Impact of octreotide long-acting release on tumour growth control as a first-line treatment in neuroendocrine tumours of pancreatic origin.

BACKGROUND: Somatostatin analogues (SSA) are widely used in the treatment of patients with functioning and non-functioning neuroendocrine tumours (NET). The aim of our investigation was to evaluate the antiproliferative effect of SSA in patients with pancreatic NET. METHODS: We retrospectively analysed records of 43 patients with pancreatic NET treated at our clinic with octreotide long-lasting release as a first-line therapy. The aim of our study was to investigate the overall best response according to the RECIST criteria, overall best response defined as disease control rate (SD+PR), response and disease control rate at 12 months, and time to tumour progression (TTP). RESULTS: The mean age (± SD) of the patients (16 female/27 male) at initial diagnosis was 54.7 ± 11.86 years. At the start of therapy, 39 of 43 patients were classified as stage IV according to ENETS-TNM. Tumours were graded, based on MiB-1/Ki67 staining, as G1 (n = 8), G2 (n = 30) or unknown (n = 5). The octreoscan was positive in 37 patients, negative in 2 and unknown in 4 cases. Nineteen patients had functioning tumours, 24 patients had non-functioning tumours. Median overall survival was 98 months, and median TTP was 13 months. Analysis of grading showed a statistically significant influence on TTP when comparing the median TTP for Ki67 >10% with Ki67 <5% (p = 0.009) and Ki67 5-10% (p = 0.036). CONCLUSION: SSA may be considered as a first-line treatment for antiproliferative purposes in metastatic NET of the pancreas. Patients with a proliferation index <10% displayed a more durable response compared to those with a higher proliferation index.

Assessment and clinical implications of RANK/RANKL/OPG pathway as markers of bone tumor progression in patients with NET harboring bone metastases.

INTRODUCTION: The impact on the survival of bone metastases (BM) in patients with neuroendocrine tumor (NET) is a matter of debate. BM have a key role in causing symptoms and in decreasing patients' quality of life. Although the mechanisms of the development of BM are not completely clear, it is now well understood that the Receptor Activator of Nuclear factor Kappa-B-/Ligand (RANK/RANKL)/osteoprotegerin (OPG) pathway plays a relevant role. AIM: To characterize the RANK/RANKL/OPG pathway in patients affected with NET. PATIENTS AND METHODS: Two cohorts of 15 patients each were enrolled in the study; one cohort was affected with NET without BM and the second cohort was affected with NET with BM. The serum RANK/RANKL/OPG pathway was assessed in both the groups. RESULTS: Serum OPG levels and RANKL/OPG ratio were lower and higher, respectively, in NET patients harboring BM than in those without BM. During the ROC analysis, a cut-off value of 1071 pg/ml for OPG and 0.62 for RANKL/OPG ratio were able to significantly distinguish between the two groups. CONCLUSIONS: This study indicates that RANK/RANKL/OPG pathway is imbalanced in patients with NET harboring BM. Specific alterations of this pathway could predict an early development of BM.

A matter of the heart: myocardial metastases in neuroendocrine tumors.

The aim of the present study was to evaluate frequency, clinical spectrum, and treatment of myocardial metastases in patients with histologically proven neuroendocrine tumors by analysis of our database and literature review. The literature on cardiac metastases in patients with neuroendocrine tumors published from 1973 to the present was reviewed for age, sex, primary tumor localization, metastases, symptoms, complications, treatment, diagnostic methods, and histology. Patient records from our institution were analyzed retrospectively for cardiac metastases detected by any diagnostic means and detailed patient histories are given. 4 patients with myocardial metastases could be identified in our database (n=550) while literature review identified 41 published cases. Mean age at initial diagnosis was 57.5 years (females=13, males=28), primary tumor localizations were foregut (n=7), midgut (n=28), hindgut (n=1), or unknown (n=3). Carcinoid syndrome was reported for 28 patients. Cardiac involvement was right-ventricular only (n=10), left-ventricular only (n=11), or biventricular (n=10). Diagnosis was obtained by echocardiography (n=21), CT/MRI (n=12) and other methods (n=9), or by autopsy (n=9). We describe visualization of cardiac metastases by (68)Ga-DOTATOC-PET/CT for the first time. Clinical presentation ranged from asymptomatic patients to cardiac arrest. Follow-up times ranged from <1 month up to 12 years. Clinicians treating patients with neuroendocrine tumors should be aware of the heart as a possible site of metastatic disease. Echocardiography and MRI are the methods of choice for follow-up, while PET/CT might contribute to earlier and more frequent detection. Management of cardiac metastases requires close cooperation between specialists of internal medicine, nuclear medicine, and cardiac surgery.

Occult metastatic intestinal adenocarcinoma resulting in pathological fracture of the proximal humerus.

Intestinal adenocarcinomas are rare but have been described in the literature. The present case is unusual in both its clinical presentation and in the distribution of metastatic lesions. The sequestrum formation and pathological fracture present are most commonly associated with osteomyelitis in horses and the details of the case highlight the need for differential diagnosis in these particular circumstances and of which clinicians should be aware.

Gastric neuroendocrine neoplasias: manifestations and comparative outcomes.

Although gastric neuroendocrine neoplasias (gNEN) are an orphan disease, their incidence is rising. The heterogeneous clinical course powers the ongoing discussion of the most appropriate classification system and management. Prognostic relevance of proposed classifications was retrospectively analysed in 142 patients from a single tertiary referral centre. Baseline, management and survival data were acquired for statistical analyses. The distribution according to the clinicopathological typification was gNEN-1 (n = 86/60.6%), gNEN-2 (n = 7/4.9%), gNEN-3 (n = 24/16.9%) and gNEN-4 (n = 25/17.6%), while hypergastrinemia-associated gNEN-1 and -2 were all low-grade tumours (NET-G1/2), formerly termed sporadic gNEN-3 could be subdivided into gNEN-3 with grade 1 or 2 and gNEN-4 with grade 3 (NEC-G3). During follow-up 36 patients died (25%). The mean overall survival (OS) of all gNEN was 14.2 years. The OS differed statistically significant across all subgroups with either classification system. According to UICC 2017 TNM classification, OS differed for early and advanced stages, while WHO grading indicated poorer prognosis for NEC-G3. Cox regression analysis confirmed the independent prognostic validity of either classification system for survival. Particularly careful analysis of the clinical course of gNEN-1 (ECLomas, gastric carcinoids) confirmed their mostly benign, but recurrent and extremely slowly progressive behaviour with low risk of metastasis (7%) and an efficient long-term control by repetitive endoscopic procedures. Our study provides evidence for the validity of current classifications focusing on typing, grading and staging. These are crucial tools for risk stratification, especially to differentiate gNEN-1 as well as sporadic gNET and gNEC (gNEN-3 vs -4).

Experimental evaluation of absorbable copolymer staples for hysterectomy.

Absorbable copolymer staples of three different variants were tested for retention of tensile strength after implantation into the peritoneal cavity of rats. One type maintained tensile strength for two weeks, but then lost it rapidly over the next week. The same three staple compounds were further compared after use for vaginal vault closure during ovariohysterectomy in adult sheep. In all ewes the absorbable staples were effective in providing a stable vaginal cuff closure. The postoperative tissue reaction was minimal. The goal of developing an absorbable staple that would degrade rapidly without compromising wound stability was achieved.

Transendoscopic electrosurgery for epiglottal entrapment in the horse.

Monopolar electrosurgical cutting was used to correct epiglottal entrapment in 5 horses. The operations were carried out in the conscious animal, using topical anesthesia. The procedure required the use of a coagulation electrode designed specifically for electrosurgery, introduced through the instrument channel of a fiberoptic endoscope. The results were satisfactory and serious complications were not encountered. In 2 horses, excessive submucosal swelling developed at the site of the surgical wound, and the tumefaction took several weeks to subside in one of these horses. In both horses, the long-term outcome was a minor degree of reentrapment. The main advantages of this technique, compared with other corrective procedures, related to the avoidance of the need for general anesthesia and laryngotomy, allowing racehorses to be treated without any major interruption in their training schedules. The surgery was simple, rapid, and bloodless, and was not followed by any dorsal displacement of the soft palate. It was suggested that transendoscopic electrosurgery has potential for use in the treatment of a number of other diseases of the respiratory tract and other systems, both in the horse and in other species. In the equine respiratory tract, the technique might usefully be applied to the treatment of guttural pouch tympany, soft palate cysts, nasopharyngeal polyps, choanal atresia, subepiglottic cysts, and tracheal granulomata. A review of 21 cases of epiglottal entrapment in horses revealed no evidence to support the suggestion that dorsal displacement of the soft palate is a cause of epiglottal entrapment or vice-versa.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic ultrasonography for evaluation of cryptorchidism in horses.

The location and size of 11 retained testes were accurately determined ultrasonographically. There was 100% correlation between the location of the testis determined by ultrasound vs that determined by surgery. Testicular size determined presurgically in all cases closely approximated the actual size obtained by gross measurement of the excised testis. The cryptorchid testicular echotexture was less dense than that of the normal descended testicles, but was easily identified. Ultrasonographic evaluations were completed by use of an ultrasound base unit with attached 5-MHz transrectal transducer. Rectal scans were started at the pelvic brim and continued in a to-and-fro pattern between the midline and the lateral abdominal wall. When the testis was located, the image was froze to allow measurement. All testicular locations were ascertained ultrasonographically either by rectal or external inguinal scans.

Treatment of lacerated flexor tendons in a dairy cow, using specialized farriery.

A heel extension shoe was used as an adjunct to primary tendon repair in a dairy cow. A shoe was placed on the foot for 6 weeks after the foot had been immobilized for 6 weeks in a cast. The shoe was continuous across the toes to provide even support for both claws and was nailed and clinched in the same way a shoe is applied to a horse's hoof. Special adaptations included drilling nail holes closer to the rim of the shoe to accommodate the narrower bovine hoof wall. The cow was permitted controlled exercise for gradual remodeling and strengthening of the tendon repair. When the shoe was removed 12 weeks after surgery, the metatarsophalangeal and distal interphalangeal joints were in normal posture. We consider application of a therapeutic shoe to be an important adjunct to surgical repair of major tendon injuries in adult cattle.

Pedal bone rotation as a prognostic sign in laminitis of horses.

We reviewed 91 cases of laminitis in horses admitted to the Michigan State University Veterinary Clinical Center between Jan 1, 1973 and Dec. 30, 1978. From information in the case records and from the results of a telephone questionnaire, cases were classified into 4 categories on the basis of return to athletic function. The degree of pedal bone rotation was inversely correlated with return to athletic performance. Horses with less than 5.5 degrees rotation returned to former athletic function, whereas horses with more than 11.5 degrees rotation lost their use as performance animals. Ponies had significantly more pedal bone rotation, when compared with horses.

TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study.

BACKGROUND: Both the European Neuroendocrine Tumor Society (ENETS) and the International Union for Cancer Control/American Joint Cancer Committee/World Health Organization (UICC/AJCC/WHO) have proposed TNM staging systems for pancreatic neuroendocrine neoplasms. This study aims to identify the most accurate and useful TNM system for pancreatic neuroendocrine neoplasms. METHODS: The study included 1072 patients who had undergone previous surgery for their cancer and for which at least 2 years of follow-up from 1990 to 2007 was available. Data on 28 variables were collected, and the performance of the two TNM staging systems was compared by Cox regression analysis and multivariable analyses. All statistical tests were two-sided. RESULTS: Differences in distribution of sex and age were observed for the ENETS TNM staging system. At Cox regression analysis, only the ENETS TNM staging system perfectly allocated patients into four statistically significantly different and equally populated risk groups (with stage I as the reference; stage II hazard ratio [HR] of death = 16.23, 95% confidence interval [CI] = 2.14 to 123, P = .007; stage III HR of death = 51.81, 95% CI = 7.11 to 377, P < .001; and stage IV HR of death = 160, 95% CI = 22.30 to 1143, P < .001). However, the UICC/AJCC/WHO 2010 TNM staging system compressed the disease into three differently populated classes, with most patients in stage I, and with the patients being equally distributed into stages II-III (statistically similar) and IV (with stage I as the reference; stage II HR of death = 9.57, 95% CI = 4.62 to 19.88, P < .001; stage III HR of death = 9.32, 95% CI = 3.69 to 23.53, P = .94; and stage IV HR of death = 30.84, 95% CI = 15.62 to 60.87, P < .001). Multivariable modeling indicated curative surgery, TNM staging, and grading were effective predictors of death, and grading was the second most effective independent predictor of survival in the absence of staging information. Though both TNM staging systems were independent predictors of survival, the UICC/AJCC/WHO 2010 TNM stages showed very large 95% confidence intervals for each stage, indicating an inaccurate predictive ability. CONCLUSION: Our data suggest the ENETS TNM staging system is superior to the UICC/AJCC/WHO 2010 TNM staging system and supports its use in clinical practice.

Strength characteristics and failure modes of locking-loop and three-loop pulley suture patterns in equine tendons.

Size 3-0 polydioxanone was used as a single strand, single braid (3 strands), or double braid (6 strands) to create six suture material-pattern combinations for equine tenorrhaphy: single-strand locking loop, single-braid locking loop, double-braid locking loop, single-strand three-loop pulley, single-braid three-loop pulley, and double-braid three-loop pulley. Maximum load to failure for the single-strand locking loop (46.1 +/- 2.9 newtons [N]) was less than for all other sutures (range, 103-155 N). The load required to form a 2 mm gap between tendon ends was greater for the single-braid three-loop pulley (66.7 +/- 6.9 N) and double-braid three-loop pulley (85.4 +/- 17.7 N) than any other sutures. The load required to produce a 10 mm gap was least for the single-strand locking loop (34.3 +/- 3.9 N) and greatest for the double-braid three-loop pulley (131.5 +/- 27.5 N). Gap between tendon ends at maximum load was greater for the single-braid (18.1 +/- 0.9 mm) and double-braid (19.2 +/- 2.2 mm) locking loops than for any other sutures. Suture material broke in 53% of the locking-loop tests but in only 17% of the three-loop pulley tests. Tendon matrix disruption accounted for 43% of the locking-loop failures and 77% of the three-loop pulley failures. The three-loop pulley pattern provided more support, less tendon distraction, and less tendon matrix constriction and distortion than the locking-loop pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthrographic observations of the equine distal interphalangeal joint (Articulationes interphalangeae distalis manus) and navicular bursa (Bursa podotrochlearis).

Twenty cadaver limbs of adult horses were examined by arthrographic examination of the distal interphalangeal joint. The joint capsule and space is described. Comparison is made with existing descriptions.

In vitro effects of epidermal growth factor or insulin-like growth factor on tenoblast migration on absorbable suture material.

OBJECTIVE: To determine the effects of epidermal growth factor (EGF) or insulin-like growth factor (IGF) on tenoblast migration on absorbable suture material using an in vitro model. STUDY DESIGN: An in vitro evaluation of tenoblast migration. ANIMAL OR SAMPLE POPULATION: Segments of the long digital flexor tendon were obtained from Cobb chickens (9-11 weeks old) immediately after the birds were euthanatized. METHODS: Tissue culture explants of tendons containing absorbable suture material were treated with either EGF or IGF. Tenoblast migration was assessed daily using an inverted microscope equipped with bright field and phase optics. Tenoblast migration was assessed according to the following criteria: time of first cell appearance, percent of explant interfaces producing cells, migration distance, and terminal migration index at 120 and 168 hours. RESULTS: EGF had a stimulatory effect on tenoblast migration for cells originating from the endotenon interfaces. No significant effect was noted on migration distance for cells originating from epitenon interfaces. A stimulatory effect on the percentage of interfaces producing cells and a significant decrease in time of first cell appearance were also observed after EGF treatment. IGF-stimulated cell migration distance for epitenon interfaces but this stimulatory effect did not occur at a higher concentration. IGF was inhibitory to percent of epitenon and endotenon interfaces producing cells but decreased time of first cell appearance at low concentration. CONCLUSIONS: Using an in vitro model, EGF had a stimulatory effect on tenoblast migration. IGF was stimulatory at low concentration levels but inhibitory at a higher concentration. Increased migration distance was observed for endotenon interfaces after EGF treatment and for epitenon interfaces after IGF treatment. CLINICAL RELEVANCE: EGF or IGF might enhance tendon repair if they could be delivered to the repair site. Incorporation of EGF or IGF into suture material would allow slow release and prolonged exposure of migrating tenoblasts to growth factors.

Moderating effects of perceived racism on John Henryism and blood pressure reactivity in Black female college students.

BACKGROUND: Relative to other ethnic groups in the United States Blacks have disproportionately higher rates of hypertension. Research suggest that perceived racism might moderate the relation between such Pearson variables as John Henryism and cardiac/vascular functioning. PURPOSE: This study examined the possible moderating influence of perceived racism on the John Henryism reactivity relation in a sample of 117 Black female college students (M age = 26.10 years, SD = 8.83). METHODS: Blood pressure was measured before and during a speaking task. John Henryism and perceived racism were assessed via self-report. RESULTS: Hierarchial regression analyses revealed that John Henryism was inversely related to systolic blood pressure reactivity (p = .007). These analyses also indicated that John Henryism and perceived racism interacted to predict both systolic (p = .007) and diastolic blood pressure reactivity (p = .0005). Follow-up regression analyses indicated that John Henryism was unrelated to systolic and diastolic blood pressure reactivity for women high in perceived racism (ps > .62) and was inversely associated with systolic and diastolic blood pressure reactivity for women low in perceived racism (ps < .01). CONCLUSIONS: The findings highlight the importance of examining the potential moderating effects of ethnically relevant situation factors when exploring the relation of John Henryism to blood pressure reactivity.

Development of malignant hyperthermia obscured by cardiopulmonary bypass.

An episode of malignant hyperthermia occurring in a two-year-old child undergoing cardiac surgery is reported. The coincidental usage of hypothermic cardiopulmonary bypass obscured the classical presenting signs and symptoms of the syndrome. Once the clinical diagnosis was confirmed, rapid reversal was achieved with the administration of dantrolene sodium.