Cumulative Relapse-free Survival Rate Research Articles

Clinical manifestations, diagnosis and long-term prognosis of adult autoimmune enteropathy: Experience from Peking Union Medical College Hospital

BACKGROUND Autoimmune enteropathy (AIE) is a rare disease whose diagnosis and long-term prognosis remain challenging, especially for adult AIE patients. AIM To improve overall understanding of this disease’s diagnosis and prognosis. METHODS We retrospectively analyzed the clinical, endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023, whose diagnosis was based on the 2007 diagnostic criteria. RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea. The common endoscopic manifestations were edema, villous blunting and mucosal hyperemia in the duodenum and ileum. Villous blunting (100%), deep crypt lymphocytic infiltration (67%), apoptotic bodies (50%), and mild intraepithelial lymphocytosis (69%) were observed in the duodenal biopsies. Moreover, there were other remarkable abnormalities, including reduced or absent goblet cells (duodenum 94%, ileum 62%), reduced or absent Paneth cells (duodenum 94%, ileum 69%) and neutrophil infiltration (duodenum 100%, ileum 69%). Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies. All patients received glucocorticoid therapy as the initial medication, of which 14/16 patients achieved a clinical response in 5 (IQR: 3-20) days. Immunosuppressants were administered to 9 patients with indications of steroid dependence (6/9), steroid refractory status (2/9), or intensified maintenance medication (1/9). During the median of 20.5 months of follow-up, 2 patients died from multiple organ failure, and 1 was diagnosed with non-Hodgkin’s lymphoma. The cumulative relapse-free survival rates were 62.5%, 55.6% and 37.0% at 6 months, 12 months and 48 months, respectively. CONCLUSION Certain histopathological findings, including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies, might be potential diagnostic criteria for adult AIE. The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressant medications, which highlights the need for early diagnosis and novel medications.

The association between dental caries and steroid-sensitive nephrotic syndrome in children.

Pathogenesis and relapse of steroid-sensitive nephrotic syndrome (SSNS) are primarily associated with infection. Dental caries is the most common chronic progressive oral infection in children. However, clinical studies of SSNS combined with dental caries in children are rare. In our retrospective cohort study from January 2021 to June 2022, 145 children with SSNS were included in the baseline analysis and 105 in the follow-up analysis. The follow-up period was 1year. The primary study endpoints were the relapse-free period and frequently relapsing nephrotic syndrome (FRNS). Secondary endpoints included the number and triggers of relapses and concomitant medications. The median age was 5.5years, with a caries rate of 60.7%, themean DMFT/dmft was 3.86, and the caries filling rate was 1.6%. Except for the lower proportion of high household income and high parental education observed in the caries group, no statistical differences were found when comparing the other baseline data with the non-caries group. The caries group had a shorter relapse-free period and a lower 1-year cumulative relapse-free survival rate (HR = 1.90, 95% CI 1.17-3.09, P = 0.009). Univariate regression analysis showed caries associated with FRNS (OR = 2.714, 95% CI 1.021-7.219, P = 0.045), but the correlation no longer remained in the multivariate analysis. Additionally, seven cases of caries-derived pulpal periapical inflammation triggered SSNSrelapses. The caries group had more infection triggers and concomitant medication use. Dental caries and relapse of SSNS are potentially associated, but careful evaluation is needed. A higher resolution version of the Graphical abstract is available as Supplementary information.

Thiopurine naivety at tacrolimus induction is a predictor of long-term remission in patients with intractable ulcerative colitis who responded to tacrolimus.

The short-term efficacy of tacrolimus (Tac) for steroid-dependent and steroid-resistant refractory ulcerative colitis (UC) has been demonstrated; however, its long-term outcomes have not been well documented. Thus, this study aimed to clarify the long-term outcomes of patients who achieved Tac-induced remission and identify its predictors. This study included patients with moderate-to-severe active UC who started receiving Tac at our hospital between July 2004 and December 2016. Short-term treatment response was assessed using the Lichtiger index 3months after starting Tac, and responding patients were further followed up to assess long-term outcomes. The primary endpoint was the relapse-free survival after Tac-induced remission, and the secondary endpoint was the identification of factors associated with relapse after Tac-induced remission. The cumulative relapse-free survival rate at 10years after Tac-induced remission was 33.2%. Multivariate analysis revealed that being thiopurine naïve at Tac induction was associated with the absence of relapse (hazard ratio: 0.45; 95% confidence interval: 0.22-0.92). Approximately one-third of patients who achieved Tac-induced remission maintained long-term remission. Being thiopurine naïve at Tac induction was a predictor of the absence of relapse.

Anti-Citrullinated Peptide Antibody Expression and Its Association with Clinical Features and Outcomes in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background and objectives: Anti-citrullinated peptide antibody (ACPA), a characteristic antibody detected in rheumatoid arthritis, could be linked to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) via the formation of neutrophil extracellular traps. We investigated the rate of ACPA positivity in patients with AAV and evaluated the association of ACPAs with their clinical features and outcomes. Materials and Methods: A total of 168 AAV patients with both ACPA and ANCA results at diagnosis were identified. Clinical and laboratory variables, including the disease-specific indices of Birmingham Vasculitis Activity Score (BVAS) and Five-Factor Score (FFS), were investigated. All-cause mortality, relapse, and end-stage renal disease, as well as interstitial lung disease (ILD) were evaluated as outcomes of the patients, and the Kaplan–Meier survival analysis was used to compare the event-free survival rates of the groups. Results: Fifteen (8.9%) and 135 (80.4%) patients were positive for ACPA and ANCA, respectively. There were no significant differences in the baseline variables of ACPA-negative and ACPA-positive patients. The absolute titre of ACPAs also did not significantly correlate with BVAS, FFS, erythrocyte sedimentation rate, or C-reactive protein. In addition, there was no difference noted regarding overall, relapse-free, and ESRD-free survival rates between ACPA-negative and ACPA-positive AAV patients. However, when the patients were divided into four groups according to ACPA and ANCA status, differences were present in the outcomes, and the ACPA-positive ANCA-positive group exhibited the lowest cumulative relapse-free survival rate, while no significant difference was present in the relapse between the ANCA-positive ANCA-positive, ACPA-positive ANCA-negative, and ACPA-negative ANCA-positive groups. Finally, the cumulative ILD-free survival rates were comparable between ACPA-positive and ACPA-negative AAV patients. Conclusions: The detection of ACPA expression is not uncommon in AAV. However, the presence of ACPA did not influence patients’ basal characteristics and outcomes, suggesting that further exploration of the role of this antibody is needed in patients with AAV.

Anti-neutrophil cytoplasmic antibody seropositivity in young adults aged up to 35 years: kidney histopathological findings and patient outcomes

ObjectiveTo investigate the clinical features, pathological renal findings, and outcomes in young adults with anti-neutrophil cytoplasmic antibody (ANCA) seropositivity.MethodsAdults aged ≤35 years, with ANCA seropositivity, who underwent renal biopsy and received treatment comprising a combination of corticosteroids and cyclophosphamide between January 2004 and May 2018, were retrospectively enrolled.ResultsThirteen patients with ANCA seropositivity were included, all of whom presented with kidney disease at diagnosis: 10 (76.9%) with ANCA-associated pauci-immune glomerulonephritis, one with ANCA-associated crescentic glomerulonephritis with immune complex deposition, one with immunoglobulin A nephropathy, and one with membranous nephropathy. The median serum creatinine level was 183.2 μmol/l (range, 55.0–1024.0 μmol/l). Respiratory symptoms (9/13 [69.2%]) and nonspecific gastrointestinal symptoms (5/13 [38.5%]) were the most common extrarenal manifestations. Remission was achieved in 10 (91%) of 11 ANCA-associated nephritis cases, and median interval from diagnosis to relapse was 30 months (range, 9–63 months). Cumulative relapse-free survival rates at 1 and 5 years were 100% and 88.9%, respectively. Overall, 1-year and 5-year renal survival rates were 80.8% and 58.9%, respectively.ConclusionRenal histopathology varied in young adults with ANCA seropositivity. Although relapse rates in this young adult population were generally low, long-term renal survival rates remain unsatisfactory.

Clinical impact of proteinase 3-antineutrophil cytoplasmic antibody positivity in eosinophilic granulomatosis with polyangiitis.

This study investigated the clinical implication of proteinase 3 (PR3)-antineutrophil cytoplasmic antibody (ANCA) in Korean patients with eosinophilic granulomatosis with polyangiitis (EGPA). Among the 242 patients with ANCA-associated vasculitis identified from the hospital database, 49 patients with EGPA were selected and analysed in this study. Demographic, clinical, and laboratory data at diagnosis were reviewed to compare the features of patients with PR3-ANCA and without, as well as the clinical outcomes of relapse and end-stage renal disease (ESRD) during the follow-up period. The outcomes of patients with PR3-ANCA and without were compared by using the Kaplan-Meier survival analysis. The median age of the patients was 54 years, 17 (34.7%) were male, and six (12.2%) patients had PR3-ANCA at baseline. The most common items of the 1990 American College of Rheumatology criteria for EGPA were sinusitis (95.9%) and asthma (or asthmatic history) (93.9%). During the follow-up, none died, eight experienced relapse and two progressed to ESRD. EGPA patients with PR3-ANCA exhibited peripheral eosinophilia less frequently than those without (50.0% vs. 88.4%, p = 0.047). On the other hand, EGPA patients with PR3-ANCA experienced relapse more often compared to those without (50.0% vs. 11.6%, p = 0.047), and the cumulative relapse-free survival rate was lower compared to those without PR3-ANCA (p = 0.012). EGPA patients possessing PR3-ANCA at disease diagnosis had distinct clinical feature and outcome compared to those without PR3-ANCA. These results should be taken into account in the management of patients with EGPA.

Predictive factors of relapse after dose reduction of oral 5-aminosalicylic acid in patients with ulcerative colitis in the remission phase.

Useful indices to determine whether to reduce the dose of 5-aminosalicylic acid (5-ASA) in patients with ulcerative colitis (UC) during remission remain unclear. We aimed to analyze the rate and risk factors of relapse after reducing the dose of oral 5-ASA used for maintenance therapy of UC. UC patients whose 5-ASA dose was reduced in clinical remission (partial Mayo score of ≤ 1) at our institution from 2012 to 2017 were analyzed. Various clinical variables of patients who relapsed after reducing the dose of oral 5-ASA were compared with those of patients who maintained remission. Risk factors for relapse were assessed by univariate and multivariate logistic regression analyses. Cumulative relapse-free survival rates were calculated using the Kaplan-Meier method. A total of 70 UC patients were included; 52 (74.3%) patients maintained remission and 18 (25.7%) patients relapsed during the follow-up period. Multivariate analysis indicated that a history of acute severe UC (ASUC) was an independent predictive factor for clinical relapse (p = 0.024, odds ratio: 21, 95% confidence interval: 1.50-293.2). Based on Kaplan-Meier survival analysis, the cumulative relapse-free survival rate within 52 weeks was 22.2% for patients with a history of ASUC, compared with 82.0% for those without. the log-rank test showed a significant difference in a history of ASUC (p < 0.001). Dose reduction of 5-ASA should be performed carefully in patients who have a history of ASUC.

Rituximab Biosimilar Prevents Poor Outcomes of Microscopic Polyangiitis and Granulomatosis with Polyangiitis as Effectively as Rituximab Originator

PurposeThere has been no extensive study to compare the efficacy between rituximab originator (Mabthera®) and its biosimilar (Truxima®) for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Here, we investigated the clinical effects of rituximab on poor outcomes of MPA and GPA in Korean patients, and compared those between Mabthera® and Truxima®.Materials and MethodsWe retrospectively reviewed the medical records of a total of 139 patients, including 97 MPA patients and 42 GPA patients. At diagnosis, antineutrophil cytoplasmic antibody positivity and comorbidities were assessed. During follow-up, all-cause mortality, relapse, end-stage renal disease, cerebrovascular accident and acute coronary syndrome were evaluated as poor outcomes. In this study, rituximab was used as either Mabthera® or Truxima®.ResultsThe median age at diagnosis was 60.1 years and 46 patients were men (97 MPA and 42 GPA patients). Among poor outcomes, patients receiving rituximab exhibited a significantly lower cumulative relapse-free survival rate compared to those not receiving rituximab (p=0.002). Nevertheless, rituximab use did not make any difference in other poor outcomes of MPA and GPA except for relapse, which might be a rebuttal to the fact that rituximab use after relapse eventually led to better prognosis. There were no significant differences in variables at diagnosis and during follow-up between patients receiving Mabthera® and those receiving Truxima®. Patients receiving Truxima® exhibited a similar pattern of the cumulative survival rates of each poor outcome to those receiving Mabthera®.ConclusionTruxima® prevents poor outcomes of MPA and GPA as effectively as does Mabthera®.

Long-Term Prognosis of Japanese Patients with Crohn’s Disease Treated by Switching Anti-Tumor Necrosis Factor-α Antibodies

Introduction: The long-term prognosis of Japanese patients with Crohn’s disease (CD) treated by switching anti-tumor necrosis factor-α (anti-TNFα) antibodies remains unclear. Objective: This study aimed to clarify the long-term prognosis and clinical factors that affect the long-term prognosis and outcomes of such patients. Methods: This retrospective, observational, single-center cohort study analyzed Japanese patients with CD treated by switching between infliximab and adalimumab in the Tohoku University Hospital between March 2003 and December 2017. Cumulative relapse-free survival and cumulative surgery-free survival rates were analyzed using the Kaplan-Meier method. Clinical factors that affected the long-term outcomes were identified using both a log-rank test and the Cox proportional hazards model. Results: The cumulative relapse-free survival rates were 68.6, 33.7, and 22.9% at 1, 3, and 5 years, respectively. The surgery-free survival rates were 91.7, 75.7, and 57.4% at 1, 3, and 5 years, respectively. The cumulative relapse-free survival rate was significantly higher in the group with ileal lesions (HR = 0.12; 95% CI 0.0066–0.64, p = 0.0086), stricture (HR = 0.24; 95% CI 0.0094–0.59, p = 0.0021), and a penetrating type (HR = 0.34; 95% CI 0.14–0.84, p = 0.020). Intolerance (HR = 0.29; 95% CI 0.12–0.63, p = 0.0013) and switching after surgery (HR = 0.41; 95% CI 0.17–0.87, p = 0.019) were clinical factors that reduced the risk of recurrence. The cumulative surgery-free survival rate was significantly higher in the group that switched after surgery (HR = 0.28; 95% CI 0.074–0.91, p = 0.034) and used concomitant thiopurine (HR = 0.32; 95% CI 0.10–0.90, p = 0.030). Conclusion: We should clarify the reason for switching anti-TNFα antibodies and investigate bowel complications before switching. Surgical reset of bowel complications including stricture and fistula could reduce the risk of recurrence after switching anti-TNFα antibodies. Concomitant thiopurine administration might reduce the risk of bowel surgery after switching anti-TNFα antibodies.

Could hypereosinophilia at diagnosis estimate the current activity or predict relapse in systemic immunosuppressive drug-naïve patients with eosinophilic granulomatosis with polyangiitis?

In this study, we investigated whether hypereosinophilia (peripheral eosinophil ≥ 1500/mm3) at diagnosis could estimate the increased current activity and predict the poor prognosis during follow-up in patients with eosinophilic granulomatosis with polyangiitis (EGPA). We retrospectively reviewed the medical records of 42 patients with EGPA and finally included 30 systemic immunosuppressive drug-naïve patients. We obtained clinical and laboratory data including clinical manifestations, Birmingham vasculitis activity score (BVAS), five-factor score (FFS) (2009), and routine laboratory results. Hypereosinophilia was defined as peripheral eosinophil ≥ 1500/mm3. We divided EGPA patients based on hypereosinophilia and compared variables between the two groups. The cumulative relapse-free survival rates were compared by the Kaplan-Meier survival analysis. Patients with hypereosinophilia more commonly exhibited cutaneous manifestation than those without (50.0% vs. 14.3%, P = 0.038), but there were no significant differences in BVAS and FFS (2009) at diagnosis. Patients with hypereosinophilia showed the higher median WBC (14,200.0/mm3 vs. 7940.0/mm3) and CRP (17.6mg/L vs. 2.0mg/L) at diagnosis than those without. During follow-up, patients with hypereosinophilia at diagnosis exhibited the similar cumulative relapse-free survival rate to those without (P = 0.393). Whereas, patients with FFS (2009) at diagnosis ≥ 2, which was a well-known predictor of the poor prognosis of EGPA, exhibited the lower cumulative relapse-free survival rate than those with FFS (2009) < 2 (P = 0.030). Hypereosinophilia at diagnosis could neither estimate the current activity nor predict relapse in systemic immunosuppressive drug-naïve patients with EGPA unlike theoretical assumption.

HBsAg-negative and anti-HBc-positive in eosinophilic granulomatosis with polyangiitis: a retrospective pilot study.

We examined whether resolved hepatitis B virus (HBV) infection was associated with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), and affected AAV activity at diagnosis and prognosis during the follow-up. We reviewed the electronic medical records of 153 AAV patients, and included 91 hepatitis B surface antigen (HBsAg)-negative patients having results of both antibody to hepatitis B core antigen (anti-HBc) and surface antigen (anti-HBs). We collected clinical and laboratory data, Birmingham vasculitis activity score (BVAS) and five factor scores (FFS) at diagnosis and relapse rates during the follow-up. We divided patients into the two groups according to the presence of anti-HBc and compared variables between them in patients with AAV or those with each variant. The mean age and follow-up duration were 59.8 ± 15.2-year-old and 48.0 ± 47.5months. Fifty patients (54.9%) had anti-HBc, and 61 patients (67.0%) had anti-HBs. Only thirty-six (39.6%) patients had ever experienced relapse after remission. There were no remarkable differences between HBsAg-negative AAV patients with and without anti-HBc. However, in eosinophilic granulomatosis with polyangiitis (EGPA) patients, patients with HBs-negative/anti-HBc-positive (resolved HBV infection) showed the higher initial mean BVAS and FFS (2009) than those without. Patients having anti-HBc exhibited significantly increased risk of relapse of EGPA than those having not (RR 16.0). Also, EGPA patients with HBs-negative/anti-HBc-positive showed meaningfully lower cumulative relapse-free survival rates than those without during the follow-up duration (p = 0.043). In conclusion, resolved HBV infection may importantly influence vasculitis activity at diagnosis and subsequently relapse after remission in EGPA patients.

Delta Neutrophil Index Is Associated with Vasculitis Activity and Risk of Relapse in ANCA-Associated Vasculitis.

PurposeDelta neutrophil index (DNI) represents the immature granulocytes count associated with neutrophil-consumption. We investigated whether DNI might be associated with Birmingham vasculitis activity score (BVAS) at diagnosis and could predict relapse during the follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).Materials and MethodsWe reviewed the medical records of 97 patients having DNI results. Twenty patients had granulomatosis with polyangiitis (GPA), 58 had microscopic polyangiitis (MPA), and 19 had eosinophilic GPA (EGPA). We collected clinical and laboratory data including BVAS, five factor score (FFS), and DNI. The correlation coefficient and cumulative relapse free survival rate were obtained. The optimal cut-off of DNI was extrapolated by calculating the area under the receiver operator characteristic curve.ResultsDNI was significantly related to cross-sectional BVAS. Furthermore, among continuous variables, only DNI could reflect BVAS of GPA and MPA, but not EGPA. Severe AAV was defined as BVAS ≥20 (the highest quartile). At diagnosis, patients having DNI ≥0.65% had a significantly higher risk of severe GPA and MPA than those having not (relative risk 4.255) at diagnosis. During the follow-up, DNI ≥0.65% could predict the higher relapse rate.ConclusionDNI could reflect BVAS at diagnosis and furthermore, DNI ≥0.65% could not only identify severe AAV at diagnosis, but also predict relapse during the follow-up in patients with GPA and MPA.

Rheumatoid factor false positivity in patients with ANCA-associated vasculitis not having medical conditions producing rheumatoid factor.

We investigated the rate of rheumatoid factor (RF) false positivity at diagnosis and its influence on clinical and prognostic features and rheumatoid arthritis (RA) development during the follow-up in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients without RA or other medical conditions triggering RF false positivity. We reviewed the medical records of 128 AAV patients. We divided patients with AAV and each variant into two groups according to RF positivity and compared variables between the two groups. Odds ratio and cumulative relapse-free survival rate were obtained by multivariate logistic regression analysis and the Kaplan-Meier survival analysis, respectively. The mean age at diagnosis was 53.6years and 41 patients were male. Of 128 AAV patients, 69 patients (53.9%) were classified as microscopic polyangiitis (MPA), 29 (22.7%) as granulomatosis with polyangiitis (GPA) and 30 (23.4%) as eosinophilic GPA (EGPA). The rate of RF false positivity was 39.1% in AAV patients. On univariate analysis, general, cutaneous and mucous and ocular manifestations and myeloperoxidase (MPO)-ANCA (or perinuclear (P)-ANCA) positivity were associated with RF false positivity in patients with AAV. On multivariate analysis, cutaneous manifestation was the only independent predictor of RF false positivity in EGPA patients. RF false positivity had no influence on cumulative relapse-free survival rate of AAV or RA development during the follow-up. RF false positivity rate was 39.1% in AAV patients and it was associated with cutaneous manifestation in EGPA patients at diagnosis, but not relapses of AAV or RA development during the follow-up.

Efficacy of Steroid Pulse Therapy for Autoimmune Pancreatitis Type 1: A Retrospective Study.

Autoimmune pancreatitis (AIP) is treatable with steroids, but relapse is frequent. The efficacy of steroid pulse therapy has been shown for various autoimmune diseases, but has not become established therapy. In this study, we reviewed the efficacy of steroid pulse therapy in 24 subjects who were diagnosed with AIP type 1 at our hospital. Patient characteristics, time-course of serum IgG4, and the cumulative relapse-free survival rate were compared between patients who received oral steroid therapy (oral group) and those who were treated with steroid pulse therapy (pulse group). Serum IgG4 was reduced significantly after therapy in both groups and the 5-year cumulative relapse-free survival rates in the two groups did not differ significantly (oral group 46.9%, pulse group 77.8%). However, in a subset of cases with diffuse pancreatic swelling, this rate was significantly lower in the oral group (33.3% vs. 100.0%, p = 0.046). These results suggest that steroid pulse therapy is effective for prevention of relapse in AIP patients with diffuse pancreatic swelling.

Leukopenia predicts remission in patients with inflammatory bowel disease and Behcet's disease on thiopurine maintenance.

The thiopurine drugs, azathioprine (AZA), and 6-mercaptopurine (6-MP) are well-established drugs for the treatment of inflammatory bowel disease (IBD). Although leukopenia is a well-recognized side effect of AZA/6-MP treatment, its association with therapeutic effects has yet to be determined. We therefore evaluated the influences of thiopurine-induced leukopenia on the long-term prognosis of IBD. We included 196 IBD patients [45 with ulcerative colitis (UC), 68 with Crohn's disease (CD), and 83 with intestinal Behçet's disease (BD)] who were treated with AZA/6-MP and achieved remission between January 2006 and December 2012. We retrospectively analyzed patient characteristics, AZA/6-MP maintenance dose (mg/kg), the lowest white blood cell (WBC) count during AZA/6-MP treatment, duration of remission, and the occurrence of relapse. We compared the clinical variables between leukopenic (n = 120, WBC count <4,000/μL) and nonleukopenic (n = 76, WBC count ≥ 4,000/μL) patients. The two groups were well matched for baseline clinical characteristics. The cumulative relapse-free survival rate was higher in the leukopenic group than the nonleukopenic group by Kaplan-Meier survival analysis (log-rank test, P < 0.001). On multivariate analysis, age, duration of AZA/6-MP treatment, presence of macrocytosis, and the presence of leukopenia were negatively associated with relapse (odds ratios 0.975, 0.988, 0.563, and 0.390, respectively). On subgroup analysis, the cumulative relapse-free survival rate was significantly higher in the leukopenic group than in the nonleukopenic group for all types of IBDs, including UC, CD, and intestinal BD (log-rank test, P = 0.032, 0.047, and 0.002, respectively). Leukopenia during thiopurine maintenance therapy was associated with prolonged remission in patients with IBD and Behcet's disease.

Management of rectal cancer – is adjuvant radiotherapy safe for the elderly?

Sirs, We read with interest Bouvier's paper, ‘Trends in the Management and Survival of Digestive Tract Cancers among Patients Aged over 80 years’, in the recent issue of Alimentary Pharmacology and Therapeutics.1 They showed the trends in the treatment of digestive tract cancers among patients aged ≥80 years. They examined time trends in three age classes and in five 4-year time intervals. Analysing postoperative survival rates for various cancers in the digestive tract, they concluded that surgery should not be restricted on the basis of age alone and further improvements can be made in particular to enhance adjuvant therapy whenever possible. In their analysis, the proportion of patients with rectal cancer receiving adjuvant radiotherapy slightly increased without reaching 20% during the last time period. They stated that comorbidity and advanced age are the more commonly cited reasons for not administering adjuvant therapies in patients with rectal cancer aged ≥75 years than patient refusal. However, although Bouvier et al. 1 addressed the importance of adjuvant therapy to improve surgical outcome, their study did not provide any specific data concerning complications related with adjuvant therapy in the treatment of rectal cancer. In the treatment of rectal cancer, we have a similar study and agree with their conclusion supporting the application of the surgical treatment for elderly patients. Furthermore, concerning adjuvant radiotherapy, we recently demonstrated that neoadjuvant radiotherapy is a safe modality for elderly patients.2 We examined a total of 230 patients with T3/T4 rectal cancer who underwent preoperative radiotherapy. According to age, patients were divided into elderly group (≥70 years: n = 44) or younger group (<70 years old: n = 186). Between two groups, there was no significant difference in curative resection rate, sphincter-preserving rate, 5-year cumulative relapse-free survival rate or 5-year cumulative local recurrence-free survival rate. Furthermore, as for adverse effects, the frequency of grade 4 radiation toxicity or grade l–3 toxicity, including nausea, fatigue, diarrhoea and dermatitis, showed no statistical difference between two groups. Postoperative mortality was 0% in both groups and postoperative morbidity rate was 58.5% in the elderly group and 50.8% in the younger group (N.S.). Postoperative major complications occurred in 9.8% in elderly group and 7.7% in younger group (N.S.). All these results showed no significant disadvantage by adjuvant radiotherapy in elderly patients. Considering that the incidence of adverse events in relation with radiotherapy did not increase in elderly patients, together with Bouvier's results, it is suggested that adjuvant radiotherapy is a safe modality for rectal cancer in elderly patients.

Serum matrix metalloproteinase‐9 in head and neck squamous cell carcinomais a prognostic marker

The aim of this study was to determine whether serum matrix metalloproteinase-9 (MMP-9) could predict cause-specific and relapse-free survival in patients with squamous cell carcinoma of head and neck. Furthermore, this study was designed to investigate whether there is an association between MMP-9 immunohistochemical staining and serum MMP-9 levels. Pretreatment serum levels of MMP-9 were quantitatively measured by ELISA assay in 67 patients presenting with a primary head and neck squamous cell carcinoma. The results were compared with the corresponding immunohistochemical staining results, clinical data and the patients' outcome. The follow-up time for all of the patients was at least 5 years. There was a statistically significant correlation between circulating MMP-9 and MMP-9 immunohistochemical staining in the corresponding tumors (p = 0.028). The cause-specific and relapse-free survival rates were clearly lower among patients with high MMP-9 serum levels (> 73 ng/ml). The 5-year cause-specific survival-rate was 40% in a patient group with high serum MMP-9, and 69% for patients with a low MMP-9 level (p = 0.027). In the same follow-up period, the cumulative relapse-free survival rate was 36% in patients presenting with a high serum MMP-9 and 66% in those with a low MMP-9 level. No correlation was found between MMP-9 serum levels and the traditional clinical or histopathologic factors. The results suggest for the first time that pretreatment serum MMP-9 level could serve as a prognostic factor in head and neck squamous cell carcinoma.

Expression of matrix metalloproteinase-9 in head and neck squamous cell carcinoma: a potential marker for prognosis.

Previous studies have shown that matrix metalloproteinase-9 (MMP-9) is expressed in malignant head and neck squamous cell carcinoma. The prognostic role of MMP-9 is still unclear. The aim of this study was to investigate the role of MMP-9 immunoreactive protein as a prognostic marker for survival in head and neck squamous cell carcinoma. Overexpression of the immunoreactive protein for MMP-9 was evaluated in tissue sections of 74 primary head and neck carcinomas with a monoclonal antibody using a biotin-streptavidin immunohistochemical staining method. The staining results were compared with the clinical data and to the patients' outcome. Positive immunostaining for MMP-9 was observed in 82% of the head and neck carcinomas, 39% of the cases being extensively positive. MMP-9 protein expression was independent of the stage or the grade of the tumor. The expression of MMP-9 was prognostic for shortened survival, the 5-year cause-specific survival being 45% in MMP-9 positive cases, and 92% in cases negative for MMP-9 (P = 0.013). MMP-9 positivity also correlated to the relapse-free survival (P = 0.019). At the 5-year follow-up, the cumulative relapse-free survival rate was 79% for patients with MMP-9-negative tumor and 42% for the patients with positive immunostaining for MMP-9. High expression of MMP-9 seemed to be linked with more aggressive relapses, appearing in 33% of the cases in local relapses, in 52% of cases with lymph node relapses, and in 60% of the cases with hematogenic relapses. This is the first study with a long follow-up showing that the immunoreactive protein of MMP-9 in head and neck carcinoma is associated with shortened relapse-free and cause-specific survival, suggesting that MMP-9 has a role in tumor progression of head and neck carcinomas, as well as in estimation of the prognosis of these diseases.

Long-term Results of Balloon-Occluded Retrograde Transvenous Obliteration for the Treatment of Gastric Varices and Hepatic Encephalopathy

To evaluate the long-term results of balloon-occluded retrograde transvenous obliteration (B-RTO) for the treatment of gastric varices (GV) and hepatic encephalopathy. A total of 43 patients who had undergone B-RTO were evaluated, 32 with GV, two with hepatic encephalopathy, and nine with both. All but one had been consecutively followed up with gastrointestinal endoscopy for more than 1 year (3-60 months; mean, 30.44 months). Collateral veins of gastric varices were graded using balloon-occluded retrograde left adrenal venography. The relation of both worsening of esophageal varices (EV) and improved Child-Pugh score after B-RTO to the grades of collateral vein development was analyzed. The relapse-free survival and the prognostic factors for survival after B-RTO were also assessed. GV disappeared or decreased markedly in size, and hepatic encephalopathy was completely cured in all patients. Improvement in Child-Pugh score was observed in 21 patient (50.0%) 6 months after B-RTO, but in only 11 patients (25.6%) 1 year after B-RTO. Worsening of EV was seen in eight patients and was related to a worsened grade of collateral veins. Cumulative relapse-free survival rate was 90.8% at 1 year and 87.4% at 3 years after B-RTO. The most significant prognostic factor was Child-Pugh classification (relative risk: 4.16) B-RTO is a safe and effective treatment for patients with GV and hepatic encephalopathy. The most important prognostic factors are the extent of Child-Pugh classification.