A case report of multiple renal aneurysms due to Klippel-Trenaunay syndrome requiring laparoscopic nephrectomy.

INTRODUCTION: Klippel-Trenaunay Syndrome (KTS) is a rare genetic disorder which is characterised by vascular nevi, venous varicosity, and hyperplasia of soft tissue or bone. Renovascular involvement is considered uncommon in KTS. PRESENTATION OF CASE: A 79-year-old man presented with a left sided varicocele, lymphedema, hydrocele, and microscopic haematuria. After a series of investigations his imaging and clinical features were suggestive KTS. His images, which showed a 2.7 cm renal artery aneurysm, were discussed in the multi-disciplinary team (MDT) meeting and the decision was made to proceed with a laparoscopic nephrectomy. DISCUSSION: Given the size of the aneurysm, treatment was offered and accepted by the patient. This is first recorded case in the literature in which a successful laparoscopic nephrectomy has been carried out for preventing severe haemorrhage in KTS. The patient presented in his 7th decade with a varicocele which would be considered unusual for KTS. Like in many cases, the renal artery aneurysm was asymptomatic. Pathological outcomes of the sample confirmed features suggestive of KTS, thus, validating the radiological findings. CONCLUSION: Here, we report a favourable outcome of a patient referred for consideration of varicocele management, diagnosed with renal artery aneurysms on a background of KTS. KTS, with significant renovascular abnormalities, can be treated with laparoscopic nephrectomy. Careful discussion in MDT with regards to management options should be performed and a shared decision reached with the patient with regards to management. Though rare, patients presenting with varicoceles and lymphedema may have underlying capillary-lymphatic-venous malformations.

Does the Mode of Anaesthesia (General or Regional) Affect Survival and Complications Following Femoropopliteal and Femorodistal Bypass?

INTRODUCTION: Femoropopliteal and femorodistal bypasses are indicated in the management of severe claudication or critical limb ischaemia. The choice of type of anaesthesia between general anaesthesia (GA) and regional anaesthesia (RA; epidural/spinal) has remained controversial. The study aimed to compare the rates of graft failure, perioperative mortality, and other major complications (including graft failure) associated with GA versus RA for lower limb bypass revascularisation in patients presenting with significant peripheral arterial disease. METHODS: All patients who had femoropopliteal and femorodistal bypass at the vascular unit of Colchester Hospital between January 2016 and September 2018 were included. The primary outcome measure was survival, and secondary outcome measures were respiratory, wound, cardiac, and graft failure complications. Technical success was defined as a successful operation with demonstrated graft patency at discharge and up to 30 days of follow-up. Secondary outcome measures included respiratory, wound, and cardiac complications. Statistical analysis included descriptive statistics and tests of association using chi-square for graft failure outcomes and the Mann-Whitney U test for the length of stay. All analyses were done at a 5% level of significance. RESULTS: There were 139 patients identified during the study period who fulfilled the inclusion criteria, of which 127 had complete records. The overall mortality and morbidity in this study were 1.6% and 14.229%, respectively. The proportion of patients who had ischaemic heart disease is almost threefold amongst those who had failed bypass compared to the successful bypass group (33.3% versus 11.9%, p = 0.018). A total of 65 patients received GA and 62 patients underwent RA; there were no significant differences in baseline preoperative comorbidities, postoperative mortality and complications, and length of stay. The majority (84%) of the patients who had RA had combined spinal and epidural (CSE) anaesthesia. The overall mortality and morbidity in this study were 1.6% and 14.2%, respectively. The proportion of patients with graft failure was 14.5% for GA versus 13.8% for RA (p = 0.914); there was no significant difference for conduit type, quality of vein conduit, the prevalence of heart failure and postoperative hypotensive episodes, redo-surgery, and major amputation, and length of stay (GA: 5.0, RA: 6.0, p = 0.854) did not differ significantly between the two groups. The proportion of patients who had ischaemic heart disease is almost threefold amongst those who had failed bypass compared to the successful bypass group (33.3% versus 11.9%, p = 0.018). CONCLUSION: The mode of anaesthesia, GA or the use of CSE RA in approximately half of the patients, did not influence survival, respiratory, cardiac, wound, graft failure, or length of stay in this study. There was a relationship between the presence of cardiac comorbidity and bypass failure, indicating a need for a standard care protocol to further optimise cardiac perioperative care to improve outcomes.

Selective Vulnerability of Senescent Glioblastoma Cells to BCL-XL Inhibition.

Glioblastoma (GBM) is a rapidly fatal malignancy typically treated with radiation and temozolomide (TMZ), an alkylating chemotherapeutic. These cytotoxic therapies cause oxidative stress and DNA damage, yielding a senescent-like state of replicative arrest in surviving tumor cells. Unfortunately, recurrence is inevitable and may be driven by surviving tumor cells eventually escaping senescence. A growing number of so-called "senolytic" drugs have been recently identified that are defined by their ability to selectively eliminate senescent cells. A growing inventory of senolytic drugs is under consideration for several diseases associated with aging, inflammation, DNA damage, as well as cancer. Ablation of senescent tumor cells after radiation and chemotherapy could help mitigate recurrence by decreasing the burden of residual tumor cells at risk of recurrence. This strategy has not been previously explored for GBM. We evaluated a panel of 10 previously described senolytic drugs to determine whether any could exhibit selective activity against human GBM persisting after exposure to radiation or TMZ. Three of the 10 drugs have known activity against BCL-XL and preferentially induced apoptosis in radiated or TMZ-treated glioma. This senolytic activity was observed in 12 of 12 human GBM cell lines. Efficacy could not be replicated with BCL-2 inhibition or senolytic agents acting against other putative senolytic targets. Knockdown of BCL-XL decreased survival of radiated GBM cells, whereas knockdown of BCL-2 or BCL-W yielded no senolytic effect. IMPLICATIONS: These findings imply that molecularly heterogeneous GBM lines share selective senescence-induced BCL-XL dependency increase the significance and translational relevance of the senolytic therapy for latent glioma.

Risk and response adapted de-intensified treatment for HPV-associated oropharyngeal cancer: Optima paradigm expanded experience.

BACKGROUND: Favorable prognosis for Human papillomavirus-associated (HPV+) oropharyngeal cancer (OPC) led to investigation of response-adaptive de-escalation, yet long-term outcomes are unknown. We present expanded experience and follow-up of risk/response adaptive treatment de-intensification in HPV+ OPC. METHODS: A phase 2 trial (OPTIMA) and subsequent cohort of sequential off-protocol patients treated from September 2014 to November 2018 at the University of Chicago were reviewed. Eligible patients had T3-T4 or N2-3 (AJCC 7th edition) HPV+ OPC. Patients were stratified by risk: High-risk (HR) (T4, ≥N2c, or >10PYH), all others low-risk (LR). Induction chemotherapy (IC) included 3 cycles of carboplatin and nab-paclitaxel (OPTIMA) or paclitaxel (off-protocol). LR with ≥50% response received low-dose radiotherapy (RT) alone to 50 Gy (RT50). LR with 30-50% response and HR with ≥50% response received intermediate-dose chemoradiotherapy (CRT) to 45 Gy (CRT45). All others received full-dose CRT to 75 Gy (CRT75). RESULTS: 91 patients consented and 90 patients were treated, of which 31% had >10PYH, 34% had T3/4 disease, and 94% had N2b/N2c/N3 disease. 49% were LR and 51% were HR. Overall response rate to induction was 88%. De-escalated treatment was administered to 83%. Median follow-up was 4.2 years. Five-year OS, PFS, LRC, and DC were 90% (95% CI 81,95), 90% (95% CI 80,95), 96% (95% CI 90,99), and 96% (88,99) respectively. G-tube placement rates in RT50, CRT45, and CRT75 were 3%, 33%, and 80% respectively (p < 0.05). CONCLUSION: Risk/response adaptive de-escalated treatment for an inclusive cohort of HPV+ OPC demonstrates excellent survival with reduced toxicity with long-term follow-up.

Lip and Oral Cavity Squamous Cell Carcinoma.

Lip and oral cavity squamous cell carcinoma (SCC) develop from progressive dysplasia of these mucosal structures. The cancers are often preceded by premalignant lesions, and any nonhealing ulcers of the lip or oral cavity should be biopsied. Some risk factors for these 2 subsites overlap and include tobacco use, alcohol use, and an immunocompromised state. Lip and oral cavity SCC are clinically staged based on physical examination and imaging. The 5-year overall survival for early-stage lip and oral cavity SCC is around 70% to 90% but decreases to about 50% for late-stage disease.

Comparison of Patient Radiation Dose and Contrast Use during EVAR in a Dedicated Hybrid Vascular OR and Mobile Imaging.

BACKGROUND: The aim of the study is to determine whether performing endovascular aortic aneurysm repair (EVAR) in a dedicated vascular hybrid operating room (OR) is associated with a decreased patient radiation and contrast dose compared with mobile C-arm imaging in a conventional OR. METHODS: This is a retrospective study of patients undergoing standard EVAR from 2009-2016. "Standard EVAR" was defined as the elective EVAR performed with bifurcated graft for infrarenal aneurysm with no iliac aneurysms. Patients were divided into 2 groups. Group 1 included EVARs performed in conventional theater with a mobile C-arm (January 2009 to June 2012) and group 2 EVARs performed in the dedicated vascular hybrid OR (July 2012 to December 2016). Data collected included patient demographics, aneurysm diameter, neck length, radiation dose, screening time, and contrast use of each patient. RESULTS: There were 286 patients, 78 and 208 patients in group 1 and 2, respectively. There was no difference in age (77.6 years [76.3-78.9] vs. 76.6 years [75.9-77.9], P > 0.05), body mass index (26.5 kg/m2 [25.1-28.0] vs. 27.9 kg/m2 [27.1-28.7] P > 0.05), and mean aneurysm diameter (6.48 cms [6.13-6.82] vs. 6.81 cms [6.0-7.7], P > 0.05) between groups. Patients in group 2 received approximately half the mean radiation dose (16,807 cGy cm2 [±11,078] vs. 8,233 cGy cm2 [±7,471], P < 0.001), shorter fluoroscopy time (36.02 min [±21.3] vs. 26.96 min [±19], P = 0.001), and less contrast use (114 mls [±44.2] vs. 158 mls [±63.9], P < 0.001). CONCLUSIONS: Performing EVAR in a dedicated vascular Hybrid OR may be associated with a lower patient radiation dose, shorter screening time, and less contrast use than performing EVAR in a conventional OR.

Management of Early Head and Neck Cancer in Elderly Patients.

Head and neck squamous cell carcinoma (HNSCC) frequently affects elderly patients. Given the frailty and comorbid conditions of this population as well as the potential toxicities associated with treatment, there is a risk of undertreatment in older patients. However, there is growing evidence that benefit with standard treatment is similar in the elderly and in younger patients. Few prospective trials specifically target the elderly, which forces clinicians to rely on subgroup analyses and retrospective data. Therefore, adequate pretreatment assessments are vital to anticipate factors that may contribute to morbidity during therapy. In addition, supportive care during treatment is essential. For patients of all ages who present with early or localized disease, curative treatment should be offered whenever possible. With more precise surgical and radiologic techniques, the ability to provide curative treatment while minimizing long-term toxicity has greatly improved. Not only our techniques but also our understanding of the disease have improved. Human papillomavirus (HPV)-related HNSCC has changed the treatment paradigm of advanced-stage disease because of the inherently better prognosis compared with tobacco- and alcohol-related HNSCC. How this will affect early-stage disease remains to be seen, but de-escalated therapy may prove a suitable strategy in eligible elderly patients. With improved therapies and understanding of the disease, additional prospective trials must be carried out in the elderly population.

A case of hepatic, renal and duodenal penetration by a Celect inferior vena caval filter.

Inferior vena caval (IVC) filters are used as a mechanical option for the treatment of venous thromboembolism (VTE) when standard anticoagulation therapy is either contraindicated or VTE recurs despite adequate anticoagulation. Filters are not without risk, however. Reported complications include filter migration and fracture of filter components, leading to IVC rupture and penetration into pericaval tissues (notably kidney, heart, pericardium, thoracic cavity, liver, bowel and aorta). Here we describe an extreme case of multiple organ penetration by a standard Celect caval filter.

Effects of convection-enhanced delivery of bevacizumab on survival of glioma-bearing animals.

OBJECT Bevacizumab (Avastin), an antibody to vascular endothelial growth factor (VEGF), alone or in combination with irinotecan (Camptosar [CPT-11]), is a promising treatment for recurrent glioblastoma. However, the intravenous (IV) administration of bevacizumab produces a number of systemic side effects, and the increase in survival it provides for patients with recurrent glioblastoma is still only a few months. Because bevacizumab is an antibody against VEGF, which is secreted into the extracellular milieu by glioma cells, the authors hypothesized that direct chronic intratumoral delivery techniques (i.e., convection-enhanced delivery [CED]) can be more effective than IV administration. To test this hypothesis, the authors compared outcomes for these routes of bevacizumab application with respect to animal survival, microvessel density (MVD), and inflammatory cell distribution. METHODS Two human glioma cell lines, U87 and U251, were used as sources of intracranial tumor cells. The glioma cell lines were implanted into the brains of mice in an orthotopic xenograft mouse tumor model. After 7 days, the mice were treated with one of the following: 1) vehicle, 2) CED bevacizumab, 3) IV bevacizumab, 4) intraperitoneal (IP) irinotecan, 5) CED bevacizumab plus IP irinotecan, or 6) IV bevacizumab plus IP irinotecan. Alzet micro-osmotic pumps were used to introduce bevacizumab directly into the tumor. Survival was monitored. Excised tumor tissue samples were immunostained to measure MVD and inflammatory cell and growth factor levels. RESULTS The results demonstrate that mice treated with CED of bevacizumab alone or in combination with irinotecan survived longer than those treated systemically; CED-treated animals survived 30% longer than IV-treated animals. In combination studies, CED bevacizumab plus CPT-11 increased survival by more than 90%, whereas IV bevacizumab plus CPT-11 increased survival by 40%. Furthermore, CED bevacizumab-treated tissues exhibited decreased MVD compared with that of IV-treated tissues. In additional studies, the infiltration of macrophages and dendritic cells into CED-treated animals were increased compared with those in IV-treated animals, suggesting a highly active inflammatory response taking place in CED-treated mice. CONCLUSIONS The administration of bevacizumab via CED increases survival over that of treatment with IV bevacizumab. Thus, CED of bevacizumab alone or in combination with chemotherapy can be an effective protocol for treating gliomas.

Successful laparoscopic repair of refractory type Ia endoleak after endovascular abdominal aortic aneurysm repair.

Type I endoleaks associated with sac enlargement after endovascular abdominal aortic aneurysm repair mandate urgent intervention. Endoluminal treatments are generally considered first, but when these fail, open surgery has been advocated as a last resort. Open surgery is associated with significant mortality and morbidity, and thus, approaches that reduce this risk would be of interest. We report a successful case of laparoscopic treatment of a refractory type Ia endoleak after endovascular abdominal aortic aneurysm repair in an 83-year-old man.

Comment on: Conservative management of an infected laparoscopic hernia mesh: A case study.

INTRODUCTION: We recently published an article in this journal describing the successful conservative treatment of a patient with an infected laparoscopically inserted hernia mesh using gentamycin flushes via a pig-tail drain and long term oral antibiotics. This prevented the need for major reconstructive surgery. However, 3 months after we published our report, the patient re-presented with symptoms of a recurrence of infection. PRESENTATION OF CASE: Seven months after stopping oral antibiotics, our patient represented with fever and swelling and redness over his left sided inguinal hernia mesh. This mesh had to be surgically removed. The procedure was laparoscopic and showed infection confined to the central 5cm of the mesh. Microbiology culture results were the same as on initial presentation. DISCUSSION: The microbiology results suggest that it is likely that the infection was never fully eradicated and that our intervention merely kept the infection at bay. Once long term antibiotics were stopped it is likely that the infection was able to eventually recur. CONCLUSION: Consequently, we have been unable to show that our method of conservative management of infected hernia meshes is effective to prevent long term recurrence of infection.

Conservative management of an infected laparoscopic hernia mesh: A case study.

INTRODUCTION: A dreaded complication of laparoscopic hernia repair is infection of the mesh. Traditionally mesh infection is managed by surgical removal of the mesh, an extensive procedure resulting in high re-herniation rates. A technique to treat such infections whilst salvaging the mesh is sorely needed. We describe a case in which a laparoscopic mesh infection was treated solely with drainage, parenteral antibiotics and antibiotic irrigation of the mesh. PRESENTATION OF CASE: A 65 year old gentleman presented 11 months post laparoscopic repair of an inguinal hernia with malaise and an uncomfortable groin swelling. Computed tomography scanning revealed a collection surrounding the mesh which was drained and cultured to show heavy growth of Staphylococcus aureus. A pigtail drain on continuous drainage was inserted and kept in situ for 7 weeks. The patient received one week of intravenous flucloxacillin and two gentamycin irrigations through the drain as an inpatient. He then received 6 weeks of oral flucloxacillin and bi-weekly saline flushes through the drain in the community. By 12 weeks an ultrasound scan showed resolution of the collection. At 7 months he remains clinically free from recurrence. DISCUSSION: Here we report a novel conservative method used to treat a hernia mesh infection, preserve the mesh and avoid major surgery. Other reports exist suggesting variations in conservative methods to treat mesh infections, however ours is by far the most conservative. CONCLUSION: Clearly, further research is required to identify which method is most effective and in which patients it is likely to be successful.

Qualitative gas chromatography-mass spectrometry analyses using amines as chemical ionization reagent gases.

Ammonia is a very useful chemical ionization (CI) reagent gas for the qualitative analyses of compounds by positive ion gas chromatography-mass spectrometry (GCMS). The gas is readily available, inexpensive, and leaves no carbon contamination in the MS source. Compounds of interest to our laboratory typically yield abundant protonated or ammoniated species, which are indicative of a compound's molecular weight. Nevertheless, some labile compounds fragment extensively by substitution and elimination reactions and yield no molecular weight information. In these cases, a CI reagent gas mixture of methylamine in methane prepared dynamically was found to be very useful in obtaining molecular weight data. Likewise, deuterated ammonia and deuterated methylamine are useful CI reagent gases for determining the exchangeable protons in organic compounds. Deuterated methylamine CI reagent gas is conveniently prepared by dynamically mixing small amounts of methylamine with excess deuterated ammonia.

Minimally invasive surgical repair of iliac artery endofibrosis.

Iliac artery endofibrosis is an uncommon condition, which should be considered in young athletes with exertional lower limb symptoms. Imaging often appears normal at rest, and the diagnosis can be missed if clinical assessment is inadequate. We report a successful case of entirely minimally invasive surgical treatment for iliac artery endofibrosis in a 41-year-old cyclist. This novel technique offers superior potential for intraoperative assessment and aids enhancement in recovery after surgery. It is likely to be particularly appealing to elite athletes.