A morphological analysis of calcium hydroxylapatite and poly-l-lactic acid biostimulator particles.

Injectable fillers, pivotal in aesthetic medicine, have evolved significantly with recent trends favoring biostimulators like calcium hydroxylapatite (CaHA-CMC; Radiesse, Merz Aesthetics, Raleigh, NC) and poly-l-lactic acid (PLLA; Sculptra Aesthetics, Galderma, Dallas, TX). This study aims to compare the particle morphology of these two injectables and examine its potential clinical implications. Utilizing advanced light and scanning electron microscopy techniques, the physical characteristics of CaHA-CMC and PLLA particles were analyzed, including shape, size, circularity, roundness, aspect ratio, and quantity of phagocytosable particles. The findings reveal several morphological contrasts: CaHA-CMC particles exhibited a smooth, homogenous, spherical morphology with diameters predominantly ranging between 20 and 45 µm, while PLLA particles varied considerably in shape and size, appearing as micro flakes ranging from 2 to 150 µm in major axis length. The circularity and roundness of CaHA-CMC particles were significantly higher compared to PLLA, indicating a more uniform shape. Aspect ratio analysis further underscored these differences, with CaHA-CMC particles showing a closer resemblance to circles, unlike the more oblong PLLA particles. Quantification of the phagocytosable content of both injectables revealed a higher percentage of phagocytosable particles in PLLA. These morphological distinctions may influence the tissue response to each treatment. CaHA-CMC's uniform, spherical particles may result in reduced inflammatory cell recruitment, whereas PLLA's heterogeneous particle morphology may evoke a more pronounced inflammatory response.

Long-term duration and safety of Radiesse (+) for the treatment of jawline.

BACKGROUND: Calcium hydroxyapatite (CaHA)-carboxymethylcellulose (CMC)+ has unique properties that make it optimal for lifting, contouring, and defining the jawline. This long-term follow-up of a randomized, multicenter, rater-blinded trial reports efficacy and safety of CaHA-CMC(+) through 48 and up to 60 weeks post-treatment. METHODS: Eligible patients were randomized (2:1) to the treatment or the control/delayed treatment group to receive CaHA-CMC(+) injections in both jawlines. While touch-ups were permitted 4 weeks post-treatment for both groups, only the treatment group was eligible for optional retreatment after 48 weeks. The primary outcome was ≥1-point improvement on both jawlines on the Merz Jawline Assessment Scale (MJAS); secondary endpoints included the Subject Global Aesthetic Improvement Scale (SGAIS) among others. Post hoc analysis included pooling up to 48-week data from the combined treatment and control/delayed groups and 60-week data for the treatment group. RESULTS: Overall, 175 received treatment. MJAS responder rates were 77.9%, 78.7%, and 62.9% at 12, 24, and 48 weeks post-treatment, respectively. Responder rate on the MJAS at 60 weeks was 74.6% for those who received retreatment and 43.5% for those patients who received only the initial and touchup treatments. SGAIS scores demonstrated 93.4%, 85.6%, and 68.5% of patients rated themselves very much improved after 12, 24, and 48 weeks, respectively. Adverse events consisted of procedure or CaHA-CMC(+)-related events that were mostly resolved and overwhelmingly mild. CONCLUSIONS: CaHA-CMC(+) produced clinically meaningful and long-lasting improvements in jawline contour and was well tolerated in patients through 60 weeks. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03583359.

Surgical Management of Polymethylmethacrylate-Collagen Gel Complications in the Lower Eyelid: A Case Series.

BACKGROUND: As nonsurgical rejuvenation with fillers continues to grow in popularity, patients are increasingly interested in more durable results. Polymethylmethacrylate (PMMA)-collagen gel is unique among fillers in that the PMMA microspheres are not completely absorbed and phagocytosed by the body. This durability coupled with the biophysical properties of PMMA makes it a poor choice for periorbital rejuvenation, an unforgiving and highly complex anatomic area. METHODS: Between 2011 and 2018, 14 patients with PMMA granulomas in various facial areas self-referred to the senior author's practice. Of these patients, 11 were managed nonsurgically; however, all 3 patients who presented with granulomas in the infraorbital area required surgery to remove the filler and restore a natural aesthetic. RESULTS: The 3 patients with significant swelling and PMMA filler nodules in the infraorbital area with unacceptable cosmetic appearance were females between the ages of 50 and 55 years. Nonsurgical protocols were unsuccessful, and surgical removal was required. All subjects have been followed for a minimum of 2 years with no immediate- or long-term postoperative complications secondary to PMMA removal. Patients remain satisfied with the outcome of the surgery. CONCLUSIONS: Despite the evidence that the periorbital area is prone to adverse events when injected with particulate fillers, misguided enthusiasm for PMMA-collagen gel as a durable treatment continues to lead to unnecessary and severe complications in patients. The case studies presented here highlight that this product should not be introduced into the periorbital area. We also describe a surgical treatment approach for its removal if complications arise.

Skin Tightening With Hyperdilute CaHA: Dilution Practices and Practical Guidance for Clinical Practice.

BACKGROUND: Over the past several years, hyperdilute calcium hydroxylapatite (CaHA) has emerged as an effective modality for improving skin quality and managing laxity in the face, arms, hands, neck, décolletage, upper arms, abdomen, buttocks, and upper legs, as well as for treating cellulite and striae. Whereas undiluted CaHA is used to provide volume, hyperdilute CaHA is distributed across a much larger surface area in a more superficial plane to stimulate neocollagenesis and elastin formation over time. The absence of lymphocytic infiltrates and predominance of type 1 collagen in the tissue response to CaHA make hyperdilute CaHA a valuable tool for nonsurgical skin tightening. OBJECTIVES: The aim of this study was to provide practical step-by-step guidance on patient selection, dilution practices, and optimal injection technique to facilitate incorporation of the technique into clinical practice. METHODS: Over the course of 3 regional meetings in the United States, 12 expert physician injectors participated in live webinars as part of a continuing medical education program. RESULTS: The practical guidance in this manuscript is based upon the most frequently requested information by audience members and the information considered critical for success by the authors. CONCLUSIONS: The minimally invasive nature of filler injection results in little downtime, making this treatment particularly appealing. The recommendations presented are consistent with previously published consensus guidelines on hyperdilute CaHA but are intended to serve as "how-to" guidance based on the experience of expert injectors who have successfully treated the face and body.

Single-center, prospective comparison of calcium hydroxylapatite and Vycross-20L in midface rejuvenation: Efficacy and patient-perceived value.

BACKGROUND: Numerous fillers can be used for midface revolumization. While rheological data, physiochemical properties, and durability measured in clinical studies can inform selection, direct comparisons between equal volumes of different fillers are lacking. AIMS: To compare aesthetic improvement achieved with 3 cc of either calcium hydroxyapatite with integral lidocaine CaHA(+) or VYC-20L in the midface. PATIENTS/METHODS: In this prospective, single-center study, 17 patients with midface volume loss received 3 cc of either CaHA(+) or VYC-20L. Outcomes at post-treatment days 1, 7, 30, 90, 180, and 365 were measured by Subject and blinded Physician using the Global Aesthetic Improvement Scale (SGAIS and PGAIS). Cost per point improvement on SGAIS over time was determined. RESULTS: Outcomes were globally positive, with a large majority of subjects at least improved at all time points. A higher proportion of subjects were at least "very improved" in the CaHA(+) treatment group at each time point, a difference that reached significance at day 90 (100% vs 50%, P = .02), day 180 (89% vs 37.5%, P = .03), and day 360 (89% vs 37.5%, P = .03). For both SGAIS and PGAIS, only subjects within the VYC-20L cohort had "unaltered" appearance within 1 year. At 1 year, the average cost per point of SGAIS improvement for VYC-20 was approximately twice that of CaHA-20L. CONCLUSION: The results of this study indicate that CaHA(+) supports better, more durable outcomes than an equal volume of VYC-20L in the midface, providing a higher value to the patient.

An algorithmic approach to breast reconstruction using latissimus dorsi myocutaneous flaps.

BACKGROUND: Innovative surgical techniques developed by surgical oncologists have changed the landscape of mastectomy defects. Latissimus dorsi myocutaneous flap-based breast reconstruction provides a reliable foundation for breast reconstruction. The purpose of this study was to evaluate differential skin island designs with latissimus dorsi myocutaneous flap breast reconstruction, and to develop an algorithmic approach to breast reconstruction that is applicable to a broad spectrum of mastectomy defects. METHODS: In this study, the authors retrospectively reviewed data of patients who underwent latissimus dorsi myocutaneous flap reconstruction following unilateral or bilateral mastectomies between February of 2001 and April of 2005. Patients were selected to undergo reconstruction under the following circumstances: (1) previously irradiated tissue, (2) body mass index greater than 30, (3) current tobacco use, (4) previous abdominopelvic surgery, and (5) patient preference. Patients were divided into three groups based on defect present: intact inframammary fold with skin deficit, intact inframammary fold without skin deficit, and absent inframammary fold with or without skin deficit. Differential skin island design was customized to the presenting mastectomy defect to optimize results and minimize donor-site scaring. RESULTS: Fifty-four patients underwent 64 latissimus dorsi myocutaneous flap reconstructions. Aesthetic outcomes and donor-site scar placement differed between groups. CONCLUSIONS: The authors have developed an algorithmic approach to latissimus dorsi myocutaneous flap breast reconstruction. Through critical evaluation of mastectomy defects, reconstructive breast surgeons can tailor skin island orientation, minimize donor-site scarring, enhance cosmetic outcomes, and provide a durable and natural aesthetic outcome in breast reconstruction with the latissimus dorsi myocutaneous flap.

Contemporary management of pelvic fractures.

BACKGROUND: Pelvic fractures occur when there is high kinetic energy transfer to the patient such as would be expected in motor vehicle crashes, auto-pedestrian collisions, motorcycle crashes, falls, and crush injuries. High-force impact implies an increased risk for associated injuries to accompany the pelvic fracture, as well as significant mortality and morbidity risks. Choosing the optimum course of diagnosis and treatment for these patients can be challenging. The purpose of this review is to supply a contemporary view of the diagnosis and therapy of patients with this important group of injuries. METHODS: A comprehensive review of the medical literature, focusing on publications produced in the last 10 years, was undertaken. The principal sources were found in surgical, orthopedic, and radiographic journals. CONCLUSIONS: The central challenge for the clinician evaluating and managing a patient with a pelvic fracture is to determine the most immediate threat to life and control this threat. Treatment approaches will vary depending on whether the main threat arises from pelvic fracture hemorrhage, associated injuries, or both simultaneously. Functional outcomes in the long-term depend on the quality of the rigid fixation of the fracture, as well as associated pelvic neural and visceral injuries.

EGF receptor antagonism improves survival in a murine model of pancreatic adenocarcinoma.

INTRODUCTION: The purpose of this study was to determine whether inhibition of the epidermal growth factor receptor (EGFR) is a plausible therapeutic strategy in pancreatic cancer. METHODS: A human pancreatic cancer cell line (HPAC) was evaluated for the presence of EGFR with rtPCR and immunohistochemistry. Cells were grown in the presence of either 50 or 100 microM of erlotinib (EGFRI) for 72 hours and evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Eighty-six athymic nude/nude mice underwent orthotopic implantation of 10(7) HPAC cells and were blindly randomized into four groups: (1) Control; (2) Batimastat, a matrix metalloproteinase inhibitor (MMPI) at 400 ng/ml qod; (3) EGFRI at 100 mg/kg qd; and (4) MMPI and EGRRI (both). In vitro and in vivo effects of EGFRI with and without MMPI were compared. RESULTS: HPAC demonstrated high levels of expression of both the EGFR gene and the gene product. In vitro, both doses of EGFRI significantly reduced proliferation of HPAC at 48 (50 microM: 1.15 + 0.05 [st dev] versus 0.63 + 0.09 abs, P < 0.001) and 72 h (50 microM: 1.48 +/- 0.09 versus 0.73 +/- 0.05 abs, P < 0.001, paired Student's t-test). In vivo, each treatment group demonstrated a significant survival advantage (P = 0.0002 group 2, P = 0.0001 group 3, P = 0.012 group 4, log rank test) over controls. Mice treated with EGFRI showed reduced tumor implantation, size, weight, metastatic potential, and jaundice as compared to controls and MMPI-treated mice (all P < 0.05, Fisher's exact test). CONCLUSION: EGF receptor antagonism is not only a plausible therapy for treatment of ductal adenocarcinoma of the pancreas, but is also superior to matrix metalloproteinase inhibition alone or in combination.

Stage does not predict survival after resection of hilar cholangiocarcinomas promoting an aggressive operative approach.

INTRODUCTION: Staging systems have been developed to predict survival after resection of hilar cholangiocarcinoma. Notably, they have not been validated nor compared for relative predictive ability. METHODS: Forty-two patients underwent resection of hilar cholangiocarcinoma and have been followed through a prospectively collected database. The tumors were staged using the Bismuth-Corlette, Blumgart, and American Joint Committee on Cancer (AJCC) systems, and a significant relationship with survival was sought. RESULTS: Eleven patients were treated by extrahepatic biliary resection alone, while 31 required extrahepatic biliary resections with in-continuity hepatic resections. All patients underwent adjuvant therapy. To date, 30 patients have died with a mean survival time of 30 months +/- 35.0 (SD). Twelve patients are alive with a mean survival of 90 months +/- 61.8. By regression analysis, none of the staging systems had a significant relationship with survival (Bismuth: P = .64; Blumgart: P = .66; AJCC: P = .31). CONCLUSIONS: Most patients with hilar cholangiocarcinoma require in-continuity hepatic resections. Survival after resection promotes an aggressive approach, with cure in as many as 30%. Staging systems should not impact the decision to operate or postoperative management, as all tumors should be aggressively resected and all patients should receive adjuvant treatment.

Full-term gestation and transvaginal delivery after wide resection of an abdominal desmoid tumor during pregnancy.

A 29-year-old female was diagnosed with a symptomatic, extra-abdominal desmoid tumor during the first trimester of pregnancy. Computerized tomography (CT) and transabdominal ultrasound (US) noted a mass within the left rectus sheath measuring up to 15 cm in greatest diameter, with mild compression of the uterus. Preoperative diagnosis was confirmed by core-needle biopsy of the lesion. At 20-weeks gestation, wide local resection of the tumor with disease-free margins, as well as abdominal wall reconstruction with polytetrafluoroethylene (PTFE) mesh was successfully undertaken. Histological examination of the tumor ex vivo confirmed that the lesion was a desmoid tumor consisting of spindle cells with dense infiltrating collagenous fibers. Subsequent to her resection, the patient completed a full-term pregnancy without complication, and proceeded with a complication-free transvaginal delivery at 39 weeks. This case illustrates the probable contribution of estrogens towards desmoid tumor development, the durability of abdominal wall reconstruction when subjected to the extraordinary strain of both a gravid uterus and labor, as well as the safety and efficacy of aggressive surgical therapy during pregnancy.

In-continuity hepatic resection for advanced hilar cholangiocarcinoma.

BACKGROUND: The purpose of this study was to examine outcomes of patients undergoing concomitant hepatectomy and bile duct excision for advanced Klatskin tumors. METHODS: Thirty-one patients, 16 men and 15 women, with an average age of 64 years, underwent concomitant biliary and hepatic resections for Klatskin tumors. Outcomes, including complications and survival, are reported. RESULTS: Fifteen patients had postoperative courses free of complications. Sixteen patients experienced a total of 50 complications; 13 patients experienced 1 or more major complications (including hemorrhage [n = 1], pneumonia [n = 5], intra-abdominal abscess [n = 8], hepatic failure [n = 3], and myocardial infarction [n = 2]). Five patients died perioperatively, 1 from adult respiratory distress syndrome and 4 from multisystem organ failure precipitated by hepatic failure. One-, 3-, and 5-year survival after resection was 69%, 33%, and 26%, respectively. American Joint Committee on Cancer stage and margin status did not impact long-term survival after resection. CONCLUSIONS: Concomitant hepatic and biliary resections for Klatskin tumors carry relatively high risk but offer hope for long-term survival. This study supports in-continuity hepatectomy and extrahepatic biliary resection for advanced Klatskin tumors even when microscopically negative margins cannot be obtained.

Differential expression of the Tie-2 receptor and its ligands in human pancreatic tumors.

BACKGROUND: Derangements in the balance of the Tie-2 receptor ligands, angiopoietin-1 and angiopoietin-2 (Ang-1 and Ang-2), have been implicated in the growth and differentiation of several human tumors. To assess the potential role of angiogenesis factors in pancreatic tumorigenesis, we confirmed previously observed oligonucleotide-based microarray data by analyzing their expression in pancreatic tumors using semiquantitative reverse transcription polymerase chain reaction and immunohistochemistry. STUDY DESIGN: RNA harvested from tissue samples obtained from patients with normal pancreata, adenocarcinoma of the pancreas, and neuroendocrine tumors of the pancreas (nine each) was grouped by tissue type, pooled, and hybridized to a cDNA microarray and global gene expression patterns were determined. Semiquantitative reverse transcription polymerase chain reaction was applied to individual pool components to specifically determine expression of Tie-2, Ang-1, and Ang-2. A separate set of tumors and matched normal pancreas were then stained for expression of Ang-2 protein using immunohistochemistry. RESULTS: Microarray data showed that Ang-2 was upregulated in neuroendocrine tumors ( approximately 8 times more than normal) and adenocarcinoma of the pancreas ( approximately 5 times more than normal) although Ang-1 and Tie-2 were not differentially expressed. Reverse transcription polymerase chain reaction confirmed these findings showing strong Ang-2 expression in nine of nine neuroendocrine tumors, eight of nine adenocarcinoma of the pancreas, and weak expression in two of nine normal pancreata. Immunohistochemistry showed tumor-specific staining of Ang-2 in 10 of 15 matched adenocarcinoma of the pancreas (67%) and 6 of 8 neuroendocrine tumors (75%). CONCLUSIONS: Although Tie-2 and Ang-1 are not differentially expressed in pancreatic tumors, Ang-2 gene and gene product are overexpressed, suggesting a significant role for Ang-2 in pancreatic tumorigenesis. Differential expression of Ang-2 in human tumors may be useful as a diagnostic and therapeutic target.

Identification of molecular markers specific for pancreatic neuroendocrine tumors by genetic profiling of core biopsies.

BACKGROUND: There is a paucity of known molecular markers that distinguish pancreatic neuroendocrine tumors from other pancreatic tumor types. We hypothesized that novel markers for pancreatic neuroendocrine tumors could be identified with molecular fingerprinting of pooled RNA samples from core biopsies. METHODS: Total RNA was harvested from nine core biopsies of normal pancreas, pancreatitis, pancreatic adenocarcinoma, pancreatic adenocarcinoma metastases, and pancreatic neuroendocrine tumors. RNA from each group of samples was pooled and hybridized to an oligonucleotide-based microarray. Four genes (ANG2, NPDC1, ELOVL4, and CALCR) were selected for further investigation by reverse transcriptase polymerase chain reaction from the top 20 highest expressed genes, on the basis of potential as novel markers. RESULTS: Neuroendocrine tumors were most unique from normal pancreas. Pancreatitis, pancreatic adenocarcinoma, and metastases are more closely related to each other and to normal pancreas. ANG2 was overexpressed in 89% of neuroendocrine tumors, compared with 22% of normal pancreas, making it the best potential molecular marker or therapeutic target of the four genes selected for analysis. CONCLUSION: We have identified a specific set of molecular markers for pancreatic neuroendocrine tumors distinct from pancreatitis and pancreatic adenocarcinoma. These novel markers may prove useful as molecular markers or therapeutic targets unique to pancreatic neuroendocrine tumors.

Early results of laparoscopic Heller myotomy do not necessarily predict long-term outcome.

BACKGROUND: We sought to evaluate how patients' symptoms evolve after laparoscopic Heller myotomy. METHODS: Before and after laparoscopic Heller myotomy, 88 patients graded dysphagia and heartburn on a Likert scale (0 = none; 5 = severe). Patients graded outcomes as excellent, good, fair, or poor. Outcomes were compared in the same patients at 1 and 3 years of follow-up. RESULTS: At early follow-up (10.6 +/- 7.8 months) significant reductions were noted in dysphagia (11% versus 100%), dysphagia scores (0.6 +/- 1.1 versus 4.7 +/- 0.7), heartburn (31% versus 72%), and heartburn scores (1.2 +/- 1.6 versus 2.7 +/- 1.9). By late follow-up (37.6 months +/- 18.0) these values increased (47%, 1.9 +/- 1.7, 48%, 1.8 +/- 1.5, respectively) but remained significantly reduced compared with before operation. Excellent/good outcomes at early and late follow-up were 89% and 85%, respectively (P = not significant). CONCLUSIONS: Laparoscopic Heller myotomy is highly effective at palliating the symptoms of achalasia. With time, symptoms may recur owing to esophageal dysmotility, mandating continued surveillance.

Surgical management of early-stage pancreatic cancer.

BACKGROUND: Pancreatic cancer remains a difficult disease to treat. Diagnosis at an early stage may allow curative treatment with resection. In the past, the mortality associated with surgical treatment of pancreatic carcinoma was prohibitive but mortality associated with resection is now commensurate with all other major oncologic resections. Thus, the focus of surgical management has shifted to address several issues: the diagnosis and evaluation of patients with suspected pancreatic cancer, the role of preoperative endobiliary stenting, the role of laparoscopy, the extent of resection, the role of adjuvant and neoadjuvant treatment, and the role of specialized centers in treating the disease. METHODS: The current literature is reviewed to address these issues and help guide physicians who first encounter patients with suspected pancreatic cancer as well as surgeons who ultimately resect them. Practical evidence-based information to guide the decision-making process is provided. RESULTS: Surgical morbidity and mortality have achieved parity with other types of major oncologic resection, and a distinct survival advantage is possible when such therapy is applied early in the disease stage. Issues regarding the use of stents, extent of resection, and pre- vs post-operative chemoradiation therapy are becoming clearer as our collective experience broadens. CONCLUSIONS: Surgical treatment of pancreatic cancer should be aggressively pursued given the clearly established survival advantage and relief of symptoms achieved when it is applied appropriately.

Defining the role of the epidermal growth factor receptor in pancreatic cancer grown in vitro.

BACKGROUND: The purpose of this study was to determine the effect of a novel epidermal growth factor (EGF) receptor tyrosine kinase inhibitor, Erlotinib, on pancreatic cancer cell lines of varying differentiation in vitro. METHODS: Six pancreatic cancer cell lines (AsPc-1, CAPAN-1, HPAC, HPAF-II, Mia PaCa-2, PANC-1) were grown in the presence of 50 microM or 100 microM of Erlotinib or recombinant EGF. Cell proliferation was determined using the MTT assay over 72 hours. The EGF receptor gene and protein expression were determined by polymerase chain reaction and immunohistochemistry respectively. RESULTS: All cell lines demonstrated the presence of the EGF receptor gene and its gene product. Five of six cell lines showed significant growth inhibition at 72 hours compared with controls (P <0.05). The EGF augmentation increased proliferation of each cell line but this increase was only significant in AsPc-1. CONCLUSIONS: Inhibition of EGF receptor is a valid therapeutic strategy in pancreatic cancer.

Post-shunt resource consumption favors small-diameter prosthetic H-graft portacaval shunt over TIPS for patients with poor hepatic reserve.

OBJECTIVE: To define the role of surgical shunting for patients with poor hepatic reserve (Child's class C) in the era of TIPS. SUMMARY BACKGROUND DATA: Most physicians prefer TIPS to surgical shunting for patients with poor hepatic reserve because of anticipated poor long-term survival. METHODS: Sixty-two patients of Child's class C with bleeding varices not amenable to endoscopic sclerotherapy or banding were prospectively randomized to undergo TIPS or 8-mm prosthetic H-graft portacaval shunt (HGPCS) from 1993 to 1999. Resource consumption and survival after shunting were determined. RESULTS: Twenty-nine patients underwent TIPS and 33 underwent HGPCS. After HGPCS, survival at 3 years was favorable but not statistically superior. TIPS was more often associated with shunt stenoses/occlusions, recurrent hemorrhage, shunt revisions, and shunt failure. Long-term follow-up documented that after HGPCS, patients required fewer hospital and ICU days and fewer units of RBCs transfused. After HGPCS, cost of care was less, as was the median cost of care per day of survival. CONCLUSIONS: For Child's class C patients undergoing HGPCS or TIPS, long-term survival is similar, though favoring HGPCS. Similarly, measures of resource consumption and cost of care following hospital discharge favor HGPCS. HGPCS should be preferentially applied for acceptable patients without access to convenient capable post-shunt care or without definitive plans for imminent transplantation.