Sequence of events leading to primary biliary cholangitis.

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that is observed more frequently in middle-aged women. This disorder is considered an autoimmune disease, since liver injury is sustained by the presence of self-directed antimitochondrial antibodies targeting the bile duct cells. The prognosis may vary depending on an early diagnosis and response to therapy. However, nearly a third of patients can progress to liver cirrhosis, thus requiring a liver transplant. Traditional immunosuppressive therapies, commonly employed for other autoimmune diseases, have limited effects on PBC. In fact, dramatic functional changes that occur in the biliary epithelium in the course of inflammation play a major role in perpetuating the injury. In this minireview, after a background on the disease and possible predisposing factors, the sequential cooperation of cellular/molecular events leading to end-stage PBC is discussed in detail. The rise and maintenance of the autoimmune process, as well as the response of the biliary epithelia during inflammatory injury, are key factors in the progression of the disease. The so-called "ductular reaction (DR)", intended as a reactive expansion of cells with biliary phenotype, is a process frequently observed in PBC and partially understood. However, recent findings suggest a strict relationship between this pathological picture and the progression to liver fibrosis, cell senescence, and loss of biliary ducts. All these issues (onset of chronic inflammation, changes in secretive and proliferative biliary functions, DR, and its relationship with other pathological events) are discussed in this manuscript in an attempt to provide a snapshot, for clinicians and researchers, of the most relevant and sequential contributors to the progression of this human cholestatic disease. We believe that interpreting this disorder as a multistep process may help identify possible therapeutic targets to prevent evolution to severe disease.

The impact of experience on recurrence rates after biopsy punch excision for pilonidal disease.

AIM: We present the outcomes and the recurrences of 848 patients with pilonidal disease (PD) treated by biopsy punch excision (BPE) and we weigh our results against progressively obtained operative experience. BPE is a modified 'merged' version of both the Bascom 'pit picking' procedure and the Gips procedure. It employs biopsy punches of different calibre, depending on whether treatment is in the natal cleft (calibre as small as possible) or lateral (larger calibre punches or even small incision). Sometimes this procedure is referred to as the Bascom-Gips procedure. METHODS: In all, 848 consecutive patients with PD were treated from January 2011 until December 2016 (sex 622 [73.4%] men and 226 [26.6%] women; median age 26.2 years, mean age 24.6 ± 28.99 [range 14-55] years, men 25.1 years, women 24.8 years). Of these 848 patients, 287 were operated in 2011-2012, 301 in 2013-2014 and 260 in 2015-2016. The recurrence rates were recorded 12, 24 and 60 months after surgery both cumulatively and by examining the outcomes of the three biennia individually (years of treatment 2011-2012 or group A, 2013-2014 or group B, 2015-2016 or group C). RESULTS: The mean operating time was 34 ± 24.45 min. Postoperative complications included early (<24 h; n = 22 or 2.6%) and delayed (>24 h; n = 26 or 3.1%) postoperative bleeding. Postoperative fluid collections (<2 weeks) occurred in 83/848 patients (9.8%) and included haematoma (n = 25) and seroma (n = 58). Full recovery was obtained after a mean of 21 ± 12.72 days and work/school/university activities were resumed after a mean of 4 ± 12.02 days. Twelve-, 24- and 60-month follow-ups were possible in 725 (85.5%), 682 (80.4%) and 595 (70.2%) patients out of 848. An overall significant (ꭓ2  = 16.87, P = 0.0002) difference was found in the recurrence rates: 59 recurrences/725 patients (or 8.1%) after 1 year, 89 recurrences/682 patients (or 13.0%) after 2 years and 98 recurrences/595 (or 16.4%) after 5 years. However, when subgrouping patients in three 24-month subsets, the recurrence rates showed a steady and progressive decrease in the three biennia 2011-2012 (group A), 2013-2014 (group B) and 2015-2016 (group C) at 12-, 48- and 60-month follow-ups. Recurrences after 12 months were 29/225 (12.9%), 19/285 (6.7%) and 11/215 (5.1%) (ꭓ2  = 8.53, P = 0.014) in groups A, B and C respectively; after 24 months, 36/226 (15.9%), 31/242 (12.8%) and 22/214 (10.2%) (ꭓ2  = 2.38, P = 0.30 N.S.) in groups A, B and C respectively; after 60 months, 38/194 (19.5%), 36/215 (16.7%) and 24/186 (12.9%) (ꭓ2  = 2.23, P = 0.32) in groups A, B and C respectively. CONCLUSIONS: BPE is an effective, disease-targeted, minimally invasive and inexpensive way to treat PD. Its results are influenced by the experience of the team involved, especially regarding early recurrences/failure of surgery. At least 5-year follow-ups are needed to ascertain the outcome of surgery for PD.