The abscopal effect in head-and-neck squamous cell carcinoma treated with radiotherapy and nivolumab: a case report and literature review.

Introduction: The abscopal effect is a rarely observed outcome of radiotherapy wherein there is a reduction in metastatic disease burden outside of the targeted treatment area. Likely due to an in situ vaccine effect of radiotherapy, the abscopal effect may be augmented by immunotherapy. This report is the first case of the abscopal effect observed in metastatic head-and-neck squamous cell carcinoma (hnscc) treated with concurrent radiotherapy and single-agent nivolumab. Case Description: An otherwise healthy 57-year-old man underwent craniofacial resection and adjuvant chemoradiotherapy for advanced sinonasal squamous cell carcinoma. Distant metastatic disease developed shortly after primary treatment, and immunotherapy in the form of nivolumab was initiated. Subsequent oligometastatic progression despite immunotherapy prompted palliative radiotherapy to a single metastasis due to pending symptomatology. Post-radiotherapy, the abscopal effect was observed with all distant sites of metastatic disease shrinking. Five months following treatment, a sustained reduction in disease burden has been demonstrated. Summary: We present the first case of the abscopal effect in a patient with metastatic hnscc treated with palliative radiotherapy concurrent with single-agent nivolumab immunotherapy, and only the third case of the abscopal effect in metastatic head-and-neck cancer. Dual treatment with immunotherapy and radiotherapy may be an important treatment option in the future, mediated through the abscopal effect.

Oncological and functional outcomes after repeat transoral laser microsurgery for the treatment of recurrent early glottic cancer.

BACKGROUND: Transoral laser microsurgery for glottic squamous cell carcinoma is the standard of care at many institutions. Repeat transoral laser microsurgery for recurrence may avoid the need for radiotherapy and total laryngectomy. This study aimed to identify oncological and functional outcomes in a cohort of patients who had undergone repeat transoral laser microsurgery procedures. METHOD: A retrospective review of prospectively collected data of patients treated with transoral laser microsurgery for carcinoma in situ or tumour stages T1 or T2 glottic cancer, from 2003 to 2018. RESULTS: Twenty patients were identified. Additional treatment was not needed in 45 per cent of patients. The five-year overall survival rate was 90 per cent. The disease-specific survival rate was 100 per cent. The laryngeal preservation rate was 85 per cent. There was improvement in mean Voice Handicap Index-10 scores following repeat transoral laser microsurgery treatment, when comparing the pre- and post-operative periods (mean scores = 15.5 vs 11.5, p = 0.373). CONCLUSION: Repeat transoral laser microsurgery can be an oncologically safe alternative to other salvage therapies for glottic squamous cell carcinoma recurrence, without sacrificing functional outcomes.

Submental island flap reconstruction reduces cost in oral cancer reconstruction compared to radial forearm free flap reconstruction: a case series and cost analysis.

BACKGROUND: In Canada, 4,400 cases of oral cancer are diagnosed yearly. Surgical resection is a key component of treatment in many of these cancers. Reconstruction of defects, with the goal of preserving function, is of utmost importance. Several choices are possible for reconstruction of larger defects, including both free and pedicled flaps. Free flap reconstruction is reliable and effective, but requires additional personnel and peri-operative resources. Pedicled flaps remain an important alternative to free flaps, and are less resource intensive. This paper reviews our inaugural experience with the submental island flap (SIF) and compares costs incurred to a matched cohort of oral cancer patients reconstructed with forearm free flaps. METHODS: Charts of patients who underwent SIF and RFFF reconstruction from January 1st 2013 to April 1st 2015 were retrospectively examined. Associated costs were obtained via online database and previously reported costs at the study institution. RESULTS: Mean length of ICU stay in glossectomy RFFF reconstruction was 4.7 days. Only one patient required ICU stay for one night in the SIF group. Mean length of hospital stay was not significantly different in SIF patients vs RFFF patients (12.4 vs 15.4 days, p > 0.05). Mean operative time was significantly lower in the SIF group compared to the RFFF group (347 vs 552 min, p < 0.05). Total mean intraoperative costs were found to be $4780.59 for RFFF operations, versus $2307.94 for SIF. Total mean cost of post-operative stay was $18158.40 in the SIF group and $43617.60 in the RFFF group. Total cost savings were therefore $27931.85 per patient for the SIF group. CONCLUSIONS: We have demonstrated the use of the submental island flap as an alternative to radial forearm free flaps, showing both decreased hospital costs and comparable patient outcomes. Pedicled flaps are making a resurgence in head and neck reconstruction, and the submental island flap offers an excellent alternative to more labour intensive and costly free flap alternatives.

Surgical staging and prognosis in serous borderline ovarian tumours (BOT): a subanalysis of the AGO ROBOT study.

BACKGROUND: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. METHODS: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). RESULTS: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. CONCLUSION: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.

Quality of life and sexual function after surgery in early stage vulvar cancer.

OBJECTIVES AND METHODS: Vulvar carcinomas are rare genital malignancies. In a retrospective study on 21 patients factors influencing the quality of life and sexual function were investigated. All patients were interviewed according to the Female Sexual Function Index questionnaire (FSFI) and the Short Form 12(®) questionnaire (SF12). RESULTS: We identified 21 patients that had been operated for vulvar carcinoma FIGO stage I or IIIa in the years 2006-2008. Patients that had adjuvant radiotherapy were excluded. 14 patients had been treated by a wide excision, the other 7 by a vulvectomy. 10 patients had undergone a total inguinal lymphadenectomy, 5 patients a sentinel node biopsy. In a multivariate analysis lymphadenectomy was the only factor influencing the patients' sexual function: Patients without lymphadenectomy or with sentinel node biopsy scored better in terms of sexual function, neither age nor the extend of the surgery resulted in a significant difference. CONCLUSION: The lymphadenectomy has a negative influence on the patients' sexual function after surgical treatment for vulvar carcinoma. The indication for lymphadenectomy should hence be seen critically.

Age-dependent differences in borderline ovarian tumours (BOT) regarding clinical characteristics and outcome: results from a sub-analysis of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) ROBOT study.

BACKGROUND: Approximately one-third of all borderline ovarian tumours (BOT) are diagnosed in patients with child-bearing potential. Detailed information regarding their specific characteristics and prognostic factors is limited. METHODS: Clinical parameters of BOT patients treated between 1998 and 2008 in 24 German centres were retrospectively investigated. Central pathology review and prospective follow-up were carried out. Patients <40 versus ≥40 years were analysed separately and then compared regarding clinico-pathological variables and prognosis. RESULTS: A total of 950 BOT patients with a median age of 49.1 (14.1-91.5) years were analysed [280 patients <40 years (29.5%), 670 patients ≥40 years (70.5%)]. Fertility-preserving surgery was carried out in 53.2% (149 of 280) of patients <40 years with preservation of the primarily affected ovary in 32 of these 149 cases (21.5%). Recurrence was significantly more frequent in patients <40 years (19.0% versus 10.1% 5-year recurrence rate, P < 0.001), usually in ovarian tissue, whereas disease-specific overall survival did not differ between the subgroups. In case of recurrent disease, malignant transformation was less frequent in younger than in older patients (12.0% versus 66.7%, P < 0.001), mostly presenting as invasive peritoneal carcinomatosis. Multivariate analysis for patients <40 years identified advanced International Federation of Gynecology and Obstetrics (FIGO) stage and fertility-sparing approach as independent prognostic factors negatively affecting progression-free survival (PFS) while, for patients ≥40 years, higher FIGO stage and incomplete staging was associated with impaired PFS. CONCLUSIONS: Despite favourable survival, young BOT patients with child-bearing potential are at higher risk for disease recurrence. However, relapses usually remain BOT in the preserved ovaries as opposed to older patients being at higher risk for malignant transformation in peritoneal or distant localisation. Therefore, fertility-sparing approach can be justified for younger patients after thorough consultation.

Pharmacological characterization of almotriptan: an indolic 5-HT receptor agonist for the treatment of migraine.

Almotriptan (3-[2-(dimethylamino)ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl )-1H-indo le) has been studied in several models predictive of activity and selectivity at 5-HT receptors. Almotriptan showed low nanomolar affinity for the 5-HT(1B) and 5-HT(1D) receptors in several species, including the human, while affinity for 5-HT receptors other than 5-HT(1B/1D) was clearly less. Affinity for 5-HT(7) and 5-HT(1A) receptors was approximately 40 and 60 times lower than that for 5-HT(1B/1D) receptors, respectively. Almotriptan did not exhibit significant affinity for several non-5-HT receptors studied up to 100 microM. Almotriptan inhibited forskolin-stimulated cyclic AMP accumulation in HeLa cells transfected with 5-HT(1B) or 5-HT(1D) human receptors. In this model, almotriptan had the same efficacy as serotonin and an affinity in the low nanomolar range. It induced vasoconstriction in several vessels in which it was compared with sumatriptan. In isolated dog saphenous veins, almotriptan elicited concentration-dependent contractions with an EC(50) of 394 nM. In both these systems, almotriptan behaved as a full agonist. Infusion of almotriptan into the porcine meningeal vasculature induced vasoconstriction. In contrast, in the pig renal and rabbit mesenteric arteries, it had a very low maximal efficacy even at 100 microM, with similar results obtained in the rabbit renal artery. The results suggest that almotriptan is a potent and selective 5-HT(1B/1D) receptor agonist, with selectivity for the cranial vasculature as compared with peripheral vessels.

Molecular structure of a complete turn of A-DNA.

We have determined the crystal structure of the dodecamer d(CCCCCGCGGGGG), showing for the first time a complete turn of A-DNA. It has average structural parameters similar to those determined in fibres. Nevertheless it shows a considerable local variation in structure which is in part associated with the presence of a bound spermine molecule. We conclude that the local DNA conformation does not only depend on the base sequence, but may be strongly modified upon interaction with other molecules. In particular, the CpG sequence, which is found in hypersensitive regions of the genome, appears to be able to easily change its conformation under external influences.

Synthesis and characterization of oligodeoxynucleotides containing the mutagenic base analogue 4-O-ethylthymine.

A method for the preparation of oligonucleotides containing the mutagenic base 4-O-ethylthymine is described for the first time. Use of p-nitrophenylethyl type base protecting groups together with phosphitetriester solid-phase methodology makes possible the rapid and efficient preparation of oligonucleotides bearing 4-O-ethylthymine, while standard base protecting groups are not compatible with the presence of this base. Possible applications of this methodology are discussed.