Complete Histological Remission Research Articles

The role of the 595-nm pulsed dye laser in treating superficial basal cell carcinoma: outcome of a double-blind randomized placebo-controlled trial.

Pulsed dye laser (PDL) treatments have been suggested to be a safe and effective therapeutic approach for treating basal cell carcinomas (BCCs). However, robust supporting evidence is lacking due to inconsistent design of available studies. To evaluate PDL efficacy and safety in treating superficial BCC (sBCC) at low-risk anatomical sites in an evidence-based study setting. Thirty-nine patients (27 men and 12 women, 75·9 ± 10 years) with a total of 100 sBCCs were randomized to receive PDL treatment (wavelength 595 nm; fluence 8 J cm(-2) ; pulse duration 0·5 ms; spot size 10 mm) or sham treatment. The primary endpoint was complete clinical and histological remission of the tumour at 6-month follow-up; the secondary endpoints were the evaluation of side-effects and pain as well as patient satisfaction. The primary endpoint showed significant superiority of the laser group to the sham group (P < 0·0001). Complete remission was achieved in 44 of 56 cases (78·6%) in the laser and in two of 44 cases (4·5%) in the sham treatment arm. The main adverse events in the laser group were crusts, hyper- and hypopigmentation. An average of 72% of patients stated at the individual sessions that they were 'satisfied' with the laser treatment, whereas 25% were 'very satisfied'. PDL is an effective and safe method for treating sBCC. However, the occurrence of persistent dyspigmentation still limits the potential for excellent cosmetic outcomes.

Efficacy and safety of the band and slough technique for endoscopic therapy of nonampullary duodenal adenomas: a case series

Endoscopic resection of nonampullary duodenal adenomas (NADAs) is effective but carries substantial procedural risks. Therapeutic banding for treatment of duodenal mucosal neoplasia has not been studied. We report a novel band and slough (BAS) technique for therapy of NADA without endoscopic resection. Efficacy and safety of BAS. Retrospective review of a prospective database. Community hospital. Patients with sporadic and familial biopsy-proven NADA without invasive cancer undergoing BAS. Patients were treated with BAS without endoscopic resection on an outpatient basis. A follow-up telephone call was made by a nurse at 24 hours. Follow-up endoscopy was performed at 8 weeks, with further therapy of residual NADA. In patients with minimal residual NADA not amenable to banding, argon plasma coagulation (APC) "touch-up" was used. Subsequent endoscopic surveillance was performed. Complete histologic remission of NADA after successful BAS and postprocedure bleeding, perforation, and pain. Ten patients, average age 65 years, 6 male, with sporadic/familial adenomatous polyposis NADA 8of 2(6 tubular adenoma and 4 tubulovillous adenoma) were treated. Mean (largest) NADA was 12.5mm (20mm). Five patients achieved complete remission after a single session. Among 5 patients requiring further therapy, 3 were treated with repeat banding with or without APC and 2 with APC alone. The average number of bands per session was 4.4. Patients were followed up to 24 months without NADA recurrence. None of the patients had acute or delayed adverse events of bleeding, perforation, or postprocedure pain. Lack of polyp tissue retrieval. BAS appears to be a safe and potentially effective endoscopic treatment for NADA. However, larger studies are needed to corroborate these findings.

P-092: The course of anaemia in children with Crohn’s disease included in a prospective registry

P-092: The course of anaemia in children with Crohn’s disease included in a prospective registry

PTU-109 Azathioprine In The Elderly – Is It Tolerated And Is It Safe?

IntroductionThe use of Azathioprine (AZA) for maintenance of remission in Inflammatory Bowel Disease (IBD) is common practice as part of national and international guidelines. Side effects however are common. Of...

Tu1328 Endoscopic Submucosal Dissection for Barrett's Esophagus: Efficacy and Safety Results in a Large Tertiary Center Series of Patients

Tu1328 Endoscopic Submucosal Dissection for Barrett's Esophagus: Efficacy and Safety Results in a Large Tertiary Center Series of Patients

The outcome of patients with oesophageal eosinophilic infiltration after an eight‐week trial of a proton pump inhibitor

Current diagnostic guidelines recommend that eosinophilic oesophagitis (EoE) should be diagnosed only after GERD is excluded by a lack of response to a trial of acid suppression. There is limited information available providing outcome data about the effectiveness of this approach. To examine the impact of double-dose proton pump inhibitor (PPI) therapy on symptoms, endoscopic and histological features in patients with documented oesophageal eosinophilia consistent with EoE (≥15 eosinophils/high-power field). Sixty consecutive symptomatic patients with documented oesophageal eosinophilia received open-label omeprazole 20mg orally twice daily before meals for 8weeks. Clinical, endoscopic and histological (resolution: 0-5 eosinophils/HPF, partial improvement: 5-14 eosinophils/HPF), or no improvement: (≥15 eosinophils/HPF) evaluation was repeated at the end of this period. An expert GI pathologist, unaware of the study aims, reviewed all slides. Clinical improvement occurred in 43 (71.6%), endoscopic signs were reduced in 34 (61.8%) and normalised in 12 (21.8%), and histologically, 34 (56.6%) improved, while 15 (25%) obtained complete resolution. Overall, 22 patients (36.7%) obtained both complete clinical and histological remission. More than 50% of patients with documented oesophageal eosinophilic infiltration in the EoE range improved when treated with a double-dose PPI trial for 8weeks. These findings support the published guidelines recommending a PPI trial prior to diagnosing EoE, and confirm the existence of an eosinophilic oesophageal infiltrationPPI-responsive population.

Therapy‐related Ph+ leukemia after both bone marrow and mesenchymal stem cell transplantation for hypophosphatasia

Bone marrow (BM) transplantation (BMT) is one of the treatment strategies for congenital metabolic disease, but leukemia secondary to intensive cytoreductive treatment is a major concern. Besides BM cells, mesenchymal stem cells (MSC) are also used for transplantation. An 8-month-old girl with hypophosphatasia underwent transplantation of haploidentical BM cells followed by two transplants of MSC obtained from her father to facilitate osteogenesis. Fludarabine(Flu)/cyclophosphamide (CPA)/anti-thymocyte globulin were used for myeloablative conditioning, but the patient developed therapy-related leukemia harboring t(9;22)(q34;q11.2); minor BCR-ABL (t-leukemia with Ph) at the age of 32 months. At the age of 40 months she underwent a second BM and third MSC transplant from the same donor. Thereafter, she achieved complete histological and molecular remission. The present case suggests that the combination of cytotoxic agents (Flu/CPA) and MSC led to t-leukemia with Ph as a consequence of chromosome instability and suppression of host anti-tumor immunity.

Microscopic colitis: Is it a spectrum of inflammatory bowel disease?

Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.

Cow's Milk Elimination

Cow's-milk protein is one of the food antigens responsible for causing eosinophilic esophageal inflammation in a majority of children. We describe our experience with treating eosinophilic esophagitis (EoE) in children by eliminating only cow's milk from their diets. This retrospective study assessed the short-term clinical and histological response to eliminating cow's-milk protein from the diet of children with EoE. Only patients undergoing a subsequent upper endoscopy to assess their histological response were included in this analysis. We identified 17 (12 boys and 5 girls) children with EoE who excluded only cow's milk from their diet. Remission was induced in 11 of 17 (65%) patients; within the remission group, 7 (41%) achieved complete histological remission and 4 patients (24%) were in significant histological remission. The mean peak pre- and posttreatment counts for those in remission were 76 ± 40 and 2 ± 4 (P < 0.01), respectively. Elimination of cow's milk-induced clinical and histological remission in 65% (95% confidence interval 42%-88%) of children with EoE in whom it was attempted. This approach offers distinct advantages over other dietary treatment approaches for the initial management of children with EoE. The role of eliminating cow's milk alone for the treatment of EoE warrants further prospective study.

Assessment of the response to gluten-free diet in an Iraqi population with coeliac disease. A histological and serological follow-up study.

IntroductionCoeliac disease (CD) is a common diagnosis among children and adults in Iraq; however, removal of gluten from the diet is essential for patients with CD. The aim of this study, the first such study in Iraq, was to assess the serological and histological recovery profiles of coeliac patients, in both children and adults groups after commencing a gluten-free diet (GFD) for at least 1 year ± 1 month.Material and methodsThe study group comprised 78 proved coeliac patients (46 children and 32 adults, median age: 15 years, range: 1–66 years) who all agreed to undergo endoscopy in addition to serological assessment before and after treatment. The duodenal biopsies were interpreted histologically according to modified Marsh criteria and the sera were tested for anti-gliadin antibody (AGA), endomysium antibody (EMA) and anti-tissue transglutaminase antibody (tTG).ResultsComplete histological remission was seen in 29 (63.1%) of 46 treated children CD patients, while only 5 (10.9%) showed Marsh IIIa changes compared with 11 (24%) before GFD. Similarly none of the 32 adults after GFD showed Marsh IIIb and Marsh IIIc compared with 46.9% and 28.1% before treatment respectively (p = 001). Meanwhile, there was strongly significant reduction in AGA, EMA, and tTG antibodies levels (p = 0.00001) following GFD.ConclusionsRepeating the duodenal biopsy 1 year ±1 month after diagnosis and starting a GFD supports the routine measurement of using histological findings as a gold standard test to confirm recovery of Iraqi CD patients along with using known coeliac serology antibodies.

Erfolgreiche Therapie einer Lichen-planus-Ösophagitis mit topischem Budesonid

Here we describe the first case of symptomatic Lichen planus oesophagitis that was successfully treated with topical budesonide. Lichen planus is a chronic inflammatory disorder of the skin and mucous membranes which is in some cases associated with oesophageal involvement and dysphagia. So far, anecdotal treatment approaches consisted of systemic steroids, retinoids or immunosuppressives. Our patient received oral budesonide suspension 2×1 mg per day for 8 weeks, followed by 2 × 0.5 mg for 3 months. At the end of treatment we observed a complete symptomatic, endoscopic and histological remission, which lasted for at least further 6 months after termination of treatment.

Treatment of Cervical Intraepithelial Neoplasia With Topical Imiquimod

Cervical intraepithelial neoplasia (CIN) is a common disease among women of reproductive age. High-grade CIN lesions (CIN 2–3) are precancerous and can progress to cervical cancer. The most important risk factor for the development of CIN and progression to cervical cancer is persistent high-risk human papillomavirus (HPV) infection. The preferred treatment in most countries is surgical excision using conization. There is high need for a medical treatment alternative to surgical therapy for CIN 2–3 largely because of the risk of preterm birth and other long-term sequelae of cervical conization in future pregnancies. No medical therapy has been established in clinical practice for patients with CIN 2–3. In 2008, a study reported on the efficacy of imiquimod, a topical immune response modulator, against HPV-related vulvar intraepithelial neoplasia. Earlier this year, a randomized controlled trial found that combined use of imiquimod and conization did not improve CIN 2–3 recurrence rates compared with use of conization alone. However, the study had a number of design flaws. A major problem was the application of imiquimod only 5 times before surgery, an uncommon and short treatment regimen. The aim of the present randomized, double-blind, placebo-controlled phase 2 trial was to estimate the therapeutic efficacy of vaginal, self-applied imiquimod in women with high-risk HPV-positive CIN 2–3. Study subjects were 59 patients with untreated, histologically proven, high-risk, HPV-positive, and newly diagnosed CIN 2–3. Eligible women were randomized to receive either treatment with self-applied vaginal suppositories containing imiquimod or placebo for 16 weeks. The primary study outcome was efficacy, defined as histologic regression to CIN 1 or less following treatment. Secondary outcomes included complete histologic remission, HPV clearance, and treatment tolerability. A sample size of 24 patients per group was calculated to detect a 35% absolute increase in CIN 2–3 regression (imiquimod vs. placebo), assuming a 2-sided 5% significance level and a power of 80%. All patients tested positive for high-risk HPV at baseline. After 16 weeks of treatment, histologic regression to CIN 1 or less was achieved in 73% in the imiquimod group compared with 39% in the placebo group (P = 0.009). There was a higher complete histologic remission in the imiquimod group (47%) than in the placebo group (14%) (P = 0.008). Human papillomavirus clearance rates after treatment were 60% in the imiquimod group and 14% in the placebo group (P < 0.001). Complete remission rates among patients with HPV-16 infection were 47% in the imiquimod group and 0% in the placebo group (P = 0.003). Three of the 59 patients (5%), all within the placebo group, were found to have microinvasive cervical cancer after treatment. Topical imiquimod had no high-grade adverse effects; treatment was well tolerated. These findings suggest that vaginal imiquimod therapy is an efficacious, feasible, and well-tolerated medical treatment for patients with CIN 2–3.

Lymphocytic Colitis: A Spectrum of Inflammatory Bowel Disease: A Case Series

Introduction: Lymphocytic colitis (LC) is characterized by chronic diarrhea and specific microscopic changes in a macroscopically normal colonic mucosa. Lymphocytic colitis progressing to ulcerative colitis (UC) has been previously reported, however there is limited data on UC evolving into LC. Here we present a series of five cases with UC subsequently developing into lymphocytic colitis suggesting LC could be a part of the spectrum of inflammatory bowel disease (IBD). Case Report: A total of five cases of UC evolving into LC were identified using a retrospective database study of 876 UC patients diagnosed during years 2001-2011 at the Cleveland Clinic. The median age at the time of UC diagnosis was 34 years. All five patients had a chronic history of UC for a median duration of 15 years prior to being diagnosed with LC by histopathology. Three out of five patients were on treatment for UC with either mesalamine or salfasalazine and the other two patients were treated with either prednisone, mesalamine or 6-mercaptopurine at the time of diagnosis of LC. All patients were under complete remission with medications. On subsequent follow up three out of five people relapsed with intermittent watery diarrhea prompting a colonoscopy which suggested no evidence of active UC but had histological pattern of LC on their random mucosal biopsies. The other two patients were asymptomatic from UC and had evidence of LC during routine surveillance colonoscopic biopsies. Discussion: Lymphocytic colitis, a subtype of microscopic colitis, with chronic inflammatory infiltrates in the colonic mucosa without specific abnormalities noted on endoscopy. We found five patients with longstanding UC who subsequently developed LC. We noted complete histological and/or symptomatic remission in three out of the five cases while two of these patients reverted back into ulcerative colitis suggesting that LC could present as a continuum of UC. There have been case reports of collagenous colitis evolving into ulcerative colitis and vice versa. Literature reveals NF- kB activation occurs early in both collagenous colitis and ulcerative colitis but downstream cellular programs appear different in both. However, in LC the exact molecular mechanism of this histological transformation or the prognostic implications is lacking and requires further evaluation on prospective studies. Until then, it might be prudent to follow up these patients with LC to assess for relapse of UC. We therefore suggest lymphocytic colitis could be part of the spectrum of inflammatory bowel disease.Table: [1160] Cases of ulcerative colitis subsequently developing lymphocytic colitis

Treatment of Cervical Intraepithelial Neoplasia With Topical Imiquimod

Alternatives to surgical therapy are needed for the treatment of high-grade cervical intraepithelial neoplasia (CIN 2-3). We aimed to estimate the efficacy of a treatment with imiquimod, a topical immune-response modulator, in patients with CIN 2-3. Fifty-nine patients with untreated CIN 2-3 were randomly allocated to a 16-week treatment with self-applied vaginal suppositories containing either imiquimod or placebo. The main outcome was efficacy, defined as histologic regression to CIN 1 or less after treatment. Secondary outcomes were complete histologic remission, human papillomavirus (HPV) clearance, and tolerability. Assuming a two-sided 5% significance level and a power of 80%, a sample size of 24 patients per group was calculated to detect a 35% absolute increase in CIN 2-3 regression. Histologic regression was observed in 73% of patients in the imiquimod group compared with 39% in the placebo group (P=.009). Complete histologic remission was higher in the imiquimod group (47%) compared with the placebo group (14%) (P=.008). At baseline, all patients tested positive for high-risk HPV. Human papillomavirus clearance rates were increased in the imiquimod group (60%) compared with the placebo group (14%) (P<.001). In patients with HPV-16 infection, complete remission rates were 47% in the imiquimod group compared with 0% in the placebo group (P=.003). Microinvasive cancer was observed in three of 59 (5% [1-14%]) patients, all within the placebo group. Topical imiquimod treatment was well tolerated, and no high-grade side effects were observed. Topical imiquimod is an efficacious and feasible treatment for patients with CIN 2-3.

Serum and tissue CTACK/CCL27 chemokine levels in early mycosis fungoides may be correlated with disease‐free survival following treatment with interferon alfa and psoralen plus ultraviolet A therapy

Neoplastic T-cell recruitment into the skin is a critical step in the pathogenesis of mycosis fungoides (MF), and the cutaneous T-cell attracting chemokine, CTACK/CCL27, might be involved. To investigate the clinical and prognostic significance of CTACK/CCL27 levels in patients with early-stage MF. Serum samples and skin biopsy specimens were collected from 15 patients at the time of diagnosis and after the end of treatment with psoralen plus ultraviolet A/interferon alfa-2b combination therapy. Serum samples were also collected from 20 healthy donors as controls. CTACK/CCL27 serum levels were analysed by enzyme-linked immunosorbent assays. CTACK/CCL27 tissue expression was determined by immunohistochemistry on skin biopsy specimens taken at diagnosis and after therapy. Event-free survival was taken as the primary clinical outcome. In patients with MF at diagnosis, CTACK/CCL27 serum levels were not significantly different from healthy controls, whereas CTACK/CCL27 expression in the skin was increased in 87% of cases compared with normal controls. After therapy, all patients obtained a clinical complete remission, serum levels did not change significantly and tissue expression remained abnormal in 80% of patients, even if complete histological remission was recorded. Serum levels were not significantly different in cases with different intensity of cutaneous immunostaining. Eight patients experienced a relapse: the combination of high CTACK/CCL27 levels both in sera and skin increased the probability of experiencing an event at 51 months from 36% to 83%. Our data seem to indicate that CTACK/CCL27 levels in skin and sera after therapy might be correlated with risk of recurrence.

Locally advanced esophageal adenocarcinoma: Response to neoadjuvant chemotherapy and survival predicted by [18F]FDG-PET/CT

Background. [18F]fluorodeoxyglycose-Positron Emission Tomography/Computer Tomography ([18F]FDG-PET/CT) is commonly used in staging of locally advanced esophageal cancer. Its predictive value for response to neoadjuvant therapy and survival after multimodality therapy is controversial. Methods. Sixty-six consecutive patients with locally advanced adenocarcinoma of the esophagus or esophagogastric junction underwent surgery after neoadjuvant chemotherapy. Staging was done prospectively with [18F]FDG-PET/CT, before and after completion of neoadjuvant therapy. Pre- and post-therapy maximal standardized uptake values for the primary tumor (SUV1 and SUV2) were determined, and their relative change (SUV∆%) calculated. Percentage change in SUV1 was compared with histopathologic response (HPR, complete or subtotal histologic remission), disease-free- (DFS) and overall survival (OS). Results. Resection with negative margins was achieved in 60 patients. HPR rate was 14 of 66 (21.2%). Median follow-up was 16 months (range 4–72). For all patients, OS probability at three years was 59% and DFS 50%. In receiver operating characteristics (ROC) analysis, HPR was optimally predicted by a > 67% change in baseline maximal SUV (sensitivity 79% and specificity 75%). In univariate survival analysis (Cox regression proportional hazards), HPR associated with improved DFS (HR 0.208, p = 0.033) but not OS (HR 0.030, p = 0.101), SUV % > 67% associated with improved OS (HR 0.249, p = 0.027) and DFS (HR 0.383, p = 0.040). In a multivariate model (adjusted by age, sex, and ASA score), neither HPR nor SUV∆% > 67% was predictive of improved OS and DFS. However, SUV∆% as a continuous variable was an independent predictor of OS (HR 0.966, p < 0.0001) or DFS (HR 0.973, p < 0.0001). Conclusion. Our results support previous results showing that [18F]FDG-PET/CT can distinguish a group of patients with worse prognosis after neoadjuvant chemotherapy in adenocarcinoma of the esophagus or esophagogastric junction. This information could offer a new independent preoperative marker of prognosis.

Auto-SCT in refractory celiac disease type II patients unresponsive to cladribine therapy

Autologous hematopoietic SCT (auto-SCT) has been effective therapy for refractory disease, in both malignancies and severe autoimmune diseases. It seems feasible and safe for refractory celiac disease (RCD) type II, although long-term results have not been evaluated yet. With current therapies, progression into enteropathy-associated T-cell lymphoma (EATL) occurs in 60-80% patients, with a high mortality rate. Therefore, it is important to evaluate new treatment strategies. Between March 2004 and February 2010, 18 RCD II patients were evaluated for auto-SCT preceded by conditioning with fludarabine and melphalan, as a consequence of unresponsiveness to cladribine therapy. Adverse events, survival rate, EATL development and change in clinical, histological and immunological course were monitored. Thirteen patients were transplanted successfully and followed up for >2 years, 4-year survival rate was 66%. Only one patient died because of transplant-related complications. The majority of patients showed an impressive clinical improvement and five a complete histological remission. In five patients, auto-SCT could not be performed; they all died with a median survival of 5.5 months. EATL was observed in one transplanted patient, only after 4 years of follow-up. Auto-SCT after conditioning with high-dose chemotherapy in RCD II patients unresponsive to cladribine therapy is feasible and seems promising.

Sirolimus addition to tacrolimus-based immunosuppression induces complete remission of post-transplant lymphoproliferative disorder in a liver transplant recipient

Sirolimus addition to tacrolimus-based immunosuppression induces complete remission of post-transplant lymphoproliferative disorder in a liver transplant recipient

Successful treatment of three cases of primary extramammary Paget’s disease of the vulva with Imiquimod – proposal of a therapeutic schedule

Extramammary Paget's disease (EMPD) is an intraepidermal adenocarcinoma of apocrine gland-bearing skin. Although surgery remains the mainstay of treatment, loss of tissue function and high recurrence rates have been reported. Recently, topical Imiquimod has been shown as a safe and effective treatment option for extramammary Paget's disease. Three patients diagnosed of EMPD of the vulva were treated with a daily application of 5% Imiquimod cream for three weeks, followed by an every other day application for an additional three weeks. Complete clinical and histological remission of the disease was achieved in the three patients. Mild irritation and tenderness were observed as the only side effects. Based on our results, we consider that Imiquimod cream is a safe and effective therapeutic option for the treatment of vulvar EMPD. These promising results warrant further studies to determine the real efficacy and safety of Imiquimod 5% cream for the treatment of this uncommon disease.

Follicular mucinosis: Clinical, histologic, and molecular remission with minocycline

Follicular mucinosis is an uncommon inflammatory disorder characterized histologically by mucin accumulation in the follicular epithelium. The condition is generally divided into primary and secondary forms, the latter being frequently associated with mycosis fungoides. Lesional skin T-cell clonality has been documented in some patients with follicular mucinosis, even those with no histologic evidence of cutaneous lymphoma. In this report, we describe a patient with clonal idiopathic primary follicular mucinosis who had complete clinical, histologic, and molecular remission with minocycline therapy.