A comparison of four leukapheresis methods to harvest an optimal dose of CD34+ cells: A single center experience.

BACKGROUND: Chemokine receptor CXCR4 antagonist plerixafor (Px) as well as high volume (HV) leukapheresis have been shown to reduce hematopoietic stem progenitor cell (HSPC) mobilization failure rates. However, no direct comparisons of such methods currently exists. METHODS AND MATERIALS: We compared the HSPC collection yield based on basal peripheral blood CD34+ cell numbers in patients diagnosed with multiple myeloma or non-Hodgkin's lymphoma undergoing autologous stem cell transplantation in a retrospective chart review. The leukapheresis methods used included HV versus regular volume (RV) with or without Px. There were 116 patients in the study group while the historical control group had 34 patients. RESULTS AND CONCLUSIONS: Control group underwent RV leukapheresis without Px. Addition of Px or HV in the study group failed to display significant improvement in CD34+ cell collection yield; however, when basal CD34+ cell numbers were taken into account, both Px + RV and HV without Px increased CD34+ cell collection yield. The collection failure rates of HV without Px group were comparable to Px + RV when the basal CD34+ cell numbers were over 20/µl. Of interest, multivariate linear regression analysis did not detect any significant difference between HV versus Px + RV or other leukapheresis methods in CD34 yields or collection failure rates from a single collection after controlling for other factors (sex, age, or underlying disease). In multivariate analysis, pre apheresis CD34+ cell number was significantly and positively associated with the CD34+ cell yields from a single apheresis. In our studies, the majority of patients can be rescued without Px by HV alone as a potential cost saving approach. In summary, trend in our studies reflects that both Px and HV are capable of reducing the mobilization failure rates except the poorest mobilizers, which will need to be validated in larger studies.

Video-Based Education in Lung Cancer Screening.

Lung cancer (LC) is the leading cause of cancer mortality in the USA; the American Cancer Society (ACS) estimates upwards of 220,000 new cases will be diagnosed this year. Recently, the Center for Medicare/Medicaid Services (CMS) agreed to cover LC screening with low-dose computed tomography (CT) for patients; however, CMS requires prior documentation of a shared decision-making (SDM) visit between the patient and the referring clinician to inform them about risks of screening. LC screening programs have begun to use YouTube for patient recruitment, education, and marketing of screening. The objective of this study is to shed light on the role of YouTube in lung cancer screening in terms of guidelines, screening options, target population, steps after screening, and risks and benefits of screening. We searched YouTube.com ™ to identify videos dealing with lung screening using the keywords: lung cancer screening. Videos without sound, uploaded before 2009, longer than 20 min, duplicate videos, and videos in a language other than English were excluded. This method yielded 123 videos that fit criteria. Videos were coded for inclusion of LC screening process, risks and benefits of screening, screening guidelines, risk factors for LC, and treatment options after LC diagnosis. One hundred twenty-three videos had a cumulative 261,261 views across all videos. A total of 38.7% of the videos included no mention of United States Preventive Services Task Force (USPSTF) or CMS guidelines for LC screening. Only 30% included any mention of the risks associated with screening: 14% mentioned false positives, 12% radiation, and 4% anxiety associated with screening. Ninety-two percent of all videos sampled were intended for patients, and the majority of videos were created by medical institutions (66%) and news channels (17%). Lung cancer screening videos on YouTube's platform have garnered a substantial amount of views. While all videos sampled highlighted the benefits of LC screening, the majority fail to discuss the risks associated with the screening process. Most videos were produced for marketing purposes rather than educational and therefore should not be used as a substitute for SDM visits.

Quality of YouTube patient information on prostate cancer screening.

Social media is used by patients for health care information. We analyzed the quality of YouTube videos on prostate cancer screening. Most videos (71.1%) mentioned the potential harms of prostate cancer screening. There was no significant difference in risk-related information between videos published before and after the publication of US Preventive Services Task Force 2012 guidelines for prostate cancer screening. In conclusion, the quality of information of YouTube videos on prostate cancer screening is low and the content is potentially misleading.

Preclinical IV busulfan dose-finding study to induce reversible myeloablation in a non-human primate model.

In this study we utilized a large animal model to identify a dose of intravenous busulfan that can cause reversible myelosuppression. Nine baboons (Papio anubis) were treated with IV busulfan at 6.4 (Group A), 8 (Group B), or 9.6 mg/kg (Group C). Peripheral blood counts were measured up to 90 days after treatment and serial bone marrow samples were obtained to analyze CD34+ cell content and colony forming units. Overall, the highest grade of peripheral blood cytopenia was observed 15 days after treatment in all three groups (n = 3/group). In particular, we observed a notable reduction of neutrophil and platelet counts in the blood and the number of marrow CD34+ cells and colony forming units. In contrast, the effect of busulfan on hemoglobin levels was mild. Baboons who received the highest dose of busulfan showed only a 25-35% recovery of marrow CD34+ cells and colony forming units after 90 days of busulfan administration. However, all three groups of animals showed a full recovery of peripheral blood counts and normal marrow cellularity and tri-lineage hematopoiesis after treatment. Notably, all three doses of busulfan were tolerated well without significant extra-medullary toxicity. These results validate the hierarchy of blood cells likely targeted by busulfan, and based on these findings, clinical trials using myelotoxic but not myeloablative doses of intravenous busulfan will be designed for patients with myeloid malignancies.

The risk of second primary malignancy in patients with stage Ia non-small cell lung cancer: a U.S. population-based study.

BACKGROUND: Lung cancer is one of the most common cancers worldwide. Patients with early stage lung cancer have improved long-term survival. With the introduction of low-dose CT scan, more patients are going to be diagnosed at an early stage. However, there is limited data on the risk of second primary malignancies (SPMs) in these subsets of patients in the United States. METHODS: We utilized SEER-13 (Surveillance, Epidemiology and End Results) registry to obtain Multiple Primary- Standardized Incidence Ratio and an Absolute Excess Risk between January 2004 and December 2010 for patients with Stage Ia non-small cell lung cancer. RESULTS: The database comprised of 12,246 patients. A total of 1431 (11.68%) patients developed 1563 SPMs with an observed to expected (O/E) ratio of 2.07 (95% CI = 1.92-2.23, p < .001) in patients with adenocarcinoma and 2.05 (95% CI = 1.92-2.19, p < .001) in squamous cell carcinoma group. CONCLUSIONS: This study showed an excess risk of SPMs in patients with early stage non-small cell lung cancer. We recommend a close follow-up, paying attention to concerning symptoms or examination findings and judicious use of age-appropriate cancer screening.

Second Primary Malignancy in Bladder Carcinoma - A Population-based Study.

BACKGROUND: A second primary malignancy is a serious long-term complication in cancer survivors. The aim of this study was to evaluate the risk of second primary malignancies (SPM) in adult patients with bladder cancer. MATERIALS AND METHODS: We selected patients ≥18 years diagnosed with bladder cancer from National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) 13 database. We calculated the risk of second primary malignancies in the bladder cancer patients using the MP-SIR session of SEER*stat software. RESULTS: A total of 103,516 cases of bladder cancer was included in the study. Among them, 17,004 (16.4%) developed 19,318 second primary malignancies. The risk of development of SPM was significantly higher compared to the general population with O/E ratio of 1.42 (95% CI=1.4-1.44, AER=89.22 and p-value of <0.001). Prostate cancer, lung and bronchial cancer and urinary bladder cancer were the three commonest SPMs. CONCLUSION: There is significant increased risk of second primary malignancies in adult patients with bladder cancer to general population. Bladder cancer survivors may benefit from life-long follow-up for development of SPM.

Second Primary Malignancies in Hepatocellular Cancer - A US Population-based Study.

BACKGROUND/AIM: A second primary malignancy is a serious long-term complication in cancer survivors. The aim of this study was to evaluate the risk of second primary malignancies in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We selected adult patients (≥18 years) diagnosed with HCC from the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) 13 database. We calculated the risk of second primary malignancies in these patients using multiple primary standardized incidence ratio (MP-SIR) session of SEER* stat software. Second primary malignancy was defined as a metachronous malignancy diagnosed 6 months or more after an index HCC. RESULTS: A total of 15,296 patients with a diagnosis of primary HCC were reported in the SEER 13 registry during January 1992 to December 2011. A total of 446 (2.83%) developed 466 second primary malignancies with an observed/expected ratio of 10.07 (95% confidence interval=0.97-1.17, p=0.16) and absolute risk of 7.17 per 10,000 population. Risk of stomach and of thyroid cancer were significantly increased among older patients. Risk of lung cancer and of hepatobiliary cancer were significantly higher compared to that of the general population after two years of latency. CONCLUSION: Risk of specific second primary malignancies in adult patients with HCC depends on age of the patient and latency.

Second Primary Malignancies in Adults with Gastric Cancer - A US Population-Based Study.

BACKGROUND: Multiple studies have examined the incidence of secondary primary malignancies (SPMs) in gastric cancer patients in Europe and Asia. This retrospective review was conducted to analyze risk of SPM in patients with gastric cancer diagnosed in the United States. METHODS: We included adult patients diagnosed with gastric cancer from the surveillance, epidemiology, and end result (SEER) 13 database. We calculated the risk of SPMs in these patients using the multiple primary standardized incidence ratio session of SEER*stat software and performed subset analyses of SPM with regard to age, sex, radiotherapy used, and latency period. RESULTS: Among 33,720 patients, 1838 (5.45%) developed 2019 SPMs with an observed/expected (O/E) ratio of 1.11 [95% confidence interval (CI) = 1.06-1.16, p < 0.001] and an absolute excess risk of 18.16 per 10,000 population. The median time to first SPM from the time of diagnosis of gastric cancer was 46.9 months (range 6-239 months). Significant excess risk was observed for gastrointestinal malignancies [O/E ratio 1.71 (CI = 1.59-1.84, p < 0.001)], thyroid [O/E ratio 2.00 (CI = 1.37-2.8, p < 0.001)], and pancreatic cancer [O/E ratio 1.60 (CI = 1.29-21.96, p < 0.001)]. Risk of secondary melanoma, breast cancer, and prostate cancer was lower than in the general population. CONCLUSION: The risk for SPMs is significantly increased in adults with gastric cancer compared to the general population.

Second Primary Malignancies in Mantle Cell Lymphoma: A US Population-based Study.

BACKGROUND/AIM: The risk of second primary malignancy (SPM) in mantle cell lymphoma (MCL) is not well-known. In this population-based study, we analyzed rates of SPM in adult patients with MCL. PATIENTS AND METHODS: We selected adult (≥18 years) patients with MCL as first primary malignancy diagnosed during January 1992 to December 2011 from National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) 13 database. We used multiple standardized incidence ratio (MP-SIR) session of SEER(*) stat software to calculate the risk of second primary malignancies. RESULTS: Among 3,149 patients, 261 (8.29%) developed 287 second primary malignancies with observed/expected (O/E) ratio of 1.32 (95% confidence interval (CI=1.17-1.48, p<0.001). The median time to SPM from the time of diagnosis was 47 months (range=6 months to 17.91 years). The significant excess risks were observed for skin, excluding basal and squamous cancer, (N=22, O/E=2.24, CI=1.4-3.39, p<0.001), thyroid malignancy (O/E=3, CI=1.1-6.52, p<0.01), acute myeloid leukemia (O/E=7.74, CI=4.54-13.94, p<0.001), chronic lymphocytic leukemia (O/E=7.27, CI=4.44-11.23, p<0.001) and Non-Hodgkin's lymphoma (NHL) (O/E=3.79, CI=2.64-5.27, p<0.001). The risk of malignancies of brain, thyroid, rectum and anal canal were higher within the first two years of diagnosis of MCL. Risk of skin cancer, excluding basal and squamous cancer, was higher after two years of latency. CONCLUSION: There is significantly higher risk of second primary malignancies in patients with mantle cell lymphoma compared to the general population. Patients may benefit from cancer-specific screening during follow-up.

Local effects of intra-articular injection of anti-rabbit tumor necrosis factor alpha monoclonal antibody in antigen-induced arthritis of the rabbit temporomandibular joint.

BACKGROUND: Local effects of intra-articular (IA) injection of anti-rabbit tumor necrosis factor alpha monoclonal antibody (anti-TNFα mAb) for antigen-induced mono-arthritis (AIA) of the rabbit temporomandibular joint (TMJ) and its systemic influences were evaluated. METHODS: Biochemical analysis of synovial fluid (SF), clinical and histopathological analyses of TMJ, and serum analysis were performed after inducing AIA in bilateral TMJs of 40 New Zealand White rabbits. IA injection of anti-TNFα mAb in unilateral TMJ (TNF blockade side; n = 12) and IgG (n = 12) was performed while saline injected on the contralateral side. TNFα and IL-1ß in SF was analyzed at Days 1, 3, 7, and 21. Joint swelling and head withdrawal reflex threshold (WRT) over TMJs were evaluated in TNF blockade side (n = 12) with histopathological analysis at Days 3, 7, and 21. In remaining four animals with TNF blockade, TNFα and anti-TNFα mAb in serum were analyzed. RESULTS: Tumor necrosis factor alpha in SF was significantly lower in TNF blockade side on all days but IL-1ß was lower only on Day 3. WRT was significantly higher at all times in the blockade side. Less inflammatory reactions and degenerative changes of cartilage were observed on Days 7 and 21 in the blockade side. TNFα and anti-TNFα mAb were under detection level in serum at all times. CONCLUSIONS: Intra-articular injection of anti-rabbit TNFα mAb in mono-arthritis model was effective to control local inflammation and degenerative joint changes. Further, low-dose IA injection of antibody may not have systemic side effects.

Correlation of mandibular bone quality with neurosensory disturbance after sagittal split ramus osteotomy.

Our aim was to find out whether the quality of bone around the inferior alveolar nerve is correlated with neurosensory disturbance to the nerve after sagittal split ramus osteotomy (SSRO) in patients with mandibular prognathism. Computed tomograms (CT) were taken of 35 patients with mandibular prognathism and 35 without. To assess the density of bone around the inferior alveolar nerve, the width of the buccal cortical bone in the mandibular second molar regions was measured on CT. The Hounsfield units (HU) in the same regions were also measured. The number of HU in the mandible around the second molar regions was significantly higher (p<0.01) in those with neurosensory disturbance (p<0.01). The quality of bone measured by HU is associated with an increased risk of neurosensory disturbance, but the width of buccal bone is not.

Relationship between inferior alveolar nerve canal position at mandibular second molar in patients with prognathism and possible occurrence of neurosensory disturbance after sagittal split ramus osteotomy.

PURPOSE: To elucidate the relationship between the anatomic position of the inferior alveolar nerve (IAN) at the mandibular second molar and the occurrence of neurosensory disturbances of the IAN after sagittal split ramus osteotomy (SSRO) in patients with mandibular prognathism. Also, the present study evaluated the difference in anatomic position of the IAN between patients with and without mandibular prognathism. PATIENTS AND METHODS: Computed tomography images were taken of 28 patients with mandibular prognathism and 30 without prognathism. On these scans, the IANs from the mandibular second molar region to the mandibular foramen in the mandibular ramus were identified. The present study was designed as a cross-sectional study. The distance from the buccal aspect of the IAN canal to the outer buccal cortical margin of the mandible in the mandibular second molar regions was measured on the computed tomography images. Also, the linear distance between the superior aspect of the IAN canal and the alveolar crest in these regions was calculated. In addition, we investigated the presence or absence of contact between the IAN canal and the inner buccal cortical margin of the mandible from the mandibular second molar to the mandibular foramen in the mandibular ramus. Next, we examined whether neurosensory disturbances occurring after SSRO were related to the position of the IAN at the mandibular second molar. RESULTS: A significant difference was found in the occurrence of neurosensory disturbances of the IAN after SSRO between men and women (χ(2) test, P < .05). For the distance from the buccal aspect of the IAN canal to the outer buccal cortical margin of the mandible in the mandibular second molar region, a significant difference was found between groups with and without neurosensory disturbances (Student's t test, P < .01). The shorter the distance from the buccal aspect of the IAN canal to the outer buccal cortical margin, the more frequent the occurrence of neurosensory disturbances of the IAN. CONCLUSIONS: The present results have demonstrated that gender and the anatomic position of the IAN canal at the mandibular second molar are significantly related to the occurrence of neurosensory disturbances of the IAN after SSRO. Therefore, surgeons should clearly inform patients of the increased possibility of neurosensory disturbances after SSRO when the patients are female and are found to have a shorter distance from the buccal aspect of the IAN canal to the outer buccal cortical margin.

Ultrasonography for intraoperative determination of tumor thickness and resection margin in tongue carcinomas.

PURPOSE: Exact estimation of tumor thickness and the status of the resection margin in tongue carcinoma are important prognostic factors for local recurrence, subclinical nodal metastasis, and survival. This study aims to evaluate the accuracy of intraoral ultrasonography-guided measurement of tumor thickness and define an adequate intraoperative resection margin in squamous cell carcinomas of the tongue. MATERIALS AND METHODS: In this prospective study, 13 patients with presurgical, biopsy-proven, clinical T1N0 or T2N0 tongue squamous cell carcinomas who underwent a partial glossectomy were examined preoperatively with ultrasonography to assess tumor thickness under general anesthesia. Nine cases underwent resection by a conventional method, whereas we introduced elastic needles with a metal core to mark a deep surgical margin of 10 mm from the deepest tumor invasion front under ultrasonographic monitoring as a new technique in the remaining 4 cases. Each resected specimen was immediately immersed in gelatin solution while maintaining its original shape and orientation and was placed under refrigeration to solidify. Ultrasonographic observations of the gelatin-embedded specimens were performed from the superior surface of the gelatin block. RESULTS: Very fine ultrasonographic images of the resected specimen could be easily obtained without any special skills, and surgical clearance could be verified intraoperatively. The ultrasonographic tumor thickness measurements corresponded well with those of histologic sections, with a consistency ratio of 91.4% to 98.2% (Pearson correlation coefficient = 0.981, P < .05). CONCLUSION: Intraoperative ultrasonography is a reliable method to objectively evaluate tumor thickness and surgical margin clearance.

Vertical ramus versus sagittal split osteotomies: comparison of stability after mandibular setback.

PURPOSE: Intraoral vertical ramus osteotomy (IVRO) offers some advantages over sagittal split ramus osteotomy (SSRO) for treatment of the prognathic patient. The purpose of this study was to compare the postoperative changes of proximal and distal segments after IVRO and SSRO with semirigid internal fixation. PATIENTS AND METHODS: Thirty Japanese adults with a diagnosis of prognathic mandible were randomized to undergo either IVRO (n = 15) or SSRO (n = 15) according to an adaptive random assignment procedure. The postoperative changes of the proximal and distal segments were assessed with posteroanterior and lateral cephalograms. RESULTS: Compared with the SSRO group, the B-point and pogonion moved significantly posteriorly and inferiorly in the IVRO group from 1 month to 3 months after surgery. At 1 year after surgery, there was no significant difference between the 2 groups in the horizontal and vertical stability of the B-point and the pogonion. In the IVRO group, the gonion deviated significantly laterally from 1 week until 1 month after surgery as compared with that of the SSRO group. There was a significant correlation between the amount of setback and the amount of lateral gonial deviation in the IVRO group from 1 week to 1 year after surgery. CONCLUSIONS: Although in IVRO cases, distal segments moved posteriorly and inferiorly immediately after the release of maxillomandibular fixation, the stability after IVRO is equal to that after SSRO with semirigid internal fixation.

Biomechanical evaluation of different types of rigid internal fixation techniques for subcondylar fractures.

PURPOSE: The aim of this study was to evaluate the biomechanical stability of various internal fixation systems for subcondylar fractures. MATERIALS AND METHODS: Eighteen identical synthetic mandibles were used. Left condylar processes were cut to mimic perpendicular subcondylar fracture and right sides were mimicked oblique subcondylar fracture. The fixation systems used included single 4-hole mini adaptation plate, double fixation with the same plates, single 4-hole mini dynamic compression plate (DCP), Eckelt lag screw system, Wurzburg lag screw plate system and double 4-hole biodegradable miniplates made of poly L-lactide (PLLA). In oblique fractures, one of the screws fixing plates was used bicortically through bone fragments. The loading vector simulated physiologic forces to the condyle on biting with servohydraulic testing machine until failure was reached. Load-displacement curve, maximum load for failure, and stiffness were measured. RESULTS: In perpendicular fracture, double adaptation plate showed the highest level of tolerance load followed by Eckelt lag and double PLLA plate. In stiffness, double adaptation plate and Eckelt lag screw showed higher level of stiffness, whereas double PLLA was almost at the same level of single DCP. In oblique fracture, double adaptation plate showed the highest strength. CONCLUSIONS: In this laboratory setting, double adaptation plates fixation proved to have superior biomechanical stability in both fracture conditions. Eckelt lag screw showed good stability in the perpendicular fracture, however, it was weak in the oblique fracture.