A study of the comparative anatomy of the lateral compound eyes of arthropods

In this thesis the interest has centered mainly on the comparative anatomy of the lateral eyes of Arthropods especially the compound eyes, with some particular reference to those of Chilopoda. The comparative anatomy of the eyes of Chilopoda seemed to be of interest, since they possess in most cases simple lateral eyes, which are not characteristic of the adults of any other group of Arthropoda, except Arachnids, to which the Chilopoda are only remotely related In a few cases - in the Scutigeridae - "compound" eyes are present, which are very unusual in their internal anatomy. The following possibilities with regard to the relationships of the Chilopod eyes present themselves. The simple eyes may be the products of degeneration of a compound eye. Alternatively they may be ocelli of a very primitive pre-compound eye type, persisting where in some cases a compound eye has failed to develop. As a third possibility they may have been separately evolved in forms, in which the compound eye was lost or failed to develop. In the last case they would appear to be unrelated to those of any other Arthropods, except possibly those of Diplopods, to which they are very similar in structure. The "compound" eyes may be or the same type as the compound eyes in the remaining Arthropods, with the differences due to degeneration, or to specialisation. Alternatively they may be of a separate type and formed secondarily, either as a single new structure. or a coalescence of ocelli. The enquiry into the interrelationship of these eyes and their relation to the eyes of other Arthropoda raises several points for investigation. For the compound eyes it is necessary to decide whether they were primarily present in the ancestors of some or all of the classes or Arthropods, and whether they have a common or more or less diverse origin with some evolutionary convergence. For the lateral simple eyes it is necessary to decide whether there are any indications in phylogeny, ontogeny or anatomy of the primitive or secondary formation of a compound eye by the aggregation of numerous ocelli or the elaboration of one or these. Such information might be expected to throw light on the origin of the Scutigerid eye. Alternatively any indications of the formation of simple from compound eyes might show whether the Chilopod simple eyes could have evolved in this way from a Scutigerid or some other compound eye. Median eyes are present in some Trilobites, Eurypterida, Crustacea, Hexapods and Arachnida. Although they exhibit considerable variations in structure, they are all clearly simple eyes. As they are absent in Chilopoda and in the remaining Arthropods are entirely separate in origin from the lateral eyes, with a separate seat of innervation, their comparative anatomy is of little interest in this case. The main portion of the thesis deals with the comparative anatomy, origins and relationships of the different types of compound lateral eyes. The second part comprises a short appendix dealing with similar aspects of the lateral ocelli. Detailed descriptions and figures have been given for the eyes of eight species. Some mention is also made of points observed in the internal or external anatomy of species which were studied in less detail. The theoretical conclusions are based on material from the available literature and from these descriptions

Critical appraisal of axitinib in the treatment of advanced renal cell carcinoma.

A growing understanding of the biology of renal cell carcinoma (RCC) has led to the development and US Food and Drug Administration approval of seven new molecular targeted agents over the past 7 years. Axitinib is a potent, selective, second-generation inhibitor of vascular endothelial growth factor receptors and the latest to join the armamentarium of drugs available for the treatment of metastatic RCC. Despite recent advances in the development of molecular targeted agents for metastatic RCC, the ideal sequencing of these agents remains unclear

Concurrent use of nivolumab and radiotherapy for patients with metastatic non‑small cell lung cancer and renal cell carcinoma with oligometastatic disease progression on nivolumab

Checkpoint inhibitors (CPIs), such as nivolumab, have transformed the treatment paradigm for patients with metastatic non‑small cell lung cancer (mNSCLC) and metastatic renal cell carcinoma (mRCC). The combination of CPIs and radiotherapy (RT) constitutes a multimodal treatment approach that may work synergistically and facilitate augmented systemic responses. The aim of the present retrospective study was to assess the efficacy and safety of continuation of nivolumab treatment with the addition of RT in patients with mNSCLC and mRCC who develop oligometastatic disease progression on single‑agent nivolumab. All patients with mNSCLC and mRCC who received nivolumab at the Department of Oncology, Prince Sultan Military Medical City (Riyadh, Saudi Arabia) between November 2016 and April 2018 were identified. The records of patients who developed oligometastatic disease progression during nivolumab treatment and were subsequently treated with RT, with nivolumab continued beyond disease progression, were retrospectively reviewed. Details of RT, clinical outcomes and toxicity data were collected. Of the 96 patients who received nivolumab, 22 received multiple courses of RT. A total of 39 sites were irradiated: Bone (n=15), lung (n=9), brain (n=8), adrenal gland (n=2), renal bed (n=2), skin (n=1), ethmoid sinus (n=1) and scalp (n=1). Partial response and complete response were noted at 25 (64%) and 3 (8%) sites, respectively. Stable disease was noted at 6 sites (15%) and disease progression was noted at 5 sites (13%). The median time on nivolumab from the date of the first fraction of RT was 4.5 months (range, 1.5‑29 months) for patients with mNSCLC and 5 months (range, 1‑38.5 months) for patients with mRCC. No patients developed grade 3‑4 toxicities. Grade 2 pneumonitis was noted in 3 patients receiving lung RT. The addition of RT appeared to initiate a response and prolong the duration of nivolumab treatment. Therefore, the combination of nivolumab and RT was found to be well tolerated, with response rates exceeding those in published studies of nivolumab monotherapy

Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer.

We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil (5-FU) in muscle invasive bladder cancer. Early dose escalation results were previously published. We report the long-term toxicity and efficacy results with the optimised regimen. Patients with muscle invasive bladder cancer with glomerular filtration rate >25 ml min(-1) were eligible. Mitomycin (12 mg m(-2) on day 1 only) and infusional 5-FU (500 mg m(-2) day(-1)) for 5 days were administered during weeks 1 and 4 of radiotherapy of 55 Gy in 20 fractions. A total of 41 patients were enrolled, median age was 68 years, 33 were male and eight female patients. Out of the 41 patients, 20 (49%) had hydronephrosis at presentation and 25 (62%) had T3b or T4 disease. Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia. There were no episodes of febrile neutropenia. Four patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria. Six patients did not undergo cystoscopic evaluation due to early metastatic spread although there was no clinical suggestion of bladder failure. In all, out of 35 evaluable patients, 25 (71%) had macroscopic complete response at 3-month cystoscopy, and biopsy confirmed in 24 out of 25. A total of 16 (39%) patients remain alive with a median follow-up of 50.7 (range 23.5-68.8) months, 14 with a functioning bladder with no reported long-term treatment-related bladder or bowel toxicity. Five out of 41 patients have undergone salvage cystectomy: two for persistent CIS, two T1 and one muscle invasive recurrence. Four patients have received intravesical chemotherapy, of whom two remain alive with a functioning bladder. Overall 12-, 24- and 60-month (m) survival rates were 68, 49 and 36%. Local and distant progression free rates were 82 and 86% at 12-m and 79 and 75% at 24-m. Organ preservation using multimodality therapy is feasible and safe, even in patients with poor renal reserve, and does not compromise salvage therapies. A national phase III trial BC2001 (www.bc2001.org.uk) exploring the effects of synchronous chemoradiotherapy with this regimen is currently recruiting

A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel

Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then monthly follow-up; open-label dosing began as needed after three blinded treatments. Tumour response was defined as complete (100% regression) or partial (50–99% regression) sustained for ⩾28 day, and patient benefit as attainment of palliative or preventive goals prospectively selected by investigators and patients. With cisplatin/epinephrine gel, 25% (14 out of 57) of tumours responded (16% complete regression, 9% partial regression), vs 3% (one out of 35, complete regression) with placebo (P=0.007). Patient benefit was positively associated with target tumour response in the blinded period among cisplatin/epinephrine gel recipients (P=0.024): 43% (six out of 14) of responders benefited, vs 12% (five out of 43) of non-responders. The most frequent adverse event was pain during injection and the next most frequent was local cytotoxic effects consistent with the gel's mode of action. Systemic adverse events typical of intravenous cisplatin were uncommon. Intratumoural therapy with cisplatin/epinephrine gel provided safe, well-tolerated, effective palliative treatment for patients with locally advanced head and neck squamous cell carcinoma, who lack other satisfactory treatment options

Rare case of chemotherapy-refractory metastatic vaginal squamous cell carcinoma with complete response to concurrent pembrolizumab and radiotherapy- case report and literature review

Primary vaginal cancer is a rare malignancy with a lack of international guidelines and supporting clinical trial evidence to guide decision making. Historical results have shown poor outcomes with chemotherapy for stage IVB vaginal squamous cell carcinoma (SCC). The evolving role of checkpoint inhibitors in rare gynaecological cancers prompted us to investigate the role of pembrolizumab in this setting. The efficacy of pembrolizumab in vaginal SCC has never been investigated in any clinical trial. There is established data to support the use of concurrent chemoradiotherapy in gynaecological cancers, however, the data for concurrent use of immunotherapy and radiotherapy is still lacking but is the subject of several clinical trials. We herein present the first reported case of chemotherapy refractory vaginal SCC with complete response to pembrolizumab and concurrent pelvic radiotherapy. We also present wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) as a rare but new immune related adverse event

Treatment of upper aerodigestive tract cancers in England and its effect on survival

The evidence base for head and neck cancers is low with relatively few randomized controlled trials of the two main treatments, surgery and radiotherapy. The aim of the study was to investigate the patterns of surgery and radiotherapy treatment for head and neck cancers in three large areas of England and to investigate their effects on survival. This was a retrospective study of 13 510 cases of head and neck cancers (ICD10: C00–C14, C30–C32) diagnosed and treated from 1984 to 1992 in England. We undertook multivariate analyses of survival using a step-wise Cox proportional hazard model and Kaplan–Meier analysis. There were regional variations in the treatments given to patients. Four in ten patients did not receive currently recommended treatments. In multivariate analyses treatment content and timing had an independent effect on survival. Better survival was associated with surgery for mouth cancers, radiotherapy for laryngeal cancers and combined treatment for pharyngeal cancers independent of tumour and demographic factors. Further research is needed to investigate the findings of this study through large randomized controlled trials and multi-centre audits. © 1999 Cancer Research Campaig