A minimally invasive approach to pilonidal disease with endoscopic pilonidal sinus treatment (EPSiT): a single-center case series with long-term results

Background

Minimally invasive techniques for treating pilonidal disease are safe and effective alternatives to conventional surgery, with improved recovery time, cosmetic results, and pain control. The aim of this study was to evaluate the 5-year surgical outcomes of a single-center case series treated with endoscopic pilonidal sinus treatment (EPSiT).

Methods

We conducted a retrospective single-center analysis of all patients treated with EPSiT, by a single surgical team, from March 2015 to December 2019, for primary or recurrent pilonidal disease. The primary outcomes were recurrence, persistence and treatment failure. The secondary outcomes were postoperative pain, painkiller use, time off work, satisfaction, complications, wound healing time, time to persistence or recurrence.

Results

Forty-two patients underwent 46 EPSiT procedures [34 males, 8 females, median age 25 (IQR 13.75) years] for primary (47.8%) or recurrent pilonidal disease (52.2%). All patients completed the follow-up [median 62 (IQR 43) months]. The single procedure healing rate was 76.1%. The healing rate for the first procedures plus the second EPSiT procedure (performed in 4 cases) was 83.3%. Among the 46 EPSiT procedures, we recorded six cases of persistence (13.0%) and five cases of recurrence (10.9%) The median operative time was 32.5 (IQR 18.75) minutes, the median pain score (visual analog scale) in week 1 was 2 (IQR 2), and the median time off work was 4 (IQR 2) days. Four patients (8.7%) experienced complications: serosanguineous (n?=?2) or seropurulent discharge (n?=?2). The satisfaction rate was 95.7%.

Conclusions

In our experience, EPSiT is safe, well accepted. and associated with a low level of postoperative pain, short hospitalization, short time off work, as well as optimal cosmetic results. Its failure rate is similar to that of excisional surgery.

     

Hepatic micrometastases outside macrometastases are present in all patients with ileal neuroendocrine primary tumour at the time of liver resection

Abstract

Background: Neuroendocrine tumours (NETs) in the ileum grow slowly but metastasise to the liver at an early stage. After resection of the primary tumour and mesenteric lymph nodes, selected patients with liver metastases have been operated with curative intention. Recurrence-free survival seems low, suggesting that micrometastases are present in the liver at the time of surgery. We have therefore examined whether NET metastases could be detected in perceived normal liver tissue at the time of liver resection.

Material and methods: Liver tissue outside the macrometastases from patients (n?=?10) operated by liver resection due to metastases from ileal NETs G1/2, were examined for NE cells by immunohistochemistry. Liver tissue from patients operated for metastatic colon cancer was used as control (n?=?6). Groups of ≥3 NE cells ≥3?mm from macrometastases were considered micrometastases. Clinical course was recorded retrospectively.

Results: Ten of 10 patients had micrometastases, consisting of multiple groups of NE cells. None of the control patients had NE cells in the liver tissue. After median follow-up time of 5.5 (0.8–18.7) years 6 of 10 patients had developed recurrent NET metastases detected by cross-sectional imaging. The follow-up time of the four patients without detectable metastases was 4.8 (0.8–7.5) years vs. with detectable metastases 7.9 (3.2–18.7) years.

Conclusions: All patient had micrometastases outside macrometastases at the time of liver resection, suggesting that subsequently recurrent liver metastases develop from NET depositions in the liver already present at the time of surgery. The likelihood of curation by hepatic resection appears very low.     

Elective surgery should be considered after successful conservative treatment of recurrent diverticular abscesses

Abstract

Purpose: The purpose of this study was to evaluate the disease pattern and treatment of diverticular abscesses.

Methods: Patients treated for diverticulitis (K57) in Västmanland, Sweden were identified for this retrospective population-based study between January 2010 and December 2014. Patients with diverticular abscesses were included. The clinical and radiological data were extracted, and the computed tomography scans were reevaluated.

Results: Of the 75 patients (45 women) with a median age of 62?years (range: 23–88?years), abscesses were localized pericolic in 42 patients (59%) and in the pelvis in 33 patients (41%). The median abscess size was 4.8?cm (range: 1.1–11.0?cm). Six patients (8%) required urgent surgical intervention during the index admission. The median follow-up time was 58?months (range: 0–95?months). During follow-up, 40 patients (58%) had disease recurrence and 35 of these patients (88%) presented with complicated diverticulitis. The median time until re-admission was 2?months (range: 3?days–94?months). Patients with pelvic abscesses developed fistulas more frequently, 3 versus 11 patients (p?=?.003). Twenty-three percent of patients with pericolic abscesses required surgery compared with 40% of patients with pelvic abscesses (p?=?.09). No patients had a recurrence of abscesses after a colonic resection.

Conclusion: The majority of patients with diverticular abscesses had recurrences with repeated admissions regardless of abscess location. An unexpectedly high proportion of patients required surgical intervention during the follow-up period. A liberal approach regarding elective surgery for patients with recurrent diverticulitis abscesses who tolerate surgery seems justified.     

The role of surgery in patients aged 85 years or older with resectable gastric cancer: a propensity score matching analysis of the SEER database

Abstract

Introduction: An increasing number of newly diagnosed resectable gastric cancer (GC) patients are over 85?years of age. However, studies on surgical treatment in these patients are limited. This study aimed to explore the prognosis of a large sample of the oldest old GC patients receiving surgery.

Methods: A total of 2914 oldest old patients with stage I-III GC were included in the linked Surveillance, Epidemiology, and End Results (SEER) database from 2006 to 2015. Based on their treatment, we assigned these patients to the surgery and no surgery groups. We used propensity score matching (1:1) to balance the baseline characteristics. The Kaplan–Meier method was used for the survival analysis. Multivariate Cox regression analysis was used to analyse the independent risk factors.

Results: After propensity score matching, the median overall survival (OS) times in the surgery and no surgery groups were 24.0 (95% CI: 20.3–27.7) and 4.0 (95% CI: 3.5–4.5) months, respectively (p?<?.01). Age, sex, stage, histological type, and treatment with surgery and chemotherapy were independent risk factors for OS in the oldest old patients with GC. In total, 19% of the oldest old patients with GC died from causes unrelated to cancer.

Conclusions: The current large-scale study demonstrated that the oldest old patients with stage I-III GC could benefit from elective surgery.     

Quality of care evaluation in non-functioning pituitary adenoma with chiasm compression: visual outcomes and timing of intervention clinical recommendations based on a systematic literature review and cohort study

Purpose

Surgery in patients with non-functioning pituitary macroadenomas (NFMA) is effective in ameliorating visual function. The urgency for decompression, and preferred timing of surgery related to the preoperative severity of dysfunction is unknown.

Methods

Systematic review for evidence to provide clinical guidance for timing of surgical decompression of the optic chiasm, and a cohort study of 30 NFMA patients, in whom mean deviation (MD), and severity of visual dysfunction was assessed.

Results

Systematic review 44 studies were included with a total of 4789 patients. Postoperatively, visual field defects improved in 87.0% of patients, stabilized in 12.8% and worsened in 1.0%. Specific protocols regarding timing of surgery were not reported. Only seven studies (16.7%) reported on either the duration of visual symptoms, or diagnostic, or treatment delay.

Cohort study 30 NFMA patients (50% female, 60 eyes, mean age 58.5?±?14.8 years), had a median MD of???5.3 decibel (IQR???3.1 to???10.1). MD was strongly correlated with clinical severity (r?=????0.94, P?<?0.0001), and were used for severity of defects cut-off values: (1) normal?>????2 dB, (2) mild???2 dB to???4 dB, (3) moderate???4 to???8 dB, (4) severe???8 to???17 dB, (5) very severe?<????17 dB.

Conclusion

Surgical decompression is highly effective in improving visual function. Uniform, quantitative grading of visual dysfunction was lacking. MD is a promising quantitative outcome measure. We provide recommendations for the evaluation of timing of surgery, considering severity of visual impairment, which will need further validation based on expert clinical practice.

     

Relationship between disease activity and patient-reported outcomes in rheumatoid arthritis: Post hoc analyses of overall and Japanese results from two phase 3 clinical trials

Abstract

Objective: To examine patient-reported outcomes (PROs) in patients with different rheumatoid arthritis (RA) disease activity levels and identify residual symptoms.

Methods: Post hoc analyses of overall and Japanese data from two randomized controlled trials including RA patients with previous inadequate responses to methotrexate (NCT01710358) or no/minimal previous disease-modifying antirheumatic drug treatment (NCT01711359) (sponsor: Eli Lilly and Company). Week 24 assessments were disease activity (Simplified Disease Activity Index, Disease Activity Score/Disease Activity Score 28 joints-erythrocyte sedimentation rate) and PROs (pain visual analog scale [VAS], morning joint stiffness [MJS], Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue, and Medical Outcomes Study Short Form 36 Health Survey Physical and Mental Component Scores).

Results: Patients achieving remission/low disease activity (LDA) at Week 24 had larger/significant improvements from baseline in pain, MJS, disability, fatigue, and physical and emotional quality of life versus patients with high/moderate disease activity. Some patients achieving remission and LDA, reported residual pain (pain VAS >10?mm): 20.8–39.3% and 48.7–70.0% (overall study populations), 16.0–34.5% and 47.1–62.0% (Japanese patients). Residual MJS and fatigue were also reported.

Conclusion: Remission/LDA were associated with improvements in PROs in overall and Japanese patient populations; however, some patients achieving remission had residual symptoms, including pain.     

Pancreaticoduodenectomy for paraduodenal pancreatitis is associated with a higher incidence of diabetes but a similar quality of life and pain control when compared to medical treatment

BackgroundParaduodenal pancreatitis is a focal form of chronic pancreatitis that affects the groove area between the duodenum and the head of the pancreas. Consensus regarding surgical or nonsurgical management as the best treatment option is still lacking.MethodsWe retrospectively evaluated all patients managed for PP at The Pancreas Institute of the University Hospital Trust of Verona from 1990 to 2017. The outcomes of surgical vs. medical treatment with regard to pain control, quality of life and pancreatic insufficiency were evaluated through specific questionnaires.ResultsThe final study population consisted of 75 patients: 62.6% underwent surgery, and 37.4% were managed without surgery. All surgical procedures consisted of pancreaticoduodenectomy. The median follow-up from the diagnosis of paraduodenal pancreatitis was 60 (12–240) months. Patients who underwent surgery experienced a similar incidence of steatorrhea (44.7 vs. 52.6%; p = 0.4) but a significantly higher incidence of diabetes (59.6 vs. 10.7%; p < 0.01) when compared to those managed without surgery. There was no difference in terms of reported chronic pain (Graded Chronic Pain Scale, median 0 vs. 1; p = 0.1) and quality of life (Pancreatitis QoL Instrument, median 82 vs. 79; p = 0.2). However, surgical patients reported a worse level of self-care activities associated with glycemic control (Diabetes Self-Management Questionnaire, median 20 vs. 28, p = 0.02).ConclusionIn patients affected by paraduodenal pancreatitis, surgery and medical therapy seem to obtain similar results in terms of quality of life and pain control. However, surgery is associated with an increased prevalence of postoperative diabetes with consequent relevant issues with self-care management. Surgery should be considered only in selected patients after adequate medical treatment.     

Early prediction for over two years efficacy of the first biologic agent for polyarticular juvenile idiopathic arthritis: A multi-institutional study in Japan

Objective: To estimate target of treatment for long-term efficacy of the first biologic agent used to treat polyarticular juvenile idiopathic arthritis (pJIA).

Methods: A retrospective cohort of patients with pJIA treated at six medical institutions in Japan between 1 March 2005 and 31 October 2014 was identified. The patients were divided by 2-year treatment periods with the first biologic agent into continuous treatment group and switching group. Three markers were examined: matrix metalloproteinase-3 (MMP-3), erythrocyte sedimentation rate (ESR), and disease activity score (DAS) 28-ESR.

Results: Thirty-two pJIA patients (8 boys, 24 girls) from 43 recruited patients were included in this study. The treatment periods with the first biologic agent in continuous treatment group (24 patients, 75%) was 40 months (median, range 24–119) and switching group (8 patients; 25%) was 9.5 months (median, 6–18). Markers [odds ratio (95% confidence interval)] at 3 months were MMP-3 [1.02 (0.99–1.05), p?=?.219], ESR [1.00 (0.78–1.30), p?=?.998], and DAS28-ESR [13.9 (2.08–409.82), p?=?.035]. The cut-off point for DAS28-ESR at 3 months to distinguish the two groups was 2.49 (sensitivity, 87.5%; specificity, 87.5%).

Conclusion: DAS28-ESR of 2.49 at 3 months after initiating the first biologic agent can be a target of sustained treatment in pJIA patients.     

Dyspareunia is associated with chronic pain in premenopausal women with sickle cell disease

Objectives: Pain is common in women with sickle cell disease (SCD), but the prevalence of dyspareunia in this unique patient population is unknown. In this study, we sought to determine whether chronic pain is associated with an increased prevalence of dyspareunia in premenopausal women with SCD.

Methods: A cross-sectional study of premenopausal women with SCD was systematically assessed for symptoms of dyspareunia and chronic pain using a standard questionnaire. These results were correlated with each subject's clinical pain phenotype determined by a review of the patient's electronic medical record.

Results: Ninety-one premenopausal women with SCD were examined. Thirty-two percent of the women reported dyspareunia. Women with dyspareunia were more likely to have a history of chronic pain (90% versus 61%, p?=?.006), report more pain days per week (median (interquartile range): 6 (4–7) vs. 3 (0–7), p?=?.005)), and had a higher oral morphine equivalent dose (145 (45–226) mg vs. 60 (9–160) mg, p?=?.030). Using a multivariable classification tree analysis, number of days of pain experienced per week was an important predictor of dyspareunia (p?=?.001).

Conclusion: Dyspareunia is common in women with SCD, and more common in women with SCD and chronic pain. Providers should assess women with SCD for dyspareunia, especially those with a chronic pain syndrome.     

Risk factors for surgery in patients with retention of endoscopic capsule

Objectives: Surgery is still the main means for removing retained endoscopic capsules. This study intended to evaluate risk factors for surgery in patients with capsule retention.

Materials and methods: The data of 5348 consecutive capsule endoscopy examinations were retrospectively analyzed. Cox regression analysis was used to evaluate risk factors.

Results: Seventy-seven patients (1.4%) had capsule retention. Spontaneous passage occurred in 16 patients, of which 14 were asymptomatic. Successful retrieval by double-balloon enteroscopy (DBE) was achieved in 14 patients, of which 11 did not need surgery during clinical follow-up. A total of 50 patients underwent surgery. The cumulative rates of surgery were 44.2%, 53.2%, 55.8%, 62.3% and 64.9% at 1, 3, 6, 12 and 60 months after capsule retention, respectively. Intestinal obstruction [hazard ratio (HR) 2.05, 95% confidence interval (CI) 1.12–3.76; p?=?.020] and overt small bowel bleeding (HR 2.01, 95%CI 1.08–3.71; p?=?.027) during capsule retention were independently associated with an increased risk for surgery. Specific treatment for primary disease (HR 0.22, 95%CI 0.07–0.74, p?=?.014) and successful endoscopic retrieval (HR 0.20, 95%CI 0.06–0.66; p?=?.008) were independently associated with a decreased risk for surgery.

Conclusions: For asymptomatic patients, specific medical treatment for primary disease can be maintained until the capsule spontaneously passes or symptoms appear. For patients with slight abdominal pain, DBE can be performed. For patients with intestinal obstruction or overt small bowel bleeding, early surgical consultation should be considered.     

Surgical strategies for chronic pancreatitis in a 1,327- patient Scandinavian Baltic pancreatic Club (SBPC) register

BackgroundChronic pancreatitis (CP) may cause intermittent or continuous pain and complications requiring invasive interventions. No specific recommendations for surgical interventions have been presented. Our aim was to determine the surgical treatment strategies for the treatment of CP in the Scandinavian and Baltic countries.MethodsThis multi-centre cross sectional study included 1327 CP patients from eight centres. The data was gathered from the Scandinavian Baltic Pancreatic Club (SBPC) database. Patients who underwent pancreatic surgery were analysed. The baseline CP population from the eight centres was used as a reference. The information registered included comorbidities, pancreatic function, previous interventions, time and type of surgery and the EORTC-30 quality of life (QOL) questionnaire.ResultsOverall, 95/1327 (7%) patients underwent pancreatic surgery. Fifty-one (54%) of these underwent pancreatic surgery for chronic pain (PSCP) and formed the final study group. Median follow-up time was two (range 0–8) years after surgery and seven (1–46) years after diagnosis. The most common surgical procedures were pancreatic resection combined with drainage (54%) followed by pancreatic resections (32%) and drainage procedures (14%). Postoperatively, 47% of the patients were pain free with or without pain medication while 16% had chronic pain episodes, this did not differ from the base CP population. In QOL questionnaires, PSCP patients reported the same QOL but worse social functioning and more symptoms compared to the CP population.ConclusionsPancreatic surgery for CP is rare: surgical procedures were performed on only 7% of the CP patients in the SBPC database. In half of the patients the indication was pain. Most of these patients underwent endoscopic procedures before surgery. Half of the patients reported being pain-free after surgery.     

Localized intrahepatic IgG4-related sclerosing cholangitis (IgG4-SC) as an additional type of IgG4-SC: a systematic analysis of 12 cases

Objectives: IgG4-related sclerosing cholangitis (IgG4-SC), a recently defined disease entity, has been classified into four types based on the stricture regions revealed by cholangiography. However, localized intrahepatic IgG4-SC is not included into the classification. This study aimed to analyze and characterize localized intrahepatic IgG4-SC and justify the inclusion of this type into the classification.

Methods: PubMed and Embase were searched for studies published from March 2001 to June 2017 reporting localized intrahepatic IgG4-SC. Data were obtained and analyzed from the included articles.

Results: Twelve cases of localized intrahepatic IgG4-SC were included. All patients were adults with the median age of 73 years (range 46–78), and had a male preponderance (88.9%). The most common clinical presentation was obstructive jaundice (50%), abdominal pain (25%) and absence of symptoms (25%). On imaging and macroscopically, localized intrahepatic IgG4-SC presented with three subtypes, i.e., mass-forming (n?=?6, 50%), stricture (n?=?5, 41.7%) and periductal infiltrating (n?=?1, 8.3%) subtypes. Among the eight cases with diagnoses reported, six patients were misdiagnosed as intrahepatic cholangiocarcinoma; one was diagnosed as hepatic mass and one as IgG4-SC before biopsy or operation. Information on treatment was available on 10 cases; eight underwent surgical resection, one received steroid treatment alone and one underwent endoscopic biliary drainage. No relapse was noted in patients with surgical resection during a period of followed up.

Conclusions: The localized intrahepatic IgG4-SC presents with mass-forming, stricture and periductal infiltrating subtypes, and should be recognized as an additional type of IgG4-SC according to the cholangiographic classification or anatomic site.     

Tolerability profile of thiopurines in inflammatory bowel disease: a prospective experience

Objectives: The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting.

Materials and methods: All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported.

Results: Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2–75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurrence of AEs (109/160 patients [68.1%]; cumulative incidence among the entire cohort: 43.1%). Overall, the most frequent AEs leading to treatment withdrawal were nausea (31/253 patients, 12.3%) and subjective symptoms, i.e., poorly defined side effects such as fatigue, headache and muscle pain (20/253 patients, 7.9%). Among the 109 AZA-intolerant patients, a switch to 6-mercaptopurine (6-MP) was performed in 44 cases (40.4%). At the end of follow-up, 6-MP was discontinued in 35/44 patients (79.5%), mostly due to AEs (29/35 patients, 82.8%). Azathioprine-induced hepatic and pancreatic toxicity was associated with male gender (p?=?.01 and p?=?.03, respectively), and occurrence of nausea with Crohn’s disease (p?=?.04).

Conclusions: Our real-life prospective cohort showed the higher cumulative incidence of thiopurine withdrawal due to AEs reported to date. Switching from AZA to 6-MP was often ineffective.     

Associations between pain catastrophizing and clinical characteristics in adults with substance use disorders and co-occurring chronic pain

Background: Pain catastrophizing refers to the tendency to interpret pain as harmful, intolerable, or uncontrollable. Greater pain catastrophizing is associated with more pain-related negative phenomena, such as pain reactivity, pain disability, and emotional distress related to pain. Several studies of patients seeking chronic pain treatment have identified an association between pain catastrophizing and misuse of opioids and alcohol; however, it is unknown whether this association would be similarly present in patients with chronic pain seeking substance use disorder treatment.

Objectives: The current study examined whether pain catastrophizing is associated with worse pain-related outcomes and psychological functioning in individuals receiving inpatient substance use disorder treatment who endorsed current chronic pain.

Methods: In a series of regression models, we tested the associations between pain catastrophizing and functioning, specifically pain interference, craving, anxiety, and days of mood difficulties in a cross-sectional sample of patients seeking substance use disorder treatment with co-occurring chronic pain (N = 244, 67.6% female).

Results: Greater pain catastrophizing was associated with more pain interference, higher levels of craving, more anxiety symptoms and more days of mood difficulties, adjusted for demographic characteristics and pain severity.

Conclusion: In patients with comorbid substance use disorder and chronic pain, pain catastrophizing may offer a potential therapeutic target to improve substance use treatment outcomes.     

Pituitary adenomas in patients with multiple endocrine neoplasia type 1: a single-center experience in China

Purpose

To explore the clinical characteristics of pituitary adenomas in patients with MEN1 and to summarize treatment strategies for MEN1 in a Chinese population.

Methods

We retrospectively analyzed 54 MEN1 patients with pituitary adenomas diagnosed at Peking Union Medical College Hospital from March 2003 to January 2017. Clinical data, laboratory testing results, treatments of involved glands and treatment responses were collected and analyzed.

Results

The mean age at pituitary adenoma diagnosis was 53.9?±?17.8. The patients initially consulted the Endocrinology, General Surgery and Neurosurgery departments, in descending frequency. The nonfunctioning adenoma, prolactinoma, GH-secreting adenoma, cosecreting adenoma, and ACTH-secreting adenoma subtypes accounted for 48.1%, 27.8%, 9.3%, 9.3% and 5.6% of the cases, respectively. The remission rate for prolactinomas was 46.2% (6/13) treated with bromocriptine. And the remission rates were 87.5% (7/8) and 100% (3/3) for GH-secreting adenomas and ACTH-secreting adenomas respectively achieved by transsphenoidal surgery. Nineteen (35.2%) patients with asymptomatic nonfunctioning pituitary adenomas showed no progression after a 35-month follow-up with close observation. Regarding treatment priority, patients with thymic carcinoid tumors received first-line surgery, 54% of the patients with enteropancreatic tumors had these tumors treated first, and 26% of all patients had their pituitary adenomas treated first. In acromegalic patients, pituitary lesions tended to be treated first (75%, p?=?0.002). PHPT and adrenocortical adenomas can be managed with elective surgery.

Conclusions

The treatment of MEN1 requires cooperation between multidisciplinary teams. Individualized treatment according to the severity of glandular involvement is needed. GH-secreting and ACTH-secreting pituitary adenomas require active treatment, while nonfunctioning pituitary adenomas can be observed closely.

     

Stereotactic body radiotherapy (SBRT) for patients with locally advanced pancreatic cancer: A single center experience

IntroductionDespite advances in treatment, notably in systemic therapy, the prognosis of pancreatic adenocarcinoma (PADC) remains dismal. Stereotactic body radiotherapy (SBRT) is an emerging tool in the complex management of PADC. We review outcomes of SBRT for PADC at our institution.MethodsWe reviewed patients treated with SBRT for either unresectable PADC or locally recurrent PADC after surgery. Treatment was delivered using a robotic radiosurgery system with respiratory tracking. The median prescribed dose was 30 Gy (30–35 Gy), delivered in 5–6 fractions. Toxicities were reported as per CTCAE v4.0. Survival was estimated using the Kaplan–Meier method.ResultsBetween October 2010 and March 2016, 21 patients were treated at our institution. The median follow-up was 7 months (range: 1–28). The 1-year local control rate was 57%. The 1-year overall survival was 25% for locally advanced patients and 67% for those with local recurrences (p = 0.27). Eighty percent of cancer related deaths were due to metastatic progression. Five patients (24%) had Grade I–II gastrointestinal acute toxicity; one patient had fatal gastrointestinal bleeding 6 months after SBRT.ConclusionIn PADC, fractionated SBRT dose schedules near 30 Gy may strike the best balance of local control and bowel toxicity. More work is required to integrate pancreatic SBRT with modern systemic therapy.     

Clinical effectiveness of golimumab in Crohn’s disease: an observational study based on the Swedish National Quality Registry for Inflammatory Bowel Disease (SWIBREG)

Abstract

Objective: The effectiveness of golimumab in Crohn’s disease (CD) is largely unknown as it is not approved for the treatment of the disease. We aimed to identify the population of CD patients treated with golimumab in Sweden, to assess the effectiveness of golimumab (defined as the drug retention rate), and to identify predictors of drug discontinuation.

Methods: Patients with CD who received at least one injection of golimumab were identified through the Swedish National Quality Registry for Inflammatory Bowel Disease, which includes prospectively collected clinical information. Cox regression models were used to identify predictors of golimumab discontinuation.

Results: The study cohort involved 94 patients of whom the majority (96.8%) had previously discontinued at least one anti-tumour necrosis factor (anti-TNF) agent. The drug retention rate at 12 weeks was 85.1%. Predictors of golimumab discontinuation at 12 weeks were previous surgery (adjusted HR?=?7.52, 95% CI: 1.12–50.36), concomitant corticosteroid use at baseline (adjusted HR?=?5.70, 95% CI: 1.13–28.68) and female sex (adjusted HR?=?6.59; 95% CI: 1.04–41.62). The median duration of follow-up was 89 (IQR: 32–158) weeks. The drug retention at the most recent follow-up was 35.1%. Predictors of golimumab discontinuation at the most recent follow-up were corticosteroid use at baseline (adjusted HR?=?2.60, 95% CI: 1.17–5.79) and female sex (adjusted HR?=?2.24; 95% CI: 1.19–4.23).

Conclusion: Patients with CD treated with golimumab were a treatment-refractory group. Despite this, more than one-third of the patients appeared to have had clinical benefit after a median follow-up of more than 1.5 years.     

Smoking is associated with severity of liver fibrosis but not with histological severity in nonalcoholic fatty liver disease. Results from a cross-sectional study

Objectives: To assess the influence of smoking on histological disease severity and fibrosis in real-world NAFLD patients.

Material and methods: Consecutive NAFLD patients were identified with liver biopsies performed between 2008 and 2015. Characteristics such as smoking status and total number of pack years were collected. Biopsies were revised and BRUNT fibrosis and NAFLD activity score (NAS) determined. Patients with a high NAS (≥5) were compared to patients with a low NAS (<5) and with advanced fibrosis (stage 3–4) to patients with no-early fibrosis (stage 0–2). Patients with a history of smoking (current or past smoker) were defined ever smokers.

Results: Fifty-six patients were included (mean age 49?±?14.3, 68.9% males and 39.3% history of smoking). Ever smokers had a higher fibrosis score than never smokers; two (IQR 0–3) versus one (IQR 1–1.5) (p?=?.040). Patients with advanced fibrosis smoked significantly more pack years than patients with no-early fibrosis; 10.6 (IQR 0–25.8) versus 0 (IQR 0–7) (p?=?.011). There is a weak to moderate correlation between fibrosis stage and number of pack years (Spearman’s Rho?=?0.341, p?=?.012). There was no difference in NAS between never and ever smokers; 2.8?±?1.5 versus 3.3?±?1.4 (p?=?.205). Patients with NAS <5 had a median number of pack years of 0 (IQR 0–9) versus a median of 10.3 pack years (IQR 0–24) in patients with NAS ≥5 (p?=?.127).

Conclusion: Smoking is associated with severity of NAFLD-related liver fibrosis but not with histological disease severity. This supports the recommendation to cease smoking for NAFLD patients.     

Effectiveness and safety of initiating adalimumab plus ≥12 mg/week methotrexate with adjustable dosing in biologic-naïve patients with early rheumatoid arthritis: HAWK study postmarketing surveillance in Japan

Abstract

Objectives: This real-world study assessed the effectiveness and safety outcomes of initiating adalimumab and methotrexate (≥12?mg/week) with adjustable dosing in Japanese patients with early rheumatoid arthritis (RA).

Methods: This single-arm, prospective postmarketing observational study (conducted from September 2012 to March 2017 at 119 sites) enrolled biologic-naïve patients with early RA (≤2 years duration) and a Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) >3.2 who were treated with methotrexate for ≥3 months and had initiated treatment with adalimumab and methotrexate (≥12?mg/week). This report presents 52-week data. The primary outcome was the proportion of patients who achieved DAS28-CRP scores <2.6 at week 52.

Results: Overall, 293 of 346 enrolled patients were included in the effectiveness population: women, 73%; mean (standard deviation) age, 54.3 (13.9) years; DAS28-CRP score, 4.51 (0.90); and modified total Sharp score (mTSS), 7.69 (9.98). At week 52, 77% of patients achieved clinical remission (DAS28-CRP <2.6), 92.3% achieved low disease activity (DAS28-CRP ≤3.2), and 86% of evaluable patients experienced structural remission (ΔmTSS ≤0.5).

Conclusion: Adalimumab plus methotrexate (≥12?mg/week) with adjustable dosing was well tolerated, and could be a beneficial treatment option for Japanese patients with early RA.

Trial registration: ClinicalTrials.gov identifier: NCT01736189.     

Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease

Background and aim: Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD.

Methods: We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled.

Results: An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76–0.97; p?=?.017). The lowest risk for fibrosis was found with the lowes`t odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08–0.66; p?=?.006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth ≥0.3?μmol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01–7.59; p?=?.047).

Conclusion: Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.