Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

Perforation of a retrocaecal appendix presenting clinically as a right lumbar abscess.

Presentations of acute appendicitis represent an ongoing challenge to surgeons. This case of retrocaecal perforated appendicitis presented clinically as a right lumbar abscess, with the concomitant new diagnosis of type 2 diabetes mellitus in a 66-year-old male. This case emphasises the importance of an abdominal CT scan in any patient presenting with unusual sepsis near the abdomen.     

Double vulva. A case report

Double vulva is an extremely rare congenital malformation; there are only 17 previously reported cases in the world literature. The syndrome usually consists of complete or partial duplication of the vulva, vagina, uterus, urethra, bladder and colon, with normal ovaries and kidneys and associated congenital malformations, especially of the lumbar spine. The etiology is uncertain. Mortality in the 18 cases reviewed was 35%. Diagnostic evaluation should include a careful newborn physical examination for associated congenital malformations, especially congenital heart disease, along with a radiologic survey of the lumbar spine, gastrointestinal tract and urinary system. No gynecologic surgical treatment is needed except for cosmetic reasons.     

Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosing intramuscular myxoma by fine-needle aspiration: A multidisciplinary approach

The gross and microscopic appearances of aspirates from ten intramuscular myxomas are reported. The specimens were obtained from seven women and three men, ages 43 to 75, who had tumors involving the muscles of the thigh (7), upper arm (2), and forearm (1). Magnetic resonance (MR) imaging performed in six of the ten cases revealed well-defined, sharply demarcated tumors exhibiting low signal intensity relative to muscle on the T1-weighted images. The tumors were hyperintense to muscle on T2-weighted images. All aspirated tissues were clear, tenacious, and viscous. Smears contained few spindled and histiocytoid cells in an abundant mucoid background. Spindle cells demonstrated long cytoplasmic processes that in areas intertwined to form fibrillar tangles. Nuclei were oval to spindled with fine chromatin and inconspicuous nucleoli. Capillaries were sparse with simple (nonplexiform) branching. The differential diagnosis of myxoid lesions of the extremities includes benign entities such as myxoid schwannoma and neurofibroma, mesenchymal repair, and ganglion cyst, as well as malignant neoplasms such as myxoid liposarcoma, fibrosarcoma, malignant fibrous histiocytoma, and extraskeletal chondrosarcoma. The findings of this study revealed that, although the cytologic features were suggestive of intramuscular myxoma, a definitive diagnosis was often difficult, owing to scant cellularity and lack of distinctive cytologic features. The MR imaging findings may be utilized as an adjunct to the cytologic features to more confidently suggest a diagnosis of intramuscular myxoma. Diagn Cytopathol 1994;11:255–261. © 1994 Wiley-Liss, Inc.     

Challenging the world: patient safety and health care-associated infection.

Improving the safety of patient care is an issue which affects health systems in both developed and developing countries. To co-ordinate and accelerate improvements in patient safety, the World Health Organization (WHO) has supported the creation of the World Alliance for Patient Safety which was launched in October 2004. The six action areas of the Alliance are Patients for Patient Safety, Taxonomy, Research, Solutions for Patient Safety, Reporting and Learning, and a biennial Global Patient Safety Challenge. The first Challenge covering 2005-2006 was launched in October 2005 under the banner 'Clean Care is Safer Care'. The Challenge addresses health care-associated infection, a major, patient safety problem affecting hundreds of millions of people worldwide.