Radiomic Features of Primary Rectal Cancers on Baseline T2 -Weighted MRI Are Associated With Pathologic Complete Response to Neoadjuvant Chemoradiation: A Multisite Study.

BACKGROUND: Twenty-five percent of rectal adenocarcinoma patients achieve pathologic complete response (pCR) to neoadjuvant chemoradiation and could avoid proctectomy. However, pretreatment clinical or imaging markers are lacking in predicting response to chemoradiation. Radiomic texture features from MRI have recently been associated with therapeutic response in other cancers. PURPOSE: To construct a radiomics texture model based on pretreatment MRI for identifying patients who will achieve pCR to neoadjuvant chemoradiation in rectal cancer, including validation across multiple scanners and sites. STUDY TYPE: Retrospective. SUBJECTS: In all, 104 rectal cancer patients staged with MRI prior to long-course chemoradiation followed by proctectomy; curated from three institutions. FIELD STRENGTH/SEQUENCE: 1.5T-3.0T, axial higher resolution T2 -weighted turbo spin echo sequence. ASSESSMENT: Pathologic response was graded on postsurgical specimens. In total, 764 radiomic features were extracted from single-slice sections of rectal tumors on processed pretreatment T2 -weighted MRI. STATISTICAL TESTS: Three feature selection schemes were compared for identifying radiomic texture descriptors associated with pCR via a discovery cohort (one site, N = 60, cross-validation). The top-selected radiomic texture features were used to train and validate a random forest classifier model for pretreatment identification of pCR (two external sites, N = 44). Model performance was evaluated via area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: Laws kernel responses and gradient organization features were most associated with pCR (P ≤ 0.01); as well as being commonly identified across all feature selection schemes. The radiomics model yielded a discovery AUC of 0.699 ± 0.076 and a hold-out validation AUC of 0.712 with 70.5% accuracy (70.0% sensitivity, 70.6% specificity) in identifying pCR. Radiomic texture features were resilient to variations in magnetic field strength as well as being consistent between two different expert annotations. Univariate analysis revealed no significant associations of baseline clinicopathologic or MRI findings with pCR (P = 0.07-0.96). DATA CONCLUSION: Radiomic texture features from pretreatment MRIs may enable early identification of potential pCR to neoadjuvant chemoradiation, as well as generalize across sites. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

High-resolution anoscopy or expectant management for anal intraepithelial neoplasia for the prevention of anal cancer: is there really a difference?

BACKGROUND: High-resolution anoscopy has been shown to improve identification of anal intraepithelial neoplasia but a reduction in progression to anal squamous-cell cancer has not been substantiated when serial high-resolution anoscopy is compared with traditional expectant management. OBJECTIVE: The aim of this study was to compare high-resolution anoscopy versus expectant management for the surveillance of anal intraepithelial neoplasia and the prevention of anal cancer. DESIGN: This is a retrospective review of all patients who presented with anal squamous dysplasia, positive anal Pap smears, or anal squamous-cell cancer from 2007 to 2013. SETTING: This study was performed in the colorectal department of a university-affiliated, tertiary care hospital. PATIENTS: Included patients had biopsy-proven anal intraepithelial neoplasia from 2007 to 2013. INTERVENTIONS: Patients were treated with high-resolution anoscopy with ablation or standard anoscopy with ablation. Both groups were treated with imiquimod and followed every 6 months indefinitely. MAIN OUTCOME MEASURES: The incidence of anal squamous-cell cancer in each group was the primary end point. RESULTS: From 2007 to 2013, 424 patients with anal squamous dysplasia were seen in the clinic (high-resolution anoscopy, 220; expectant management, 204). Three patients (high-resolution anoscopy, 1; expectant management, 2) progressed to anal squamous-cell cancer; 2 were noncompliant with follow-up and with HIV treatment, and the third was allergic to imiquimod and refused to take topical 5-fluorouracil. The 5-year progression rate was 6.0% (95% CI, 1.5-24.6) for expectant management and 4.5% (95% CI, 0.7-30.8) for high-resolution anoscopy (p = 0.37). LIMITATIONS: This was a retrospective review. There is potential for selection and referral bias. Because of the rarity of the outcome, the study may be underpowered. CONCLUSIONS: Patients with squamous-cell dysplasia followed with expectant management or high-resolution anoscopy rarely develop squamous-cell cancer if they are compliant with the protocol. The cost, morbidity, and value of high-resolution anoscopy should be further evaluated in lieu of these findings.

Protection of rat hepatocytes from apoptosis by inhibition of c-Jun N-terminal kinase.

BACKGROUND: Apoptotic cell death and c-Jun N-terminal kinase (JNK) activation occur after hepatic ischemia/reperfusion injury. In other cell types, JNK activation was shown to be required for apoptosis. This study tested the hypotheses that JNK contributes to hepatocellular apoptosis, and that inhibition of JNK activity improves cell viability. METHODS: Rat hepatocytes were harvested from Sprague-Dawley rats and pretreated with SP600125, a JNK inhibitor. Subsequently, they were exposed to apoptotic stimuli consisting of either the bile salt glycochenodeoxycholic acid (GCDC) or tumor necrosis factor (TNF)-alpha and actinomycin D. RESULTS: Western blotting demonstrated specific inhibition of JNK by SP600125. Inhibition of JNK resulted in improved viability measured with crystal violet, decreased in situ DNA nick end labeling positivity, and decreased cleavage of poly (ADP-ribose) polymerase and caspase-3. TNF-alpha and actinomycin D induced apoptosis, upregulated p53, and downregulated expression of the anti-apoptotic protein X-linked inhibitor of apoptosis protein. These effects were abrogated by JNK inhibition. CONCLUSIONS: These data show that pharmacologic inhibition of JNK activity reduces bile salt or TNF-alpha-induced apoptosis by maintaining expression of anti-apoptotic proteins. The results indicate that JNK is an important component of the apoptosis signaling cascade and suggest a possible therapeutic strategy in certain liver disorders.

Patient safety: effect of institutional protocols on adverse events related to feeding tube placement in the critically ill.

BACKGROUND: Inadvertent passage of a nasoenteric feeding tube into the tracheobronchial tree can result in pneumothorax. Measures requiring feeding tube passage to 35 cm only followed by a radiograph to verify intraesophageal placement and creation of a specialized placement team were implemented to decrease the incidence of procedure-related pneumothorax. This study evaluates the effectiveness of our safety measures. STUDY DESIGN: Radiology reports from January 2000 through July 2003 were searched by computer with an algorithm designed to detect feeding tube placements possibly associated with the complication of intrabronchial placement or pneumothorax. Results were manually examined to eliminate false positives and verify causality. RESULTS: Feeding tubes were placed in 4,190 unique patients during the study period; 87 patients had an intrabronchial malposition, and 9 experienced a pneumothorax caused by their feeding tube. The safety measures resulted in a significant decrease in procedure-related pneumothorax (0.09% versus 0.38%, p < 0.05), and a decrease in pneumothorax among patients with an intrabronchial placement (3% versus 27%, p < 0.05). More than two-thirds of patients with a misplaced tube had an endotracheal tube or tracheostomy, illustrating that such patients are not protected. Repeated malposition in the same patient was surprisingly common; 32% of patients with one intrabronchial misplacement ultimately had multiple misplacements. The risk of pneumothorax increased with misplacement at night (p < 0.05) and increased exponentially with each additional misplacement (p < 0.05). CONCLUSIONS: Creating a specialized placement team, and initiating the safety measure of limiting feeding tube placement to 35 cm and obtaining a radiograph before full advancement reduced the incidence of procedure-related pneumothorax.

Classic "outlet" rectal bleeding does not require full colonoscopy to exclude significant pathology.

PURPOSE: Full diagnostic colonoscopy often is performed to exclude significant pathology in patients presenting with rectal bleeding. In patients with classic "outlet" bleeding, defined as bright red blood after or during defecation, with no family history of colorectal neoplasia or change in bowel habits, we hypothesize that the diagnostic yield of complete colonoscopy will be low. The purpose of this study was to determine whether complete colonoscopy is necessary in the evaluation of patients with "outlet" rectal bleeding. METHODS: Information for all patients undergoing colonoscopy by a single endoscopist was prospectively recorded. Before each colonoscopy, a complete history, including indication for the examination, was obtained. Using standard definitions, patients with outlet bleeding, suspicious bleeding, hemorrhage, and occult bleeding were accessed and the findings of their colonoscopies were analyzed. Institutional permission was obtained. RESULTS: A total of 9,098 patients had colonoscopy recorded in the database, and 703 had the indication of outlet bleeding, 251 suspicious bleeding, 204 occult bleeding, and 67 hemorrhage. Of the patients with outlet bleeding, only 47 (6.7 percent) had significant lesions on colonoscopy (adenomas >1 cm, villous adenomas, cancer in situ, or invasive cancer). By contrast a greater number of significant lesions were present in patients with all other types of bleeding (17.2 percent; P<0.001). The incidence of invasive cancer was significantly lower in the outlet bleeding group compared with other types of bleeding (1 vs. 3.6 percent; P<0.01). Patients with outlet bleeding were much less likely than patients with other bleeding to have isolated right-sided colonic pathology. Younger patients with outlet bleeding have a particularly low yield on colonoscopy. In 182 patients younger than aged 50 years with outlet bleeding, only 3 (1.6 percent) had adenomas >1 cm and no invasive cancers were detected. CONCLUSIONS: In patients with classic outlet bleeding, the yield of a complete diagnostic colonoscopy is low. If the history is classic for outlet bleeding and no other indication for colonoscopy exists, flexible sigmoidoscopy is enough to exclude significant pathology.

Management of postoperative ileus: focus on alvimopan.

Postoperative ileus (POI) is a transient loss of coordinated peristalsis precipitated by surgery and exacerbated by opioid pain medication. Ileus causes a variety of symptoms including bloating, pain, nausea, and vomiting, but particularly delays tolerance of oral diet and liquids. Thus POI is a primary determinant of hospital stay after surgery. 'Fast-track' recovery protocols, opioid sparing analgesia, and laparoscopic surgery reduce but do not eliminate postoperative ileus. Alvimopan is a mu opioid receptor antagonist that blocks the effects of opioids on the intestine, while not interfering with their centrally mediated analgesic effect. Several large randomized clinical trials have demonstrated that alvimopan accelerates the return of gastrointestinal function after surgery and subsequent hospital discharge by approximately 20 hours after elective open segmental colectomy. However, it has not been tested in patients undergoing laparoscopic surgery and is less effective in patients receiving nonsteroidal anti-inflammatory agents in a narcotic sparing postoperative pain control regimen. Safety concerns seen with chronic low dose administration of alvimopan for opioid bowel dysfunction have not been noted with its acute use for POI.

Surgical management of rectal prolapse.

This article reviews the pathogenesis, clinical presentation and surgical management of rectal prolapse. Full-thickness prolapse of the rectum causes significant discomfort because of the sensation of the prolapse itself, the mucus that it secretes, and because it tends to stretch the anal sphincters and cause incontinence. Treatment of rectal prolapse is primarily surgical. Perineal surgical repairs are well tolerated, but are generally associated with higher recurrence rates. Abdominal repairs involve fixing the rectum to the sacrum by using either mesh or sutures, and tend to have the lowest recurrence rates. If significant preoperative constipation is present, a sigmoid resection can be performed at the time of rectopexy. For many patients, diarrhea and incontinence improve after surgery. Laparoscopic repair of rectal prolapse has similar morbidity and recurrence rates to open surgery, with attendant benefits of reduced length of hospital stay, postoperative pain and wound complications.