Novel treatment strategies for malignant melanoma: a new beginning?

Malignant melanoma is one of the most common cancer types among the Caucasian population. While the prognosis is excellent for patients diagnosed at an early stage and treated by adequate surgery, unresectable or advanced metastatic diseases shrink the overall survival at 5 years dramatically to less than 10%. For disseminated malignant melanoma, the appropriate systemic medical treatment is still controversial. Fortunately, progress in the molecular biology and in the understanding of pathogenesis has been made recently and should in the near future translate into molecular-based therapeutic strategies. In this review, we briefly describe the status of current treatment strategies and existing standards for malignant melanoma. We will focus on the new and emerging compounds including recent developments of targeted therapy such as antiangiogenic and immunomodulatory drugs, Bcl-2 antisense therapy, raf kinase inhibitors, heat shock protein modulators, anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 monoclonal antibody and finally PARP and proteasome inhibitors.     

Recovery rates and functional results after repair for rectovaginal fistula in Crohn’s disease: a comparison of different techniques

Background and objectives Rectovaginal fistulas (RVF) in Crohn’s disease continue to be a challenging problem. Several operations are often necessary to attain definitive healing of the disease process. There are no guidelines concerning optimal therapeutic approaches. Endoanal mobilization techniques such as the advancement flap technique were considered the therapy of choice for many years, but are now regarded ever more critically. We have implemented several less aggressive closure techniques that take account of the anatomy and morphology of the anorectum. The long-term results are presented in this paper. Materials and methods The method used was observational analysis with a standard protocol of all patients with RVF and Crohn’s disease treated surgically at a single institution. Results/Findings Between January 1985 and December 2002, we treated 72 patients with low rectovaginal fistulas. The operations comprised 56 procedures performed in 37 women presenting with RVF. The patients’ median age was 34.6 ± 10 years; the follow-up period was 7.15 years (10 months–18 years). Several techniques were performed: transverse transperineal repair (n = 20), endoanal direct closure multilayer without flap (n = 15), anocutaneous flap (n = 14), and advancement mucosal or full-thickness flap (n = 7). Diverting ileostomies were created in 28 patients (76%). Recovery was achieved with the initial repair in 19 patients (51.4%). An additional 12 patients underwent repeat procedures (2–5), with an overall success rate of 27:37 (73%). The rate of recurrence was 30% during a follow-up period of 7.1 years. The rate of proctectomy was 13.5%. The success rates for each of the techniques in the above group were 70, 73, 86, and 29%, respectively. They were significantly higher with the direct closure and anocutaneous flap technique than with the advancement flap technique. However, the transperineal repair led to decreased postoperative resting pressures. In the advancement flap technique, the resting and squeezing pressure decreased significantly. The risk of developing a suture line dehiscence leading to a persisting fistula was higher in the advancement flap procedure with 43%. Interpretation/conclusion Techniques with a low degree of tissue mobilization such as the direct closure and anocutaneous flap show higher success rates without significant postoperative changes in continence and manometric outcome. Impaired continence was observed only in the advancement flap group, resulting in significant changes in manometric values and recovery rates. The authors prefer to apply the direct multilayer closure technique without flap.     

3D-printed “fistula stent” designed for management of enterocutaneous fistula: An advanced strategy

Enterocutaneous fistulas(ECFs) are great challenges during the open abdomen. The loss of digestive juice, water-electrolyte imbalance and malnutrition are intractable issues during management of ECF. Techniques such as fistula patch and vacuumassisted closure therapy have been applied to prevent contamination of open abdominal wounds by intestinal fistula drainage. However, failures are encountered due to high-output fistula and anatomical complexity. Here, we report 3 D-printed patient-personalized fistula stent for ECF treatment based on 3 D reconstruction of the fistula image. Subsequent follow-up demonstrated that this stent was well-implanted and effective to reduce the volume of enteric fistula effluent.     

Hepatopancreatoduodenectomy –a controversial treatment for bile duct and gallbladder cancer from a European perspective

BackgroundHepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers.MethodMembers of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed.ResultsIn total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival.ConclusionHPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.     

Immunomodulatory treatment for lymphocytic myocarditis—a systematic review and meta-analysis

Deleterious inflammatory responses are seen to be the trigger of heart failure in myocarditis and therapies directed towards immunomodulation have been assumed to be beneficial. The objective of the present review was to systematically assess the effect of immunomodulation in lymphocytic myocarditis. Studies were included if diagnosis of lymphocytic myocarditis was based on EMB as well as on the exclusion of other etiologies of heart failure and if the patients had at least moderately decreased left ventricular ejection fraction (<?45%). All immunomodulatory treatments at any dose that target the cause of myocarditis leading to cardiomyopathy were included. Retrieval of PUBMED, SCOPUS, Cochrane Central Register of Controlled Trials, and LILACs from January 1950 to January 2016 revealed 444 abstracts of which nine studies with a total of 612 patients were included. As primary effectivity endpoint, a change in left ventricular ejection was chosen. No benefits of corticosteroids or intravenous immunoglobulin alone were reported. Immunoadsorption and subsequent IVIG substitution was associated with a greater improvement in left ventricular ejection fraction (LVEF) in one study. Single studies found a beneficial effect of interferon and statins on LVEF. We performed a meta-analysis for the combination of corticosteroids with immunosuppressants and found a non-significant increase of LVEF of +?13.06% favoring combined treatment (95%CI 1.71 to +?27.84%, p?= 0.08). The current evidence does not support the routine use of immunosuppression in traditional lymphocytic myocarditis. Nevertheless, in histologically proven virus-negative myocarditis of high-risk patients, combined immunosuppression might be beneficial. Future research should focus on translation of these effects to clinical outcome.     

Total therapy-based treatment for multiple myeloma—a single center experience

Incorporation of novel biological agents has become the cornerstone of treatment in multiple myeloma. For the last 4 years we have adopted the more intensified approach, previously published as total therapy 3 by the Arkansas group and used it with local modifications. This study aims to evaluate the efficacy and safety of the Arkansas protocol-based treatment outside clinical trial in a tertiary medical center in Israel. We retrospectively analyzed 23 patients. Seventy-three percent of the patients achieved very good partial remission (VGPR) before autologous stem cell transplantation (ASCT). Eighty-six percent of the patients achieved at least VGPR after tandem ASCT. Two-year overall survival was estimated as 70%. Four patients died during treatment, one as a result of disease progression. We conclude that this protocol is effective and rather safe. Further clinical trials should assess which subgroups of patients would benefit most from this approach.     

Psycho-echo-biofeedback: a novel treatment for anismus—results of a prospective controlled study

Background

Anismus or non-relaxing puborectalis muscle (PRM), detectable with anal/vaginal ultrasound (US), is a cause of obstructed defecation (OD) and may be treated with biofeedback (BFB). Many patients with anismus are anxious and/or depressed. The aim of this prospective study was to evaluate the outcome of the novel procedure psycho-echo-BFB in patients with anismus and psychological disorders.

Methods

Patients presenting at our unit with anismus and psychological disorders between January 2009 and December 2013, and not responding to conventional conservative treatment, were enrolled in the study. All underwent four sessions of psycho-echo-BFB, carried out by two psychologists and a coloproctologist, consisting of guided imagery, relaxation techniques and anal/vaginal US-assisted BFB. A validated score for OD was used, and PRM relaxation on straining measured before and after the treatment. PRM relaxation was also measured in a control group of 7 patients with normal bowel habits.

Results

Ten patients (8 females, median age 47 years, range 26–72 years) underwent psycho-echo-BFB. The OD score, evaluated prior to and at a median of 25 months (range 1–52 months) after the treatment, improved in 7 out of 10 patients, from 13.5 ± 1.2 to 9.6 ± 2.2 (mean ± standard error of the mean (SEM)), p = 0.06. At the end of the last session, PRM relaxed on straining in all cases, from 0 to 7.1 ± 1.1 mm, i.e., physiological values, not statistically different from those of controls (6.6 ± 1.5 mm). Two patients reported were cured, 3 improved and 5, all of whom had undergone prior anorectal surgery, unchanged. No side effects were reported.

Conclusions

Psycho-echo-BFB is safe and inexpensive and allows all patients with anismus to relax PRM on straining. Previous anorectal surgery may be a negative predictor.     

Risk factors for anal fistula: a case–control study

Background

The aim of our study was to identify potential risk factors for anal fistula in order to improve prevention and treatment of anal fistula.

Methods

A retrospective case–control study for anal fistula was conducted at our unit. Logistic regression analyses were carried out to identify associated risk factors for anal fistula.

Results

The final model obtained by the stepwise forward logistic regression analysis method identified the following items as independent risk factors: body mass index of >25.0 kg/m², high daily salt intake, history of diabetes, hyperlipidemia, dermatosis, anorectal surgery, history of smoking and alcohol intake, sedentary lifestyle, excessive intake of spicy/greasy food, very infrequent participation in sports and prolonged sitting on the toilet for defecation.

Conclusions

Our results indicate that lifestyle factors and certain medical conditions increase an individual’s risk of developing anal fistula.     

Polymyositis occurring during α-interferon treatment for malignant melanoma: a case report and review of the literature

Polymyositis is a systemic autoimmune disorder characterised by proximal muscle weakness which most frequently involves the limbs, neck and trunk. Alpha interferon is an antiviral molecule with well-known immunomodulatory and antiproliferative effects, but its use is often associated with a variety of side effects, in particular autoimmune phenomena. We report the occurrence of polymyositis during treatment with alpha-interferon in a patient affected by malignant melanoma. Indirect evidence suggests that in this case the patient's myositis was not linked to her neoplasia, since the melanoma was confirmed to be in remission both at the time of the diagnosis of the muscle disease and again after more than one year of follow-up. Received: 11 January 1999 / Accepted: 16 June 1999