.227, P = 0.039) , but showed no differences to that with sphincter-removing at 2-3 cm from anal verge (81.0% (17/21),χ(2) = 2.864, P = 0.091) . The multivariate analysis showed that post-treatment lymphatic node status was the only prognostic factor to 3-year DFS (Wald = 4.454, P = 0.035) . CONCLUSIONS: Lateral resection margin and post-treatment lymphatic node status play an important role on DFS for patients with low rectal cancer after neoadjuvant chemoradiotherapy. The distance from anal verge is correlated with 3-year disease-free survival. Patients with tumor at 4-5 cm from annal verge can not benefit for survival when they get sphincter-preserving operations.

[Postoperative pathological staging correlates the prognosis of rectal cancer after neoadjuvant chemoradiotherapy].

OBJECTIVE: The present study assessed the pathological staging features of rectal cancer after neoadjuvant chemoradiotherapy, and its relation to prognosis. METHODS: Pathologic data related to TNM classification were analyzed on the surgical specimens of 135 patients with mid-low rectal cancer after neoadjuvant themoradiotherapy from 2005 to 2012. Tumor invasion, nodal status, local invasive factors (including cancer deposit, radial margin, perivascular or perineural invasion) were investigated with patients' 3-year disease-free survival (DFS). RESULTS: The overall 3-year DFS was 85.2%, with a pathological complete response (pCR) rate of 19.26%. Three out of 29 patients (10.4%) with ypT0 were found to have positive lymph nodes. There was a trend towards decreased survival as the ypT category and ypTNM staging increased (χ(2) = 14.296 and 52.643, P = 0.006 and 0.000). ypT0-T2 in T category and yp0-I in TNM staging showed a favorable survival above 92%, while the patients with ypT3, or ypIIIB had a comparable lower DFS of 70.2% and 46.7%. DFS in patients with negative lymph node were significantly improved than those with positive nodes (93.5% vs. 66.7%, χ(2) = 34.125, P = 0.000). Patients with or without local invasive factor significantly differed in DFS (42.9% vs. 90.1%, χ(2) = 32.666, P = 0.000) . Cox regression analyze showed that the nodal status (RR = 12.312, 95%CI: 2.828-39.258, P = 0.000) and local invasive factors (RR = 5.422, 95%CI: 1.202-8.493, P = 0.020) were independent risk factors to 3-year survival. As the concept of clinical complete response (cCR) is obscure, there were 27.6% of patients with ypT0 had normal mucosa or no evidence of tumor by EUS or MRI tests before surgery. CONCLUSION: Postoperative pathologic staging features were closely associated with patient's prognosis. The increasing of ypT or ypTNM staging was correlated to decreasing of DFS. Nodal status, positive radial margin, perivascular and perineural invasion were independent risk factors to DFS. Since cCR did not correlate and could not predict pCR, the ongoing radical surgery could not be avoided even there was no evidence of tumor existing before operation.

[Impact of neoadjuvant therapy on lymph nodes retrieval in locally advanced mid-low rectal carcinoma].

OBJECTIVE: To study the impact of neoadjuvant therapy on lymph nodes retrieval in locally advanced mid-low rectal carcinoma. METHODS: Data collected from 120 patients with locally advanced mid-low rectal cancer (T2-4 and/or N1-2M0) treated from January 2005 to June 2008 was investigated. The patients were divided into two groups: the study group (n=54) was treated with neoadjuvant therapy (preoperative radiation with a total dosage of 50 Gy and synchronous 5-Fu-based chemotherapy) followed by radical tumor resection 4-6 weeks after;the control group (n=66) underwent primary surgery without neoadjuvant therapy. The clinical stage was evaluated before and after neoadjuvant therapy. The total lymph nodes yields, as well as the tumor-positive lymph nodes of each resected specimen was compared between the two groups statistically. RESULTS: Clinical downstage was achieved in 30 cases (56%) in study group after neoadjuvant therapy. The number of total lymph nodes and positive lymph nodes harvested from each resected specimen in the control group were 14+/-7 and 2.2+/-3.7, meanwhile those were 9+/-6 and 0.7+/-2.4 in study group, which were all significantly lower than those in control group (P<0.01). CONCLUSIONS: Preoperative radiotherapy combined with chemotherapy can downstage the tumor and reduce the retrieval rate of total lymph nodes and positive lymph nodes in locally advanced rectal cancer. It is necessary to retrieve as many lymph nodes as possible for it has some prognostic significance for the patients.

Color Doppler ultrasonography appearances of renal vein thrombosis and its diagnostic value.

OBJECTIVE: To evaluate color Doppler ultrasonography (CDU) appearances of renal vein thrombosis (RVT) and its diagnostic value. METHODS: Ten patients with RVT were analyzed retrospectively. Renal structure, distributions of intrarenal flow signals, echogenicity, and flow fullness in main renal veins were observed with CDU. Resistance index (RI) was recorded from the waveforms of segmental or interlobar renal artery. RESULTS: Ten kidneys in nine patients were confirmed to have thrombus within the main renal veins, and one patient was confirmed to have thrombus within the small intrarenal veins. The appearances of the main renal vein thrombosis included full of solid echogenicity or strip echogenicity and complete or partial filling defect within the main renal veins, and absent or a few intrarenal venous flow signals in 70% of kidneys involved. The appearances of intrarenal vein thrombosis included obscure renal structure and no venous flow signal within the involved part of the kidneys. Reverse diastolic flow in the intrarenal artery had only a sensitivity of 36% (4/11); in other 7 kidneys without intrarenal arterial reverse diastolic flow, increased RI (mean, 0.84; range, 0.74-0.96) was found. CONCLUSION: CDU is helpful for rapid clinical diagnosis and follow-up of RVT, and therefore can be the first imaging modality of choice for RVT.

Initial application of transanal endoscopic microsurgery for high-risk lower rectal gastrointestinal stromal tumor after imatinib mesylate neoadjuvant chemotherapy: A case report.

RATIONALE: The lower rectal gastrointestinal stromal tumor (GIST) is a rare entity and warrants special attentions because of the considerations of preserving of anal and urinal functions. Neoadjuvant therapy with imatinib mesylate (IM) has achieved great success in GIST, which potentially extends the applications of function-preserving minimally invasive surgical procedures. Transanal endoscopic microsurgery (TEM) is a well-developed minimally invasive technique for benign tumors in lower rectum. Herein, we reported the initial application of TEM for high risk GIST after IM treatment. PATIENT CONCERNS: A 52-year-old woman suffered mild lower abdominal pain and perianal discomfort. Physical examination found a soft mass 4 cm far away from anal verge. Rectal MRI and transrectal ultrasound (TRUS) showed that there was a 1.9 × 1.6 cm submucosal mass in the lower rectum. The incisional biopsy was performed and the pathological result reported it was a high-risk GIST. DIAGNOSES: High-risk lower rectal GIST. INTERVENTIONS: IM was given for neoadjuvant therapy. Then TEM was adopted to resect the residual tumor. IM was restored 4 weeks after surgery. OUTCOMES: The final pathological results reported the margin was clear. After an 18-month follow up, no recurrence and metastasis was found and the patient had a satisfactory anal and urinal functions. LESSONS: TEM in combination with IM could be a practical strategy for the high-risk lower rectal GIST simultaneously to achieve curative resection and to preserve the anal and urinal functions that can significantly improve the life quality of the patients.

Value of endorectal ultrasonography in measuring the extent of mesorectal invasion and substaging of T3 stage rectal cancer.

The present study aimed to determine the value of endorectal ultrasound (ERUS) and magnetic resonance imaging (MRI) for T3 rectal cancer, and substaging of T3 rectal cancer by measuring the extent of mesorectal invasion (EMI). The clinical data of patients with rectal cancer who were admitted to the general surgical department of Peking Union Medical College Hospital (Beijing, China) were reviewed and analyzed. Two ultrasound practitioners independently measured the EMI on ERUS, and a radiologist measured the EMI on MRI. The consistency of ERUS measurements between the two doctors was assessed using intraclass consistency (ICC) analysis. T3 stages were subdivided into T3a (EMI ≤5 mm) and uT3b (EMI >5 mm). The accuracy of MRI and ERUS in T3 rectal cancer, and T3 substaging of rectal cancer was assessed and compared according to the pathological results. The Bland-Altman scatter plot demonstrated good consistency between the ERUS measurement and pathology measurement. Furthermore, the consistency of the ERUS measurement between the two doctors was good (ICC, 0.9344; 95% confidence interval, 0.8789-0.9645). The diagnostic accuracies for T3 rectal cancer, for the two ultrasound doctors and for MRI were 86.9% (53/61), 85.2% (52/61), and 90.2% (55/61), respectively. The accuracy, sensitivity and specificity for the two individual ultrasound doctors in the substaging of T3 tumors were 79.1% (34/43), 66.7% (10/15), and 85.7% (24/28), compared with 67.4% (31/43), 60% (9/15), and 82.1% (23/28), respectively. The accuracy of MRI in the substaging of T3 tumors was 86.0% (37/43), which was not statistically higher compared with those of ERUS (P>0.05). In conclusion, ERUS is a valuable tool for measuring the EMI and substaging T3 rectal cancer, and thus, can be complementary to MRI in selecting the appropriate treatment for rectal cancer.

Resection of multiple rectal carcinoids with transanal endoscopic microsurgery: case report.

Multiple rectal carcinoids are rare. Due to the unreliability of endoscopic polypectomy in treating these submucosal lesions, a laparotomy is usually performed. We present a case report on multiple rectal carcinoids with three carcinoid foci<10 mm in diameter located in the mid-rectum. Preoperative examination showed the lesions to be confined to the submucosal layer with no perirectal nodal involvement. A transanal endoscopic microsurgery was successfully performed to remove the three lesions with accurate full-thickness resection followed by secured suture closure. The postoperative pathology revealed neuroendocrine tumors G1 (carcinoids) located within the submucosal layer without lymphatic or vessel infiltration. Both the deep and lateral surgical margins were completely free of tumor cells. The patient recovered quickly and uneventfully. No tumor recurrence was observed at the six-month follow-up. For the multiple small rectal carcinoids without muscularis propria or lymphatic invasion, transanal endoscopic microsurgery offers a reliable and efficient alternative approach to traditional laparotomy for select patients, with the added advantages of minimally invasive surgery.

[Value of endorectal ultasound in predicting the circumferential resection margin and maximum tumor thickness of T3 rectal cancer].

OBJECTIVE: To evaluate the accuracy of endorectal ultrasound (ERUS) in predicting the circumferential resection margin (CRM) and maximum tumor thickness (MTT) of in T3 rectal cancer. METHODS: Clinicl data of 53 patients with pT3 rectal cancer admitted to the Department of General Surgery in the Peking Union Medical College Hospital from June 2011 to January 2014 were retrospectively analyzed. CRM and MTT measured by ERUS were compared with corresponding pathologic measurements to assess the accuracy of ERUS diagnosis. RESULTS: ERUS correctly predicted CRM status in 52 patients (98.1%, 52/53), whose sensitivity was 100%, specificity was 97.8%, positive predictive value was 85.7%, and negative predictive value was 100%. ERUS correctly predicted MTT status in 51 patients (96.2%, 51/53), whose sensitivity was 100%, specificity was 95.5%, positive predictive value was 66.6%, and negative predictive value was 100%. In the Bland and Altman plot, the agreement between ERUS and pathology was good. CONCLUSION: Endorectal ultrasonography can accurately diagnose CRM and MTT, which can satisfy the clinical need for preoperative staging of rectal cancer.

[Predictive value of preoperative imaging and postoperative pathology on clinical complete response after neoadjuvant chemoradiation for locally advanced rectal cancer].

OBJECTIVE: To evaluate the accuracy and clinical significance of clinical complete response (cCR) after neoadjuvant themoradiotherapy for locally advanced rectal cancer. METHODS: Locally advanced rectal cancer patients who received neoadjuvant chemoradiotherapy following radical resection were retrospectively assessed for tumor response during 2005 to 2014 from the database of colorectal cancer. The concomitant preoperative chemoradiation consisted of 50 Gy radiation, fractionated within 5 weeks and 5-FU combined with oxaliplatin. Endorectal ultrasound and MRI were applied to preoperative staging, and postoperative gross pathologic inspection was retrospectively employed to evaluate the status of clinical complete response(cCR). RESULTS: A total of 227 patients undergoing radical surgery were enrolled in the study. Complete pathological response (ypT0N0, pCR) was found in 40 patients(17.6%) by postoperative pathologic examination while the rate of node involved in ypT0 patients was 11.1%. The preoperative rectal MRI was more sensitive to correlate ypT0 than endorectal ultrasound and gross pathologic inspection(60.0% vs 19.4% and 17.8%), but the accuracy and specificity showed no significant differences among these three tests. Multivariate Logistic regression analysis revealed preoperative MRI evaluation of cT0 might predict ypT0 independently(OR=4.975, 95% CI: 1.073 to 23.067, P=0.040). CONCLUSION: It is difficult to diagnose the primary tumor to be a cCR status based on preoperative MRI, EUS, or ulceration of rectal mucosa, and further to predict pCR. Preoperative MRI is more sensitive. The strategy of "wait and see" for cCR patients after neoadjuvant chemoradiation should be seriously considered in the decision-making before surgery.

[Downstaging correlates the prognosis of rectal cancer after intensified neoadjuvant chemoradiotherapy].

OBJECTIVE: To evaluate the impact of downstaging factors on oncologic outcomes in a cohort of patients with rectal cancer after intensified neoadjuvant chemoradiotherapy. METHODS: Clinical and follow-up data of 135 patients with mid-low rectal cancer receiving intensified neoadjuvant chemoradiotherapy in our hospital from 2005 to 2012 were analyzed retrospectively. Tumor stages before chemoradiotherapy (uTNM) and after surgery (ypTNM) were compared. The therapeutic regimen consisted of 25 fractions of totaled 50 Gy radiation and 2-3 cycles of combination chemotherapy with 5-Fu/capecitabine plus oxaliplatin. Association of 3-year disease-free survival (DFS) with T-stage, N-stage and TNM-stage was examined through the comparison of uTNM and ypTNM. RESULTS: The mean follow-up of 135 patients was 37.1 (12 to 87) months. The 3-year DFS was 85.2%. The 3-year DFS of patients with downstaging of T-stage (n=76) was 90.8%, which was significantly better compared to those without downstaging (n=48, 75.0%, P=0.040). The 3-year DFS of patients with downstaging of N-stage (n=54) was 98.1%, which was n=53, better compared to those without downstaging (significantly 77.4%) and those with progressive disease (n=16, 75.0%) (P=0.009). Multivariate analysis showed downstaging in N-stage was a prognostic factor for DFS (HR=0.793, 95%CI:0.626-1.004, P=0.054). CONCLUSIONS: Patients with pathologic downstaging in T-stage, N-stage and TNM classification after intensified neoadjuvant chemoradiotherapy may improve patient survival. Downstaging in N-stage may be an independent predictor of survival.

A phase II study of neoadjuvant chemoradiotherapy with oxaliplatin and capecitabine for rectal cancer.

PURPOSE: This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy with the XELOX regimen in rectal cancer patients. PATIENTS AND METHODS: Twenty-five patients with histopathologically confirmed and locally advanced rectal cancer (T3/T4 or N+) were enrolled in the study. Radiotherapy of 5000 cGy was delivered in 25 fractions of 200 cGy five times per week for a total of 5 weeks. During the first, second, fourth and fifth weeks of radiotherapy, the patients also received the following chemotherapy: 50 mg/m2 oxaliplatin on day one and 850 mg/m2 capecitabine bid for 5 days. Surgery was scheduled 5-6 weeks after the completion of the preoperative chemoradiotherapy. Four weeks after the surgery, four more cycles of chemotherapy were administered every 3 weeks. The postoperative chemotherapy consisted of 130 mg/m2 oxaliplatin on day 1 and 1000 mg/m2 capecitabine bid from day 1 to day 14. The end points were the downstage rate, R0 resection rate, and sphincter preservation rate. RESULTS: Twenty-five patients received the neoadjuvant chemoradiotherapy. The overall regression rate was 85%, with a Grade 3/4 regression rate of 30% and a pathological complete response rate of 12%. Among the 17 patients with lower rectal cancer, thirteen (76%) were originally indicated for abdominal-perineal resection (APR). However, after the neoadjuvant chemoradiotherapy, the anus could be preserved in nine patients (53%). The most frequent toxicities of the chemoradiotherapy were diarrhea (64%) and hematological toxicity (60%), followed by nausea and vomiting (48%), urinary tract irritation (28%), and anal pain (24%). Grade 3 or 4 adverse events were relatively infrequent and presented as diarrhea (12%), myelosuppression (8%), and elevated transaminase (4%). Six cases also experienced long-term anal exudates after surgery. CONCLUSIONS: Neoadjuvant chemoradiotherapy using the XELOX regimen in rectal cancer patients obviously reduced the TNM staging and improved the pathological complete response rate. The therapy was well-tolerated and had mild adverse events and no serious perioperational complications.