Zhiyang Zhou

Modified FOLFOX6 With or Without Radiation Versus Fluorouracil and Leucovorin With Radiation in Neoadjuvant Treatment of Locally Advanced Rectal Cancer: Initial Results of the Chinese FOWARC Multicenter, Open-Label, Randomized Three-Arm Phase III Trial

PURPOSE Total mesorectal excision with fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy is a standard treatment of locally advanced rectal cancer. This study investigated the addition of oxaliplatin with and without preoperative radiotherapy. METHODS In this multicenter, open-label, phase III trial, we randomly assigned (1:1:1) Chinese adults (age 18 to 75 years) with locally advanced stage II/III rectal cancer to three treatments: five 2-week cycles of infusional fluorouracil (leucovorin 400 mg/m(2), fluorouracil 400 mg/m(2), and fluorouracil 2.4 g/m(2) over 48 h) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 through 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m(2) on day 1 of each cycle (modified FOLFOX6 [mFOLFOX6]), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. Random assignment was performed by using computer-generated block randomization codes. The primary end point was 3-year disease-free survival. Secondary end points of histopathologic response and toxicity are reported. RESULTS A total of 495 patients were enrolled from June 2010 to February 2015; 475 were evaluable (fluorouracil-radiotherapy, n = 155; mFOLFOX6-radiotherapy, n = 157; mFOLFOX6, n = 163). In the fluorouracil-radiotherapy, mFOLFOX6-radiotherapy, and mFOLFOX6 groups, the rate of pathologic complete response (pCR) was 14.0%, 27.5%, and 6.6%, and downstaging (ypStage 0 to 1) was achieved by 37.1%, 56.4%, and 35.5% of patients, respectively. Higher toxicity and more postoperative complications were observed in patients who received radiotherapy. CONCLUSION mFOLFOX6-based preoperative chemoradiotherapy results in a higher pCR rate than fluorouracil-based treatment. Perioperative mFOLFOX6 alone had inferior results and a lower pCR rate than chemoradiotherapy but led to a similar downstaging rate as fluorouracil-radiotherapy, with less toxicity and fewer postoperative complications.

Diagnostic efficacy of whole-body diffusion-weighted imaging in the detection of tumour recurrence and metastasis by comparison with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography or computed tomography in patients with gastrointestinal cancer

Objective: The primary aim of this study was to assess the efficacy of whole-body diffusion-weighted imaging (WB-DWI) in detecting tumour recurrence and metastasis of gastrointestinal cancers by comparison with 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography or computed tomography (18F-FDG-PET/CT). A secondary aim was to evaluate the change of apparent diffusion coefficient (ADC) value between metastases and normal tissues. Methods: Twenty-eight previously confirmed gastrointestinal cancer patients with suspected tumour recurrence or metastasis were recruited. WB-DWI and PET/CT images were evaluated by two radiologists and a nuclear medicine physician. Agreement between WB-DWI and PET/CT for detective efficacy was compared using kappa statistics. Additionally, diagnostic accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were also statistically analysed. ADC values between metastatic and normal tissues were compared. Results: There was no statistically significant difference (P > 0.05) in the overall diagnostic performances of PET/CT (accuracy 98.9%; sensitivity 95.2%; specificity 99.8%; PPV 98.9%; NPV 98.9%) and WB-DWI (accuracy 95.9%; sensitivity 81.7%; specificity 99.1%; PPV 95.0%; NPV 96.1%). WB-DWI showed agreement with PET/CT (κ = 0.877) for detecting recurrence and distant metastases. A statistically significant difference in ADC value was observed between tissues of normal healthy volunteers and metastases in lymph nodes, liver and bones (P < 0.05). Conclusions: WB-DWI is reliable in detecting tumour recurrence and metastasis of colorectal cancer and offers the same diagnostic performance as 18F-PET/CT without ionizing radiation. The quantitative value of ADC provides extra information to determine cancer metastasis.

Impact of Preoperative Radiotherapy on Anastomotic Leakage and Stenosis After Rectal Cancer Resection: Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Evidence regarding the effect of preoperative radiotherapy on anastomotic integrity remains conflicting in rectal cancer surgery. Prospective comparisons with appropriate controls are needed. OBJECTIVE: This study aimed to assess the impact of preoperative radiotherapy on anastomotic leakage and stenosis after rectal cancer resection. DESIGN: This was a post hoc analysis of a randomized controlled trial (NCT01211210). SETTINGS: Data were retrieved from the leading center of the trial, which is a tertiary hospital. PATIENTS: The full analysis population of 318 patients was included. INTERVENTIONS: Patients were randomly assigned to receive preoperative radiation (50 Gy per 25 fractions) and 5-fluorouracil infusion, alone (arm A) or combined with oxaliplatin (arm B), or preoperative chemotherapy with 5-fluorouracil and oxaliplatin without radiation (arm C). MAIN OUTCOME MEASURES: The rates of anastomotic leakage and stenosis were calculated for each treatment arm. Multivariate analysis was used to verify the effect of preoperative radiotherapy. RESULTS: The treatment arms were comparable in terms of most baseline characteristics, but more diversions were used in the chemoradiotherapy arms. Anastomotic leakage occurred in 20.2% of patients in arm A, 23.6% of patients in arm B, and 8.5% of patients in arm C (p = 0.007). The corresponding rates of stenosis were 17.0%, 18.9%, and 6.8% (p = 0.02). Multivariate analysis confirmed the correlation between preoperative radiotherapy and clinical leakage (p = 0.02), which was associated with delayed stenosis (p < 0.001). For patients undergoing chemoradiotherapy, radiation proctitis was identified as an independent risk factor for clinical leakage (p = 0.01) and stenosis (p < 0.001). LIMITATIONS: The main limitations were discrepancies in stoma creation and chemotherapy regimen among the treatment arms. CONCLUSIONS: Preoperative radiotherapy increases the risk of anastomotic leakage and stenosis after rectal cancer resection. Clinical leakage independently contributes to the development of stenosis.

Clinical Significance of 2 Deep Posterior Perianal Spaces to Complex Cryptoglandular Fistulas.

BACKGROUND: Confusion exists regarding the clinical significance of the deep posterior intersphincteric space and deep postanal space to complex perianal fistulas. OBJECTIVE: The purpose of this study was to assess the clinical significance of the 2 deep posterior perianal spaces and to describe in detail the courses of posterior complex cryptoglandular fistula extensions. DESIGN: This was a retrospective study. MRI-based characteristics of selected perianal fistulas were independently evaluated by examiners who focused on lesions in these 2 spaces and were blinded to each other’s findings. SETTINGS: This study was conducted in the colorectal surgery and radiology departments of a large university teaching hospital in China. PATIENTS: Included in the study were patients who underwent pelvic MRI for posterior perianal fistula between October 2012 and December 2014. MAIN OUTCOME MEASURES: The occurrence rates of these 2 deep perianal space lesions in posterior cryptoglandular fistulas were determined. RESULTS: A total of 513 primary posterior cryptoglandular fistulas were identified in 508 patients, including 167 deep posterior intersphincteric space lesions (32.6%) and 23 deep postanal space lesions (4.5%). Of those, 173 fistulas (33.7%) were evaluated as complex. The former and latter spaces were involved in 79.2% (137/173) and 13.3% (23/173) of posterior complex fistulas. Compared with deep postanal space lesions, deep posterior intersphincteric space lesions were more common in cases with high transsphincteric or suprasphincteric fistulas (80.1% vs 15.8%), synchronous multiple transsphincteric fistulas (82.4% vs 20.6%), horseshoe-like fistulas (85.5% vs 14.5%), and supralevator fistulas (93.5% vs 16.1%). Similar incidences were also seen in cases with ischioanal-involved horseshoe-like fistulas (75.0% vs 25.0%). LIMITATIONS: This study was limited by its retrospective nature. CONCLUSIONS: The deep posterior intersphincteric space is more likely than the deep postanal space to be involved in complex cryptoglandular fistulas and is likely to play a more important role in the management of complex cryptoglandular fistulas.

Bowel Dysfunction After Low Anterior Resection With Neoadjuvant Chemoradiotherapy or Chemotherapy Alone for Rectal Cancer: A Cross-sectional Study from China

BACKGROUND: Neoadjuvant therapy plays a vital role in the treatment of locally advanced rectal cancer but impairs bowel function after restorative surgery. Optimal decision making requires adequate information of functional outcomes. OBJECTIVE: This study aimed to assess postoperative bowel function and to identify predictors for severe dysfunction. DESIGN: The study included a cross-sectional cohort and retrospective assessments of pelvic anatomic features. SETTINGS: The study was conducted at a tertiary GI hospital in China. PATIENTS: Included patients underwent neoadjuvant chemoradiotherapy or chemotherapy without radiation and curative low anterior resection for rectal cancer between 2012 and 2014. MAIN OUTCOME MEASURES: Bowel function was assessed using the validated low anterior resection syndrome score. The thicknesses of the rectal wall, obturator internus, and levator ani were measured by preoperative MRI. RESULTS: A total of 151 eligible patients were identified, and 142 patients (94.0%) participated after a median of 19 months from surgery. Bowel dysfunction was observed in 71.1% (101/142) of patients, with 44.4% (63/142) reporting severe dysfunction. Symptoms of urgency and clustering were found to be major disturbances. Regression analysis identified preoperative long-course radiotherapy (p < 0.001) and a lower-third tumor (p = 0.002) independently associated with severe bowel dysfunction. Irradiated patients with a lower-third tumor (OR = 14.06; p < 0.001) or thickening of the rectal wall (OR = 11.09; p < 0.001) had a markedly increased risk of developing severe dysfunction. LIMITATIONS: The study was based on a limited cohort of patients and moderate follow-up after the primary surgery. CONCLUSIONS: Bowel function deteriorates frequently after low anterior resection for rectal cancer. Severe bowel dysfunction is significantly associated with preoperative long-course radiotherapy and a lower-third tumor, and the thickening of rectal wall after radiation is a strong predictor. Treatment decisions and patient consent should be implemented with raising awareness of bowel symptom burdens. See Video Abstract at http://links.lww.com/DCR/A317.

Rectal cancer restaging using 3D CUBE vs. 2D T2-weighted technique after neoadjuvant therapy: a diagnostic study

Abstract Objective. This study aimed to compare the accuracy of rectal cancer restaging after neoadjuvant therapy with 3D CUBE sequence with 2D T2-weighted fast spin-echo (FSE) sequence. Methods. This retrospective study comprised 72 patients with rectal cancer confirmed by colonoscopy and biopsy. After neoadjuvant therapy, all patients underwent pelvic magnetic resonance imaging (MRI) examination at 1.5T MRI sequences including a single coronal 3D CUBE T2-weighted FSE sequence with 1.4 mm thickness and a 2D T2-weighted FSE sequence in the sagittal, coronal and axial planes with 5 mm thickness. The total acquisition time of the two sequences was recorded. Results were compared with postsurgical pathology (gold standard). The diagnostic accuracy was evaluated; and receiver operating characteristic (ROC) curves and the area under the curves (AUC) were calculated. Results. The T category staging accuracy of 3D T2WI and 2D T2WI was 81.9% and 72.2%, respectively, for reviewer 1 and 86.1% and 75.0% for reviewer 2. The AUC of 3D was higher than that of 2D (0.878 vs. 0.783 for reader 1 and 0.905 vs. 0.796 for reader 2; both P < 0.05) when judging whether the tumor broke through the muscle layer. There was no significant difference between 3D and 2D in judging whether lymph nodes were malignant (AUC 0.719 vs. 0.698 for reader 1 and 0.740 vs. 0.698 for reader 2; both P > 0.05). There were no significant differences in the visibility of the rectal wall layer, tumor lesion and the overall image quality (all P > 0.05). Compared with 2D sequences, the 3D sequence had shorter acquisition time and higher signal intensity ratio (both P < 0.05). Conclusion. 3D CUBE T2-weighted sequences offer better diagnostic accuracy in rectal cancer restaging after neoadjuvant therapy when compared with 2D T2-weighted FSE sequences; it has a shorter scanning time and more versatility of orientation reconstruction.

Recurrent granular cell tumor of the anal-perianal region: how much anal sphincter can be resected?

A 48-year-old Chinese woman presented with a 6-month history of a progressively growing perianal mass but no pain, hematochezia, tenesmus, or weight loss. She had a history of hyperlipidemia and of perianal granular cell tumor (GCT) resection 7 years prior. Physical examination showed a 5-cm surgical scar on the skin 3 cm from the anus, a tough perianal mass adhering to the external anal sphincter (EAS) and extending to the left half of the anal circumference under the old scar. The mass was 3 9 4 cm with smooth borders and fixed to the underlying tissues. All blood and biochemical test results were within the normal range with one exception: the CA 19–9 level was 70 U/L. Pelvic magnetic resonance imaging (MRI) revealed a brightly enhancing mass Fig. 1a. Considering the presence of a tumor involving more than half of the EAS and the high risk of fecal incontinence and recurrence, we recommended abdominoperineal excision. However, the patient refused a permanent colostomy and consented only to a sphincter-sparing procedure, accepting the risk of recurrence and of anal incontinence. We therefore performed a local excision with sphincteroplasty. The patient underwent bowel preparation with polyethylene glycol solution the night before surgery. A broad spectrum parenteral antibiotic was administered preoperatively and was continued for 48 h after the operation. The patient was given epidural anesthesia without any local infiltration anesthesia, was placed in the jackknife position, and had a urinary catheter placed. An incision was made using Peng’s multifunctional operational dissectors (PMOD) (Shuyou Surgical Instrument Co., Ltd. Zhejiang, China), beginning at the original incision with arc-shaped extensions under the mass. The incision reaching the perianal skin was carried back along the expected outer edge of the EAS. The mass presented as white and tough and infiltrated almost half of the EAS. The perianal skin, internal anal sphincter (IAS), rectal muscularis propria, and puborectalis muscle were then dissected free along the mass. The excision included more than half of the peripheral part of the EAS. Care was taken to preserve the underlying IAS as much as possible. The free edges of the EAS and IAS were approximated separately. Then, the EAS was brought together in an overlapping fashion using an 3–0 vicryl suture (Ethicon, Somerville, NJ, USA), followed by levatorplasty, which was accomplished with a 2 cm 9 3 cm, 4-ply sheet of bioprosthetic mesh (Surgisis ES, Cook surgical Inc, Bloomington, IN, USA) (Fig. 2). Finally, the perianal skin was sutured. Postoperatively, the patient’s diet consisted of liquids and then a soft diet, supplemented with stool softeners and fiber. The patient was discharged on postoperative day 5, after return of bowel function and was seen as an outpatient every 2 weeks until full wound healing was achieved (Fig. 3). X. Y. Wan B. Hu D. L. Ren (&) Division of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26 Yuanchun Erheng Road, Guangzhou 510655, Guangdong, People’s Republic of China e-mail: rxyz111@yahoo.com.cn