The effect of an elemental diet on oral mucositis of esophageal cancer patients treated with DCF chemotherapy: a multi-center prospective feasibility study (EPOC study)

Purpose

Oral mucositis (OM) is one of the most uncomfortable adverse events experienced by cancer patients undergoing chemotherapy. Previous reports have revealed that the oral administration of an elemental diet (ED) may prevent OM. However, the incidence of OM has not been accurately determined by specialized diagnostic methods and the effects of an ED on OM remain unclear. We investigated the dose that could feasibly be administered and its effects with regard to the suppression of OM in esophageal cancer patients undergoing chemotherapy.

Methods

We performed a prospective multi-center feasibility study of the administration of an ED (160 g/day) with 2 cycles of docetaxel/cisplatin/5-FU (DCF) chemotherapy. We assessed compliance to the ED for 49 days and the incidence of OM according to the amount of the ED that was orally administered. The incidence of OM was graded by a dental specialist who was experienced in dental oncology using a central OM review system.

Results

Fourteen of 20 patients (70%) were able to complete the orally administered ED (160 g/day) during the course of chemotherapy. Three patients (15%) could not take the ED orally for 9, 14, and 21 days, respectively, while 1 patient (5%) took the ED orally at an average dose of 80 g/day for 35 days. The remaining 2 patients (10%) could not take the 80 g/day dose for 11 and 12 days, respectively. The incidence of grade?≥?2 OM in the ED completion group (15.4%, 2 of 13 patients) was significantly lower than that in the non-completion group (66.7%, 4 of 6 patients) (p?=?0.046).

Conclusions

An ED might be a one of the test treatment to reduce the incidence of OM in esophageal cancer patients treated with DCF and should be evaluated in further randomized study.

Clinical trial

The date of submission: Dec 08th, 2017.

     

Expression of cell cycle regulators and biomarkers of proliferation and regrowth in human pituitary adenomas

Purpose

The pathogenesis of pituitary adenomas (PA) is complex. Ki-67, pituitary tumour transforming gene (PTTG), vascular endothelial growth factor (VEGF), cyclin D1, c-MYC and pituitary adenylate cyclase-activating peptide (PACAP) protein expression were analysed and correlated with tumour and patient characteristics.

Methods

74 pituitary tumour samples (48 non-functional PA, 26 functional PAs); Immunohistochemical analysis of protein expression, retrospective analysis of MR images and in vitro analysis of octreotide treatment was carried out on GH3 cells.

Results

PTTG expression was negatively associated with age and positively with PA size, regrowth and Ki-67 index. Cyclin D1 correlated with Ki-67 and tumour size. c-MYC negatively correlated with size of tumour and age; and correlated with PTTG expression. Somatostatin analogue treatment was associated with lower Ki-67, PTTG and Cyclin D1 expression while T2 hypointense PAs were associated with lower PTTG, cyclin D1, c-MYC and Ki-67. In vitro analyses confirmed the effect of somatostatin analogue treatment on Pttg and Cyclin D1 expression.

Conclusions

Interesting and novel observations on the differences in expression of tumour markers studied are reported. Correlation between Ki-67 expression, PTTG nuclear expression and recurrence/regrowth of PAs, emphasizes the role that Ki-67 and PTTG expression have as markers of increased proliferation. c-MYC and PTTG nuclear expression levels were correlated providing evidence that PTTG induces c-MYC expression in PAs and we propose that c-MYC might principally have a role in early pituitary tumorigenesis. Evidence is shown that the anti-proliferative effect of somatostatin analogue treatment in vivo occurs through regulation of the cell cycle.

     

Cholangiozelluläres Karzinom

Background

At diagnosis, the majority of patients with cholangiocarcinoma (CCC) cannot be offered curative resection.

Objectives

The current state of knowledge concerning palliative treatment options (endoscopic interventions, selective internal radiotherapy, systemic chemotherapy) for CCC are summarized.

Materials and methods

A summary of key publications is presented and differential treatment considerations are discussed.

Results

The basis of palliative treatment is biliary decompression to avoid liver failure and infectious complications. In selected patients—without extrahepatic tumor spread—photodynamic therapy (PDT) and biliary radiofrequency ablation (RFA) offer prolonged overall survival. In patients with intrahepatic CCC or with hepatic metastases, selective internal radiotherapy is well tolerated and can offer marked survival benefit. Infrequently, downstaging to resectable disease stages can be achieved. Standard systemic palliative therapy of CCC combines gemcitabine with cisplatin or oxaliplatin. A number of targeted therapy approaches are under investigation.

Conclusion

Palliative therapy of CCC consists of biliary drainage with/without locoregional therapy and systemic chemotherapy. Multimodal approaches are promising, but to date are still insufficiently evaluated.

     

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.

     

Effects of a Video on Organ Donation Consent Among Primary Care Patients: A Randomized Controlled Trial

BACKGROUND

Low organ donation rates remain a major barrier to organ transplantation.

OBJECTIVE

We aimed to determine the effect of a video and patient cueing on organ donation consent among patients meeting with their primary care provider.

DESIGN

This was a randomized controlled trial between February 2013 and May 2014.

SETTING

The waiting rooms of 18 primary care clinics of a medical system in Cuyahoga County, Ohio.

PATIENTS

The study included 915 patients over 15.5 years of age who had not previously consented to organ donation.

INTERVENTIONS

Just prior to their clinical encounter, intervention patients (n?=?456) watched a 5-minute organ donation video on iPads and then choose a question regarding organ donation to ask their provider. Control patients (n?=?459) visited their provider per usual routine.

MAIN MEASURES

The primary outcome was the proportion of patients who consented for organ donation. Secondary outcomes included the proportion of patients who discussed organ donation with their provider and the proportion who were satisfied with the time spent with their provider during the clinical encounter.

KEY RESULTS

Intervention patients were more likely than control patients to consent to donate organs (22 % vs. 15 %, OR 1.50, 95%CI 1.10–2.13). Intervention patients were also more likely to have donation discussions with their provider (77 % vs. 18 %, OR 15.1, 95%CI 11.1–20.6). Intervention and control patients were similarly satisfied with the time they spent with their provider (83 % vs. 86 %, OR 0.87, 95%CI 0.61–1.25).

LIMITATION

How the observed increases in organ donation consent might translate into a greater organ supply is unclear.

CONCLUSION

Watching a brief video regarding organ donation and being cued to ask a primary care provider a question about donation resulted in more organ donation discussions and an increase in organ donation consent. Satisfaction with the time spent during the clinical encounter was not affected.

TRIAL REGISTRATION

clinicaltrials.gov Identifier: NCT01697137

     

Targeting for insulin-like growth factor-I receptor with short hairpin RNA for human digestive/gastrointestinal cancers

Background and aims

Insulin-like growth factor (IGF)-I receptor (IGF-IR) signaling plays important parts in both the tumorigenicity and progression of digestive/gastrointestinal malignancies. In this study, we sought to test the effectiveness of a practical approach to blocking IGF-IR signaling using RNA interference delivered by recombinant adenoviruses.

Methods

We constructed a recombinant adenovirus expressing short hairpin RNA targeting IGF-IR (shIGF-IR) and assessed its effect on signal transduction, proliferation, and survival in digestive/gastrointestinal cancer cell lines representing colorectal, gastric, and pancreatic adenocarcinoma, esophageal squamous cell carcinoma, and hepatoma. We analyzed the effects of shIGF-IR alone and with chemotherapy in vitro and in nude mouse xenografts, as well as on insulin signaling and hybrid receptor formation between IGF-IR and insulin receptor.

Results

shIGF-IR blocked expression and autophosphorylation of IGF-IR and downstream signaling by the IGFs, but not by insulin. shIGF-IR suppressed proliferation and carcinogenicity in vitro and up-regulated apoptosis in a dose-dependent fashion. shIGF-IR augmented the effects of chemotherapy on in vitro growth and apoptosis induction. Moreover, the combination of shIGF-IR and chemotherapy was highly effective against tumors in mice. shIGF-IR reduced hybrid receptor formation without effect on expression of insulin receptor.

Conclusions

shIGF-IR may have therapeutic utility in human digestive/gastrointestinal cancers, both alone and in combination with chemotherapy.

     

Nephrotoxizität bei Chemotherapie

Background

Renal function plays a crucial role in the choice and administration of chemotherapy. The chemotherapy of malignant diseases is associated with potential renal and non-renal adverse side effects and should, therefore, be correctly selected and implemented.

Objective

Chemotherapy can induce acute kidney injury or lead to the development or aggravation of chronic kidney disease. In addition, impaired renal function can exacerbate adverse events, necessitate reduction in dosing or even lead to termination of therapy.

Material and methods

We present commonly used potentially nephrotoxic chemotherapeutic substances and the corresponding preventive measures. Furthermore, we present thrombotic microangiopathy (TMA) as an undesired side effect triggered by various chemotherapeutic agents.

Results

Potential nephrotoxicity should be recognized before induction of therapy as acute kidney failure as well as chronic kidney disease are associated with increased morbidity and mortality during the acute phase as well as during long-term follow-up.

Conclusion

Cooperation between nephrologists and hematologist-oncologists is very important in order to provide the best therapy with the lowest rate of side effects for patients.

     

Receipt of Cancer Screening Is a Predictor of Life Expectancy

Background

Obtaining cancer screening on patients with limited life expectancy has been proposed as a measure for low quality care for primary care physicians (PCPs). However, administrative data may underestimate life expectancy in patients who undergo screening.

Objective

To determine the association between receipt of screening mammography or PSA and overall survival.

Design

Retrospective cohort study from 1/1/1999 to 12/31/2012. Receipt of screening was assessed for 2001–2002 and survival from 1/1/2003 to 12/31/2012. Life expectancy was estimated as of 1/1/03 using a validated algorithm, and was compared to actual survival for men and women, stratified by receipt of cancer screening.

Participants

A 5 % sample of Medicare beneficiaries aged 69–90 years as of 1/1/2003 (n?=?906,723).

Interventions

Receipt of screening mammography in 2001–2002 for women, or a screening PSA test in 2002 for men.

Main Measures

Survival from 1/1/2003 through 12/31/2012.

Key Results

Subjects were stratified by life expectancy based on age and comorbidity. Within each stratum, the subjects with prior cancer screening had actual median survivals higher than those who were not screened, with differences ranging from 1.7 to 2.1 years for women and 0.9 to 1.1 years for men. In a Cox model, non-receipt of screening in women had an impact on survival (HR?=?1.52; 95 % CI?=?1.51, 1.54) similar in magnitude to a diagnosis of complicated diabetes or heart failure, and was comparable to uncomplicated diabetes or liver disease in men (HR?=?1.23; 1.22, 1.25).

Conclusions

Receipt of cancer screening is a powerful marker of health status that is not captured by comorbidity measures in administrative data. Because life expectancy algorithms using administrative data underestimate the life expectancy of patients who undergo screening, they can overestimate the problem of cancer screening in patients with limited life expectancy.

     

A novel endoscopic treatment for anastomotic leakage post anterior resection: Padlock over the scope clip

Background

Anastomotic dehisense is a serious complication of anterior resections. We have had success in our centre utilising Endosponge therapy to salvage anastomotic leaks but this requires multiple endoscopic sessions and can take around 6 weeks to heal in some cases. This can delay further management such as chemotherapy.

Aim

We describe the novel use of Padlock over the scope clips to manage patients with anastomotic dehisense post anterior resection.

Method

Padlock over the scope clips were used to manage three patients who presented with anastomotic breakdown post laparoscopic anterior resection between February 2016 and July 2017.

Results

These patients were initially managed conservatively with IV antibiotics and fluids. One case was first managed with Endosponge treatment before a Padlock clip was utilised to bridge a narrow defect. The other cases were managed initially with CT-guided percutaneous drains before clip deployment. Patients were followed up with regular clinic and sigmoidoscopies. All three cases demonstrated anastomotic salvage and satisfactory healing. This allowed the patients to be fit for their chemotherapy in less than 4 weeks from presentation. There were no complications from utilising the Padlock clips in these cases.

Conclusion

Utilising over the scope endoclips previously has been thought to be limited by the size of defect. Our experience details novel combination techniques that allow for quick resolution and the expeditious commencement of further management such as chemotherapy. These clips also proved to be cost-effective in our centre, utilising less inpatient and outpatient resources than alternative management plans.

     

Interdisziplinäre Therapie kolorektaler Lebermetastasen

Background

Liver metastases occur in every second patient with colorectal carcinoma.

Objectives

Therapeutic options for patients with hepatic metastases from colorectal cancer (CRC), specific indications, and interdisciplinary concepts are presented.

Methods

Based on the current literature and guidelines, novel study results and expert opinions are discussed.

Results

Surgical resection of primarily resectable liver metastases from CRC is standard and allows long-term control or healing in up to 36?% of cases. Adjuvant chemotherapy after resection can be performed, but the current study data are insufficient to generally recommend perioperative chemotherapy in this setting. Secondary resectability of primarily irresectable metastases can be reached by interventional induction of liver hypertrophy or neoadjuvant chemotherapy (conversion therapy). New study results suggested a benefit for more intensive combination chemotherapies, but possible side effects have to be considered. Finally, locoregional ablative therapies have gained increasing importance in the multimodal treatment of hepatic CRC metastases, and current clinical trials suggest a possible benefit of combination strategies together with chemotherapy and surgery even in early therapy lines.

Conclusions

Liver metastases from CRC require an multidisciplinary approach. Therefore, patients should be presented to a multidisciplinary tumor board not only at the beginning, but also along different therapy lines.

     

Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection

Purpose

We report on a kidney transplant recipient treated with fecal microbiota transplantation (FMT) for recurrent urinary tract infections.

Methods

FMT was administered via frozen capsulized microbiota. Before and after FMT, urinary, fecal and vaginal microbiota compositions were analyzed.

Results

The patient remained without symptoms after FMT.

Conclusions

Underlying mechanisms of action need to be addressed in depth by future research.

     

Cost of Transformation among Primary Care Practices Participating in a Medical Home Pilot

Background

Medical home initiatives encourage primary care practices to invest in new structural capabilities such as patient registries and information technology, but little is known about the costs of these investments.

Objectives

To estimate costs of transformation incurred by primary care practices participating in a medical home pilot.

Design

We interviewed practice leaders in order to identify changes practices had undertaken due to medical home transformation. Based on the principles of activity-based costing, we estimated the costs of additional personnel and other investments associated with these changes.

Setting

The Pennsylvania Chronic Care Initiative (PACCI), a statewide multi-payer medical home pilot.

Participants

Twelve practices that participated in the PACCI.

Measurements

One-time and ongoing yearly costs attributed to medical home transformation.

Results

Practices incurred median one-time transformation-associated costs of $30,991 per practice (range, $7694 to $117,810), equivalent to $9814 per clinician ($1497 to $57,476) and $8 per patient ($1 to $30). Median ongoing yearly costs associated with transformation were $147,573 per practice (range, $83,829 to $346,603), equivalent to $64,768 per clinician ($18,585 to $93,856) and $30 per patient ($8 to $136). Care management activities accounted for over 60% of practices’ transformation-associated costs. Per-clinician and per-patient transformation costs were greater for small and independent practices than for large and system-affiliated practices.

Limitations

Error in interviewee recall could affect estimates. Transformation costs in other medical home interventions may be different.

Conclusions

The costs of medical home transformation vary widely, creating potential financial challenges for primary care practices—especially those that are small and independent. Tailored subsidies from payers may help practices make these investments.

Primary Funding Source

Agency for Healthcare Research and Quality

     

Cancer Center Volume and Type Impact Stage-Specific Utilization of Neoadjuvant Therapy in Rectal Cancer

Background

Neoadjuvant chemoradiation reduces local recurrence in locally advanced rectal cancer, and adherence to national and societal recommendations remains unknown.

Objective

To determine variability in guideline adherence in rectal cancer treatment and investigate whether hospital volume correlated with variability seen.

Design

We performed a retrospective analysis using the National Cancer Database rectal cancer participant user files from 2005 to 2010. Stage-specific predictors of neoadjuvant chemotherapy and radiation use were determined, and variation in use across hospitals analyzed. Hospitals were ranked based on likelihood of preoperative therapy use by stage, and observed-to-expected ratios for neoadjuvant therapy use calculated. Hospital outliers were identified, and their center characteristics compared.

Results

A total of 23,488 patients were identified at 1183 hospitals. There was substantial variability in the use of neoadjuvant chemoradiation across hospitals. Patients managed outside clinical guidelines for both stage 1 and stage 3 disease tended to receive treatment at lower-volume, community cancer centers.

Conclusions

There is substantial variability in adherence to national guidelines in the use of neoadjuvant chemoradiation for rectal cancer across all stages. Both hospital volume and center type are associated with over-treatment of early-stage tumors and under-treatment of more invasive tumors. These findings identify a clear need for national quality improvement efforts in the treatment of rectal cancer.

     

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone

Background

Pirfenidone is a novel anti-fibrotic agent in idiopathic pulmonary fibrosis with proven clinical benefit. Better human tissue models to demonstrate the immunomodulatory and anti-fibrotic effect of pirfenidone are required.

Objectives

The purpose of the study was to use transbronchial lung cryobiopsy (TBLC), a novel technique which provides substantial tissue samples, and a large panel of biomarkers to temporally assess disease activity and response to pirfenidone therapy.

Methods

Thirteen patients with confirmed idiopathic pulmonary fibrosis (IPF) underwent full physiological and radiological assessment at diagnosis and after 6-month pirfenidone therapy. They underwent assessment for a wide range of potential serum and bronchoalveolar lavage biomarkers of disease activity. Finally, they underwent TBLC before and after treatment. Tissue samples were assessed for numbers of fibroblast foci, for Ki-67, a marker of tissue proliferation and caspase-3, a marker of tissue apoptosis.

Results

All patients completed treatment and investigations without significant incident. There was no significant fall in number of fibroblast foci per unit tissue volume after treatment (pre-treatment: 0.14/mm² vs. post-treatment 0.08/mm², p?=?0.1). Likewise, there was no significant change in other markers of tissue proliferation, Ki-67 or Caspase-3 with pirfenidone treatment. We found an increase in three bronchoalveolar lavage angiogenesis cytokines, Placental Growth Factor, Vascular Endothelial Growth Factor-A, and basic Fibroblast Growth Factor, two anti-inflammatory cytokines Interleukin-10 and Interleukin-4 and Surfactant Protein-D.

Conclusions

TBLC offers a unique opportunity to potentially assess the course of disease activity and response to novel anti-fibrotic activity in IPF.

     

Cancer Risk Communication with Low Health Literacy Patients: A Continuing Medical Education Program

BACKGROUND

Low health literacy (HL) is an important risk factor for cancer health disparities.

OBJECTIVE

Describe a continuing medical education (CME) program to teach primary care physicians (PCP) cancer risk communication and shared decision-making (SDM) with low HL patients and baseline skills assessment.

DESIGN

Cluster randomized controlled trial in five primary care clinics in New Orleans, LA.

PARTICIPANTS

Eighteen PCPs and 73 low HL patients overdue for cancer screening.

INTERVENTION

Primary care physicians completed unannounced standardized patient (SP) encounters at baseline. Intervention physicians received SP verbal feedback; academic detailing to review cancer screening guidelines, red flags for identifying low HL, and strategies for effective counseling; and web-based tutorial of SP comments and checklist items hyperlinked to reference articles/websites.

MAIN MEASURES

Baseline PCP self-rated proficiency, SP ratings of physician general cancer risk communication and SDM skills, patient perceived involvement in care.

RESULTS

Baseline assessments show physicians rated their proficiency in discussing cancer risks and eliciting patient preference for treatment/decision-making as “very good”. SPs rated physician exploration of perceived cancer susceptibility, screening barriers/motivators, checking understanding, explaining screening options and associated risks/benefits, and eliciting preferences for screening as “satisfactory”. Clinic patients rated their doctor’s facilitation of involvement in care and information exchange as “good”. However, they rated their participation in decision-making as “poor”.

DISCUSSION

The baseline skills assessment suggests a need for physician training in cancer risk communication and shared decision making for patients with low HL. We are determining the effectiveness of teaching methods, required resources and long-term feasibility for a CME program.

     

Radiotherapy with concurrent temozolomide for the management of extraneural metastases in pituitary carcinoma

Background

Pituitary carcinomas (PC) are uncommon neuroendocrine tumors, accounting for 0.1 % of all pituitary tumors. The diagnosis of PC is based on the presence of metastases from a pituitary adenoma, and not by local invasion or pathological features alone. PC is typically resistant to therapy, with a median overall survival of only 31 months. There is no standard treatment for PC, but maximal safe resection and radiation are performed when possible. Encouraging preliminary data on the use of temozolomide (TMZ)-based therapy has been previously reported.

Methods

We report the response to therapy and safety of radiation with concurrent temozolomide (RT/TMZ) in 2 adult patients with heavily pretreated PC and extraneural metastases.

Results

Both patients had prior history of pituitary macroadenoma. At the time of diagnosis of PC, Ki-67 % was 24.2 and 10 %, with positive p53 staining in one case. Metastatic sites included lymph nodes, liver and bone. Case-1 received RT/TMZ to the tumor bed in the skull base and to the metastases in the cervical lymph nodes. Case-2 received RT/TMZ to recurrent tumor involving portacaval lymph nodes. Both patients achieved excellent long-term control of the sites of treated extraneural metastases, with no significant acute or delayed toxicity.

Conclusions

RT/TMZ was safely delivered and might provide sustained control of extraneural metastases in PC. Although this retrospective report has limitations, RT/TMZ can be considered as a therapeutic option for the management of extraneural metastases in PC.

     

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.

     

Application of the qSOFA score to predict mortality in patients with suspected infection in a resource-limited setting in Malawi

Purpose

To determine the predictive value of qSOFA (quick Sequential Organ Failure Assessment) in Malawian patients with suspected infection.

Methods

Prospective observational study in a tertiary referral hospital in Malawi.

Results

Predictive ability of qSOFA was reasonable [AUROC 0.73 (95% CI 0.68–0.78)], increasing to 0.77 (95% CI 0.72–0.82) when classifying all patients with altered mental status as high risk. Adding HIV status as a variable to the qSOFA score did not improve predictive value.

Conclusion

qSOFA is a simple tool that can aid risk stratification in resource-limited settings.