Predicting tumor response after preoperative chemoradiation using clinical parameters in rectal cancer

AIM: To evaluate the clinical parameters and identify a better method of predicting pathological complete response (pCR). METHODS: We enrolled 249 patients from a database of 544 consecutive rectal cancer patients who underwent surgical resection after preoperative chemoradiation therapy (PCRT). A retrospective review of morphological characteristics was then performed to collect data regarding rectal examination findings. A scoring model to predict pCR was then created. To validate the ability of the scoring model to predict complete regression.RESULTS: Seventy patients (12.9%) achieved a pCR. A multivariate analysis found that pre-CRT movability (P = 0.024), post-CRT size (P = 0.018), post-CRT morphology (P = 0.023), and gross change (P = 0.009) were independent predictors of pCR. The accuracy of the scoring model was 76.8% for predicting pCR with the threshold set at 4.5. In the validation set, the accuracy was 86.7%. CONCLUSION: Gross changes and morphological findings are important predictors of pathological response. Accordingly, PCRT response is best predicted by a combination of clinical, laboratory and metabolic information.

Colon adenoma features and their impact on risk of future advanced adenomas and colorectal cancer

AIMTo review the evidence on the association between specific colon adenoma features and the risk of future colonic neoplasia [adenomas and colorectal cancer (CRC)]. METHODSWe performed a literature search using the National Library of Medicine through PubMed from 1/1/2003 to 5/30/2015. Specific Medical Subject Headings terms (colon, colon polyps, adenomatous polyps, epidemiology, natural history, growth, cancer screening, colonoscopy, CRC) were used in conjunction with subject headings/key words (surveillance, adenoma surveillance, polypectomy surveillance, and serrated adenoma). We defined non-advanced adenomas as 1-2 adenomas each 25% villous histology or high-grade dysplasia. A combined endpoint of advanced neoplasia included advanced adenomas and invasive CRC. RESULTSOur search strategy identified 592 candidate articles of which 8 met inclusion criteria and were relevant for assessment of histology (low grade vs high grade dysplasia, villous features) and adenoma size. Six of these studies met the accepted quality indicator threshold for overall adenoma detection rate > 25% among study patients. We found 254 articles of which 7 met inclusion criteria for the evaluation of multiple adenomas. Lastly, our search revealed 222 candidate articles of which 6 met inclusion criteria for evaluation of serrated polyps. Our review found that villous features, high grade dysplasia, larger adenoma size, and having ≥ 3 adenomas at baseline are associated with an increased risk of future colonic neoplasia in some but not all studies. Serrated polyps in the proximal colon are associated with an increased risk of future colonic neoplasia, comparable to having a baseline advanced adenoma. CONCLUSIONData on adenoma features and risk of future adenomas and CRC are compelling yet modest in absolute effect size. Future research should refine this risk stratification.

Current understanding of the neuropathophysiology of pain in chronic pancreatitis

Chronic pancreatitis(CP) is a chronic inflammatory disease of the pancreas. The main symptom of patients with CP is chronic and severe abdominal pain. However, the pathophysiology of pain in CP remains obscure.Traditionally, researchers believed that the pain was caused by anatomical changes in pancreatic structure. However, treatment outcomes based on such beliefs are considered unsatisfactory. The emerging explanations of pain in CP are trending toward neurobiological theories. This article aims to review current evidence regarding the neuropathophysiology of pain in CP and its potential implications for the development of new treatments for pain in CP.

NKX2-3 and IRGM variants are associated with diseasesu sceptibility to IBD in Eastern European patients

AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.

Multiplex neuritis in a patient with autoimmune hepatitis:A case report

A 37oyear old woman presented with a 9oyear history of hepatitis of unknown origin and aminotransferases within a 3-fold upper limit of normal. Autoimmune hepatitis （AIH） was diagnosed on the basis of elevated aminotransferases, soluble liver antigen/liver pancreas （SLA/LP） autoantibodies and characteristic histology. Immunosuppressive therapy led to rapid normalization of aminotransferases. Two years later, the patient developed left sided hemisensory deficits under maintenance therapy of prednisolone and azathioprine （AZT）. Later she developed right foot drop and paraesthesia in the ulnar innervation territory on both sides. Magnetic resonance imaging （MRI） and cerebral panangiography suggested cerebral vasculitis. Neurological investigation and electromyography disclosed multiplex neuritis （MN） probably due to vasculitis. Consistent with this diagnosis, autoantibodies to extractable nuclear antigens were detectable in serum. Immunosuppression was changed to oral 150 mg cyclophosphamide （CPMO） per day. Prednisolone was increased to 40 mg/d and then gradually tapered to 5 mg. Oral CPM was administered up to a total dose of 40 g and then substituted by 6 times of an intervall infusion therapy of CPM （600 mg/m^2）. Almost complete motoric remission was achieved after 3 mo of CPM. Sensibility remained reduced in the right peroneal innervation territory. Follow-up of cranial MRI provided stable findings without any new or progressive lesions. This is the first report of multiplex neuritis in a patient with autoimmune hepatitis.

Optimal timing of same-admission orthotopic heart transplantation after left ventricular assist device implantation

AIM To investigate the impact of timing of same-admission orthotopic heart transplant(OHT) after left ventricular assist device(LVAD) implantation on in-hospital mortality and post-transplant length of stay.METHODS Using data from the Nationwide Inpatient Sample from 1998 to 2011, we identified patients 18 years of age or older who underwent implantation of a LVAD and for whom the procedure date was available. We calculated in-hospital mortality for those patients who underwent OHT during the same admission as a function of time from LVAD to OHT, adjusting for age, sex, race, household income, and number of comorbid diagnoses. Finally, we analyzed the effect of time to OHT after LVAD implantation on the length of hospital stay post-transplant.RESULTS Two thousand and two hundred patients underwent implantation of a LVAD in this cohort. One hundred and sixty-four(7.5%) patients also underwent OHT duringthe same admission, which occurred on average 32 d(IQR 7.75-66 d) after LVAD implantation. Of patients who underwent OHT, patients who underwent transplantation within 7 d of LVAD implantation("early") experienced increased in-hospital mortality(26.8% vs 12.2%, P = 0.0483) compared to patients who underwent transplant after 8 d("late"). There was no statistically significant difference in age, sex, race, household income, or number of comorbid diagnoses between the early and late groups. Post-transplant length of stay after LVAD implantation was also not significantly different between patients who underwent early vs late OHT. CONCLUSION In this cohort of patients who received LVADs, the rate of in-hospital mortality after OHT was lower for patients who underwent late OHT(at least 8 d after LVAD implantation) compared to patients who underwent early OHT. Delayed timing of OHT after LVAD implantation did not correlate with longer hospital stays post-transplant.

Boceprevir or telaprevir in hepatitis C virus chronic infection:The Italian real life experience

AIM: To check the safety and efficacy of boceprevir/telaprevir with peginterferon/ribavirin for hepatitis C virus(HCV) genotype 1 in the real-world settings. METHODS: This study was a non-randomized, observational, prospective, multicenter. This study involved 47 centers in Italy. A database was prepared for the homogenous collection of the data, was used by all of the centers for data collection, and was updated continuously. All of the patients enrolled in this study were older than 18 years of age and were diagnosed with chronic infection due to HCV genotype 1. The HCV RNA testing was performed using COBAS-Taq Man2.0(Roche, LLQ 25 IU/m L). RESULTS: All consecutively treated patients were included. Forty-seven centers enrolled 834 patients as follows: Male 64%; median age 57(range 18-78), of whom 18.3% were over 65; mean body mass index 25.6(range 16-39); genotype 1b(79.4%); diagnosis of cirrhosis(38.2%); and fibrosis F3/4(71.2%). The following drugs were used: Telaprevir(66.2%) and PEG-IFN-alpha2a(67.6%). Patients were na?ve(24.4%), relapsers(30.5%), partial responders(14.8%) and null responders(30.3%). Overall, adverse events(AEs) occurred in 617 patients(73.9%) during the treatment. Anemia was the most frequent AE(52.9% of cases), especially in cirrhotic. The therapy was stopped for 14.6% of the patients because of adverse events or virological failure(15%). Sustained virological response was achieved in 62.7% of the cases, but was 43.8% in cirrhotic patients over 65 years of age. CONCLUSION: In everyday practice, triple therapy is safe but has moderate efficacy, especially for patients over 65 years of age, with advanced fibrosis, nonresponders to peginterferon + ribavirin.

Transmitted cardiovascular pulsations on high resolution esophageal impedance manometry, and their significance in dysphagia

AIM To investigate the behavior of pulsatile pressure zones(PPZ's) as noted on high resolution esophageal impedance manometry(HREIM), and determine their association with dysphagia.METHODS Retrospective, single center case control design scr-eening HREIM studies for cases(dysphagia) and controls(no dysphagia). Thoracic radiology studies were reviewed further in cases for(thoracic cardiovascular) thoracic cardiovascular(TCV) structures in esophageal proximity to compare with HREIM findings. Manometric data was collected for number, location, axial length, PPZ pressure and esophageal clearance function(impedance). RESULTS Among 317 screened patients, 56% cases and 64% controls had PPZ's. Fifty cases had an available thoracic radiology comparison. The distribution of PPZ's in these 50 cases and 59 controls was similar(average 1.4 PPZ/patient). Controls(mean 31.2 ± SD 12 years) were a significantly younger population than cases(mean 67.3 ± SD 14.9 years) with P < 0.0001. The upright posture PPZ pressure was higher in controls(15.7 ± 10.0 mm Hg) than cases(10.8 ± 9.7 mm Hg). Although statistically significant(P = 0.005), it was a weak predictor using logistic regression and ROC model(AUC = 0.65). Three dysphagia patients had partial compression from external TCV on radiology(1 aberrant subclavian artery, 2 dilated left atrium). The posture(supine vs upright) with more prominent PPZ's impaired bolus clearance in 9 additional cases by > 20%. CONCLUSION Transmitted TCV pulsations observed in HREIM bear no significant impact on swallowing. However, in older adults with dysphagia, evidence of impaired bolus clearance on impedance should be evaluated for external TCV compression. These associations have never been explored previously in literature, and are novel.