5-year Remission Rate Research Articles

Pediatric Inflammatory Bowel Disease Type Unclassified: A Nationwide Cohort Study in Scotland With up to 20 Years Follow-up Shows Reclassification in the Majority and Mild Course in Those Whose Diagnosis Is Unchanged.

Given the paucity of long-term longitudinal data for inflammatory bowel disease type unclassified (IBDU), we aimed to clarify IBDU disease course and reclassification rate by presenting nationwide data with up to 20 years of follow-up. We analyzed a prospectively identified 11-year cohort of pediatric patients diagnosed with IBDU between January 1, 2003 and December 31, 2013 at all Scottish pediatric IBD centers and followed up into adult services until December 31, 2022. Data were obtained from electronic medical records at fixed timepoints (5 and 10 years post-diagnosis) and at the final follow-up. Overall, 102 patients were included in the analysis (57/102 [56%] male, median [interquartile range {IQR}] age at diagnosis: 11.5 [9.1-13.2] years) with a median (IQR) follow-up length of 10.5 (8.6-14.0) years. A change of diagnosis was made in 61 of 102 patients (60%); of these, 30 patients (29%) were reclassified to Crohn's disease (CD) and 31 patients (30%) to ulcerative colitis (UC). Patients who remained with IBDU had higher 1- to 5-year remission rates (IBDU 30/39 [77%] vs reclassified 16/57 [28%], P < .05), with lower rates of moderate-to-severe disease (IBDU 3/39 [8%] vs reclassified 31/57 [54%], P < .05) and less need for biologics across all timepoints (IBDU vs reclassified: first timepoint 1/39 [3%] vs 17/57 [30%], second timepoint 1/33 [3%] vs 26/56 [46%], third timepoint 0/18 [0%] vs 16/33 [49%]; all P < .05). Higher rates of surgical resections were observed in reclassified patients (reclassified 11/61 [18%] vs IBDU 1/41 [2%], P = .02). In our nationwide pediatric IBDU cohort, 60% of patients were reclassified to either UC or CD over 10.5 years of median follow-up; those who remained with IBDU had a milder disease course.

Treatment Patterns and Preferences for Graves' Disease in Korea: Insights from a Nationwide Cohort Study.

Treatment patterns and preferences for patients with Graves' disease (GD) vary across countries. In this study, we assessed the initial therapies and subsequent treatment modalities employed for GD in real-world clinical practice in Korea. We analyzed 452,001 patients with GD from 2004 to 2020, obtained from the Korean National Health Insurance Service database. Initial treatments included antithyroid drug (ATD) therapy (98% of cases), thyroidectomy (1.3%), and radioactive iodine (RAI) therapy (0.7%). The rates of initial treatment failure were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Even among cases of ATD treatment failure or recurrence, the rates of RAI therapy remained low. Regarding initial treatment, the 5-year remission rate was 46.8% among patients administered ATDs versus 91.0% among recipients of RAI therapy; at 10 years, these rates were 59.2% and 94.0%, respectively. Our findings highlight a marked disparity in the use of RAI therapy in Korea compared to Western countries. Further research is required to understand the reasons for these differences in treatment patterns.

Proteomics Landscape and Machine Learning Predictor of Response to Splenectomy in Immune Thrombocytopenia

Introduction Immune thrombocytopenia (ITP) is an auto-immune disease characterized by antibody-mediated platelet destruction. Splenectomy remains the effective curative treatment for patients with ITP who failure to respond to TPO-RAs and/or rituximab (Mageau et al, Am J Hematol. 2022). The effectiveness rate of splenectomy for ITP is reported to be roughly 80%, with a 5-year remission rate ranging from 50% to 75% (Chaturvedi et al, Blood. 2018). For subjects presenting with severely low platelet counts or active bleeding, splenectomy represents the primary approach for rapidly increasing platelet levels and potentially saving lives. To achieve personalized and precise treatment, the prediction efficacy on splenectomy remains an urgent problem. Here, we have characterized immune features of ITP patients with splenectomy, and developed a predictive model for assessing the response to splenectomy. Methods Bone marrow plasma samples before splenectomy were collected and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Weight protein co-expression network analysis (WPCNA) was applied to generate modules from all proteins and mapped them to clinical characteristics. We used least absolute shrinkage and selection operator (Lasso) regression, recursive feature elimination (RFE) for predictors selection. Next, multivariable logistic regression (LR), support vector machine (SVM), and decision tree algorithms were used to develop a predictive model. Results 60 patients with ITP undergoing splenectomy treatment were enrolled into our study, and divided into three groups according to the response [patients with CR (n=30), NR (n=7), and Relapse (n=23)]. A pathway enrichment analysis of WPCNA modules by ClueGO revealed that megakaryocyte differentiation, humoral immune response mediated by circulating immunoglobulin, Fc receptor signaling pathway, and cGMP-PKG signaling pathway were correspondingly enriched in MEtan, MEturquoise, MEblue, and MEpink modules, which were associated with treatments with TPO-RA, IVIG, rhTPO, and post-operation platelet level, respectively. We then performed KEGG pathway enrichment analyses on the different expression proteins (DEPs) to deciphering the immune landscape among each group. For the relapse group, DEPs were primarily enriched in ribosome, spliceosome, neutrophil extracellular trap formation, and necroptosis pathways, comparing with the CR group. For the NR group, most DEPs were enriched in natural killer cell mediated cytotoxicity, NF-kappa B signaling, Fc gamma R-mediated phagocytosis pathways, comparing with the CR group. The models were based on a multi-step predictor pipeline. Inside the pipeline, features were first filtered by lasso regression and RFE algorithm. We identified five proteomic features present in the bone marrow plasm that associated with relapsed to therapy, which included CD40, COL4A3, GALNT6, GSTM3, and UBE2A (Figure). Each ensemble consisted of three algorithms acting in parallel: LR, SVM and decision tree. The AUC values of LR, SVM, and decision tree were 0.962 (95%CI: 0.915-1), 0.957 (95%CI: 0.897-1), and 0.875 (95%CI: 0.782-0.967), respectively. The three algorithms were then tested for performance. The sensitivity, specificity, positive predictive value, and negative predictive value analysis revealed that LR model reached the best performance. Targeting CD40 represents a promising therapeutic approach for enhancing clinical outcomes in patients with ITP who have shown inadequate response following splenectomy. Conclusion Our analysis revealed that ITP patients with splenectomy showed distinct immune characteristics when achieving different response. Protein features extracted from bone marrow plasma can be selected as predictors of response to splenectomy.

ODP286 A Case of Synchronous Growth Hormone and Adrenocorticotrophic Hormone Secretion in a Patient with an Incidental Pituitary Adenoma.

Abstract The most common type of co-secreting functional pituitary adenoma is a tumor-producing growth hormone and prolactin. Other types of co-existing functioning adenomas are extremely rare. We present a 68-year-old male patient with a pituitary adenoma presenting with acromegaly and Cushing's disease (CD). A 68-year-old male was referred for an incidental pituitary macroadenoma found on magnetic resonance imaging (MRI) for his chronic nasal congestion. He denied headaches or blurry vision. He reported an increase in shoe size, worsening hypertension and diabetes, and a 40-pounds weight gain over several years. Past medical history included arthritis, type two diabetes mellitus, hypertension, sleep apnea, hypogonadism, chronic kidney disease, and coronary artery disease. Physical exam was notable for BMI of 51 kg/m2 and enlarged hands and feet. No stigmata of Cushing's syndrome were present. MRI showed a 2. 0×2.5 cm sellar mass involving the right cavernous sinus without a mass effect on the optic chiasm. Laboratory workup showed an elevated IGF-1 level of 703 ng/mL and 678 on repeat, growth hormone (GH) 1.1 ng/mL, adrenocorticotropic hormone (ACTH) 41 pg/mL, and am cortisol 15 mcg/dL. Am cortisol after 1 mg of dexamethasone was 6.2 mcg/dL with an appropriate dexamethasone level. His and 24-hour urine-free cortisol was elevated at 87.1 mcg/24h, HgbA1C was 8.3%, testosterone level was low, and PRL and thyroid levels were normal. He underwent transsphenoidal surgery (TSS). Postoperative morning cortisol day 1 was 18.9 mcg/dL. Pathology showed a sparsely granulated somatotroph adenoma. Seven days post-surgery, he presented with diplopia, ophthalmoplegia, and ptosis. MRI showed enlargement of the right cavernous sinus with possible residual tumor and blood products. He underwent a second TSS with evacuation of a hematoma. The patient's nadir postoperative serum cortisol was 14.4 mcg/dL and IGF-1 level 513 ng/mL one month after his initial surgery. Pathology showed organizing hemorrhage and necrotic pituitary adenoma. His ophthalmoplegia resolved, and diplopia partially improved. The synchronous occurrence of CD and acromegaly is an extremely rare condition. It can be secondary to either a plurihormonal adenoma or two functional adenomas. In our case, the pathology findings suggest double adenomas. Surgical resection is first-line therapy for acromegaly and CD. Stereotactic radiosurgery and medical therapy are second-line options in persistent disease. The 5-year remission rates with Gamma Knife radiosurgery are higher in CD (81%) as compared to acromegaly. 1 Pasireotide, a somatostatin receptor ligand approved for both CD and acromegaly. Worsening glycemic control is a significant challenging aspect of its use. Presentation: No date and time listed

Evaluation of appropriate treatment for IgA nephropathy with mild proteinuria and normal renal function.

Tonsillectomy and steroid pulse therapy (TSP) for immunoglobulin A nephropathy (IgAN) is frequently employed in many Japanese institutions; however, performing this invasive treatment in patients with mild IgAN is controversial. This study aimed to evaluate the appropriate treatment for IgAN patients with mild proteinuria. In this retrospective cohort analysis, 122 IgAN patients with mild proteinuria (0.5-1.0g/day) and estimated glomerular filtration rate of ≥ 60mL/min/1.73 m2 were classified into three groups as follows: patients treated with TSP (n = 32), oral prednisolone (oPSL, n = 33), and conservative therapy (CONS, n = 47). The clinical and histological backgrounds, 5-year remission rates of urinary findings, and 10-year renal survival rates were analyzed. The backgrounds were similar among the three groups. The remission rates of hematuria, proteinuria, and both were significantly higher for TSP and oPSL than for CONS; however, they were similar for TSP and oPSL. In the multivariate Cox regression analysis, TSP and oPSL were independent factors for the remission of urinary findings compared with CONS; however, the relapse rates of urinary abnormalities were similar among the three groups. No patient progressed to end-stage renal disease (ESRD) within 10years. Adverse effects of corticosteroid therapy were significantly more frequent in oPSL than in TSP. In IgAN patients with mild proteinuria and stable renal function, similar to oPSL, TSP showed higher remission rates of hematuria and/or proteinuria than CONS, and no case progressed to ESRD regardless of the treatment methods. Therefore, appropriate treatments should be carefully considered for each patient.

5-year remission rate after the discontinuation of adalimumab in patients with rheumatoid arthritis: Long-term follow-up results of the HONOR study

Objectives: To determine the rate and factors associated with remission (disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) of <2.6) during a 5-year follow-up after the discontinuation of adalimumab (ADA) in patients with rheumatoid arthritis (RA).Methods: 75 patients who had been treated with ADA + methotrexate (MTX) and maintained DAS28-ESR <2.6 for at least 6 months were enrolled. Among them, 52 patients discontinued ADA, and 46 patients completed a 5-year follow-up.Results: During the 5 years, 11 patients had DAS28-ESR <2.6. In 15 patients with DAS28-ESR <3.2, no significant changes were found in the health assessment questionnaire disability index (HAQ-DI) and modified total Sharp score (mTSS). When comparing patients with DAS28-ESR ≤1.61 versus 1.61 <DAS28-ESR <2.6, 50% and 15% of the two groups demonstrated sustained remission, respectively. Remission was more common in patients with shorter disease duration (≤2 years) than those with longer duration (>2 years). Among 31 patients who experienced flare, ADA was restarted in 24 patients, and 17 patients of these achieved DAS28-ESR <3.2 within 1-year.Conclusion: During the 5-year ADA-free period, remission rate was persistent in 21% of the patients. ADA-free remission was possible especially in patients with deeper remission (DAS28-ESR ≤1.61) and shorter disease duration (≤2 years).

The impact of tonsillectomy combined with steroid pulse therapy in patients with advanced IgA nephropathy and impaired renal function.

Preventing progression to end-stage renal disease (ESRD) in advanced IgA nephropathy (IgAN) patients with impaired renal function remains challenging. We analyzed the efficacy of tonsillectomy combined with steroid pulse therapy (TSP). In this retrospective analysis, IgAN patients with proteinuria > 0.5g/day and estimated glomerular filtration rate (eGFR) < 60mL/min/1.73 m2 were divided into three groups: patients treated with TSP (TSP group; n = 23), oral prednisolone (oPSL group; n = 41), and conservative therapy (CONS group, n = 51). We analyzed the clinical and histological backgrounds, remission of urinary findings, and renal survival rate to a 25% decline in eGFR from baseline, and incidence of ESRD. There were significant differences in the patients' backgrounds among the groups. Therefore, we adjusted the background using propensity score marching between TSP group and oPSL or CONS group. The 5-year remission rate of hematuria was significantly higher in the TSP group than in the oPSL group, and that of both hematuria and proteinuria was significantly higher in the TSP group than in the CONS group. The 10-year renal survival rate was significantly higher in the TSP group than in the oPSL and CONS groups. In a multivariate Cox regression analysis, TSP was found to be an independent factor for the 25% decline in eGFR in entire cohort. The adverse effect frequency in the TSP group was similar to the CONS group. TSP can effectively induce remission of urinary abnormality and improve the prognosis without frequent adverse effects in IgAN patients with impaired renal function.

Clinical Course of Chronic Spontaneous Urticaria in the Korean Adult Population.

Knowledge of the clinical course of chronic spontaneous urticaria (CSU) remains unclear. The purpose of our study was to investigate the clinical course of CSU in the Korean adult population. Each patient in the CSU group who was defined by disease codes between 2003 and 2007 was tracked whether he or she went into remission or not until 2013. Kaplan-Meier survival analysis was carried out to analyze remission, and log-rank tests were performed for between-group comparisons. Demographic differences between subjects who went into remission 1 year after the initial diagnosis and those who did not were analyzed using χ2 tests. A total of 13,969 subjects were included in the CSU group. The 1-, 2-, 3-, 4-, and 5-year remission rates of CSU were 21.5%, 33.0%, 38.9%, 42.6%, and 44.6%, respectively. The proportion of subjects in the 65+ age group (P=0.050) and with male gender (P=0.002) was significantly higher among subjects who did not go into remission 1 year after the initial diagnosis. Our study indicates that CSU could have a more persistent course than previously reported.

Laparoscopic Heller myotomy is not superior to pneumatic dilation in the management of primary achalasia: Conclusions of a systematic review and meta-analysis of randomized controlled trials.

Achalasia is an esophageal motility disorder, of unknown cause, which results in increased lower esophageal sphincter tone and symptoms of difficulty swallowing. Current major therapeutic options include laparoscopic Heller myotomy (LHM) and pneumatic dilation (PD). We undertake a systematic review comparing the efficacy and safety of these 2 treatments in the treatment of esophageal achalasia. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trial investigating LHM versus PD in the treatment of primary achalasia. The primary outcome was symptom remission rates. The Mantel-Haenszel method with fixed-effect or random-effects model was used to calculate relative risks and 95% confidence intervals (CIs). Five studies involving 498 participants were included. The cumulative remission rate was significantly higher with LHM at 3 months and 1 year (short-term), with a risk ratio of 1.16 (95% CI 1.01-1.35, P = 0.04) and 1.14 (95% CI 1.02-1.27, P = 0.02), respectively. There were no significant differences between LHM and PD in 2-year and 5-year remission rate (long-term), with a risk ratio of 1.05 (95% CI 0.91-1.22, P = 0.49) and 1.17 (95% CI 0.84-1.64, P = 0.34), respectively. Rates of major mucosal tears requiring subsequent intervention with LHM were significantly lower than those of esophageal perforation with PD requiring postprocedural medical or surgical therapy, with a risk ratio of 0.25 (95% CI 0.08-0.81, P = 0.02). Postprocedural rates of gastroesophageal reflux, lower esophageal sphincter pressures, and quality of life scores did not differ in trials with sufficient data. There were no significant differences between LHM and PD in 2-year and 5-year remission rate. This study indicates that either treatment can be proposed as initial treatment for achalasia.

Drug survival and reasons for discontinuation of the first biological disease modifying antirheumatic drugs in Thai patients with rheumatoid arthritis: Analysis from the Thai Rheumatic Disease Prior Authorization registry

To evaluate and compare the retention rate of biological disease-modifying antirheumatic drugs (bDMARDs) in real-life practice and identify risk factors related to remission and drug discontinuation in patients with rheumatoid arthritis (RA). A total of 256 patients fulfilling criteria for RA and starting bDMARD between December 2009 and October 2014 were selected from the Rheumatic Disease Prior Authorization registry. Baseline demographic and clinical data were recorded. The cumulative probability of bDMARD discontinuation over 5 years of follow-up and factors associated with RA remission and bDMARD withdrawal were analyzed. Almost half (46%) of patients were initially treated with rituximab (RTX), with 33% treated with etanercept (ETN) and 21% with infliximab (IFX). Fewer than 10% were subsequently switched to a second bDMARD. The 1- and 5-year remission rates in patients continuing their first bDMARD were 7.2% and 21.5%, respectively. At 5 years, the drug survival rates for RTX, ETN and IFX were 50%, 25% and 22%, respectively. Multivariate analysis showed that RTX was significantly associated with highest drug survival. Relative to RTX, the hazard ratios for discontinuation of IFX and ETN were 2.60 (95% confidence interval [CI] 1.53-4.42) and 2.15 (95% CI 1.36-3.42), respectively. Thirty-nine percent of patients stopped treatments, due to inadequate response (42%), serious adverse events (22%), nonadherence (14%) or remission/low disease activity (13%). Over 5 years, only one-third of patients continued using their first bDMARD. The leading cause of drug discontinuation was inadequate response.

Abstract B05: Mesenchymal-driven hedgehog signaling drives tumor cell growth and is a potential new target for triple-negative breast cancer

Abstract Triple negative breast cancer (TNBC) is a clinical therapeutic challenge due to the lack of receptors for estrogen, progesterone, and human epidermal growth factor receptor 2 which limits treatment options to chemotherapy and radiation. With current standard therapy less than 30% will survive the 5-year remission rate, especially Hispanic and African-American women where TNBC is more frequent and has the lowest (&amp;lt;14%) 5-year survival rates. Recent studies indicate that Hedgehog (Hh) signaling is active and correlates with reduced survival rates in TNBC patients. However, the role of the Hh signaling in the breast tumor microenvironment is not well understood. A main cellular mediator of Hh signaling is the adjacent mesenchyme which promotes tumor growth via a paracrine interaction, but which is also highly heterogeneous. As mesenchymal sub-types have been associated to specific pharmacological therapies, understanding of the mechanisms in mesenchymal-driven tumors is necessary for combinatorial pharmacological treatments that can increase survival rates and eliminate tumor relapse in patients. We developed a tumor-mesenchymal in vitro model to evaluate the role of mesenchymal cell sub-types from different sources in the proliferative potential and stem cell markers of breast cancer cells using a custom designed multiwell array. Cells were culture in adjacent compartments and active Hh signaling was confirmed by up-regulation of canonical Hh target genes Gli1, Patch1 and SMO. As a source of mesenchymal cell sub-types we evaluated TGF-β treated fibroblasts, cancer- associated and normal breast primary fibroblasts, and tumor epithelial cells that undergo epithelial-mesenchymal transition (EMT). Paracrine Hh signaling significantly increased proliferation (5-10%) of tumor cells after 72-96hrs in co-culture. Cells that undergo EMT promoted cell growth at higher rates than myofibroblasts. SHH treatment alone (without TGF-β pre-treatment) had an inhibitory effect in the proliferation rates of the adjacent epithelium compartment. Observed increase in tumor cell proliferation was abolished when treated with the Hh signaling inhibitor cyclopamine. Stem cell surface markers CD44+CD24- remained unchanged but a significant increase was observed in the proliferating CD44+/CD24+ sub-population. Similar results were observed in normal human breast cells suggesting that activation of Hh signaling in the mesenchyme is sufficient to promote cell growth in the epithelium. Computational analysis of a panel of genes associated to Hh signaling in breast cancer patients (&amp;gt;500 samples) show a strong correlation among TNBC patients and mesenchymal-driven Hh signaling in &amp;gt;80% of samples. We evaluated the distribution of mesenchymal cell-sub-types and stem cells among the sub-set of basal TNBC samples (82 samples). Gene markers associated to myofibroblasts, EMT, mesenchymal stem cell and cancer stem cell were found in samples with active Hh signaling and co-expressed in groups of two or more which represented the 45.6% of the total samples. The most abundant cell sub-type were cancer stem cells with 43% of the total samples and alone by itself in 13.9% of samples. Together, these results indicate that the Hh-pathway and adjacent tumor microenvironment are key players in the progression of TNBC. Mesenchymal cell component can modulate tumor growth behavior induced by Hh signaling and is a potential new clinical target for TNBC. Citation Format: Maribella Domenech, Karla P. Ramos, Wandaliz Torres, Fernando Boria. Mesenchymal-driven hedgehog signaling drives tumor cell growth and is a potential new target for triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr B05.

Leukemia Therapy: Mechanisms of Drug Resistance and Investigational Strategies

Certain types of leukemia are amongst the first neoplasias to be “cured” with relatively high 5-year remission rates. This is largely due to targeted therapeutics. However, considerable resistance to tumor-specific targeting drugs has developed due to the presence of abundant cancer stem cells, profound genetic diversity, redundant growth/survival pathways and residual disease. Although these issues propose a challenge, they also provide the opportunity for novel innovations of therapy which currently include the development of multi-target kinase inhibitors, multiple drugs acting on multiple targets, key upstream targets covering multiple downstream targets and the future direction of hybrid molecules targeting two or more targets in different pathways.

Medium and Long-term Outcomes After Pneumatic Dilation or Laparoscopic Heller Myotomy for Achalasia

Recent randomized studies comparing outcomes after pneumatic dilation (PD) and laparoscopic Heller myotomy (LHM) for the treatment of achalasia are conflicting and limited to short-term follow-up. Our meta-analysis compared the long-term durability of these approaches, with the hypothesis that LHM offers superior long-term remission compared with PD. We identified 36 studies published between 2001 and 2011 with at least 5 years of follow-up. Those studies describing PD included 3211 patients (mean age, 49.8 y). For PD, the mean 5-year remission rate was 61.9% and the mean 10-year remission rate was 47.9%. Overall, 1526 patients (mean age, 46.3 y) were treated with LHM; 83% received a fundoplication. In contrast, the mean 5- and 10-year remission rates after LHM were 76.1% and 79.6%, respectively. Finally, the perforation rate for LHM was twice that of PD (4.8% vs. 2.4%; P<0.05). We conclude that despite a higher frequency of perforation, LHM affords greater long-term durability.

Remission of seizures in a population-based adult cohort with a newly diagnosed unprovoked epileptic seizure.

To investigate the probability of achieving remission of seizures after a newly diagnosed unprovoked epileptic seizure in an adult population-based cohort. 107 patients aged 17 years or older with a newly diagnosed unprovoked epileptic seizure (index seizure) in 1985 through 1987 were followed up until the date of death or to the end of 1996. The proportion of cases during follow-up that attained a 1-year, 3-year, 5-year remission was calculated by actuarial analyses. Variables for stratification were age at diagnosis, seizure type, etiology, EEG, and the occurrence of seizures within 1 year of initiation of antiepileptic drug (AED) therapy. Cumulative 1-, 3- and 5-year remission rates were 68, 64, and 58%. There was no statistically significant difference regarding time points of achieving a 1-year remission after epilepsy diagnosis and the subsequent probability during follow-up of attaining a 5-year remission. Having seizures within 1 year after beginning with an AED was a statistically significant predictor of never achieving 1-year remission of seizures during follow-up (refractory seizures). Other stratified variables were not statistically significant predictors. Seizure prognosis for the majority of patients with newly diagnosed epilepsy is good. The time required after epilepsy diagnosis to achieve a 1-year remission of seizures does not affect the probability of additionally achieving a 5-year remission. Patients with refractory seizures can be identified within a few years from diagnosis of epilepsy. These patients must be targeted early for optimization of pharmacologic treatment, possible surgery, and psychosocial intervention.

Complications and their impact after pneumatic dilation for achalasia: prospective long-term follow-up study

Background: With the exception of esophageal perforations, complications of pneumatic dilation are incompletely defined. This study analyzes the incidence of all complications of this procedure and their impact on the patients' clinical course. Methods: Sixty-seven consecutive patients with achalasia underwent pneumatic dilation with a Browne-McHardy dilator. Patients were observed for 24 hours after treatment and evaluated 4 weeks later as well as at 2-year intervals for a mean follow-up period of 4.9 ± 3.8 years. In patients with and without complications, the length of remission was evaluated by Kaplan-Meier life table analysis. Results: Twelve patients (18%) developed morphologic complications consisting in one perforation, two intramural hematomas, and nine diverticula at the gastric cardia. Ten patients (15%) complained of prolonged postdilation chest pain. The 5-year remission rate in the latter patients was 51% compared to 42% for patients without complications and 11% for patients developing traumatic diverticula. Surgery was ultimately performed in one third of all patients, a rate that remained unaffected by the type of complication. Conclusions: Complications of pneumatic dilation are underestimated and underreported. More than 30% of all patients develop either prolonged pain or morphologic lesions. Although prolonged pain does not indicate an unfavorable prognosis, the appearance of diverticula may be associated with a shorter clinical remission. (Gastrointest Endosc 1997;45:349-53.)

子宮頚部病変のレーザー蒸散療法

Between 1979 and 1991, three hundred and sixty-five patients with biopsy proven cervical intraepithelial neoplasia (CIN) with satisfactory colposcopy were treated with the carbon dioxide laser in an outpatient setting and 293 have been followed for one year to 12 years after the laser vaporization. There have been 43 treatment failures, of which 56%of the patients had the second lesion detected during the first year of follow-up. The second lesion consisted of 22 mild dysplasias, 14 moderate dysplasias, 4 severe dysplasias, and 3 CIS. In 6 cases, the grade of the second lesions were higher than that before the laser treatment. There have been no case diagnosed as invasive cancer after laser treatment. The estimated 5-year remission rates calculated by Kaplan-Meier methods were 81.6%for mild dysplasia, 8 2.2%for moderate dysplasia, 82.6%for severe dysplasia and 92.0%for CIS. Of the 43 failures, 11 of the lesions disappeared spontaneously, 26 were treated with repeated laser vaporization, and 6 were treated by conization and/or hysterectomy. Four of the patients with repeated laser recurred and were treated by conization or TVH. All the failure cases have been followed for more than one year after the last treatment and found to have no evidence of disease. Consequently, 283 of 293 cases (96.6%) have been managed satisfactorily by laser treatment alone at outpatient setting. No patients experienced postoperative infection or bleeding requiring hospitalization. These results reconfirm the efficacy and safety of laser vaporization for all form of CIN.

Radiotherapy of primary carcinoma of the vagina: Management and results of different therapy schemes

Three hundred and sixty-two cases of primary vaginal carcinoma were treated at the Irradiation Department of the University Clinic for Obstetrics and Gynecology, Vienna, from 1950 to 1977. As the method of choice an individually dosed, fractioned, and protracted radium-telecobalt therapy was employed. Comparing the last period analyzed (1971–1977) with another period 20 years earlier (1951–1956), a marked increase of advanced stages and older patients can be observed. These changes are reflected in the 5-year remission rate: in the total population it was 39.8%, as compared to 32% for the period from 1971 to 1977. For a group of 99 patients, who were treated between 1971 and 1977, the therapeutic effect of different therapy schemes is reported. The benefit of teletherapy is remarkable for advanced states, whereas for stages I and II an intrauterine application may be of importance. The complication rate amounted to 8% recto- or vesicovaginal fistulas and 41% and 43% cystitis and proctitis. The central importance of gynecological screening, especially for older women, is emphasized.