The long-term outcome of anti-TNF alpha therapy in perianal Crohn’s disease

Background

The aim of the present study was to evaluate the long-term outcomes of anti-tumour necrosis factor alpha therapy in perianal Crohn’s disease and identify factors predicting response to treatment.

Methods

Data from hospital clinical records and coding databases were retrospectively reviewed from a tertiary care hospital in Christchurch, New Zealand. The study included 75 adult patients with perianal Crohn’s disease commenced on anti-tumour necrosis factor alpha therapy from January 2000 to December 2012. Response to treatment was determined from records relating to clinical evaluation, magnetic resonance imaging follow-up and whether further surgical intervention was required.

Results

73% (55) of all patients and 38 of the 57 (67%) patients with perianal fistulas responded to anti-tumour necrosis factor alpha therapy. Patients with complex fistulas were less likely to improve as compared to patients without fistulising disease. Five of the 57 (13%) patients with perianal fistulas demonstrated complete healing on clinical evaluation; however, magnetic resonance imaging confirmed complete healing in only two. Patients that had taken antibiotics and those that had previously required abscess drainage were less likely to respond to treatment [relative risk (RR) = 0.707 and 0.615, respectively; p = 0.03, p = 0.0001]. Responders were less likely to require follow-up surgery (RR = 0.658, p = 0.014) including ileostomy or proctectomy.

Conclusions

Although anti-tumour necrosis factor alpha tends to improve symptoms of perianal Crohn’s disease, in the long term, it rarely achieves complete healing. Perianal fistulising disease, a history of perianal abscess and antibiotic treatment are predictors of poor response to therapy.

     

Effect of rituximab on the long-term outcome after high-dose therapy for relapsed B-cell non-Hodgkin’s lymphoma

To better define the role of rituximab in salvage and high-dose therapy (HDT) for relapsed or refractory non-Hodgkin’s lymphoma (NHL), patients treated before the implementation of rituximab in salvage and HDT (n=57, control group) were compared with patients with rituximab included in this procedure (n=36, study group). All patients had been antibody-naive at this point, and analyses were performed separately for 22 and 31 patients with aggressive, and 14 and 26 patients with indolent NHL, respectively. All patients received two courses of salvage therapy, predominantly dexamethasone, BCNU, etoposide, cytosine arabinoside, melphalan. Conditioning regimens included BCNU, etoposide, cytosine arabinoside, melphalan; BCNU, etoposide, cytosine arabinoside, cyclophosphamide or total body irradiation and cyclophosphamide, with rituximab added for patients in the study group. Despite the absence of differences in stem cell collection, haematopoietic recovery was delayed in patients with aggressive NHL treated in the study group: median days to absolute neutrophil count more than 0.5×10⁹/l, 11 vs 10 (p=0.01), and platelets more than 20×10⁹/l, 14 vs 11 (p=0.0005), with an increased requirement for platelet transfusions. No similar observations were made in indolent lymphoma patients. Remission rates were superior for patients with aggressive NHL in the study group. With a median follow-up of 7.25 and 4.5 years, this resulted in an improvement in OS at 4.5 years: 67 vs 45% (95% confidence interval, 47–87% vs 28–64%; p=0.0468). For patients with indolent lymphoma, no comparable benefit was detectable. Our data support the use of rituximab in HDT for patients with aggressive NHL. For patients with indolent NHL, only longer follow-up and/or randomized trials may help to fully determine the impact of rituximab on the outcome after HDT.     

The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox?

OBJECTIVES: The purpose of this study was to assess the impact of body mass index (BMI) on the short- and long-term outcomes after percutaneous coronary intervention (PCI). BACKGROUND: Obesity is associated with advanced coronary artery disease (CAD). However, the relation between BMI and outcome after PCI remains controversial. METHODS: We studied 9,633 consecutive patients who underwent PCI between January 1994 and December 1999. Patients were divided into three groups according to BMI: normal, BMI between 18.5 and 24.9 (n = 1,923); overweight, BMI between 25 and 30 (n = 4,813); and obese, BMI >30 (n = 2,897). RESULTS: Obese patients were significantly younger and had consistently worse baseline clinical characteristics than normal or overweight patients, with a higher incidence of hypertension, diabetes, hypercholesterolemia and smoking history (p < 0.0001). Despite similar angiographic success rates among the three groups, normal BMI patients had a higher incidence of major in-hospital complications, including cardiac death (p = 0.001). At one-year follow-up, overall mortality rates were significantly higher for normal BMI patients compared with overweight or obese patients (p < 0.0001). Myocardial infarction and revascularization rates did not differ among the three groups. By multivariate Cox regression analysis, diabetes, hypertension, age, BMI and left ventricular function were independent predictors of long-term mortality. CONCLUSIONS: In patients with known CAD who undergo PCI, very lean patients (BMI <18.5) and those with BMI within the normal range are at the highest risk for in-hospital complications and cardiac death and for increased one-year mortality.     

Post-operative recurrence of Crohn’s disease after definitive stoma: an underestimated risk

Introduction

Crohn’s disease (CD) is a progressive inflammatory disease affecting the entire gastrointestinal tract. The need for a definitive stoma (DS) is considered as the ultimate phase of damage. It is often believed that the risk of further disease progression is small when a DS has been performed.

Aims

The goals of the study were to establish the rate of CD recurrence above the DS and to identify predictive factors of CD recurrence at the time of DS.

Methods

We retrospectively reviewed all medical records of consecutive CD patients having undergone DS between 1973 and 2010. We collected clinical data at diagnosis, CD phenotype, treatment, and surgery after DS and mortality. Stoma was considered as definitive when restoration of continuity was not possible due to proctectomy, rectitis, anoperineal lesions (APL), or fecal incontinence. Clinical recurrence (CR) was defined as the need for re-introduction or intensification of medical therapy, and surgical recurrence (SR) was defined as a need for a new intestinal resection.

Results

Eighty-three patients (20 males, 63 females) with a median age of 34 years at CD diagnosis were included. The median time between diagnosis and DS was 9 years. The median follow-up after DS was 10 years. Thirty-five patients (42%) presented a CR after a median time of 28 months (2–211) and 32 patients (38%) presented a SR after a median time of 29 months (4–212). In a multivariate analysis, APL (HR = 5.1 (1.2–21.1), p = 0.03) and colostomy at time of DS (HR = 3.8 (1.9–7.3), p = 0.0001) were associated factors with the CR.

Conclusion

After DS for CD, the risk of clinical recurrence was high and synonymous with surgical recurrence, especially for patients with APL and colostomy.

     

Cortisol diurnal rhythm and quality of life after successful medical treatment of Cushing’s disease

Cushing’s disease (CD) is associated with severely impaired quality of life (QoL). Moreover, the physiological cortisol diurnal rhythm (CDR) is disturbed in CD. QoL can improve after successful surgery, the primary treatment for CD. We evaluated the effects of medical treatment on QoL and CDR. In 17 patients, stepwise medical treatment was applied with the somatostatin analog pasireotide, the dopamine agonist cabergoline and the adrenal-blocking agent ketoconazole. After 80 days, 15/17 (88 %) patients had reached normal urinary free cortisol excretion (UFC). Subsequently, patients continued medical therapy or underwent surgery. UFC, plasma and salivary CDR and QoL-related parameters (assessed using 5 questionnaires: Nottingham Health Profile, Hospital Anxiety and Depression Scale, Multidimensional Fatigue Index-20, RAND-36, CushingQoL) were measured. At baseline, 5/17 patients had preserved CDR. In 6/12 patients with disturbed baseline CDR, recovery was observed, but without any correlation with QoL. QoL was significantly impaired according to 18/20 subscales in CD patients compared to literature-derived controls. According to the RAND-36 questionnaire, patients reported more pain at day 80 (p < 0.05), which might reflect steroid-withdrawal. Generally, QoL did not improve or deteriorate after 80 days. CushingQoL scores seemed to improve after 1 year of remission in three patients that continued medical therapy (p = 0.11). CDR can recover during successful pituitary- and adrenal-targeted medical therapy. Patients with CD have impaired QoL compared to controls. Despite the occurrence of side-effects, QoL does not deteriorate after short-term biochemical remission induced by medical therapy, but might improve after sustained control of hypercortisolism.     

The clinical characteristics and outcome of intraabdominal abscess in Crohn’s disease

Background We aimed to elucidate the incidence and natural course of abdominal abscess complicating Crohns disease (CD).Methods Of 352 patients with CD who were observed at our hospital between 1985 and October 2001, we studied 35 patients (9.9%) with abscesses in the mid-abdominal region (the abdominal wall, peritoneal cavity, retroperitoneum, and subphrenic region).Results The cumulative incidence of complication with an abscess was 9% and 25%, respectively, 10 and 20 years after CD onset. Of the 35 CD patients with abscess, 60% had had surgery by the time of the present study. The age when the abscess developed was 30.1 ± 8.1 years, and the duration of illness from the onset of CD until development of an abscess was 10.8 ± 6.3 years (range, 0–29 years). The location of involvement was: abdominal wall, n = 14 (40%); peritoneal cavity, n = 10 (29%); retroperitoneum or iliopsoas, n = 9 (26%); and subphrenic region, n = 2 (6%). In terms of location of abscess, it occurred most often on the right side (65.7%). Almost all abscesses occurred near the site of an anastomosis. Diseased segments of the bowel responsible for abscess formation were categorized radiographically as showing mild stenosis (6.5%), intermediate stenosis and/or simple fistula (41.9%), and severe stenosis and/or multiple fistulas (51.6%). Conservative treatment (including drainage of abscess) alone was effective in 7 patients (20%) and surgery was needed in 28 patients (80%). During the 5.3-year follow-up after treatment for the abdominal abscess, 9 of the 35 patients (26%) had recurrence of an abscess, mostly within 3 years.Conclusions Abscess formation was noted in about 10% of patients with CD, with 46% of abscesses occurring in a diseased bowel segment near an anastomotic site. Of the diseased bowel segments responsible for abscess formation, half had neither severe stenosis nor multiple fistulas. Almost all patients underwent surgery for the abscess, and, in more than a quarter of the patients, there was recurrence within a few years after surgery.     

The effect of smoking after surgery for Crohn’s disease: a meta-analysis of observational studies

Objective  The aim of the study was to quantify the risk of disease recurrence associated with cigarette smoking for individuals with Crohn’s disease after disease-modifying surgery. Design  Meta-analysis of observational studies. Data sources  Medline, Embase, Ovid and the Cochrane database. Materials and methods  A literature search was performed to identify studies published between 1966 and 2007 comparing outcomes of smokers, ex-smokers and non-smokers with Crohn’s disease. Random-effect meta-analytical techniques were employed to assess the risk of medical or surgical recurrence. Results  Sixteen studies encompassing 2,962 patients including 1,425 non-smokers (48.1%), 1,393 smokers (47.0%) and 137 ex-smokers (4.6%) were included. Smokers had significantly higher clinical post-operative recurrence than non-smokers (odds ratio [OR] = 2.15; 95%CI = 1.42, 3.27; p < 0.001). Smokers were also more likely to experience surgical recurrence by 5 (OR = 1.06; 95%CI = 0.32; 3.53, p = 0.04) and 10 years of follow-up (OR = 2.56; 95%CI = 1.79, 3.67; p < 0.001) compared to non-smokers, although the crude re-operation rate was not statistically significant. When matched for operation and disease site, smokers had significantly higher re-operation rates to non-smokers (OR = 2.3; 95%CI = 1.29, 4.08; p = 0.005). There was no significant difference between ex-smokers and non-smokers in re-operation rate at 10 years (OR = 0.30; 95%CI = 0.09, 1.07; p = 0.10) or in post-operative acute relapses (OR = 1.54; 95%CI = 0.78, 3.02; p = 0.21). Conclusions  Patients with Crohn’s disease who smoke have a 2.5-fold increased risk of surgical recurrence and a twofold risk of clinical recurrence compared to non-smokers. Patients with Crohn’s disease should be encouraged to stop smoking since the risk of disease relapse is minimised upon its cessation. George E. Reese and Theodore Nanidis with equal contribution.     

The addition of radiotherapy to chemotherapy does not improve outcome of early stage Hodgkin’s lymphoma patients: a retrospective long-term follow-up analysis of a regional Italian experience

We retrospectively reviewed 139 stage I–II HL patients who were diagnosed and followed up in an Italian northern region (Liguria) from 1995 to 2007, and who received either chemotherapy (CT) alone (mainly doxorubicin, bleomycin, vinblastine, and dacarbazine; ABVD) or a combined modality treatment (chemotherapy + radiotherapy, CT + RT). The two therapeutic groups were comparable for clinical and histologic features. Complete remission rate after CT + RT was higher than what was achieved with CT alone (96% vs. 84%, respectively, p = 0.03). Relapse rate (12%) was the same in both groups and disease-free survival curves were comparable (82% and 83%, p = 0.47). The overall survival of the two therapeutic groups is comparable. No second tumors have been reported among patients receiving chemotherapy alone, whereas a second neoplasia has been diagnosed in four patients (in two cases possibly radiotherapy related) in the CT + RT group (5%, p = 0.09) In conclusion, our retrospective study shows that CT + limited RT is an effective and well-tolerated option for early stage Hodgkin’s lymphoma, even if the use of RT is associated with a certain risk of developing a second tumor. However, four to six courses of ABVD can lead to similar, optimal, long-term disease control without exposing patients to the risk of a second neoplasia.     

The effect of pre-operative optimization on post-operative outcome in Crohn’s disease resections

Background

The timing of surgical intervention in Crohn’s disease (CD) may depend on pre-operative optimization (PO) which includes different interventions to decrease the risk for unfavourable post-operative outcome. The objective of this study was to investigate the effect of multi-model PO on the post-operative outcome in CD.

Method

This is a multicentre retrospective cohort study. The primary outcome was 30-day post-operative complications. Secondary outcomes were intra-abdominal septic complications, surgical site infection (SSI), re-operation, length of post-operative stay in a hospital and re-admission. PO included nutritional support, discontinuation of medications, pre-operative antibiotic course and thrombosis prophylaxis.

Results

Two hundred and thirty-seven CD elective bowel resections were included. Mean age was 39.9 years SD 14.25, 144 (60.8 %) were female and 129 (54.4 %) had one or more types of medical treatment pre-operatively. Seventy-seven patients (32.5 %) optimized by at least nutritional support or change in pre-operative medications. PO patients were more likely to have penetrating disease phenotype (p = 0.034), lower albumin (p = 0.015) and haemoglobin (p = 0.021) compared to the non-optimized. Multivariate analyses showed that treatment with anti-TNF alpha agents OR 2.058 CI [1.043–4.4.064] and low haemoglobin OR 0.741 CI [0.572–0.0.961] increased the risk of overall post-operative complications. Co-morbidity increased the risk of SSI OR 2.567 CI [1.182–5.576] while low haemoglobin was a risk factor for re-admission OR 0.613 CI [0.405–0.926]. Low pre-operative albumin correlated with longer stay in hospital.

Conclusions

PO did not change post-operative outcome most likely due to selection bias. Anti-TNF alpha agents, low haemoglobin, low albumin and co-morbidity were associated with unfavourable outcome.

     

Intraabdominal septic complications following bowel resection for Crohn’s disease: detrimental influence on long-term outcome

Background  A number of studies deal with factors affecting postoperative recurrence; however, they do not analyze the influence of postoperative morbidity on the long-term outcome. This was the aim of the present study. Materials and methods  Two hundred eighty-two patients underwent 331 intestinal resections for primary or recurrent Crohn’s disease between 1992 and 2005. Closure of ileostomy or colostomy, isolated stricturoplasty, abdominoperineal resection for perianal disease, and reoperations for postoperative complications were excluded. “Surgical recurrence” was defined as a development of stricturing or perforating disease necessitating repeat surgical therapy. Results  Anastomotic leak, intraabdominal abscess, enterocutaneous fistula (intraabdominal septic complications, IASC) occurred after 46 operations (16%). Four patients died (1.2%). By multivariate analysis, articular disease manifestation (p = 0.03), duration of symptoms leading to surgery (p = 0.009), and weight loss (p = 0.03) were associated with occurrence of postoperative complications. Surgical recurrence occurred following 86 bowel resections, and 36 occurred during the first postoperative year. The following factors were associated with an increased risk of surgical recurrence by multivariate analysis: postoperative IASC (p = 0.0002) and previous bowel resections (p = 0.002). Patients suffering IASC had statistically significantly higher 1-, 2-, 5-, and 10-year surgical recurrence rate (25%, 29%, 50%, and 57%) than patients without IASC (4%, 7%, 19%, and 38%, p = 0.0003). Conclusion  The incidence of the postoperative IASC is predominantly determined by preoperative disease severity. IASC have a detrimental influence on the long-term outcome following intestinal resections in patients with Crohn’s disease, leading to increased number of repeat resection surgery.     

The risk of Parkinson’s disease in type 1 Gaucher disease

In Gaucher disease, defective lysosomal glucocerebrosidase due to mutations in the GBA1 gene results in lysosomal accumulation of glucocerebroside in mononuclear phagocytes and a multisystemic phenotype. Observations of occurrence of Parkinson’s disease in some patients with non-neuronopathic type 1 Gaucher disease (GD1) and their first degree relatives has led to the identification of GBA1 heterozygous mutations as a genetic risk factor for idiopathic Parkinson’s disease (PD). However, the magnitude of risk of PD in patients with known GD1 has not been determined, and it is not known whether GD1/PD represents a specific sub-phenotype of GD1 with distinctive genotype/phenotype characteristics. We estimated the risk of PD in a cohort of 444 consecutively evaluated patients with GD1 compared to that in the general population. Eleven patients developed parkinsonian syndrome during a 12-year follow-up period. The adjusted life-time risk ratio of PD in GD1 compared to that in the general population was 21.4 [95% confidence interval (95% CI) 10.7–38.3], with a higher risk in men compared to women. In our cohort, GD1/Parkinson’s disease phenotype (GD1/PD) was characterized by higher GD1 severity score, due to higher incidence of avascular osteonecrosis. The clinical spectrum of PD varied from mild to potentially life-threatening disease. All but one patient with GD1/PD phenotype had at least one N370S GBA1 allele. In conclusion, compared to the general population, patients with GD1 have an almost 20-fold increased life-time risk of developing PD.     

India’s first successful intestinal transplant: The road traveled and the lessons learnt

Intestinal transplant is a therapeutic challenge not just surgically but also logistically because of the multidisciplinary expertise and resources required. A large proportion of patients who undergo massive bowel resection and develop intestinal failure have poor outcome, because of inability to sustain long-term parenteral nutrition and limited availability of intestinal and multi-visceral transplantation facilities. We report the first successful isolated intestinal transplant from India.