Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Abstract

Introduction

Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(−) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods

The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results

At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions

These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(−) B-precursor ALL compared with salvage chemotherapy.

Funding

Amgen.

Trial Registration

ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

http://ift.tt/2genv6u

Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS)

Abstract

Introduction

An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here.

Methods

Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity.

Results

Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids.

Conclusions

These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients' satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients.

Funding

Molteni Farmaceutici, Italy.

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Association of Performance Status and Pain in Metastatic Bone Pain Management in the Spanish Clinical Setting

Abstract

Introduction

Bone metastasis is the most common cause of cancer-related pain, and metastatic bone pain (MBP) is not only severe but also progressive in many patients. The aim of this study was to investigate the association between pain management and performance status in patients with metastatic bone cancer in the Spanish clinical setting.

Methods

A 3-month follow-up prospective, epidemiologic, multicenter study was conducted in 579 patients to assess the evolution of their performance, the impact of pain control on sleep and functionality, and the degree of pain control according to analgesic treatment.

Results

In patients with MBP, Eastern Cooperative Oncology Group (ECOG) status (1.5 ± 0.7–1.3 ± 0.7 and 1.3 ± 0.8; p < 0.001) and pain (6.5 ± 1.4–2.8 ± 1.9 and 2.1 ± 1.9; p < 0.001) improved significantly from baseline to months 1 and 3, as did functionality and sleep, after a treatment change consisting of increasing the administration of opioids. Evolution of ECOG and pain were closely related. ECOG and pain outcomes were significantly more favorable in patients treated with opioids versus non-opioid treatment, and in patients who did not need rescue medication versus those who did.

Conclusions

MBP is currently poorly managed in Spain. ECOG improvement is closely and directly related to pain management in MBP. Opioid treatment and a lack of requirements for rescue medication are associated with better ECOG and pain outcomes in MBP patients.

Funding

Mundipharma Pharmaceuticals S.L.

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Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data

Abstract

Introduction

Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(−) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.

Methods

The objective of the current analysis was to estimate long-term survival of patients receiving blinatumomab beyond the observed time period in the clinical study using a large historical observational dataset. Conditional survival probabilities of blinatumomab-treated patients beyond month 60 were assumed to be the same as the US general population.

Results

At month 60, the estimated proportion of blinatumomab-treated patients alive was more than double that of historical patients (12.6% vs 5.4%). The mean overall survival was 76.1 months for blinatumomab patients and 39.8 months for historical patients. Sensitivity analyses including additional follow-up data from the clinical study showed consistent results.

Conclusions

These findings suggest that blinatumomab provides substantial overall survival benefit to patients with (R/R) Ph(−) B-precursor ALL compared with salvage chemotherapy.

Funding

Amgen.

Trial Registration

ClinicalTrials.gov identifier NCT01466179 and NCT02003612.

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Newly designed retentive posts of mandibular reconstruction plate in oral cancer patients based on preliminary FEM study

Abstract

Background

The reconstruction of a large mandibular defect poses a challenging issue in oral cancer ablation surgery. One popular option for mandibular continuity reconstruction after tumor resection involves the use of a reconstruction plate (R-plate), which maintains space and contour without bone harvesting. An R-plate, however, cannot provide final functional loading rehabilitation with implants or dentures.

Methods

We suggest a new method of functional mandibular reconstruction using retentive posts and an upper prosthesis. The finite element method (FEM) was used to optimize the design. Surgery was needed to adapt the retentive posts. Prosthodontic procedures were required for the upper prosthesis.

Results

Eight patients were treated with retentive posts and prostheses. All patients underwent wide resections of the mandible, and reconstruction with an R-plate and microvascular soft tissue transfer. We adapted the retentive posts on an R-plate and fabricated the upper prostheses with a flexible denture or a fixed resin prosthesis. Finally, the patients had functional rehabilitation, which restored proper mastication.

Conclusions

The retentive posts of the R-plate and upper prosthesis allow functional dental rehabilitation without the need for a bone graft. Virtual simulation using FEM will help to design and optimize the retentive posts. Two or three regular size posts are suitable for the quadrant jaw. This first preliminary step will allow improved patient-specific retentive post designs in the near future.

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Newly designed retentive posts of mandibular reconstruction plate in oral cancer patients based on preliminary FEM study

Abstract

Background

The reconstruction of a large mandibular defect poses a challenging issue in oral cancer ablation surgery. One popular option for mandibular continuity reconstruction after tumor resection involves the use of a reconstruction plate (R-plate), which maintains space and contour without bone harvesting. An R-plate, however, cannot provide final functional loading rehabilitation with implants or dentures.

Methods

We suggest a new method of functional mandibular reconstruction using retentive posts and an upper prosthesis. The finite element method (FEM) was used to optimize the design. Surgery was needed to adapt the retentive posts. Prosthodontic procedures were required for the upper prosthesis.

Results

Eight patients were treated with retentive posts and prostheses. All patients underwent wide resections of the mandible, and reconstruction with an R-plate and microvascular soft tissue transfer. We adapted the retentive posts on an R-plate and fabricated the upper prostheses with a flexible denture or a fixed resin prosthesis. Finally, the patients had functional rehabilitation, which restored proper mastication.

Conclusions

The retentive posts of the R-plate and upper prosthesis allow functional dental rehabilitation without the need for a bone graft. Virtual simulation using FEM will help to design and optimize the retentive posts. Two or three regular size posts are suitable for the quadrant jaw. This first preliminary step will allow improved patient-specific retentive post designs in the near future.

http://ift.tt/2gvQWDG

Severe changes in colon epithelium in the Mecp2 -null mouse model of Rett syndrome

Abstract

Background

Rett syndrome is best known due to its severe and devastating symptoms in the central nervous system. It is produced by mutations affecting the Mecp2 gene that codes for a transcription factor. Nevertheless, evidence for MECP2 activity has been reported for tissues other than those of the central nervous system. Patients affected by Rett presented with intestinal affections whose origin is still not known. We have observed that the Mecp2-null mice presented with episodes of diarrhea, and decided to study the intestinal phenotype in these mice.

Methods

Mecp2-null mice or bearing the conditional intestinal deletion of MECP2 were used. Morphometirc and histologic analysis of intestine, and RT-PCR, western blot and immunodetection were perfomed on intestinal samples of the animals. Electrical parameters of the intestine were determined by Ussing chamber experiments in freshly isolated colon samples.

Results

First we determined that MECP2 protein is mainly expressed in cells of the lower part of the colonic crypts and not in the small intestine. The colon of the Mecp2-null mice was shorter than that of the wild-type. Histological analysis showed that epithelial cells of the surface have abnormal localization of key membrane proteins like ClC-2 and NHE-3 that participate in the electroneutral NaCl absorption; nevertheless, electrogenic secretion and absorption remain unaltered. We also detected an increase in a proliferation marker in the crypts of the colon samples of the Mecp2-null mice, but the specific silencing of Mecp2 from intestinal epithelium was not able to recapitulate the intestinal phenotype of the Mecp2-null mice.

Conclusions

In summary, we showed that the colon is severely affected by Mecp2 silencing in mice. Changes in colon length and epithelial histology are similar to those observed in colitis. Changes in the localization of proteins that participate in fluid absorption can explain watery stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce colon changes observed in the Mecp2-null mice, indicating the participation of other cells in this phenotype and the complex interaction between different cell types in this disease.

http://ift.tt/2fiIItF

Severe changes in colon epithelium in the Mecp2 -null mouse model of Rett syndrome

Abstract

Background

Rett syndrome is best known due to its severe and devastating symptoms in the central nervous system. It is produced by mutations affecting the Mecp2 gene that codes for a transcription factor. Nevertheless, evidence for MECP2 activity has been reported for tissues other than those of the central nervous system. Patients affected by Rett presented with intestinal affections whose origin is still not known. We have observed that the Mecp2-null mice presented with episodes of diarrhea, and decided to study the intestinal phenotype in these mice.

Methods

Mecp2-null mice or bearing the conditional intestinal deletion of MECP2 were used. Morphometirc and histologic analysis of intestine, and RT-PCR, western blot and immunodetection were perfomed on intestinal samples of the animals. Electrical parameters of the intestine were determined by Ussing chamber experiments in freshly isolated colon samples.

Results

First we determined that MECP2 protein is mainly expressed in cells of the lower part of the colonic crypts and not in the small intestine. The colon of the Mecp2-null mice was shorter than that of the wild-type. Histological analysis showed that epithelial cells of the surface have abnormal localization of key membrane proteins like ClC-2 and NHE-3 that participate in the electroneutral NaCl absorption; nevertheless, electrogenic secretion and absorption remain unaltered. We also detected an increase in a proliferation marker in the crypts of the colon samples of the Mecp2-null mice, but the specific silencing of Mecp2 from intestinal epithelium was not able to recapitulate the intestinal phenotype of the Mecp2-null mice.

Conclusions

In summary, we showed that the colon is severely affected by Mecp2 silencing in mice. Changes in colon length and epithelial histology are similar to those observed in colitis. Changes in the localization of proteins that participate in fluid absorption can explain watery stools, but the exclusive deletion of Mecp2 from the intestine did not reproduce colon changes observed in the Mecp2-null mice, indicating the participation of other cells in this phenotype and the complex interaction between different cell types in this disease.

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Effects of acetaminophen on mitochondrial complex I activity in the rat liver and kidney: a PET study with 18 F-BCPP-BF

Abstract

Background

In the present study, 2-tert-butyl-4-chloro-5-[6-(4-¹⁸F-fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one (¹⁸F-BCPP-BF), a PET probe for mitochondrial complex I (MC-I), was used to validate whether MC-I is a useful biomarker for detecting acetaminophen-induced dysfunctions in the liver and kidney.

The kinetic and distribution of ¹⁸F-BCPP-BF were assessed in rats using high-resolution animal PET in vivo. The binding specificity of ¹⁸F-BCPP-BF to MC-I in the liver and kidney was confirmed by the pre-administration of rotenone, a specific MC-I inhibitor. The effects of acetaminophen on MC-I activity were assessed 2 and 24 h after the administration of vehicle or acetaminophen at a dose of 100 or 300 mg/kg. Biochemical parameters in plasma and urine were assessed 2, 6, and 24 h after the administration of vehicle or acetaminophen.

Results

The uptake of ¹⁸F-BCPP-BF by the liver and kidney was significantly inhibited by the pre-administration of rotenone. Two and more hours after the administration of acetaminophen, the uptake of ¹⁸F-BCPP-BF was dose-dependently reduced in the liver, even at 100 mg/kg, and in the kidney at 300 mg/kg, whereas biological parameters started to be affected 6 h or later at doses of 300 mg/kg.

Conclusions

The present study demonstrated that ¹⁸F-BCPP-BF has potential as a PET probe for the quantitative imaging of hepatic and renal dysfunction as impaired MC-I activity in the early phase of the treatment for an overdose of acetaminophen in the living body with PET.

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Predictive factors of 18 F-choline PET/CT positivity in patients with prostate cancer recurrence after radiation therapy: is the impact of PSA nadir underestimated?

Abstract

Background

The objective of this study is to explore the impact of PSA nadirs on detection rates of prostate cancer (PCa) recurrence with ¹⁸F-choline (CH) PET/CT after external beam radiation therapy (EBRT).

Methods

In this retrospective study, data were collected from 54 patients with suspicion of PCa biochemical recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage therapy in the absence of PSA decrease after initial treatment), who underwent ¹⁸F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected from patient files. Relative PSA was calculated by subtracting the nadir from the trigger PSA.

Results

Median PSA nadir was 0.31 (0.01–13.31) ng/mL, trigger PSA was 7.85 (0.47–111.60) ng/mL, and relative PSA was 6.05 (0.24–104.59) ng/mL. Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or regional in 29 patients, distant in 15 and combined both in four, with no association between PSA values and sites of recurrence.

In univariate analysis, trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p = 0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In subgroup analysis, these significant differences were only found in the salvage EBRT group. Akaike Information Criterion multivariate model comparison found that relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt).

¹⁸F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4 patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt <2 ng/mL, 2≤ PSAt ≤4 ng/mL, and PSAt >4 ng/mL, respectively, and 14% (1/7 patients), 50% (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into account instead of trigger PSA, with seven (13%) patients changing subgroups.

Conclusions

We found a high overall detection rate and an increase in detection rates proportional to trigger and relative PSAs. Although relative PSA, taking into account PSA nadir, was a better predictive factor of PET/CT positivity in univariate analysis, this was most noticeable for high PSAs. For low PSAs, trigger PSA remains most relevant. Larger series with intermediate PSA values need to be studied to fully apprehend nadir impact.

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Improved safety and efficacy of 213 Bi-DOTATATE-targeted alpha therapy of somatostatin receptor-expressing neuroendocrine tumors in mice pre-treated with l -lysine

Abstract

Background

Targeted alpha therapy (TAT) offers advantages over current β-emitting conjugates for peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors. PRRT with ¹⁷⁷Lu-DOTATATE or ⁹⁰Y-DOTATOC has shown dose-limiting nephrotoxicity due to radiopeptide retention in the proximal tubules. Pharmacological protection can reduce renal uptake of radiopeptides, e.g., positively charged amino acids, to saturate in the proximal tubules, thereby enabling higher radioactivity to be safely administered. The aim of this preclinical study was to evaluate the therapeutic effect of ²¹³Bi-DOTATATE with and without renal protection using L-lysine in mice. Tumor uptake and kinetics as a function of injected mass of peptide (range 0.03–3 nmol) were investigated using ¹¹¹In-DOTATATE. These results allowed estimation of the mean radiation absorbed tumor dose for ²¹³Bi-DOTATATE. Pharmacokinetics and dosimetry of ²¹³Bi-DOTATATE was determined in mice, in combination with renal protection. A dose escalation study with ²¹³Bi-DOTATATE was performed to determine the maximum tolerated dose (MTD) with and without pre-administration of l-lysine as for renal protection. Neutrophil gelatinase-associated lipocalin (NGAL) served as renal biomarker to determine kidney injury.

Results

The maximum mean radiation absorbed tumor dose occurred at 0.03 nmol and the minimum at 3 nmol. Similar mean radiation absorbed tumor doses were determined for 0.1 and 0.3 nmol with a mean radiation absorbed dose of approximately 0.5 Gy/MBq ²¹³Bi-DOTATATE. The optimal mass of injected peptide was found to be 0.3 nmol. Tumor uptake was similar for ¹¹¹In-DOTATATE and ²¹³Bi-DOTATATE at 0.3 nmol peptide. Lysine reduced the renal uptake of ²¹³Bi-DOTATATE by 50% with no effect on the tumor uptake. The MTD was <13.0 ± 1.6 MBq in absence of l-lysine and 21.7 ± 1.9 MBq with l-lysine renal protection, both imparting an LD₅₀ mean renal radiation absorbed dose of 20 Gy. A correlation was found between the amount of injected radioactivity and NGAL levels.

Conclusions

The therapeutic potential of ²¹³Bi-DOTATATE was illustrated by significantly decreased tumor burden and improved overall survival. Renal protection with l-lysine immediately prior to TAT with ²¹³Bi-DOTATATE prolonged survival providing substantial evidence for pharmacological nephron blockade to mitigate nephrotoxicity.

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Effects of acetaminophen on mitochondrial complex I activity in the rat liver and kidney: a PET study with 18 F-BCPP-BF

Abstract

Background

In the present study, 2-tert-butyl-4-chloro-5-[6-(4-¹⁸F-fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one (¹⁸F-BCPP-BF), a PET probe for mitochondrial complex I (MC-I), was used to validate whether MC-I is a useful biomarker for detecting acetaminophen-induced dysfunctions in the liver and kidney.

The kinetic and distribution of ¹⁸F-BCPP-BF were assessed in rats using high-resolution animal PET in vivo. The binding specificity of ¹⁸F-BCPP-BF to MC-I in the liver and kidney was confirmed by the pre-administration of rotenone, a specific MC-I inhibitor. The effects of acetaminophen on MC-I activity were assessed 2 and 24 h after the administration of vehicle or acetaminophen at a dose of 100 or 300 mg/kg. Biochemical parameters in plasma and urine were assessed 2, 6, and 24 h after the administration of vehicle or acetaminophen.

Results

The uptake of ¹⁸F-BCPP-BF by the liver and kidney was significantly inhibited by the pre-administration of rotenone. Two and more hours after the administration of acetaminophen, the uptake of ¹⁸F-BCPP-BF was dose-dependently reduced in the liver, even at 100 mg/kg, and in the kidney at 300 mg/kg, whereas biological parameters started to be affected 6 h or later at doses of 300 mg/kg.

Conclusions

The present study demonstrated that ¹⁸F-BCPP-BF has potential as a PET probe for the quantitative imaging of hepatic and renal dysfunction as impaired MC-I activity in the early phase of the treatment for an overdose of acetaminophen in the living body with PET.

http://ift.tt/2geWzn1

Predictive factors of 18 F-choline PET/CT positivity in patients with prostate cancer recurrence after radiation therapy: is the impact of PSA nadir underestimated?

Abstract

Background

The objective of this study is to explore the impact of PSA nadirs on detection rates of prostate cancer (PCa) recurrence with ¹⁸F-choline (CH) PET/CT after external beam radiation therapy (EBRT).

Methods

In this retrospective study, data were collected from 54 patients with suspicion of PCa biochemical recurrence after EBRT (28 patients treated initially with EBRT and 26 as salvage therapy in the absence of PSA decrease after initial treatment), who underwent ¹⁸F-CH PET/CT between 2010 and 2015. PSA nadir and trigger PSA were collected from patient files. Relative PSA was calculated by subtracting the nadir from the trigger PSA.

Results

Median PSA nadir was 0.31 (0.01–13.31) ng/mL, trigger PSA was 7.85 (0.47–111.60) ng/mL, and relative PSA was 6.05 (0.24–104.59) ng/mL. Overall, 40 (74%) PET/CT scans were positive: recurrence was local and/or regional in 29 patients, distant in 15 and combined both in four, with no association between PSA values and sites of recurrence.

In univariate analysis, trigger (p = 0.015) and relative (p = 0.0005) PSA values and PSA velocity (p = 0.01) were significantly linked to positive PET/CT, but PSA nadir was not. In subgroup analysis, these significant differences were only found in the salvage EBRT group. Akaike Information Criterion multivariate model comparison found that relative PSA was a better predictor of positive PET/CT than trigger PSA (PSAt).

¹⁸F-CH PET/CT detection rates increased with trigger and relative PSA: 0% (0/4 patients), 71% (5/7 patients), and 81% (35/43 patients) for PSAt <2 ng/mL, 2≤ PSAt ≤4 ng/mL, and PSAt >4 ng/mL, respectively, and 14% (1/7 patients), 50% (5/10 patients), and 92% (34/37 patients) when relative PSA was taken into account instead of trigger PSA, with seven (13%) patients changing subgroups.

Conclusions

We found a high overall detection rate and an increase in detection rates proportional to trigger and relative PSAs. Although relative PSA, taking into account PSA nadir, was a better predictive factor of PET/CT positivity in univariate analysis, this was most noticeable for high PSAs. For low PSAs, trigger PSA remains most relevant. Larger series with intermediate PSA values need to be studied to fully apprehend nadir impact.

http://ift.tt/2gCO88E

Improved safety and efficacy of 213 Bi-DOTATATE-targeted alpha therapy of somatostatin receptor-expressing neuroendocrine tumors in mice pre-treated with l -lysine

Abstract

Background

Targeted alpha therapy (TAT) offers advantages over current β-emitting conjugates for peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors. PRRT with ¹⁷⁷Lu-DOTATATE or ⁹⁰Y-DOTATOC has shown dose-limiting nephrotoxicity due to radiopeptide retention in the proximal tubules. Pharmacological protection can reduce renal uptake of radiopeptides, e.g., positively charged amino acids, to saturate in the proximal tubules, thereby enabling higher radioactivity to be safely administered. The aim of this preclinical study was to evaluate the therapeutic effect of ²¹³Bi-DOTATATE with and without renal protection using L-lysine in mice. Tumor uptake and kinetics as a function of injected mass of peptide (range 0.03–3 nmol) were investigated using ¹¹¹In-DOTATATE. These results allowed estimation of the mean radiation absorbed tumor dose for ²¹³Bi-DOTATATE. Pharmacokinetics and dosimetry of ²¹³Bi-DOTATATE was determined in mice, in combination with renal protection. A dose escalation study with ²¹³Bi-DOTATATE was performed to determine the maximum tolerated dose (MTD) with and without pre-administration of l-lysine as for renal protection. Neutrophil gelatinase-associated lipocalin (NGAL) served as renal biomarker to determine kidney injury.

Results

The maximum mean radiation absorbed tumor dose occurred at 0.03 nmol and the minimum at 3 nmol. Similar mean radiation absorbed tumor doses were determined for 0.1 and 0.3 nmol with a mean radiation absorbed dose of approximately 0.5 Gy/MBq ²¹³Bi-DOTATATE. The optimal mass of injected peptide was found to be 0.3 nmol. Tumor uptake was similar for ¹¹¹In-DOTATATE and ²¹³Bi-DOTATATE at 0.3 nmol peptide. Lysine reduced the renal uptake of ²¹³Bi-DOTATATE by 50% with no effect on the tumor uptake. The MTD was <13.0 ± 1.6 MBq in absence of l-lysine and 21.7 ± 1.9 MBq with l-lysine renal protection, both imparting an LD₅₀ mean renal radiation absorbed dose of 20 Gy. A correlation was found between the amount of injected radioactivity and NGAL levels.

Conclusions

The therapeutic potential of ²¹³Bi-DOTATATE was illustrated by significantly decreased tumor burden and improved overall survival. Renal protection with l-lysine immediately prior to TAT with ²¹³Bi-DOTATATE prolonged survival providing substantial evidence for pharmacological nephron blockade to mitigate nephrotoxicity.

http://ift.tt/2geZ9t0

Therapy Processes, Progress, and Outcomes for Two Therapies for Gynecological Cancer Patients

Abstract

Objective

Although a number of effective psychotherapies have been identified for cancer patients, little is known about therapy processes as they unfold the course of treatment and the role of therapy processes in treatment outcome. We used growth curve modeling to evaluate the associations between therapy processes and outcomes among gynecological cancer patients participating in two types of therapy.

Methods

Two hundred twenty five women newly diagnosed with gynecological cancer were randomly assigned to receive eight sessions of a coping and communication intervention (CCI) or a client-centered supportive therapy (SC). Participants completed measures of pre-intervention and post-intervention depression, working alliance after Session 2, and post-session progress and depressive symptoms after each session. Therapists completed measures of perceived patient progress.

Results

Both patients and therapists reported a steady increase in session progress and patients reported a steady decrease in depressive symptoms over the course of both the CCI and SC sessions. Perceived progress in one session predicted progress in the subsequent session. Early working alliance predicted improved session progress and reductions in post-session depressive symptoms over sessions. Working alliance did not predict pre-post treatment changes in depression. Patient-rated session progress predicted greater reductions in pre-to post-treatment depression, but therapist-rated progress did not.

Conclusions

For two types of treatment delivered to women diagnosed with gynecological cancer, patient-rated session progress and depressive symptoms rated over therapy sessions may serve as a yardstick that can be useful to therapists to gauge patient's response to treatment.

http://ift.tt/2fimckz

Development of practice guidelines for psychological interventions in the rehabilitation of patients with oncological disease (breast, prostate or colorectal cancer): methods and results

Abstract

Objective

The goal of this project was to develop evidence- and consensus-based practice guidelines for psychological interventions in the rehabilitation of patients with oncological disease (breast, prostate, or colorectal cancer).

Methods

First of all, we conducted a literature search and survey of all oncological rehabilitation centers in Germany (N = 145) to obtain a thorough perspective of the recent evidence, guidelines, the structural framework and practice of psychological services in oncological rehabilitation. Next, an expert workshop was held with national experts from scientific departments, clinicians from rehabilitation centers and patients. In this workshop, we drafted and agreed upon an initial version of the practice guidelines. Afterwards, the practice guidelines were sent to all head physicians and senior psychologists at oncological rehabilitation centers in Germany for approval (N = 280 questionnaires). In addition, key recommendations were discussed with a group of rehabilitation patients. Finally, the practice guidelines were revised by the expert panel and made available online to the public.

Results

The practice guidelines have been widely accepted by both the expert panel and the surveyed clinicians and patients. They include recommendations for psycho-oncological interventions that should be offered to all rehabilitation patients with breast, prostate, or colorectal cancer. They also comprise recommendations for specific problem areas concerning psychological functions, body functions, environmental, and personal factors.

Conclusions

The practice guidelines provide detailed recommendations for high-quality psycho-social care in an oncological rehabilitation context. It is their aim to guide the multidisciplinary team, especially psychologists and physicians, in their daily practice.

http://ift.tt/2gvznnf

Therapy Processes, Progress, and Outcomes for Two Therapies for Gynecological Cancer Patients

Abstract

Objective

Although a number of effective psychotherapies have been identified for cancer patients, little is known about therapy processes as they unfold the course of treatment and the role of therapy processes in treatment outcome. We used growth curve modeling to evaluate the associations between therapy processes and outcomes among gynecological cancer patients participating in two types of therapy.

Methods

Two hundred twenty five women newly diagnosed with gynecological cancer were randomly assigned to receive eight sessions of a coping and communication intervention (CCI) or a client-centered supportive therapy (SC). Participants completed measures of pre-intervention and post-intervention depression, working alliance after Session 2, and post-session progress and depressive symptoms after each session. Therapists completed measures of perceived patient progress.

Results

Both patients and therapists reported a steady increase in session progress and patients reported a steady decrease in depressive symptoms over the course of both the CCI and SC sessions. Perceived progress in one session predicted progress in the subsequent session. Early working alliance predicted improved session progress and reductions in post-session depressive symptoms over sessions. Working alliance did not predict pre-post treatment changes in depression. Patient-rated session progress predicted greater reductions in pre-to post-treatment depression, but therapist-rated progress did not.

Conclusions

For two types of treatment delivered to women diagnosed with gynecological cancer, patient-rated session progress and depressive symptoms rated over therapy sessions may serve as a yardstick that can be useful to therapists to gauge patient's response to treatment.

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Development of practice guidelines for psychological interventions in the rehabilitation of patients with oncological disease (breast, prostate or colorectal cancer): methods and results

Abstract

Objective

The goal of this project was to develop evidence- and consensus-based practice guidelines for psychological interventions in the rehabilitation of patients with oncological disease (breast, prostate, or colorectal cancer).

Methods

First of all, we conducted a literature search and survey of all oncological rehabilitation centers in Germany (N = 145) to obtain a thorough perspective of the recent evidence, guidelines, the structural framework and practice of psychological services in oncological rehabilitation. Next, an expert workshop was held with national experts from scientific departments, clinicians from rehabilitation centers and patients. In this workshop, we drafted and agreed upon an initial version of the practice guidelines. Afterwards, the practice guidelines were sent to all head physicians and senior psychologists at oncological rehabilitation centers in Germany for approval (N = 280 questionnaires). In addition, key recommendations were discussed with a group of rehabilitation patients. Finally, the practice guidelines were revised by the expert panel and made available online to the public.

Results

The practice guidelines have been widely accepted by both the expert panel and the surveyed clinicians and patients. They include recommendations for psycho-oncological interventions that should be offered to all rehabilitation patients with breast, prostate, or colorectal cancer. They also comprise recommendations for specific problem areas concerning psychological functions, body functions, environmental, and personal factors.

Conclusions

The practice guidelines provide detailed recommendations for high-quality psycho-social care in an oncological rehabilitation context. It is their aim to guide the multidisciplinary team, especially psychologists and physicians, in their daily practice.

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Differential regulation of angiogenic cellular processes and claudin-5 by histamine and VEGF via PI3K-signaling, transcription factor SNAI2 and interleukin-8

Abstract

Aims

Histamine and vascular endothelial growth factor A (VEGF) are central regulators in vascular pathologies. Their gene regulation leading to vascular remodeling has remained obscure. In this study, EC regulation mechanisms of histamine and VEGF were compared by RNA sequencing of primary endothelial cells (ECs), functional in vitro assays and in vivo permeability mice model.

Methods and results

By RNA sequencing, similar transcriptional alterations of genes involved in activation of primary ECs, cell proliferation and adhesion were observed between histamine and VEGF. Seventy-six commonly regulated genes were found, representing ~53% of all VEGF-regulated transcripts and ~26% of all histamine-regulated transcripts. Both factors regulated tight junction formation and expression of pro-angiogenic transcription factors (TFs) affecting EC survival, migration and tube formation. Novel claudin-5 upstream regulatory genes were identified. VEGF was demonstrated to regulate expression of SNAI2, whereas pro-angiogenic TFs NR4A1, MYCN and RCAN1 were regulated by both histamine and VEGF. Claudin-5 was shown to be regulated VEGFR2/PI3K-Akt dependently by VEGF and PI3K-Akt independently by histamine. Interleukin-8 was shown to downregulate claudin-5 by histamine. Additionally, SNAI2, NR4A1 and MYCN were shown to mediate EC survival, migration and tube formation and to regulate expression of claudin-5. Further systemic delivery of VEGF and histamine was shown to induce a fast vascular hyperpermeability response in intact vasculature of C57/Bl6 mice followed by regulation of NR4A1 and MYCN.

Conclusions

Our study identifies novel claudin-5 upstream regulatory genes of histamine and VEGF that induce cellular angiogenic processes. Our results increase knowledge of angiogenic EC phenotype and provide novel treatment targets for vascular pathologies.

http://ift.tt/2eZo0DI

Differential regulation of angiogenic cellular processes and claudin-5 by histamine and VEGF via PI3K-signaling, transcription factor SNAI2 and interleukin-8

Abstract

Aims

Histamine and vascular endothelial growth factor A (VEGF) are central regulators in vascular pathologies. Their gene regulation leading to vascular remodeling has remained obscure. In this study, EC regulation mechanisms of histamine and VEGF were compared by RNA sequencing of primary endothelial cells (ECs), functional in vitro assays and in vivo permeability mice model.

Methods and results

By RNA sequencing, similar transcriptional alterations of genes involved in activation of primary ECs, cell proliferation and adhesion were observed between histamine and VEGF. Seventy-six commonly regulated genes were found, representing ~53% of all VEGF-regulated transcripts and ~26% of all histamine-regulated transcripts. Both factors regulated tight junction formation and expression of pro-angiogenic transcription factors (TFs) affecting EC survival, migration and tube formation. Novel claudin-5 upstream regulatory genes were identified. VEGF was demonstrated to regulate expression of SNAI2, whereas pro-angiogenic TFs NR4A1, MYCN and RCAN1 were regulated by both histamine and VEGF. Claudin-5 was shown to be regulated VEGFR2/PI3K-Akt dependently by VEGF and PI3K-Akt independently by histamine. Interleukin-8 was shown to downregulate claudin-5 by histamine. Additionally, SNAI2, NR4A1 and MYCN were shown to mediate EC survival, migration and tube formation and to regulate expression of claudin-5. Further systemic delivery of VEGF and histamine was shown to induce a fast vascular hyperpermeability response in intact vasculature of C57/Bl6 mice followed by regulation of NR4A1 and MYCN.

Conclusions

Our study identifies novel claudin-5 upstream regulatory genes of histamine and VEGF that induce cellular angiogenic processes. Our results increase knowledge of angiogenic EC phenotype and provide novel treatment targets for vascular pathologies.

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Cancer risks after solid organ transplantation and after long-term dialysis

ABSTRACT

Immunosuppression involves an inability to control virus infections and increased incidence of virus-associated cancers. Some cancers without known viral etiology are also increased, but data on exactly which cancer forms are increased has been inconsistent.

To provide a reliable and generalizable estimate, with high statistical power and long follow-up time, we assessed cancer risks using comprehensive, population-based registries in 2 different countries and from 2 different immunosuppressed patient groups (solid organ transplant recipients (OTRs) and long-term dialysis patients (LDPs)).

National registries in Denmark and Sweden identified 20804 OTRs and 31140 LDPs that were followed up using national cancer registries. Standardized incidence ratios (SIR) compared to the general population were estimated.

We found highly similar results, both for the 2 different countries and for the 2 different immunosuppressed cohorts, namely an increased incidence for the following specific cancer forms: Non-melanoma skin cancer (NMSC), Non-Hodgkin's lymphoma and cancers of the lip, kidney, larynx and thyroid.

The SIR for overall cancer among OTRs was 3.5 [n=2142, 95% CI, 3.4-3.7] in Sweden, 2.9 [n=1110, 95% CI, 2.8-3.1] in Denmark and 1.6 [n=1713, 95% CI, 1.5-1.6] among LDP. The SIR for NMSC among OTRs was 44.7 [n=994, 95% CI, 42-47.5] in Sweden and 41.5 [n=445, 95% CI, 37.8-45.5] in Denmark. The increased SIR for NMSC among LDPs was 5.3 [n=304, 95% CI, 4.7-5.9]). In summary, an increased SIR for a specific, similar set of cancer forms is consistently found among the immunosuppressed. Conceivable explanations include surveillance bias and immunosuppression-related susceptibility to viral infections. This article is protected by copyright. All rights reserved.

http://ift.tt/2gb6U5J

False and Mycoplasma-Contaminated Leukemia-Lymphoma Cell Lines – Time for a Reappraisal

Abstract

Leukemia-lymphoma cell lines are important research tools in a variety of fields. In order to represent adequate model systems it is of utmost importance that cell lines faithfully model the primary tumor material and are not cross-contaminated with unrelated cell material (or contaminated with mycoplasma). As it has been previously reported that cross-contaminated cell lines represent a significant problem, it is of interest to know whether any improvement in the prevalence of such "false cell lines" had occurred since we called the alert in 1999. A retrospective review of our data archives covered 848 cell lines received from 1990-2014 from 290 laboratories in 23 countries spanning the spectrum of leukemia-lymphoma entities. Two variables were considered: authenticity and freedom from mycoplasma infection. Regarding provenance, we separately considered primary sources (original investigators having established the cell lines or reference repositories) and secondary sources. The percentages of mycoplasma-contaminated cell lines decreased significantly over the 25-year timespan. Among primary sourced material: mycoplasma-contamination fell from 23% to 0%; among secondary sourced: from 48% to 21%. The corresponding figures for cross-contamination declined from 15% to 6%, while among material obtained from secondary sources prevalence remained remarkably high, throughout the time periods at 14-18%. Taken together, our data indicate that using non-authenticated cell lines from secondary sources carries a risk of about 1:6 for obtaining a false cell line. The use of authentic leukemia-lymphoma cell lines holds important translational value for their model character and the reproducibility of the laboratory data in the clinical arena. This article is protected by copyright. All rights reserved.

http://ift.tt/2fy4Zoi

Cure of cancer for 7 cancer sites in the Flemish Region

Abstract

Cumulative relative survival curves for many cancers reach a plateau several years after diagnosis, indicating that the cancer survivor group has reached "statistical" cure. Parametric mixture cure model analysis on grouped relative survival curves provide an interesting way to determine the proportion of statistically cured cases and the mean survival time of the fatal cases in particular for population-based cancer registries. Based on the relative survival data from the Belgian Cancer Registry, parametric cure models were applied to seven cancer sites (cervix, colon, corpus uteri, skin melanoma, pancreas, stomach and oesophagus), at the Flemish Regional level for the incidence period 1999 to 2011. Statistical cure was observed for the examined cancer sites except for oesophageal cancer. The estimated cured proportion ranged from 5.9% [5.7, 6.1] for pancreatic cancer to 80.8% [80.5, 81.2] for skin melanoma. Cure results were further stratified by gender or age group. Stratified cured proportions were higher for females compared to males in colon cancer, stomach cancer, pancreas cancer and skin melanoma, which can mainly be attributed to differences in stage and age distribution between both sexes. This study demonstrates the applicability of cure rate models for the selected cancer sites after 14 years of follow-up and presents the first population-based results on the cure of cancer in Belgium. This article is protected by copyright. All rights reserved.

http://ift.tt/2gb9GI7

HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?

Abstract

The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV-related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma, and prostate cancer suggest other mechanisms for the anti-neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV-PIs in the therapy of cancer relies on their relatively weak anticancer potency, and important side effects. This has propelled several groups to generate derivatives of HIV-PIs for anticancer use, through modifications such as attachment of different moieties, ligands, and transporters, including saquinavir-loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV-PIs. In this paper, we discuss the current preclinical and clinical evidences for the potential use of HIV-PIs, and of novel derivatives, such as saquinavir-NO in the treatment of cancer. This article is protected by copyright. All rights reserved.

http://ift.tt/2fy7KWx

Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Abstract

Insulin-like growth factor-I (IGF-I) has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested case-control study of 1072 cases of lymphoid malignancies and 1072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF-I concentration was not associated with overall lymphoma risk (multivariable-adjusted OR for highest versus lowest third = 0.77 [95% CI=0.57-1.03], P_trend = 0.06). There was no statistical evidence of heterogeneity in this association with IGF-I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (P_{heterogeneity for all} ≥ 0.05). There were no associations between IGF-I concentration and risk for specific BCL subtypes, T-cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF-I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF-I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF-I concentrations with lymphoma subtypes. This article is protected by copyright. All rights reserved.

http://ift.tt/2gb4yDT

Cancer risks after solid organ transplantation and after long-term dialysis

ABSTRACT

Immunosuppression involves an inability to control virus infections and increased incidence of virus-associated cancers. Some cancers without known viral etiology are also increased, but data on exactly which cancer forms are increased has been inconsistent.

To provide a reliable and generalizable estimate, with high statistical power and long follow-up time, we assessed cancer risks using comprehensive, population-based registries in 2 different countries and from 2 different immunosuppressed patient groups (solid organ transplant recipients (OTRs) and long-term dialysis patients (LDPs)).

National registries in Denmark and Sweden identified 20804 OTRs and 31140 LDPs that were followed up using national cancer registries. Standardized incidence ratios (SIR) compared to the general population were estimated.

We found highly similar results, both for the 2 different countries and for the 2 different immunosuppressed cohorts, namely an increased incidence for the following specific cancer forms: Non-melanoma skin cancer (NMSC), Non-Hodgkin's lymphoma and cancers of the lip, kidney, larynx and thyroid.

The SIR for overall cancer among OTRs was 3.5 [n=2142, 95% CI, 3.4-3.7] in Sweden, 2.9 [n=1110, 95% CI, 2.8-3.1] in Denmark and 1.6 [n=1713, 95% CI, 1.5-1.6] among LDP. The SIR for NMSC among OTRs was 44.7 [n=994, 95% CI, 42-47.5] in Sweden and 41.5 [n=445, 95% CI, 37.8-45.5] in Denmark. The increased SIR for NMSC among LDPs was 5.3 [n=304, 95% CI, 4.7-5.9]). In summary, an increased SIR for a specific, similar set of cancer forms is consistently found among the immunosuppressed. Conceivable explanations include surveillance bias and immunosuppression-related susceptibility to viral infections. This article is protected by copyright. All rights reserved.

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via IFTTT

False and Mycoplasma-Contaminated Leukemia-Lymphoma Cell Lines – Time for a Reappraisal

Abstract

Leukemia-lymphoma cell lines are important research tools in a variety of fields. In order to represent adequate model systems it is of utmost importance that cell lines faithfully model the primary tumor material and are not cross-contaminated with unrelated cell material (or contaminated with mycoplasma). As it has been previously reported that cross-contaminated cell lines represent a significant problem, it is of interest to know whether any improvement in the prevalence of such "false cell lines" had occurred since we called the alert in 1999. A retrospective review of our data archives covered 848 cell lines received from 1990-2014 from 290 laboratories in 23 countries spanning the spectrum of leukemia-lymphoma entities. Two variables were considered: authenticity and freedom from mycoplasma infection. Regarding provenance, we separately considered primary sources (original investigators having established the cell lines or reference repositories) and secondary sources. The percentages of mycoplasma-contaminated cell lines decreased significantly over the 25-year timespan. Among primary sourced material: mycoplasma-contamination fell from 23% to 0%; among secondary sourced: from 48% to 21%. The corresponding figures for cross-contamination declined from 15% to 6%, while among material obtained from secondary sources prevalence remained remarkably high, throughout the time periods at 14-18%. Taken together, our data indicate that using non-authenticated cell lines from secondary sources carries a risk of about 1:6 for obtaining a false cell line. The use of authentic leukemia-lymphoma cell lines holds important translational value for their model character and the reproducibility of the laboratory data in the clinical arena. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2fy4Zoi
via IFTTT

Cure of cancer for 7 cancer sites in the Flemish Region

Abstract

Cumulative relative survival curves for many cancers reach a plateau several years after diagnosis, indicating that the cancer survivor group has reached "statistical" cure. Parametric mixture cure model analysis on grouped relative survival curves provide an interesting way to determine the proportion of statistically cured cases and the mean survival time of the fatal cases in particular for population-based cancer registries. Based on the relative survival data from the Belgian Cancer Registry, parametric cure models were applied to seven cancer sites (cervix, colon, corpus uteri, skin melanoma, pancreas, stomach and oesophagus), at the Flemish Regional level for the incidence period 1999 to 2011. Statistical cure was observed for the examined cancer sites except for oesophageal cancer. The estimated cured proportion ranged from 5.9% [5.7, 6.1] for pancreatic cancer to 80.8% [80.5, 81.2] for skin melanoma. Cure results were further stratified by gender or age group. Stratified cured proportions were higher for females compared to males in colon cancer, stomach cancer, pancreas cancer and skin melanoma, which can mainly be attributed to differences in stage and age distribution between both sexes. This study demonstrates the applicability of cure rate models for the selected cancer sites after 14 years of follow-up and presents the first population-based results on the cure of cancer in Belgium. This article is protected by copyright. All rights reserved.

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via IFTTT

HIV-protease inhibitors for the treatment of cancer: Repositioning HIV protease inhibitors while developing more potent NO-hybridized derivatives?

Abstract

The possible use of HIV protease inhibitors (HIV-PI) as new therapeutic option for the treatment of cancer primarily originated from their success in treating HIV-related Kaposi's sarcoma (KS). While these findings were initially attributed to immune reconstitution and better control of oncogenic viral infections, the number of reports on solid tumors, KS, lymphoma, fibrosarcoma, multiple myeloma, and prostate cancer suggest other mechanisms for the anti-neoplastic activity of PIs. However, a major drawback for the possible adoption of HIV-PIs in the therapy of cancer relies on their relatively weak anticancer potency, and important side effects. This has propelled several groups to generate derivatives of HIV-PIs for anticancer use, through modifications such as attachment of different moieties, ligands, and transporters, including saquinavir-loaded folic acid conjugated nanoparticles and nitric oxide (NO) derivatives of HIV-PIs. In this paper, we discuss the current preclinical and clinical evidences for the potential use of HIV-PIs, and of novel derivatives, such as saquinavir-NO in the treatment of cancer. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/2fy7KWx
via IFTTT

Prediagnostic circulating concentrations of plasma insulin-like growth factor-I and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition

Abstract

Insulin-like growth factor-I (IGF-I) has cancer promoting activities. However, the hypothesis that circulating IGF-I concentration is related to risk of lymphoma overall or its subtypes has not been examined prospectively. IGF-I concentration was measured in pre-diagnostic plasma samples from a nested case-control study of 1072 cases of lymphoid malignancies and 1072 individually matched controls from the European Prospective Investigation into Cancer and Nutrition. Odds ratios (ORs) and confidence intervals (CIs) for lymphoma were calculated using conditional logistic regression. IGF-I concentration was not associated with overall lymphoma risk (multivariable-adjusted OR for highest versus lowest third = 0.77 [95% CI=0.57-1.03], P_trend = 0.06). There was no statistical evidence of heterogeneity in this association with IGF-I by sex, age at blood collection, time between blood collection and diagnosis, age at diagnosis, or body mass index (P_{heterogeneity for all} ≥ 0.05). There were no associations between IGF-I concentration and risk for specific BCL subtypes, T-cell lymphoma or Hodgkin lymphoma, although number of cases were small. In this European population, IGF-I concentration was not associated with risk of overall lymphoma. This study provides the first prospective evidence on circulating IGF-I concentrations and risk of lymphoma. Further prospective data are required to examine associations of IGF-I concentrations with lymphoma subtypes. This article is protected by copyright. All rights reserved.

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Nodular sclerosis classical Hodgkin lymphoma grade 2: A diagnostic challenge to the cytopathologists

BACKGROUND

Grade 2 nodular sclerosis classical Hodgkin lymphoma (NSCHL) is less common than grade 1 lymphoma and has a worse overall prognosis. To the best of the authors' knowledge, no study of a large series of cases has been performed until now. The objective of this study was to assess the diagnostic efficacy of cytology for grade 2 NSCHL versus grade 1 NSCHL and study the morphological features of grade 2 NSCHL in fine-needle aspiration cytology (FNAC).

METHODS

Fifteen of 51 histopathology-proven cases of NSCHL (18 FNAC procedures) were grade 2, and 36 were grade 1. The efficacy of FNAC for detecting grade 1 and 2 NSCHL was assessed, and the frequency of misdiagnosis was compared. The clinical details and cytomorphological features of grade 2 NSCHL were studied in detail.

RESULTS

Among the grade 1 NSCHL patients, 58.4% were diagnosed with Hodgkin lymphoma (HL) or had findings suggestive of HL, whereas 20% of the grade 2 patients were diagnosed HL or suggestive of HL. Two cases of grade 2 NSCHL were misdiagnosed as anaplastic large cell lymphoma, and 4 were misdiagnosed as malignant neoplasms. Grade 2 NSCHL cases showed clusters and sheets of mononuclear, multinucleated, and bizarre cells, with some cases showing a suppurative background. However, extensive searching showed occasional Reed-Sternberg (RS) cells in most of the cases, and lacunar cells were seen in 12 cases.

CONCLUSIONS

The diagnostic efficacy of FNAC is much lower for grade 2 NSCHL versus grade 1 NSCHL. The search for an occasional RS cell and the identification of lacunar cells can provide a clue for the diagnosis. Cancer Cytopathol 2016. © 2016 American Cancer Society.

http://ift.tt/2gvlSUS

Infections with multiple high-risk HPV types are associated with high-grade and persistent low-grade intraepithelial lesions of the cervix

BACKGROUND

Infections with multiple human papillomavirus (HPV) types (mHPV) in Papanicolaou tests have been reported but the histologic correlation and clinical meaning remains debatable.

METHODS

The authors prospectively tested 37 HPV types using the Linear Array HPV Genotyping Test and correlated the results to cytology and histology findings in 260 women evaluated from June 2009 to October 2011 and followed for up to 60 months.

RESULTS

HPV was detected in 148 of 235 samples (63%) and high-risk HPV was detected in 132 samples (56%). mHPV infection was found to be twice as common as single HPV (sHPV) infection and was detected more frequently in low-grade squamous intraepithelial lesion (LSIL) (48 of 83 samples [58%]) and high-grade squamous intraepithelial lesion or invasive carcinoma (HSIL + (26 of 47 samples [55%]) compared with other categories (P<.001). Of 34 LSIL/cervical intraepithelial neoplasia 1 (CIN1) index cases, 13 of 21 patients with mHPV (61.9%) persisted on CIN1, whereas no histologic abnormality was detected during follow-up in all 12 patients with sHPV infection (high risk or low risk) (P<.001). Eighteen of 20 patients with HSIL/cervical intraepithelial neoplasia 2 (CIN2) (90%) and high-risk mHPV persisted on HSIL+/CIN2 + whereas 6 of 11 patients with sHPV infection did not demonstrate HSIL+/CIN2 + on follow-up (54.5%) (P = .066). Approximately 40% of women with HSIL were infected by high-risk HPV types other than types 16 or 18.

CONCLUSIONS

High-risk mHPV infection identified patients with persistent LSIL/CIN1 and may to help identify patients at higher risk of disease progression to HSIL+/CIN2+. Longer follow-up will clarify the role of mHPV testing in patient care. Cancer Cytopathol 2016. © 2016 American Cancer Society.

http://ift.tt/2fi5Gkz

Nodular sclerosis classical Hodgkin lymphoma grade 2: A diagnostic challenge to the cytopathologists

BACKGROUND

Grade 2 nodular sclerosis classical Hodgkin lymphoma (NSCHL) is less common than grade 1 lymphoma and has a worse overall prognosis. To the best of the authors' knowledge, no study of a large series of cases has been performed until now. The objective of this study was to assess the diagnostic efficacy of cytology for grade 2 NSCHL versus grade 1 NSCHL and study the morphological features of grade 2 NSCHL in fine-needle aspiration cytology (FNAC).

METHODS

Fifteen of 51 histopathology-proven cases of NSCHL (18 FNAC procedures) were grade 2, and 36 were grade 1. The efficacy of FNAC for detecting grade 1 and 2 NSCHL was assessed, and the frequency of misdiagnosis was compared. The clinical details and cytomorphological features of grade 2 NSCHL were studied in detail.

RESULTS

Among the grade 1 NSCHL patients, 58.4% were diagnosed with Hodgkin lymphoma (HL) or had findings suggestive of HL, whereas 20% of the grade 2 patients were diagnosed HL or suggestive of HL. Two cases of grade 2 NSCHL were misdiagnosed as anaplastic large cell lymphoma, and 4 were misdiagnosed as malignant neoplasms. Grade 2 NSCHL cases showed clusters and sheets of mononuclear, multinucleated, and bizarre cells, with some cases showing a suppurative background. However, extensive searching showed occasional Reed-Sternberg (RS) cells in most of the cases, and lacunar cells were seen in 12 cases.

CONCLUSIONS

The diagnostic efficacy of FNAC is much lower for grade 2 NSCHL versus grade 1 NSCHL. The search for an occasional RS cell and the identification of lacunar cells can provide a clue for the diagnosis. Cancer Cytopathol 2016. © 2016 American Cancer Society.

from Cancer via ola Kala on Inoreader http://ift.tt/2gvlSUS
via IFTTT

Infections with multiple high-risk HPV types are associated with high-grade and persistent low-grade intraepithelial lesions of the cervix

BACKGROUND

Infections with multiple human papillomavirus (HPV) types (mHPV) in Papanicolaou tests have been reported but the histologic correlation and clinical meaning remains debatable.

METHODS

The authors prospectively tested 37 HPV types using the Linear Array HPV Genotyping Test and correlated the results to cytology and histology findings in 260 women evaluated from June 2009 to October 2011 and followed for up to 60 months.

RESULTS

HPV was detected in 148 of 235 samples (63%) and high-risk HPV was detected in 132 samples (56%). mHPV infection was found to be twice as common as single HPV (sHPV) infection and was detected more frequently in low-grade squamous intraepithelial lesion (LSIL) (48 of 83 samples [58%]) and high-grade squamous intraepithelial lesion or invasive carcinoma (HSIL + (26 of 47 samples [55%]) compared with other categories (P<.001). Of 34 LSIL/cervical intraepithelial neoplasia 1 (CIN1) index cases, 13 of 21 patients with mHPV (61.9%) persisted on CIN1, whereas no histologic abnormality was detected during follow-up in all 12 patients with sHPV infection (high risk or low risk) (P<.001). Eighteen of 20 patients with HSIL/cervical intraepithelial neoplasia 2 (CIN2) (90%) and high-risk mHPV persisted on HSIL+/CIN2 + whereas 6 of 11 patients with sHPV infection did not demonstrate HSIL+/CIN2 + on follow-up (54.5%) (P = .066). Approximately 40% of women with HSIL were infected by high-risk HPV types other than types 16 or 18.

CONCLUSIONS

High-risk mHPV infection identified patients with persistent LSIL/CIN1 and may to help identify patients at higher risk of disease progression to HSIL+/CIN2+. Longer follow-up will clarify the role of mHPV testing in patient care. Cancer Cytopathol 2016. © 2016 American Cancer Society.

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Management strategies in Lynch syndrome and familial adenomatous polyposis: a national healthcare survey in Japan

Summary

Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are major sources of hereditary colorectal cancer (CRC) and associated with other malignancies. There is some heterogeneity in management strategies in Japan. We performed a survey of management of hereditary CRC in hospitals that are members of the Japan Society of Colorectal Cancer Research (JSCCR). One hundred and ninety departments responded, of which 127 were from designated cancer care hospitals (DCCHs) according to the Japanese government. There were 25 488 operations for CRC in these departments in 2015. DCCHs performed better with regard to usage of JSCCR guidelines, referring new CRC patients for LS screening, and having in-house genetic counselors and knowledge of treatment for LS. There were 174 patients diagnosed with LS and 602 undergoing follow-up in 2011–2015, which is less than those expected from CRC operations in 2015. These numbers were not affected by whether the institution was a DCCH. Universal screening for LS was performed in 8% of the departments. In contrast, 541 patients were diagnosed with FAP and 273 received preventive proctocolectomy/colectomy in 2011–2015. DCCH departments performed more surgery, although most of the management, including surgical procedures and use of nonsteroidal anti-inflammatory drugs, was similar to that in non-DCCHs. Management of desmoid tumor in the abdominal cavity differed according to the number of patients treated. In conclusion, there was heterogeneity in management of LS but not FAP. Most patients with LS may be overlooked and universal screening for LS is not common in Japan.

This article is protected by copyright. All rights reserved.

http://ift.tt/2fhY1ms

Antizyme inhibitor 1: a potential carcinogenic molecule

Abstract

Polyamines are multivalent and organic cations essential for cellular growth, proliferation, differentiation and apoptosis. Increased levels of polyamines are closely associated with numerous forms of cancer. An autoregulatory circuit composed by the ornithine decarboxylase(ODC), antizymes(AZ) and antizyme inhibitor (AZI) governs the intracellular level of polyamines. AZ binds with ODC to inhibit the ODC activity and to promote the ubiquitin-independent degradation of ODC. AZI binds to AZ with a higher affinity than ODC. Consequently, ODC is released from the ODC-AZ complex to rescue its activity. AZI increases the ODC activity to accelerate the formation of intracellular polyamines, triggering gastric and breast carcinogenesis as well as hepatocellular carcinoma and esophageal squamous cell carcinoma development. Especially, AZIN1, a primary member of AZI family, has aroused more attention because of its contributing to cancer. Even though its conformation is changed by the adenosine-to-inosine RNA editing, it plays an important role in tumorigenesis through regulating intracellular polyamines. Encouragingly, AZIN1 has been revealed to have an additional function outside the polyamine pathway so as to bypass the deficiency of targeting the polyamine biosynthetic pathway, promising to become a critical target for cancer therapy. Here, we congregate the latest advances on the AZIN1 and its potential contribution to carcinogenesis.

This article is protected by copyright. All rights reserved.

http://ift.tt/2eYUnmh

Management strategies in Lynch syndrome and familial adenomatous polyposis: a national healthcare survey in Japan

Summary

Lynch syndrome (LS) and familial adenomatous polyposis (FAP) are major sources of hereditary colorectal cancer (CRC) and associated with other malignancies. There is some heterogeneity in management strategies in Japan. We performed a survey of management of hereditary CRC in hospitals that are members of the Japan Society of Colorectal Cancer Research (JSCCR). One hundred and ninety departments responded, of which 127 were from designated cancer care hospitals (DCCHs) according to the Japanese government. There were 25 488 operations for CRC in these departments in 2015. DCCHs performed better with regard to usage of JSCCR guidelines, referring new CRC patients for LS screening, and having in-house genetic counselors and knowledge of treatment for LS. There were 174 patients diagnosed with LS and 602 undergoing follow-up in 2011–2015, which is less than those expected from CRC operations in 2015. These numbers were not affected by whether the institution was a DCCH. Universal screening for LS was performed in 8% of the departments. In contrast, 541 patients were diagnosed with FAP and 273 received preventive proctocolectomy/colectomy in 2011–2015. DCCH departments performed more surgery, although most of the management, including surgical procedures and use of nonsteroidal anti-inflammatory drugs, was similar to that in non-DCCHs. Management of desmoid tumor in the abdominal cavity differed according to the number of patients treated. In conclusion, there was heterogeneity in management of LS but not FAP. Most patients with LS may be overlooked and universal screening for LS is not common in Japan.

This article is protected by copyright. All rights reserved.

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via IFTTT

Antizyme inhibitor 1: a potential carcinogenic molecule

Abstract

Polyamines are multivalent and organic cations essential for cellular growth, proliferation, differentiation and apoptosis. Increased levels of polyamines are closely associated with numerous forms of cancer. An autoregulatory circuit composed by the ornithine decarboxylase(ODC), antizymes(AZ) and antizyme inhibitor (AZI) governs the intracellular level of polyamines. AZ binds with ODC to inhibit the ODC activity and to promote the ubiquitin-independent degradation of ODC. AZI binds to AZ with a higher affinity than ODC. Consequently, ODC is released from the ODC-AZ complex to rescue its activity. AZI increases the ODC activity to accelerate the formation of intracellular polyamines, triggering gastric and breast carcinogenesis as well as hepatocellular carcinoma and esophageal squamous cell carcinoma development. Especially, AZIN1, a primary member of AZI family, has aroused more attention because of its contributing to cancer. Even though its conformation is changed by the adenosine-to-inosine RNA editing, it plays an important role in tumorigenesis through regulating intracellular polyamines. Encouragingly, AZIN1 has been revealed to have an additional function outside the polyamine pathway so as to bypass the deficiency of targeting the polyamine biosynthetic pathway, promising to become a critical target for cancer therapy. Here, we congregate the latest advances on the AZIN1 and its potential contribution to carcinogenesis.

This article is protected by copyright. All rights reserved.

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Receptor Tyrosine Kinases as Targets for Enhancing Tumor Radiosensitivity

Abstract

The advent of the modern era of molecularly targeted therapies in oncology has generated considerable excitement in the field of oncology. While there have been successes with molecularly targeted agents as monotherapies, most solid tumors display only a transient and modest response to single-targeted agents. As such, there has been significant effort in combining molecularly targeted agents with radiotherapy. Receptor tyrosine kinases (RTKs) play central roles in oncogenesis, stress sensitivity, tumor maintenance/progression, and clinical prognosis. Secondary to these roles, receptor tyrosine kinases are attractive targets for cancer therapy and specifically in combination with radiation therapy to enhance tumor radiosensitivity. Significant preclinical and clinical investigations have been performed to understand their roles in regulating the cellular response to radiation. A number of RTKs with relevance to radiation oncology have been identified including EGFR, VEGFR, IGF-1R, c-MET, and HER2. This chapter will highlight the preclinical and clinical findings associated with the combination of radiotherapy and inhibitors of the aforementioned receptors.

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Classic IL-6R signalling is dispensable for intestinal epithelial proliferation and repair

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Short-term and long-term effects of childhood cancer on income from employment and employment status: A national cohort study in Sweden

BACKGROUND

There is insufficient knowledge regarding the economic impact of childhood cancer on parents. The objectives of the current study were to investigate the short-term and long-term effects of childhood cancer on mothers' and fathers' income from employment and employment status.

METHODS

The study sample consisted of the parents of children diagnosed with cancer from 2004 to 2009 in Sweden (3626 parents of 1899 children). Annual register data concerning income from employment and employment status (employed/not employed) were retrieved from the Longitudinal Integration Database for Health Insurance and Labor Market Studies. Using generalized linear models, the mean income from employment and employment status were compared with a matched control cohort of 34,874 parents sampled from the general population.

RESULTS

Parents' income was found to decrease significantly after the child's cancer diagnosis. The effect was most pronounced for mothers, whose income was reduced for 6 years after diagnosis, whereas fathers' income was similar to that of control fathers 3 years after the diagnosis. Mothers were more likely to stop working after a child's cancer diagnosis compared with controls. No association was found for fathers' employment status. Younger age of parents; lower level of education; and, among mothers, being born outside of Sweden were found to be associated with more adverse effects on income.

CONCLUSIONS

Parents' income from employment and employment status appear to be adversely affected by having a child with cancer. Socioeconomic consequences are not distributed equally: the income of fathers appears to catch up after a few years, whereas mothers tend to be disadvantaged in their professional life for several years after a child's cancer diagnosis. Cancer 2016. © 2016 American Cancer Society.

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Addressing multilevel barriers to cervical cancer screening in Korean American women: A randomized trial of a community-based intervention

BACKGROUND

Korean American women have among the lowest rates of cervical cancer screening in the United States. The authors evaluated a multicomponent intervention combining community education with navigation services to reduce access barriers and increase screening rates in this underserved population. It was hypothesized that cervical cancer screening rates would be higher among women who received the intervention program compared with those in the control program.

METHODS

Korean American women (N = 705) were recruited from 22 churches. In this matched-pair, group-randomized design, 347 women received the intervention, which consisted of a culturally relevant cancer education program combined with provision of navigation services. The control group (N = 358) received general health education, including information about cervical cancer risk and screening and where to obtain low-cost or no-cost screening. Screening behavior was assessed 12 months after the program.

RESULTS

Screening behavior data were obtained from 588 women 12 months after the program. In both site-level and participant-level analyses, the intervention program contributed to significantly higher screening rates compared with the control program (odds ratio [OR], 25.9; 95% confidence interval [CI], 10.1-66.1; P < .001). In sensitivity analysis, the treatment effect remained highly significant (OR, 16.7; 95% CI, 8.1-34.4; P < .001).

CONCLUSIONS

A multicomponent intervention combining community cancer education with navigation services yielded significant increases in cervical cancer screening rates among underscreened Korean American women. Community-accessible programs that incorporate cancer education with the delivery of key navigation services can be highly effective in increasing cervical cancer screening rates in this underserved population. Cancer 2016. © 2016 American Cancer Society.

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Molecular pathogenesis of chronic myelomonocytic leukemia

Summary

Recent insights into the pathophysiology of chronic myelomonocytic leukemia (CMML) have been obtained by the molecular and biological characterization of primary leukemic cells from patients and from animal models. Almost 3 decades ago extensive myeloid colony growth in semisolid cultures without exogenous growth factors was observed as an in vitro characteristic of a subgroup of CMML patients. Recent data suggest that this phenomenon was probably the first indication of an hyperactive RAS signaling pathway in these patients. Although the mutation landscape in CMML is heterogeneous and molecular aberrations in other signaling components can be found in some patients, the RAS pathway seems to play the major pathophysiological role in the majority of CMML patients with myeloproliferation (MP), disease progression and transformation into secondary acute myeloid leukemia (AML). There is also increasing evidence indicating that the MP-CMML is a RAS pathway driven disease which is superimposed onto age-related clonal hematopoiesis.

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Classic IL-6R signalling is dispensable for intestinal epithelial proliferation and repair

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Short-term and long-term effects of childhood cancer on income from employment and employment status: A national cohort study in Sweden

BACKGROUND

There is insufficient knowledge regarding the economic impact of childhood cancer on parents. The objectives of the current study were to investigate the short-term and long-term effects of childhood cancer on mothers' and fathers' income from employment and employment status.

METHODS

The study sample consisted of the parents of children diagnosed with cancer from 2004 to 2009 in Sweden (3626 parents of 1899 children). Annual register data concerning income from employment and employment status (employed/not employed) were retrieved from the Longitudinal Integration Database for Health Insurance and Labor Market Studies. Using generalized linear models, the mean income from employment and employment status were compared with a matched control cohort of 34,874 parents sampled from the general population.

RESULTS

Parents' income was found to decrease significantly after the child's cancer diagnosis. The effect was most pronounced for mothers, whose income was reduced for 6 years after diagnosis, whereas fathers' income was similar to that of control fathers 3 years after the diagnosis. Mothers were more likely to stop working after a child's cancer diagnosis compared with controls. No association was found for fathers' employment status. Younger age of parents; lower level of education; and, among mothers, being born outside of Sweden were found to be associated with more adverse effects on income.

CONCLUSIONS

Parents' income from employment and employment status appear to be adversely affected by having a child with cancer. Socioeconomic consequences are not distributed equally: the income of fathers appears to catch up after a few years, whereas mothers tend to be disadvantaged in their professional life for several years after a child's cancer diagnosis. Cancer 2016. © 2016 American Cancer Society.

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Addressing multilevel barriers to cervical cancer screening in Korean American women: A randomized trial of a community-based intervention

BACKGROUND

Korean American women have among the lowest rates of cervical cancer screening in the United States. The authors evaluated a multicomponent intervention combining community education with navigation services to reduce access barriers and increase screening rates in this underserved population. It was hypothesized that cervical cancer screening rates would be higher among women who received the intervention program compared with those in the control program.

METHODS

Korean American women (N = 705) were recruited from 22 churches. In this matched-pair, group-randomized design, 347 women received the intervention, which consisted of a culturally relevant cancer education program combined with provision of navigation services. The control group (N = 358) received general health education, including information about cervical cancer risk and screening and where to obtain low-cost or no-cost screening. Screening behavior was assessed 12 months after the program.

RESULTS

Screening behavior data were obtained from 588 women 12 months after the program. In both site-level and participant-level analyses, the intervention program contributed to significantly higher screening rates compared with the control program (odds ratio [OR], 25.9; 95% confidence interval [CI], 10.1-66.1; P < .001). In sensitivity analysis, the treatment effect remained highly significant (OR, 16.7; 95% CI, 8.1-34.4; P < .001).

CONCLUSIONS

A multicomponent intervention combining community cancer education with navigation services yielded significant increases in cervical cancer screening rates among underscreened Korean American women. Community-accessible programs that incorporate cancer education with the delivery of key navigation services can be highly effective in increasing cervical cancer screening rates in this underserved population. Cancer 2016. © 2016 American Cancer Society.

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Molecular pathogenesis of chronic myelomonocytic leukemia

Summary

Recent insights into the pathophysiology of chronic myelomonocytic leukemia (CMML) have been obtained by the molecular and biological characterization of primary leukemic cells from patients and from animal models. Almost 3 decades ago extensive myeloid colony growth in semisolid cultures without exogenous growth factors was observed as an in vitro characteristic of a subgroup of CMML patients. Recent data suggest that this phenomenon was probably the first indication of an hyperactive RAS signaling pathway in these patients. Although the mutation landscape in CMML is heterogeneous and molecular aberrations in other signaling components can be found in some patients, the RAS pathway seems to play the major pathophysiological role in the majority of CMML patients with myeloproliferation (MP), disease progression and transformation into secondary acute myeloid leukemia (AML). There is also increasing evidence indicating that the MP-CMML is a RAS pathway driven disease which is superimposed onto age-related clonal hematopoiesis.

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Vaginal and sexual health treatment strategies within a female sexual medicine program for cancer patients and survivors

Abstract

Purpose

We sought to evaluate patient adherence and response to simple vaginal and sexual health treatment strategies in female cancer patients receiving treatment at a female sexual medicine and health program and identify improvements of physical symptoms, per patient and clinical evaluation.

Methods

Evaluability criteria included gynecologic exam at initial visit, at least one follow-up with gynecologic exam within 8 months of initial visit, and all consecutive follow-ups <6 months apart. Demographics, medical information, and clinical assessments from 175 evaluable patients with at least one follow-up from 09/12 to 10/14 were analyzed. The majority of patients were being treated for or had a history of breast (n = 90, 53 %), gynecologic (n = 54, 32 %), or colorectal/anal (n = 15, 9 %) cancers. An assessment form included a clinician evaluation, Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), and patient-reported outcomes. Compliance with treatment recommendations were summarized, and changes over time were compared for clinical outcomes.

Results

Mean number of visits was 3.43. Mean age was 55.4 years; 92 % (n = 155/169) were in menopause. Treatment strategies included rationale and instruction for use of vaginal moisturizers, lubricants, pelvic floor exercises, and dilator therapy, in addition to psychosexual education regarding sexual changes (response, anatomy, and function) associated with cancer treatment and support. At last assessment, 89 % had complied with the clinical recommendation (moisturize 2–5+ times/week). Vaginal pH scores >6.5 declined over time (p = 0.03). VAS scores improved by last assessment (p < 0.001), as did VuAS scores (p = 0.001). Sexual function scores significantly improved (p < 0.001), confidence about future sexual activity increased (p = 0.004), and sexual/vaginal health concerns decreased (p = 0.00003).

Conclusion

Significant changes were observed in women using treatment strategies, with improvement in vulvovaginal symptoms, a decrease in elevated vaginal pH and pain with exams, enhanced sexual function, and increased intimacy confidence.

Implications for Cancer Survivors

These findings have high clinical relevance for symptom management with improvement of sexual function using simple strategies and clinical tools in the oncology setting.

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Vaginal and sexual health treatment strategies within a female sexual medicine program for cancer patients and survivors

Abstract

Purpose

We sought to evaluate patient adherence and response to simple vaginal and sexual health treatment strategies in female cancer patients receiving treatment at a female sexual medicine and health program and identify improvements of physical symptoms, per patient and clinical evaluation.

Methods

Evaluability criteria included gynecologic exam at initial visit, at least one follow-up with gynecologic exam within 8 months of initial visit, and all consecutive follow-ups <6 months apart. Demographics, medical information, and clinical assessments from 175 evaluable patients with at least one follow-up from 09/12 to 10/14 were analyzed. The majority of patients were being treated for or had a history of breast (n = 90, 53 %), gynecologic (n = 54, 32 %), or colorectal/anal (n = 15, 9 %) cancers. An assessment form included a clinician evaluation, Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), and patient-reported outcomes. Compliance with treatment recommendations were summarized, and changes over time were compared for clinical outcomes.

Results

Mean number of visits was 3.43. Mean age was 55.4 years; 92 % (n = 155/169) were in menopause. Treatment strategies included rationale and instruction for use of vaginal moisturizers, lubricants, pelvic floor exercises, and dilator therapy, in addition to psychosexual education regarding sexual changes (response, anatomy, and function) associated with cancer treatment and support. At last assessment, 89 % had complied with the clinical recommendation (moisturize 2–5+ times/week). Vaginal pH scores >6.5 declined over time (p = 0.03). VAS scores improved by last assessment (p < 0.001), as did VuAS scores (p = 0.001). Sexual function scores significantly improved (p < 0.001), confidence about future sexual activity increased (p = 0.004), and sexual/vaginal health concerns decreased (p = 0.00003).

Conclusion

Significant changes were observed in women using treatment strategies, with improvement in vulvovaginal symptoms, a decrease in elevated vaginal pH and pain with exams, enhanced sexual function, and increased intimacy confidence.

Implications for Cancer Survivors

These findings have high clinical relevance for symptom management with improvement of sexual function using simple strategies and clinical tools in the oncology setting.

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Tolosa-Hunt syndrome and comorbidity of obsessive compulsive disorder and aortic aneurysm

Description

A 59-year-old man with obsessive compulsive disorder (OCD) was on antidepressant treatment for years. Six months ago, he got a severe headache on the left side of his head, reported pain behind his left eye, diplopia and ptosis displayed on his left eyelid. The patient had mild migraine attacks occasionally. However, his previous headache was very intense when compared with earlier ones. By cranial MRI, a lesion (22x7 mm horizontally, 13x8 mm vertically) adjacent to carotid segment 4 (C4) of the left internal carotid artery was found. The lesion showed a hyperintense signal in contrast-enhanced T2-weighted images, which was the result of enhanced abnormal soft tissue extending through the orbital fissure and into the orbital apex. This did not cause compression on the optic nerve and there was slight bulging into the left cavernous sinus (figure 1). The patient's blood and cerebrospinal fluid biochemical parameters were within...

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Methotrexate induces DNA damage and inhibits homologous recombination repair in choriocarcinoma cells

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Comparison of internal target volumes defined on 3-dimensional, 4-dimensonal, and cone-beam CT images of non-small-cell lung cancer

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Correction: Aortic valve replacement for Libman-Sacks endocarditis

Keenan JB, Janardhanan R, Larsen BT, et al. Aortic valve replacement for Libman-Sacks endocarditis. BMJ Case Reports 2016; doi:10.1136/bcr-2016-215914

The revised author list of this paper is as follows:

Jack B Keenan, Taufiek Konrad Rajab, Rajesh Janardhanan, Brandon T Larsen, Zain Khalpey

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Cutaneous neck lesion of occult odontogenic origin: search for the tooth

The differential diagnosis for inflammatory neck swellings is vast. A swelling of dental origin should be considered because, while rare, they mimic more common causes of neck lumps. We report the case involving a recurrent submandibular swelling in a young female patient that was presumed to be an epidermoid cyst by her general medical practitioner. After 6 months of unsuccessful treatment in the community, an odontogenic source was identified and treated successfully following referral to a local Oral and Maxillofacial department.

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Thyroid metastasis from lung adenocarcinoma with EML4-ALK rearrangement

Thyroid metastases from lung cancer are very rare. A woman aged 42 years with a tumour in the lower lobe of the right lung was diagnosed as having lung adenocarcinoma positive for echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase. Positron emission tomography demonstrated fluorodeoxyglucose accumulation in the lower lobe of the right lung, the right thyroid lobe and both adrenal glands. We performed fine-needle aspiration biopsy (FNAB) and used reverse transcriptase-PCR (RT-PCR) to diagnose the patient as having metastatic lung adenocarcinoma to the thyroid gland. We believe that FNAB combined with RT-PCR can be an effective method for diagnosing metastatic lung adenocarcinoma to the thyroid gland.

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Successful improvement of Buschke-Löwenstein tumour in an HIV-infected patient with antiretroviral therapy alone

Buschke-Löwenstein tumour (BLT), also defined as giant condyloma acuminatum, is a rare exophytic tumour affecting the anogenital and perianal regions associated with human papillomavirus (HPV) infections, with a potential of malignant transformation and which is at a greater risk in T-cell mediated immunodeficient patients. Different therapeutic options, alone or in combination, have been reported for the treatment of BLT including local therapy but wide surgical local excision is however recommended as the most important therapeutic intervention. We report a case of a HIV-infected man who developed a voluminous pelvic BLT which disappeared progressively under antiretroviral therapy with no additional treatment, contemporary to an improvement of his immunity, highlighting the possible spontaneous reversibility of HPV-induced tumours in treated HIV infection.

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Metastatic trichilemmal carcinoma in a patient with breast cancer

Trichilemmal carcinoma (TC) is described as a very rare cancer of the skin adnexa.^{1 2} Ninety per cent of the lesions present on the scalp. Prognostic factors in TC are limited to lymph node status and surgical margins, with no statistical significance observed for age or gender of the patient, size of tumour or locoregional recurrence. We present a 46-year-old black patient who developed TC during treatment for breast cancer. Postoperative histology of the scalp lesion excision confirmed no involved margins. At the three monthly appointment, the patient was reviewed and multiple, new scalp lesions were noted. A CT scan of the head, neck found multiple lesions on the scalp, limited to the soft tissue, not involving the outer table of the skull. There was bilateral invasion of the parotid glands. To the best of our knowledge, no syndromes or associations between breast cancer and adnexal skin tumours exist.

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Never forget basics

Description

A patient with open fracture of both bones of a leg was posted for wound debridement and external fixation. L3–L4 space was identified by the loss of resistance technique with Tuohy's needle. An epidural catheter was passed through the Tuohy's needle. Aspiration of epidural catheter resulted in cerebro spinal fluid (CSF) tap. We tried to pull the catheter while the needle was in situ. Although there was a little resistance, we could remove the catheter. When we inspected the catheter, it was found that epidural catheter tip with only the 8 cm mark was visible (figure 1). Immediately the Tuohy's needle was removed and it was concluded that the epidural catheter tip was neither palpable nor visible. The patient was given general anaesthesia and allowed surgeons to proceed with the planned surgery. We decided to document and explain to the patient about sheared catheter and not...

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Vascular compression of left renal vein: the nutcracker phenomenon

Description

A 75-year-old woman presented to the outpatient clinic with symptoms of upper abdominal pain radiating to the back. On evaluation with contrast-enhanced CT of the abdomen, she was found to have carcinoma of the body of pancreas. Incidentally, vascular compression of the left renal vein was seen between the superior mesenteric artery and the aorta (the nutcracker sign) (figure 1). In view of poor performance status, she underwent palliation with percutaneous splanchnic nerve radiofrequency ablation. Since she was asymptomatic for the vascular compression and serum creatinine was normal (1.2 mg/dL), she was observed for the same.

Figure 1

(A) Axial contrast-enhanced CT image showing mass lesion in the body of pancreas (asterisk) with dilated left renal vein, (B) magnified image showing compression of the left renal vein between the superior mesenteric artery and aorta with dilation of the proximal left renal vein (arrow).

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Exophytic Verrucous Hyperplasia of the Oral Cavity – Application of Standardized Criteria for Diagnosis from a Consensus Report

Related Articles

Exophytic Verrucous Hyperplasia of the Oral Cavity – Application of Standardized Criteria for Diagnosis from a Consensus Report

Asian Pac J Cancer Prev. 2016 Jan 9;17(9):4491

Authors: Rosnah BZ, Thomas GK, Anand R, Jin K, Wm T, Takashi T, Saman W, Vinay KH, Alison R, Haizal MH, Ajura J

Abstract
Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC) need to be further clarified for better understanding of their predictable biologic behavior and appropriate treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of the 'First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral Cavity' held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named 'Exophytic Verrucous Hyperplasia'. Previously described clinical features of OVH such as the 'blunt' or 'sharp' variants; and the 'mass' or 'plaque' variants can now collectively fall under this newly described entity. This paper discusses in detail the application of the standardized criteria guidelines of 'Exophytic Verrucous Hyperplasia' as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool of OVH cases and facilitate a better understanding of OVH malignant potential.

PMID: 27865210 [PubMed - as supplied by publisher]

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