Application of microwave ablation in the emergent control of intraoperative life-threatening tumor hemorrhage during hepatic surgeries

Purpose: This study was designed to evaluate the efficacy and safety of microwave ablation (MWA) in the treatment of intraoperative life-threatening tumour haemorrhage during hepatic surgeries.

Methods: Three cases of MWA application in the emergent control of life-threatening hepatic tumour haemorrhage were analysed and reported.

Results: Satisfactory hemostasis for hepatic tumour rupture was achieved by MWA in all three cases. No major complications, such as post-operative haemorrhage, bile duct injury, liver abscess, colon perforation, skin burns, tumour seeding or renal dysfunction, were identified.

Conclusions: MWA may be a feasible, effective and simple strategy for the emergent control of intraoperative hepatic tumour bleeding. To the best of our knowledge, this study represents the first reported cases of this novel application of MWA.     

Risk factors for acute kidney injury associated with the treatment of bacterial endocarditis at a tertiary academic medical center*

Background: Acute kidney injury (AKI) is a common complication of endocarditis.

Objective: To determine risk factors for the development of AKI in patients treated for endocarditis.

Methods: This single centre, retrospective univariate and multivariate analysis to determine risk factors for the development of AKI included patients diagnosed with endocarditis between January 2009 and October 2013.

Results: Of 211 included patients, a total of 84 (39.8%) patients developed AKI. We identified multiple independent variables associated with the development of AKI, including: age ≥ 65 years, presence of hardware, chronic kidney disease, AKI on admission, infection with Staphylococcus spp, receipt of nafcillin or oxacillin or aminoglycoside and nafcillin or oxacillin or aminoglycoside and vancomycin, vancomycin trough level ≥ 20.0 mcg/ml, aminoglycoside total daily dose reduction, duration of vancomycin exceeding three days, receipt of loop diuretic or more than three concomitant nephrotoxins and duration of loop diuretic or non-steroidal anti-inflammatory drug therapy exceeding seven days.

Conclusions: In patients treated for endocarditis, multiple risk factors for AKI were identified. Prospective studies are needed to evaluate these variables for causation of AKI in patients treated for endocarditis.     

The safety and efficacy of sonidegib for the treatment of locally advanced basal cell carcinoma

Introduction: Basal cell carcinomas (BCCs) are the commonest malignancy in the Western world. Locally advanced BCCs (laBCCs) represent tumours that have developed in difficult-to-treat facial sites, aggressively recurrent tumours, large neglected tumours and those in which current treatment options are excluded by clinical or patient-driven criteria. It is estimated laBCCs represent 1% of BCCs.

Areas covered: Sonidegib is an oral hedgehog pathway inhibitor with a novel structure. It has recently been licensed for the treatment of laBCC.

This article provides a comprehensive review of the literature regarding sonidegib, detailing the pharmacology of the compound, clinical trial data, competitor compounds and a future perspective.

Expert commentary: Sonidegib is a novel smoothened (SMO) inhibitor with comparable efficacy to vismodegib, with patient response rates of 44% (sonidegib) and 43% (vismodegib). The adverse effect profile of these two treatments is similar with the main effects being considered to be class effects of SMO inhibitors.     

Use of specific immunoglobulins and vaccines for the management of accidental needlestick injury in the child: a practical review in the anti-vaccination movement era

Introduction: Accidental needle injury is a common but still discussed problem.

Objective: We discuss possible options to optimize the management of injured children in light of the available literature findings.

Results: The risk of viral infection is low. However, blood investigations are mandatory, as well as appropriate counselling. Anti-HBV immunoglobulins are recommended in all unvaccinated subjects exposed to a HBsAg-positive source; however, there is no agreement regarding their administration in unvaccinated children. Use of anti-tetanus immunoglobulins in unvaccinated child with minor and clean wound is well defined; however, wound type classification in the event of needlestick injury may be difficult and subjective. There is no agreement on the routine use of antiretroviral prophylaxis.

Conclusion: From a practical point of view, several unsolved issues have emerged regarding the management of the children with needlestick injury, which appear particularly relevant in the anti-vaccination movement era. International guidelines should be encouraged at this regard.     

Female cancer patients' perceptions of the fertility preservation decision-making process: An exploratory prospective study

Purpose: To assess female cancer patients' perceptions of the fertility preservation decision-making process and to examine the effect of clinicians' support on the decision quality.

Methods: A total of 71 patients participated in this longitudinal study with two assessment time points (before cancer therapy, after cancer therapy). Self-report measures assessed the decision-making process, the decision quality and the clinicians' support.

Results: A less positive experience in the decision-making process was associated with higher decisional regret and lower decisional satisfaction. In the group that decided not to pursue FP, participants who perceived higher oncologist's support reported higher decisional satisfaction.

Conclusions: A higher quality decision is positively associated with a better experience in the decision-making process. The oncologist's support is crucial for the decisional satisfaction of patients who decide not to pursue FP.

Implications for psychosocial providers: Psychologists may be important in helping patients to adequately cope with the FP decision so that they can make a high-quality decision.     

The safety and efficacy of olaparib therapy in patients with relapsed ovarian cancer

Introduction: PARP inhibition is an exciting new anticancer strategy. Olaparib has recently obtained a first in class license in Europe and the USA for the treatment of relapsed BRCA-mutant ovarian cancer.

Areas covered: We review the key preclinical and clinical data surrounding its use in the maintenance setting.

Expert commentary: We also consider the market profile, regulatory issues surrounding the agent and offer a five year speculative viewpoint of its future development in ovarian cancer.     

Isolated cardiac peripheral primitive neuroectodermal tumor: A case report

Background: Peripheral primitive neuroectodermal tumor isolated in the heart, presenting as a primary cardiac tumor is considered as extremely rare.

Methods: We present a 53-year-old Chinese female with a cardiac tumor which was discovered by CT.

Results: A hypo-intense tumorous mass was shown extending from the left ventricle by Cardiac CT, and fused FDG positron emission tomography demonstrated no other abnormal FDG active lesions in the body. We performed a total resection surgery of the tumor subsequently and the patient recovered well and discharged from hospital 6 d after surgery.

Conclusion: The pathological diagnosis was primary cardiac peripheral primitive neuroectodermal tumor. No tumor recurrence was shown by echocardiography during the 24 months follow-up visits.     

Comparison of the effects of local treatment strategies in non-metastatic Ewing sarcoma of bone

Background: To investigate the optimal local treatment strategies for patients with non-metastatic Ewing sarcoma (ES) of bone.

Methods: Patients with ES of bone were identified using the Surveillance Epidemiology and End Results database. Kaplan-Meier log-rank test and Cox regression models were performed to assess the effect of the types of local treatment strategies on cause-specific survival and overall survival.

Results: 560 patients were included with a median age of 16 years. A total of 284, 162 and 114 patients received surgery alone, surgery and radiotherapy, and radiotherapy alone, respectively. The types of local treatment strategies had no effect on survival outcomes in multivariate analysis. In the subgroup analysis of patients with tumor diameter <8 cm, surgery ± radiotherapy had a significantly improved cause-specific survival (P = 0.039), and had potential to improve overall survival (P = 0.070) in multivariate analysis. The local treatment strategies had no effect on survival in patients with different tumor location.

Conclusion: There is no local treatment of choice for non-metastatic ES of bone in terms of survival. More well-designed studies are needed to confirm our findings and investigate the role of various local treatment strategies in relation to primary tumor diameter.     

An analysis of clinical characteristics and patient outcomes in primary mediastinal sarcomas

Background: Published data concerning primary mediastinal sarcomas are limited to small-sized retrospective series. This study reviewed the clinical outcomes of these cases from the SEER (surveillance, epidemiology and end results) database.

Methods: Primary mediastinal sarcomas (1988 - 2013) were assembled from the SEER database. The incidence and 10-year cancer-specific survival rates were compared to other primary mediastinal malignancies (thymic carcinoma, germ cell tumors, neurogenic tumors, Hodgkin / non Hodgkin lymphomas) as well as to non mediastinal sarcomas.

Results: A total of 204 patients were recruited into this cohort. Multivariate analysis showed better overall survival for patients with younger age at diagnosis, low grade [hazard ratio 0.427 (95% CI: 0.224-0.814; P= 0.010)], posterior mediastinum location [hazard ratio 0.458 (95% CI: 0.268-0.781; P= 0.004)], node negative disease [hazard ratio 0.463 (95% CI: 0.232-0.923; P= 0.029)] and surgical treatment [hazard ratio 0.488 (95% CI: 0.336-0.709; P <0.0001)]. Compared to other mediastinal malignancies, primary mediastinal sarcomas have the worst 10-year overall survival. Similarly compared to non mediastinal sarcomas, primary mediastinal sarcomas have worse 10-year overall survival (23% versus 55%).

Conclusion: Primary mediastinal sarcoma is a rare entity with worse prognosis compared to non-mediastinal counterparts. Surgical resection plays a particularly important role in the management.     

EGFR expression in circulating tumor cells from high-grade metastatic soft tissue sarcomas

Introduction: Soft tissue Sarcomas (STS) are rare malignances, with high mortality rates. Half of patients develop metastasis. The presence of isolated Circulating Tumor Cells (CTCs) and Circulating Tumor Microemboli (CTM) in the blood may be early markers of tumor invasion. Epidermal Growth Factor (EGF) family receptors can also influence this process.

Objectives: to quantify CTCs and identify CTM as well as the EGF Receptor (EGFR) protein expression in these cells and correlate with clinical outcome in metastatic STS.

Materials and methods: Approximately 8mL of blood was prospectively collected from patients with different types of high-grade STS, before the beginning of chemotherapy. The samples were processed and filtered by ISET (Rarecells, France) for the isolation and quantification of CTCs and CTMs. EGFR expression was analyzed by immunocytochemistry (ICC) on CTCs/ CTMs.

Results: We analyzed 18 patients with median age of 49 years (18-77 y). The positivity for EGFR protein expression in CTCs was observed in 93.75% of the patients. This result shows that targeting EGFR positive CTCs from STS origen can be translated in clinical benefit for some patients. In addition, if target therapy is chosen, the EGFR expression in CTCs can be used in follow-up to measure treatment effectiveness.

Conclusions: This is the first study to demonstrate the expression of EGFR protein in CTCs from sarcoma patients. It may open an area for future investigations. The next step is to characterize CTCs in a larger cohort of patients to better understand the role of EGFR in sustaining tumor metastasis in sarcomas.     

Opportunities and challenges of long term anti-estrogenic adjuvant therapy: treatment forever or intermittently?

Introduction: Extended adjuvant (5–10 years) therapy targeted to the estrogen receptor (ER) has

significantly decreased mortality from breast cancer (BC).

Areas covered: Translational research advanced clinical testing of extended adjuvant therapy with tamoxifen or aromatase inhibitors (AIs). Short term therapy or non-compliance increase

recurrence, but surprisingly recurrence and death does not increase dramatically after 5 years of adjuvant therapy stops.

Expert commentary: Compliance ensures optimal benefit from extended antihormone adjuvant therapy.Retarding acquired resistance using CDK4/6 or mTOR inhibitors is discussed. Preventing acquired resistance from mutations of ER could be achieved with Selective ER Downregulators (SERDs), eg fulvestrant. Fulvestrant is a depot injectable so oral SERDs are sought for extended use. In reality, a ‘super SERD’ which destroys ER but improves women’s health like a Selective ER Modulator (SERM), would aid compliance to prevent recurrence and death. Estrogen-induced apoptosis occurs in 30% of BC with antihormone resistance. The ‘one in three’ rule that dictates that one in three unselected patients respond to either hormonal or antihormonal therapy in BC occurs with estrogen or antiestrogen therapy and must be improved. The goal is to maintain patients for their natural lives by blocking cancer cell survival through precision medicine using short cycles of estrogen apoptotic salvage therapy, and further extended antihormone maintenance.     

CT-guided radiofrequency ablation of spinal osteoblastoma: treatment and long-term follow-up

Objective: Osteoblastoma (OB) is a painful, rare, benign bone tumour usually observed in young populations, and this condition involves the spine in up to one-third of cases. We sought to focus on the minimally invasive treatment of spinal OB with radiofrequency ablation (RFA) under computed tomography (CT) guidance. When performed near the spinal cord, surgery can lead to instability of the spine, sometimes requiring additional interventions to stabilise the segments involved, and can cause the precocious onset of arthrosis or other degenerative diseases.

The results were evaluated both clinically and with the aid of diagnostic imaging techniques during a 5-year follow-up study.

Materials and methods: Eleven patients affected by spinal OB were treated in a single session with biopsy and CT-guided RFA. Pre- and post-evaluations of the patients were performed both clinically and with CT and magnetic resonance imaging (MRI).

Results: Complete success in terms of pain relief was achieved in all patients. Additional treatments were not required in any patients. There were no complications. During follow-up, neither complications nor pathological findings related to the treatment were observed.

Conclusions: Our experience demonstrates that RFA for spinal OB is safe and effective. One of the main advantages of this technique is represented by its lower grade of invasiveness compared with that for potentially hazardous surgical manoeuvres.     

First-line treatment of NSCLC with bevacizumab: real world data from an Italian regional based survey

Background: We aimed to explore the use of platinum plus bevacizumab in a real world NSCLC population.

Patients and methods: We retrospectively collected data from patients affected by NS-NSCLC treated with platinum plus bevacizumab across Tuscany.

Results: We evaluated 62 (median age: 63.5 [30–77] years) pts. All but one presented with adenocarcinoma and the majority had ECOG PS of 0/1. 17.7% presented with central lesion, 11.3% with brain metastasis, 38.7% with hypertension and 4.8% with mild haemoptysis. We observed a median time to progression (TTP) of 6.5 [2–37] and a median overall survival (OS) of 10.5 [2–39] months. Overall response rate (ORR) was 59.6% with a disease control rate (DCR) of 80.6%. Safety profile was acceptable. We observed five cardiovascular events and two major bleedings with no toxic deaths.

Conclusion: Safety and efficacy real world data are consistent with those from clinical trials even in a less selected population.     

Cardiovascular mortality trends in non-Hodgkin’s lymphoma: a population-based cohort study

Background: Non-Hodgkin’s lymphoma (NHL) survivors are at a higher risk of cardiovascular diseases (CVDs).

Methods: A population-based study was conducted to investigate the cardiovascular mortality trends to identify NHL survivors at the highest risk.

Results: The CVDs mortality was the second most common cause of death (13.07%) after NHL. There were more patients ≥ 60 years old in the cardiovascular group (87.2%), P < 0.001. Patients who died from CVDs had the best survival while patients who died from NHL had a significantly lower mean survival. The overall survival rate was 92.4%. Consistently, older age, unmarried, male patients, not recently diagnosed with NHL and not receiving radiation and/or surgery were associated with a worse survival across all models. The black race and stage IV only had a worse cardiovascular specific survival (CVSS).

Conclusions: Although the CVSS improved over time, the mortality from the CVDs is still the second most common cause of death after NHL. Older age, not married, black, male patients, not recently diagnosed with NHL, with an advanced stage and not receiving radiation and/or surgery were associated with a worse survival. Risk factor modification along with CVDs screening should be intensified in NHL patients with these mortality predictors.     

Platinum agents and mitomycin C-specific complications in cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

Introduction: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in patients with peritoneal disease but is associated with significant morbidity. We evaluate the perioperative complications and the association with the chemotherapy agent used for HIPEC.

Methods: Retrospective analysis of a prospectively collected database of CRS–HIPEC cases between April 2001 and February 2016 was performed. Patients were stratified by the chemotherapy used, and perioperative complications were compared.

Results: Out of 214 CRS–HIPEC cases, 113 procedures used Mitomycin-C(MMC), 92 used cisplatin, 8 used oxaliplatin and the HIPEC regimen for one procedure was not recorded and excluded. 94 patients (44%) suffered low-grade complications (grade I–II), and 49 patients (23%) suffered high-grade complications (grade III–V). The frequency of low-grade complications for the cisplain, oxaliplatin and MMC groups were 49%, 50% and 40%, respectively, whereas that of high-grade complications were 24%, 50% and 20%, respectively. HIPEC with platinum agents was associated with a higher rate of acute renal impairment (ARI) compared to MMC (32% and 62% for cisplatin and oxaliplatin vs. 5.6% for MMC), whereas grade IV ARI requiring dialysis occurred only in the cisplatin group (5.6%). HIPEC with oxaliplatin was associated with higher rates of post-operative bleeding (25% vs. 1.1% and 0.88%). Rates of other complications did not differ significantly between the groups receiving different HIPEC regimens.

Conclusions: The overall complication rates do not significantly differ after HIPEC with MMC and platinum based agents. Renal impairment tends to be more common and of greater severity when a platinum agent is used, whereas oxaliplatin is associated with significant post-operative bleeding.     

Therapeutic strategies for organ-confined and non-organ-confined bladder cancer after radical cystectomy

Introduction: In patients with muscle invasive or Bacillus Calmette-Guérin refractory urothelial carcinoma of the urinary bladder (UCUB) radical cystectomy represents the standard of care. However, a proportion of patients experience disease progression, local recurrence and/or metastatic disease.

Areas covered: This review provides an overview of available therapeutic strategies after radical cystectomy and examines ongoing clinical trials including cytotoxic chemotherapy and immunotherapy.

Expert commentary: Cytotoxic chemotherapy offers limited benefit in UCUB patients. However, the recent introduction of immunotherapy provides new hope for durable responses or possibly complete cures.     

Factors influencing radiation treatment recommendations in early-stage Merkel cell carcinoma: a survey of US-based radiation oncologists

Background: It is unclear which subgroups of Merkel cell carcinoma (MCC) patients benefit the most from radiation. We surveyed radiation oncologists (RO) that regularly see and treat MCC to understand how they approach the treatment of early-stage MCC.

Methods: A web-based survey was emailed to 63 ROs, who were identified through publications, guideline panel membership, and/or affiliation with institutions of high MCC volume. ROs provided treatment recommendations for two hypothetical case scenarios of early stage MCC.

Results: Among 28 respondents (45%), 26 regularly saw and treated MCC patients for a median 7 years (range, 0–30). While all ROs recommended adjuvant radiation for a stage II upper extremity MCC, only 48% recommended adjuvant radiation for stage I head and neck MCC.

Conclusion: Among US-based MCC RO ‘specialists,’ there is equipoise on the role of radiotherapy for stage I MCC. Ideally, prospective studies are needed to identify which patients may benefit from radiation.     

Challenging a dogma: five-year survival does not equal cure in all colorectal cancer patients

Background: The current study tried to evaluate the factors affecting 10- to 20- years’ survival among long term survivors (>5 years) of colorectal cancer (CRC).

Methods: Surveillance, Epidemiology and End Results (SEER) database (1988-2008) was queried through SEER*Stat program.Univariate probability of overall and cancer-specific survival was determined and the difference between groups was examined. Multivariate analysis for factors affecting overall and cancer-specific survival was also conducted.

Results: Among node positive patients (Dukes C), 34% of the deaths beyond 5 years can be attributed to CRC; while among M1 patients, 63% of the deaths beyond 5 years can be attributed to CRC. The following factors were predictors of better overall survival in multivariate analysis: younger age, white race (versus black race), female gender, Right colon location (versus rectal location), earlier stage and surgery (P <0.0001 for all parameters). Similarly, the following factors were predictors of better cancer-specific survival in multivariate analysis: younger age, white race (versus black race), female gender, Right colon location (versus left colon and rectal locations), earlier stage and surgery (P <0.0001 for all parameters).

Conclusion: Among node positive long-term CRC survivors, more than one third of all deaths can be attributed to CRC.     

Liver metastases resection for gastric and esophageal tumors: is there enough evidence to go down this path?

Introduction: Surgical resection of liver metastases from colorectal and neuroendocrine tumours has become a standard of care for resectable patients with isolated hepatic disease and good performance status, leading to extended survival in a carefully selected subgroup of these patients. However, the role of hepatic surgery in gastric and oesophageal liver metastases is controversial and not clearly defined.

Areas covered:a systematic electronic literature search was performed to select the most representative evidence regarding hepatectomies in liver metastases from these two tumours. PubMed, Medline, Embase Ovid and Google Scholar databases were scanned for articles written in English and published in peer-reviewed journals between 1994 and May 2016.

Expert commentary: Given the shortage of randomised studies and the limited number of patients in many of the studies discussed here, the evidence base for the use of hepatectomies in these settings is not strong. Thus, while the data for resections of gastric liver metastases may in particular seem encouraging, the results should be interpreted with caution.