Management of cystic prolactinomas: a review

Introduction

Cystic prolactinoma is a variant of prolactin-secreting pituitary adenoma. The strategies for the management of cystic prolactinoma have not been addressed thoroughly in clinical guidelines.

Methods

A literature search was performed using Pubmed to review the current approaches to the treatment of cystic prolactinoma.

Results

Transsphenoidal resection is an effective and relatively safe approach for the treatment of cystic prolactinoma, however, morbidity of surgery is dependent on the skill of the surgeon. Emerging studies allude to the efficacy and safety of dopamine agonists in the management of cystic prolactinoma. Dopamine agonists are associated with considerable rates of clinical improvement and tumor shrinkage, hence reducing the need for surgical intervention.

Conclusions

Recent studies suggest that dopamine agonist therapy may be an effective and safe treatment option in a considerable portion of patients with cystic prolactinomas. We suggest that dopamine agonists should be considered as a first-line therapy for cystic prolactinoma in the absence of indications for early surgical intervention.

     

Treatment of acute hepatitis C: recommendations from an expert panel of the Italian Society of Infectious and Tropical Diseases

Aim

This paper is aimed at providing practical recommendations for the management of acute hepatitis C (AHC).

Methods

This is an expert position paper based on the literature revision. Final recommendations were graded by level of evidence and strength of the recommendations.

Results

Treatment of AHC with direct-acting antivirals (DAA) is safe and effective; it overcomes the limitations of INF-based treatments.

Conclusions

Early treatment with DAA should be offered when available.

     

Prostate Artery Embolization: Current Status 2018

Purpose of Review

Prostate artery embolization (PAE) is a promising new treatment option for men with symptomatic benign prostatic hyperplasia (BPH). Our goal is to review the data on PAE with regard to outcomes, risks versus benefits, and safety.

Recent Findings

Current data suggests that PAE is safe and effective for men with symptomatic BPH. The two most robust randomized controlled trials comparing PAE with TURP both found comparable short-term results with regard to improvements in symptoms. However, the side effects of PAE were higher than those of TURP. There remain ongoing randomized controlled trials comparing the two modalities of treatment.

Summary

Though the largest randomized controlled trials comparing these two modalities of treatment of BPH are still underway, current data suggest PAE may be a promising, safe, and effective treatment option for men with symptomatic BPH. Additionally, PAE can be safely performed on larger prostates of any size and is generally performed via a single, femoral artery puncture under local anesthesia. Therefore, it is particularly appealing for patients with prostate glands >?80 g and who are poor candidates for general anesthesia.

     

Antithrombotic Therapy for ACS in Elderly Patients

Background

Patients over 75 account for more than one third of those presenting with myocardial infarction and more than 50% of intrahospital mortality. There are no specific guidelines for the management of acute coronary syndromes (ACS) in the elderly.

Setting

Although antithrombotic therapy seems to be effective and safe in such patients, it requires specific precautions and treatment adjustments because of the higher bleeding risk due to comorbidities such as renal function impairment and malnutrition.

Results

Scientific evidence concerning elderly patients is scarce as they are either excluded or underrepresented in most randomized trials. Overall, the antithrombotic therapy needs to be adapted to avoid complications, mainly bleeding complications, without compromising the effectiveness of the treatment in this high-risk population.

Conclusion

In the present paper, we review the current treatment strategies in ACS while focusing on data concerning the elderly, according to available data in pivotal trials and in both AHA/ACC and ESC guidelines.

     

Re-evaluation of lipiodolized transarterial chemoembolization therapy for intrahepatic recurrence of hepatocellular carcinoma after curative liver resection

Background/Purpose

While lipiodolized transarterial chemoembolization (lip-TACE) is effective for treating unresectable hepatocellular carcinoma (HCC), its effect for treating recurrent HCC after curative liver resection needs to be clarified.

Methods

Of 163 patients who had undergone curative liver resection between 1992 and December 2003, 65 patients (39.8%) had recurrent HCC in the liver without extrahepatic recurrence and were indicated for lip-TACE. The overall survival rate after lip-TACE was calculated, and its correlation with factors such as the histology of the primary HCC and background noncancerous tissue were analyzed.

Results

The overall survival rates after lip-TACE after the detection of the first recurrent HCC were 82.6%, 44.5%, and 24.8% at 1, 3, and 5 years, respectively. The factors affecting patient survival after lip-TACE were microscopic portal venous involvement of HCC at liver resection, grade of inflammation in the noncancerous liver parenchyma, and recurrence within 1 year after the initial liver resection. Multivariate analysis showed that the period between the resection and first recurrence had the highest hazard ratio.

Conclusions

Lip-TACE is a reasonable procedure for treating recurrent HCC in selected patients who are not eligible for hepatic re-resection. When HCC recurred within 1 year from the primary liver resection, the effect of lip-TACE on patient survival was limited.

     

Zytomegalievirus nach Nierentransplantation

Background

Despite widespread use of antiviral cytomegalovirus (CMV) prophylaxis, active CMV infections with progression to CMV disease remain of paramount importance after renal transplantation, which can lead to severe complications particularly in CMV seronegative recipients of a CMV seropositive donor kidney.

Objective

Risk stratification of active CMV infections and CMV disease, immune reactivity, clinical challenges, and development of approaches to disease management.

Methods

Discussion of recent developments and expert recommendations.

Results

There is a particularly high risk for the development of active CMV infections and CMV disease in CMV seronegative recipients of a CMV seropositive donor kidney. In this case CMV prophylaxis followed by preemptive therapy is recommended. The focus of this combined strategy is to prevent severe tissue-invasive CMV disease and to reduce the indirect effects of active CMV infections with inferior patient and transplant survival. Patients at increased risk who do not generate adequate CMV-specific cellular immunity after transplantation, nevertheless develop severe and occasionally recurrent active CMV infections after termination of prophylactic measures. In the case of life-threatening therapy-resistant CMV disease, adoptive transfer of CMV-specific T?cells has been proven to be a safe and effective therapy option.

Conclusion

Clinically problematic courses of active CMV infections are limited to those patients with severely impaired CMV-specific immunity. The quantification of CMV-specific cellular immunity represents an appropriate instrument to achieve a better stratification of the risk of active CMV infections in patients at increased risk and is the subject of current research studies.

     

Selection of EMR and ESD for Laterally Spreading Lesions of the Colon

Introduction

Colonic laterally spreading lesions (LSL) are increasingly managed using endoscopic methods that comprise two main techniques: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD).

Purpose of Review

In this review, we aimed to review the most recent literature on selection of the best endoscopic technique in the management of colonic LSL.

Recent Findings

EMR and ESD are complimentary techniques in the management of patients with colonic LSL.

Summary

EMR is safe and effective in most patients with LSL, except for cancers with submucosal invasion in whom R0 resection is favored.

     

Effects of Vedolizumab Therapy on Extraintestinal Manifestations in Inflammatory Bowel Disease

Background

Approximately 15–20% of ulcerative colitis patients and 20–40% of those with Crohn’s disease experience extraintestinal manifestations (EIMs) of their inflammatory bowel disease (IBD). Clinicians who treat IBD must manage EIMs affecting multiple organs that variably correlate with intestinal disease activity. Vedolizumab is a monoclonal antibody for the treatment of IBD with a gut-selective mechanism of action.

Aims

This report evaluates whether vedolizumab is an effective treatment of EIMs, given its gut-specific mechanism of action.

Methods

We report 8 case studies of patients with various EIMs, including pyoderma gangrenosum, peripheral arthralgia/arthritis, axial arthropathies, erythema nodosum, and uveitis, who received vedolizumab therapy.

Results

Vedolizumab therapy was effective for pyoderma gangrenosum in ulcerative colitis, uveitis, erythema nodosum, polyarticular arthropathy, and ankylosing spondylitis/sacroiliitis but did not provide sustained benefit for the treatment of pyoderma gangrenosum in a patient with Crohn’s disease.

Conclusions

These cases demonstrate the potential of vedolizumab as a treatment of EIMs in patients with IBD.

     

The clinicopathological significance of heat shock protein 70 and glutamine synthetase expression in hepatocellular carcinoma

Background/purpose

Heat shock protein 70 (HSP70) and glutamine synthetase (GS) have been proposed to be promising markers for the differentiation of malignant and benign hepatocellular lesions. The aim of this study was to investigate the clinicopathological significance of the expression of HSP70 and GS in surgically resected hepatocellular carcinoma (HCC).

Methods

The authors collected 412 HCC samples and 120 non-neoplastic hepatic tissue samples and performed an immunohistochemical study.

Results

HSP70 staining was observed in 282 of 392 HCC samples (71.9%), and GS immunoreactivity was observed in 212 of 395 HCC cases (53.7%). Of the several clinicopathological parameters examined, microscopic vascular invasion, a large tumor size, and a high Edmonson–Steiner grade were found to be correlated with positive staining for HSP70 (P = 0.032, 0.002, and 0.012, respectively). Survival analysis showed a correlation between HSP70 expression and disease-free survival. GS was not found to be related to clinicopathological parameters.

Conclusions

The findings of the present study suggest that HSP70 be viewed as a predictor of prognosis as well as a useful diagnostic marker for HCC.

     

The Validity of HCC Diagnosis Codes in Chronic Hepatitis B Patients in the Veterans Health Administration

Background

Administrative databases that include diagnostic codes are valuable sources of information for research purposes.

Aim

To validate diagnostic codes for hepatocellular carcinoma (HCC) in chronic hepatitis B patients.

Methods

We conducted a retrospective study of patients with chronic HBV seen in the national Veterans Administration (VA). HCC cases were identified by the presence of ICD-9 code 155.0. We randomly selected 200 HBV controls without this code as controls. We manually reviewed the electronic medical record (EMR) of all cases and controls to determine HCC status. We calculated the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity for the HCC code. We conducted an implicit review of the false-positive cases to determine possible reasons for the miscoding.

Results

Of the 8350 patients with HBV, 416 had an ICD-9 code for HCC. Of these 416, 332 patients had confirmed HCC and 61 did not; HCC status was indeterminate for 23 patients. Of the 200 controls, none had HCC confirmed in the EMR. The PPV ranged from 85.3 to 80.0% and specificity ranged from 99.2 to 99.0% based on classification of indeterminate cases as true versus false positives, respectively. The NPV, sensitivity, and specificity were 100%. Two-thirds of false-positive cases were diagnosed with HCC prematurely as a workup of liver mass and latter imaging and/or biopsy were not diagnostic for HCC.

Conclusion

The diagnostic code of HCC in chronic HBV patients in the VHA data is predictive of the presence of HCC in medical records and can be used for epidemiological and clinical research.

     

Overexpression of Protein Phosphatase 1γ (PP1γ) Is Associated with Enhanced Cell Proliferation and Poor Prognosis in Hepatocellular Carcinoma

Background

Protein phosphatase 1γ (PP1γ), as a member of the protein phosphatase 1 family, may be involved in regulation of multiple cellular processes, such as mitosis, cell survival, and apoptosis. However, little is known about the underlying mechanisms by which PP1γ regulates hepatocellular carcinoma development.

Aim

We investigated the expression profile of PP1γ in hepatocellular carcinoma (HCC) cell lines and human HCC specimens, as well as its potential prognostic significance in HCC.

Methods

PP1γ expression profile was detected in 94 HCC specimens using immunohistochemistry. PP1γ levels in HCC cells were downregulated by small interfering RNA (siRNA) transfection. Cell cycle progression and proliferation status of HCC cells and the effectiveness of doxorubicin were evaluated by flow cytometry and CCK-8 assay. The levels of PP1γ, CyclinD1, PCNA, Mdmx, p53, p21, and active caspase-3 were evaluated by Western blot analysis.

Results

PP1γ was upregulated in tumorous specimens, compared with adjacent nontumorous tissues. Univariate and multivariate survival analyses were conducted to determine the prognostic significance of PP1γ in HCC. The expression pattern of PP1γ was positively correlated with tumor size, histological grade, Ki-67 expression, and poor prognosis in HCC. In addition, depletion of PP1γ by siRNA could inhibit cell proliferation, resulted in G1 phase arrest, and attenuated resistance to doxorubicin in Huh7 cells.

Conclusions

PP1γ is upregulated in HCC cell lines and HCC specimens, promotes cancer cell proliferation through regulation of p53, and may be a potential target for treatment of HCC.

     

Treatment with daclatasvir and sofosbuvir for 24 weeks without ribavirin in cirrhotic patients who failed first-generation protease inhibitors

Background

Treatment of patients with chronic hepatitis C who failed the triple therapy with first generation of protease inhibitors is not still defined. The combined use of sofosbuvir (SOF) and daclatasvir (DCV) seems to be promising due to higher genetic barrier, good tolerance and effectiveness.

Methods

We described the treatment with this drug combination in a real-life cohort of 20 cirrhotic patients with genotype 1 who failed the triple therapy.

Results

18 of them (90%) with Child–Pugh A, 11 (55%) with genotype 1a, 17 (85%) with more than 1 and 8 (40%) with more than 2 previous failed treatment; all patients had at baseline NS3 resistance-associated variants related to triple therapy failure. RBV was not administered due to anemia in previous treatments. The sustained virological response was 100%.

Conclusion

Treatment with SOF + DCV without RBV for 24 weeks is safe and effective in cirrhotic patients who failed triple therapy with the first generation of protease inhibitors.

     

The History of Psoriatic Arthritis (PsA): From Moll and Wright to Pathway-Specific Therapy

Purpose of Review

Psoriatic arthritis is a distinct disorder, separate from rheumatoid arthritis, and first recognized in a thirteenth century Saxon skeleton. It was, however, the monumental work of Verna Wright in the 1950s that led to the acceptance by the American Rheumatism Association (now American College of Rheumatology) in 1964 as a distinct entity. Wright’s work provided the framework for a better understanding of the pathogenic mechanisms operating on this condition, and eventually led to the development of targeted therapy that has proven to be more effective and safe than conventional therapy.

Recent Findings

Pathogenesis of psoriatic arthritis has been better delineated in recent years, as well as the use of biological therapy. Recent findings are discussed in detail.

Summary

Historical aspects of psoriatic arthritis, recent developments in pathogenesis, and therapy are discussed, and the contributions of Verna Wright to our understanding of the disorder are presented.

     

Robotic transanal surgery (RTAS) with utilization of a next-generation single-port system: a cadaveric feasibility study

Purpose

Transanal surgery remains both an innovative approach to rectal pathology and a demonstrated technical challenge. Improved technology using a single-port system robotic platform (SPS) offers a promising option for this surgery.

Methods

SPS robotic system was utilized to perform submucosal, full-thickness and cylindrical excision on four cadavers. Operative performance and surgeon fatigue were measured.

Results

On all types of resections, the SPS system performed well. There were no piecemeal or fragmented resections. Closure was judged to be good to excellent in all cases. Surgeon assessment of setup and performance of the SPS was excellent in all cases.

Conclusions

SPS robotic transanal surgery represents an exciting new option for transanal surgery.

     

Die Rolle der Selbsthilfegruppen in der Onkologie

Background

Little is known about self-help associations and their possibilities. Obstacles often prevent early contacts between affected people.

Objectives

The psychosocial support given by self-help associations in different phases is evaluated.

Materials and methods

Based on the experience of the Deutsche ILCO and from cooperation with other organizations and institutions, various dimensions of self-help groups are investigated.

Results

On the professional side, there is a lack of knowledge and of attitude. Suitable structures are rare.

Conclusions

The removal of barriers and development of effective structures are overdue.

     

A challenging case of carbapenemase-producing <Emphasis Type="Italic">Klebsiella pneumoniae</Emphasis> septic thrombophlebitis and right mural endocarditis successfully treated with ceftazidime/avibactam

Introduction

The emergence of carbapenemase-producing Klebsiella pneumonia (KPC-Kp) has become a significant problem in terms of public health and clinical outcome in many hospitals in Southern Europe. Treatment options are usually limited and effective treatment of infections caused by these pathogens is a considerable challenge for clinicians. Ceftazidime–avibactam has been recently approved for the treatment of difficult-to-treat infections due to aerobic Gram-negative organisms in patients with limited treatment options.

Case report

We reported the first case of KPC-Kp septic thrombophlebitis and right atrial endocarditis associated with metastatic lung abscesses successfully treated with a prolonged ceftazidime/avibactam plus ertapenem treatment course, suggesting that this combination therapy could be safe and effective for serious Gram-negative infections. Interestingly, we also observed an apparent discrepancy between clinical and microbiological courses: the patient became rapidly afebrile; hemodynamically stable and his procalcitonin levels showed a prompt decreasing trend. Nevertheless, blood cultures remained persistently positive for a prolonged period.

Conclusion

In conclusion, ceftazidime–avibactam plus ertapenem was a safe and effective therapy of serious endovascular infection due to KPC-Kp. Moreover, in this setting, follow-up blood cultures might represent an irreplaceable tool to guide the therapy.

     

Current State of Immunotherapy for HCC—Supporting Data and Toxicity Management

Purpose of Review

After having tyrosine kinase inhibitor as only available one drug class to treat advanced hepatocellular carcinoma (HCC) for more than a decade, immunotherapy agents are now approved for second-line therapy and are currently being compared head-to-head with sorafenib for first-line treatment. It is becoming increasingly important for hepatologists to become aware of agents in development, potential adverse events, and suggested treatment monitoring.

Recent Findings

Nivolumab and pembrolizumab have both shown promising phase II data in the second-line setting for HCC and phase III data in both the first-line and second-line settings are anticipated soon. Durable responses of 15–20% is seen as a potential breakthrough and may translate into improved survival for patients with advanced HCC. While immunotherapies are well tolerated overall, rare but serious immune-mediated adverse events are possible and warrant monitoring to facilitate early treatment when needed. There is ongoing research of combinations with immunotherapy agents and other systemic agents and/or locoregional therapies to further enhance response rates.

Summary

Ongoing studies will define the role of immunotherapy for treatment of HCC, both as single agents as well as in combination with other therapies.

     

The Role of Therapeutic Endoscopy in Patients With Cirrhosis-Related Causes of Gastrointestinal Bleeding

Purpose of Review

This article aims to review current therapeutic endoscopic treatments available for the management of gastrointestinal bleeding related to cirrhosis.

Recent Findings

Endoscopic band ligation is an effective treatment for primary prophylaxis, acute bleeding, and secondary prophylaxis of esophageal varices as well as for acute bleeding and secondary prophylaxis of select gastric varices. Sclerotherapy is a treatment option for acute bleeding and secondary prophylaxis of esophageal varices when band ligation is technically difficult. Cyanoacrylate glue injection is an effective treatment for acute bleeding of gastric and ectopic varices. Argon plasma coagulation is first-line and radiofrequency ablation is second-line treatment for chronic bleeding secondary to gastric antral vascular ectasia.

Summary

There are a variety of endoscopic treatment modalities for cirrhosis-related gastrointestinal bleeding, and the appropriate therapy depends on the location of the bleed, history or presence of acute bleeding, and risk factors for intervention-related adverse events.

     

Strategies for Effective Discontinuation of Proton Pump Inhibitors

Purpose of Review

Proton pump inhibitors (PPIs) are effective for many conditions but are often overprescribed. Recent concerns about long-term risks have made patients re-evaluate their need to take PPIs chronically, though these population-based studies have methodological weaknesses. The goal of this review is to provide evidenced-based strategies for discontinuation of PPI therapy.

Recent Findings

Given that some patients experience rebound symptoms when abruptly stopping continuous PPI therapy due to its effect on hypergastrinemia, strategies focus on avoiding rebound. Tapering the PPI and then initiating a “step-down” approach with the use of alternative medications may be effective. “On-demand therapy” provides patients with the option to take intermittent PPI courses, reducing overall use and cost while preserving patient satisfaction. It is important for providers to consider ambulatory pH or pH/impedance testing to rule out diagnoses that may require alternative medications like neuromodulators.

Summary

A number of studies reviewed here can provide guidance in counseling patients on PPI discontinuation. It is important for the provider to obtain a baseline needs assessment for PPI therapy and to elucidate predictors of difficulty in discontinuation prior to initiating a strategy.