Drug Coated Balloons for Dysfunctional Haemodialysis Venous Access: A Patient Level Meta-Analysis of Randomised Controlled Trials.

OBJECTIVE: To perform an individual patient data level meta-analysis of randomised controlled trials comparing drug coated balloon angioplasty (DCB) against conventional percutaneous transluminal angioplasty (PTA) in the treatment of dysfunctional haemodialysis venous access. METHODS: A search was conducted from inception to 13 November 2020. Kaplan-Meier curves comparing DCB with PTA by target lesion primary patency (TLPP) and access circuit primary patency (ACPP) were graphically reconstructed to retrieve patient level data. One stage meta-analyses with Cox models with random effects shared frailties were conducted to determine hazard ratios (HRs). Dynamic restricted mean survival times (RMST) were conducted in view of violation of the proportional hazards assumption. Conventional two stage meta-analyses and network meta-analyses under random effects Frequentist models were conducted to determine overall and comparative outcomes of paclitaxel concentrations used. Where outliers were consistently detected through outlier and influence analyses, sensitivity analyses excluding those studies were conducted. RESULTS: Among 10 RCTs (1 207 patients), HRs across all models favoured DCB (one stage shared frailty HR 0.62, 95% CI 0.53 - 0.73, p < .001; two stage random effects HR 0.60, 95% CI 0.42 - 0.86, p = .018, I2 = 65%) for TLPP. Evidence of time varying effects (p = .005) was found. TLPP RMST was + 3.54 months (25.0%) longer in DCB treated patients compared with PTA (p = .001) at three years. TLPP at six months, one year, and two years was 75.3% vs. 58.1%, 51.1% vs. 37.1%, and 31.4% vs. 26.0% for DCB and PTA, respectively. The P-Scores within the Frequentist network meta-analysis suggest that higher concentrations of paclitaxel were associated with better TLPP and ACPP. Among six RCTs (854 patients), the one stage model favoured DCB (shared frailty HR 0.72, 95% CI 0.60 - 0.87, p < .001) for ACPP. Conversely, the two stage random effects model demonstrated no significant difference (HR 0.76, 95% CI 0.35 - 1.67, p = .41, I2 = 81%). Sensitivity analysis excluding outliers significantly favoured DCB (HR 0.61, 95% CI 0.41 - 0.91, p = .027, I2 = 62%). CONCLUSION: Overall evidence suggests that DCB is favoured over PTA in TLPP and ACPP.

Percutaneous Endovascular Treatment to Salvage Non-Maturing Arteriovenous Fistulas in a Multiethnic Asian Population.

INTRODUCTION: An arteriovenous fistula (AVF) is the preferred method for haemodialysis in patients with end-stage renal failure. Previous studies have shown value in attempting percutaneous transluminal angioplasty (PTA) to salvage AVFs that fail to mature, but they are relatively small in size and mainly reported in Western populations. We reviewed our data of PTA in non-maturing AVFs to establish whether this technique is translatable to our local multiethnic population. MATERIALS AND METHODS: We retrospectively reviewed the medical records and procedural images of 105 patients who had PTA for non-maturing AVFs performed at our department from January 2008 to January 2011. Technical success was defined as ≤30% residual stenosis after angioplasty. Clinical success was defined as at least 1 successful haemodialysis session within 4 weeks after PTA. RESULTS: All 105 patients underwent angioplasty for at least 1 haemodynamically significant stenosis. Six (5.7%) had additional embolisation of accessory veins. Technical success was achieved in 95.2% of cases. The clinical success rate was 76.2%. Primary patency rates at 3, 6 and 12 months were 83%, 45% and 28%, respectively. Secondary patency rates at 3, 6 and 12 months were 90%, 79% and 70%, respectively. The minor complication rate was 18.1%. No major complications were encountered. An average of 1.7 interventions per access-year was required to maintain AVF patency. Patients with a preoperative vein size >2.0 mm and age <55 years were more likely to achieve clinical success, although not statistically significant. CONCLUSION: PTA is a viable option to help salvage non-maturing AVFs in a multiethnic Asian population.

A thymic neuroendocrine tumour in a young female: a rare cause of relapsing and remitting Cushing's syndrome.

UNLABELLED: We present a case of a young female patient with a rare cause of relapsing and remitting Cushing's syndrome due to ectopic ACTH secretion from a thymic neuroendocrine tumour. A 34-year-old female presented with a constellation of symptoms of Cushing's syndrome, including facial swelling, muscle weakness and cognitive impairment. We use the terms 'relapsing and remitting' in this case report, given the unpredictable time course of symptoms, which led to a delay of 2 years before the correct diagnosis of hypercortisolaemia. Diagnostic workup confirmed ectopic ACTH secretion, and a thymic mass was seen on mediastinal imaging. The patient subsequently underwent thymectomy with complete resolution of her symptoms. Several case series have documented the association of Cushing's syndrome with thymic neuroendocrine tumours (NETs), although to our knowledge there are a few published cases of patients with relapsing and remitting symptoms. This case is also notable for the absence of features of the MEN-1 syndrome, along with the female gender of our patient and her history of non-smoking. LEARNING POINTS: Ectopic corticotrophin (ACTH) secretion should always be considered in the diagnostic workup of young patients with Cushing's syndromeThere is a small but growing body of literature describing the correlation between ectopic ACTH secretion and thymic neuroendocrine tumours (NETs)The possibility of a MEN-1 syndrome should be considered in all patients with thymic NETs, and we note the observational association with male gender and cigarette smoking in this cohortAn exception to these associations is the finding of relatively high incidence of thymic NETs among female non-smoking MEN-1 patients in the Japanese compared with Western populationsThe relapsing and remitting course of our patient's symptoms is noteworthy, given the paucity of this finding among other published cases.

Post-radioembolization yttrium-90 PET/CT - part 1: diagnostic reporting.

BACKGROUND: Yttrium-90 (90Y) positron emission tomography with integrated computed tomography (PET/CT) represents a technological leap from 90Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) by coincidence imaging of low abundance internal pair production. Encouraged by favorable early experiences, we implemented post-radioembolization 90Y PET/CT as an adjunct to 90Y bremsstrahlung SPECT/CT in diagnostic reporting. METHODS: This is a retrospective review of all paired 90Y PET/CT and 90Y bremsstrahlung SPECT/CT scans over a 1-year period. We compared image resolution, ability to confirm technical success, detection of non-target activity, and providing conclusive information about 90Y activity within targeted tumor vascular thrombosis. 90Y resin microspheres were used. 90Y PET/CT was performed on a conventional time-of-flight lutetium-yttrium-oxyorthosilicate scanner with minor modifications to acquisition and reconstruction parameters. Specific findings on 90Y PET/CT were corroborated by 90Y bremsstrahlung SPECT/CT, 99mTc macroaggregated albumin SPECT/CT, follow-up diagnostic imaging or review of clinical records. RESULTS: Diagnostic reporting recommendations were developed from our collective experience across 44 paired scans. Emphasis on the continuity of care improved overall diagnostic accuracy and reporting confidence of the operator. With proper technique, the presence of background noise did not pose a problem for diagnostic reporting. A counter-intuitive but effective technique of detecting non-target activity is proposed, based on the pattern of activity and its relation to underlying anatomy, instead of its visual intensity. In a sub-analysis of 23 patients with a median follow-up of 5.4 months, 90Y PET/CT consistently outperformed 90Y bremsstrahlung SPECT/CT in all aspects of qualitative analysis, including assessment for non-target activity and tumor vascular thrombosis. Parts of viscera closely adjacent to the liver remain challenging for non-target activity detection, compounded by a tendency for mis-registration. CONCLUSIONS: Adherence to proper diagnostic reporting technique and emphasis on continuity of care are vital to the clinical utility of post-radioembolization 90Y PET/CT. 90Y PET/CT is superior to 90Y bremsstrahlung SPECT/CT for the assessment of target and non-target activity.

Post-radioembolization yttrium-90 PET/CT - part 2: dose-response and tumor predictive dosimetry for resin microspheres.

BACKGROUND: Coincidence imaging of low-abundance yttrium-90 (90Y) internal pair production by positron emission tomography with integrated computed tomography (PET/CT) achieves high-resolution imaging of post-radioembolization microsphere biodistribution. Part 2 analyzes tumor and non-target tissue dose-response by 90Y PET quantification and evaluates the accuracy of tumor 99mTc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry. METHODS: Retrospective dose quantification of 90Y resin microspheres was performed on the same 23-patient data set in part 1. Phantom studies were performed to assure quantitative accuracy of our time-of-flight lutetium-yttrium-oxyorthosilicate system. Dose-responses were analyzed using 90Y dose-volume histograms (DVHs) by PET voxel dosimetry or mean absorbed doses by Medical Internal Radiation Dose macrodosimetry, correlated to follow-up imaging or clinical findings. Intended tumor mean doses by predictive dosimetry were compared to doses by 90Y PET. RESULTS: Phantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D70 > 100 Gy (D70, minimum dose to 70% tumor volume), whereas incomplete responses were generally at D70 < 100 Gy; smaller tumors (<80 cm3) achieved D70 > 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D70 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D70 53 Gy. In two patients, a mean dose of 18 Gy to the stomach was asymptomatic, 49 Gy caused gastritis, 65 Gy caused ulceration, and 53 Gy caused duodenitis. In one patient, a bilateral kidney mean dose of 9 Gy (V20 8%) did not cause clinically relevant nephrotoxicity. Under near-ideal dosimetric conditions, there was excellent correlation between intended tumor mean doses by predictive dosimetry and those by 90Y PET, with a low median relative error of +3.8% (95% confidence interval, -1.2% to +13.2%). CONCLUSIONS: Tumor and non-target tissue absorbed dose quantification by 90Y PET is accurate and yields radiobiologically meaningful dose-response information to guide adjuvant or mitigative action. Tumor 99mTc MAA SPECT/CT predictive dosimetry is feasible. 90Y DVHs may guide future techniques in predictive dosimetry.

Intra-arterial CT angiography visualization of arterial supply to inferior vena cava tumor thrombus prior to radioembolization of hepatocellular carcinoma.

Unresectable hepatocellular carcinoma has a high frequency of vascular invasion and arterial parasitization. Trans-arterial radioembolization using yttrium-90 (Y90) microspheres is a possible treatment option. Paramount to its success is the meticulous angiographic interrogation of tumor feeding arteries and extra-hepatic supply. We describe a patient with tumor invasion of the inferior vena cava with arterial supply from the right inferior phrenic artery, which was exquisitely visualized using intra-arterial computed tomographic angiography (IACTA) during the planning technetium-99m macro aggregated albumin phase. This technique was useful in planning which artery to administer Y90 microspheres into for maximal brachytherapy. Although patient outcome was poor due to significant arterio-portal shunting, we believe that IACTA is a useful adjunct to conventional digital subtraction angiography in planning radioembolization therapy.

Radioembolization after portal vein embolization in a patient with multifocal hepatocellular carcinoma.

Radioembolization is an effective locoregional therapy for patients with intermediate or advanced stage hepatocellular carcinoma (HCC). It has been shown that radioembolization is safe in patients with portal vein thrombosis. This case report describes safe radioembolization after portal vein embolization in a patient with multifocal HCC.

Moxonidine improves cardiac structure and performance in SHR through inhibition of cytokines, p38 MAPK and Akt.

BACKGROUND AND PURPOSE: Regression of left ventricular hypertrophy by moxonidine, a centrally acting sympatholytic imidazoline compound, results from a sustained reduction of DNA synthesis and transient stimulation of DNA fragmentation. Because apoptosis of cardiomyocytes may lead to contractile dysfunction, we investigated in spontaneously hypertensive rats (SHR), time- and dose-dependent effects of in vivo moxonidine treatment on cardiac structure and function as well as on the inflammatory process and signalling proteins involved in cardiac cell survival/death. EXPERIMENTAL APPROACH: 12 week old SHR received moxonidine at 0, 100 and 400 µg·kg(-1)·h(-1) , s.c., for 1 and 4 weeks. Cardiac function was evaluated by echocardiography; plasma cytokines were measured by elisa and hearts were collected for histological assessment of fibrosis and measurement of cardiac proteins by Western blotting. Direct effects of moxonidine on cardiac cell death and underlying mechanisms were investigated in vitro by flow cytometry and Western blotting. KEY RESULTS: After 4 weeks, the sub-hypotensive dose of moxonidine (100 µg) reduced heart rate and improved global cardiac performance, reduced collagen deposition, regressed left ventricular hypertrophy, inhibited Akt and p38 MAPK phosphorylation, and attenuated circulating and cardiac cytokines. The 400 µg dose resulted in similar effects but of a greater magnitude, associated with blood pressure reduction. In vitro, moxonidine inhibited norepinephrine-induced neonatal cardiomyocyte mortality but increased fibroblast mortality, through I(1)-receptor activation and differential effects on downstream Akt and p38 MAPK. CONCLUSIONS AND IMPLICATIONS: While the antihypertensive action of centrally acting imidazoline compounds is appreciated, new cardiac-selective I(1)-receptor agonists may confer additional benefit.

Endovenous laser therapy in the treatment of lower-limb venous ulcers.

PURPOSE: To assess the efficacy of endovenous laser therapy (EVLT) in the treatment of lower-limb venous ulcers secondary to venous reflux. MATERIALS AND METHODS: Forty-four of 139 patients referred for EVLT from January 2004 to August 2007 had nonhealing venous ulcers. Preprocedural duplex ultrasound (US) was performed to document saphenous venous reflux secondary to saphenofemoral/saphenopopliteal junction incompetence, deep venous insufficiency, and deep vein thrombosis. Follow-up intervals were within 1 week, monthly until ulcer healing, and every 6 months thereafter. Mean follow-up period was 35.8 months (range, 8.1-59.3 months). RESULTS: Mean great saphenous vein (GSV) diameter and length treated were 9.9 mm (range, 5.5-16.0 mm) and 36.7 cm (range, 20.0-60.0 cm). Mean laser energy used was 3,292 J (range, 1,392-4,971 J). Mean energy deposited per centimeter of vein was 93.6 J/cm (range, 45.2-182.0 J/cm). Mean laser time was 232 seconds (range, 99-347 sec). Fifteen patients with follow-up duplex US had no GSV flow at 6 months, with nonvisualization indicating complete obliteration. Ulcer healing occurred as early as 1 week after the procedure in some patients. Cumulative healing rates at 1, 3, 6, and 12 months were 82.1%, 92.5%, 92.5%, and 97.4%, respectively. No ulcer had recurred at 1 year, but ulcers recurred in five patients at 14, 14, 23, 35, and 52 months after EVLT, respectively. One patient with a nonhealing ulcer 2 years after treatment developed well differentiated squamous cell carcinoma. CONCLUSIONS: Ulcer epithelization occurred with continued GSV occlusion and loss of flow. Most ulcers healed within 3 months with no recurrence at 1 year. Nonhealing ulcers should undergo biopsy to exclude malignant transformation.

Traumatic carotid cavernous fistula associated with a mandibular fracture.

Carotid cavernous sinus fistula is an abnormal vascular interconnection between a branch of the carotid artery and the cavernous sinus. This is an uncommon complication of craniofacial injuries, as it occurs in only 0.17-0.27% of cases, according to the literature. The differential diagnosis should include superior orbital fissure syndrome, orbital apex syndrome, orbital haematoma and cavernous sinus thrombosis. The case is reported of an 18-year-old white woman who was involved in a motor vehicle accident. Clinical examination revealed only mandibular fractures, with the absence of skull-base, mid-face or any other fractures. Two days after the trauma, her condition deteriorated, and extraocular movements were totally absent. Magnetic resonance angiographic scanning was performed, and a carotid cavernous sinus fistula was found. This was treated by embolization resulting in restoration of eye movement and vision.

Does leukofiltration reduce pulmonary infections in CABG patients? A prospective, randomized study with early results and mid-term survival.

BACKGROUND: We present the first prospective randomized study of primary coronary artery bypass grafting (CABG) patients who were analyzed for postoperative infections after undergoing blood and/or blood product transfusion (BBPT) with a Pall Purecell leukoreducing filter. METHODS AND RESULTS: One hundred and four patients were enrolled between March 1998 and March 1999. Seventy-two of the patients received BBPT (average 5.6 units BBPT/filter patient and 5.6 units/control patient). Three patients who had CABG without extracorporeal circulation or mixed transfusions of filtered and unfiltered BBPT were excluded. The remaining 69 transfused patients (38 filtered, 31 control) were analyzed and the incidence of culture proven infections was recorded. Mid-term survival data were obtained from the National Death Index and Kaplan-Meier survival plots were constructed. All patients were stratified and matched according to the EuroSCORE.Thirty-day mortality was 2.6% and 3.2% for the filtered and control patients, respectively. There were 5 cases of culture proven infections in 38 filtered patients (13.2%) and 8 in 31 controls (25.8%), P = 0.224. No pulmonary tract infections were recorded in the filter group vs. 4 (12.9%) in controls, P = 0.048. Reduced length for mechanical ventilation (16.3 hours vs. 57.8, P = 0.103), length of stay (9.1 vs. 10.8 days, P = 0.685), as well as increased 50-month actuarial survival, (45.5 vs. 42.3 months, P=0.695) in filtered vs. control, respectively, were recorded. CONCLUSIONS: The use of leukoreduced BBPT reduced the incidence of pulmonary tract infections in patients undergoing CABG.

Quality improvement guidelines for placement of esophageal stents.

Esophageal cancer is now the sixth leading cause of death from cancer worldwide. During the past three decades, important changes have occurred in the epidemiologic patterns associated with this disease. Due to the distensible characteristics of the esophagus, patients may not recognize any symptoms until 50% of the luminal diameter is compromised, explaining why cancer of the esophagus is generally associated with late presentation and poor prognosis. Esophageal cancer has a poor outcome, with an overall 5 year survival rate of less than 10%, and fewer than 50% of patients are suitable for resection at presentation. As a result palliation is the best option in this group of patients. The aims of palliation are maintenance of oral intake, minimizing hospital stay, relief of pain, elimination of reflux and regurgitation, and prevention of aspiration. For palliative care, current treatment options include thermal ablation, photodynamic therapy, radiotherapy, chemotherapy, chemical injection therapy, argon beam or bipolar electrocoagulation therapy, enteral feeding (nasogastric tube/percutaneous endoscopic gastrostomy), and intubation (self-expanding metal stents (SEMS) or semi-rigid prosthetic tubes) with different success and complications rates.

True caecal diverticulitis.

Nine patients (six females and three males), median age = 27.5 years (range 13-36) with caecal diverticulitis are presented. All underwent surgery with a suspected diagnosis of acute appendicitis. Per-operative diagnosis was possible in five cases, two cases were thought to have other benign pathology, but malignancy could not be excluded in the remaining two cases. Local excision was carried out in five cases, a right hemicolectomy was performed in the rest. Histology showed true diverticuli in eight cases, severity of the inflammation made it difficult to comment on the ninth case. Postoperative barium enema was carried out in six cases, which showed no further diverticuli in the colon. We conclude that preoperative diagnosis of caecal diverticulitis is difficult, and that true solitary caecal diverticuli present in a younger age group than the false caecal and ascending colon diverticuli and that they are probably congenital in origin.

Multiple breast papillomas in adolescence.

The condition of multiple breast duct papillomas although relatively common in adult women is not a well recognized clinical entity in adolescent females. The risk of adolescents with this condition developing carcinoma is presently unknown, although in adulthood it is regarded by some authorities as a precancerous condition. We report a case of a 14-year-old girl with such a lesion who remains well with no breast abnormalities 2 years after surgery. The clinicopathological features of the condition and the relevant literature are discussed.

Volvulus of the sigmoid colon in Jordan.

This report discusses 27 patients with sigmoid volvulus treated at Jordan University Hospital (JUH) during a 15-year period. These patients represented 4.7 percent of adult patients treated for intestinal obstruction in the same period. The average age was 54.5 years, and none of the patients was institutionalized. Twenty-five patients presented with acute symptoms, and two had chronic symptoms. Sigmoidoscopic detorsion was achieved in 15 patients. Emergency resection was required in two of these patients: for the development of gangrene a few hours after detorsion in one patient and for recurrence within 24 hours in the other despite the presence of a rectal tube. Early recurrence occurred in two other patients and was managed endoscopically. Emergency surgery was performed in 10 other patients: for a failed endoscopic detorsion in three patients, for ulcerated and bleeding mucosa forecasting gangrene in another, and as a primary treatment in six patients who were either misdiagnosed or suspected to have gangrenous bowel. Elective resection was performed in 13 patients. The mortality rate was 15 percent (4/27) for the whole series and 33.3 percent (1/3) for those with gangrenous bowel.

Adrenal cysts: diagnosis and management.

We present 7 patients (5 adult females and 2 neonate males) with adrenal cysts. The cysts included 1 hydatid, 1 lymphatic and 5 pseudocysts. Three cysts were diagnosed preoperatively and all were resected surgically. The existence of true epithelial cysts of the adrenal gland is doubted by many authors; the present series includes most types of adrenal cyst.

Massive bleeding in neurofibromatosis associated with congenital hypofibrinogenaemia: a case report.

A 22 year old male who bled profusely at operation for excision of an extensive scalp and facial neurofibromata is reported. He was found to have congenital hypofibrinogenaemia. It is suggested that hypofibrinogenaemia should be considered as a cause of excessive bleeding in cases of Von Recklinghausen's neurofibromatosis.

Tumores rari et inusitati. Chordoma in a lumbar vertebral transverse process: a case report and review of the literature.

Chordoma is a rare tumour of the skeleton that develops from notochordal elements. It occurs in the midline of the body particularly at the upper and lower ends of the vertebral columns. This paper reports a case of chordoma of unusual localization in the transverse process of a lumbar vertebra in a 30-year-old man with review of the literature. The early confinement of the tumour to a vertebral transverse process has never been reported. The scarcity with which chordoma is diagnosed in Jordan and the clinical presentation of the case reported are discussed.

Clear cell sarcoma: report of two cases with ultrastructural observations and review of the literature.

Two cases of clear cell sarcoma of tendons and aponeuroses, one with prominent melanogenesis, are reported. One tumour arose in the left buttock of a young male and the other in the left fourth toe of a young female. Both had a rapid fatal course with local and distant metastases. Electron microscopy shows melanosomes in one case, suggesting a melanotic origin.