Phase I PIANO trial-PIPAC-oxaliplatin and systemic nivolumab combination for gastric cancer peritoneal metastases: clinical and translational outcomes.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416). METHODS: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures. RESULTS: In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased. CONCLUSIONS: The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments.

Diagnostic challenges in tuberculous otitis media.

OBJECTIVES: To demonstrate the different clinical presentations of tuberculous otitis media and the management of selected cases. CASE REPORT: We report four cases of tuberculous otitis media with different clinical presentations, encountered between 1998 and 2002. None of the cases showed improvement with local or systemic antibiotics. The diagnosis, complications and management of these cases are discussed. CONCLUSIONS: A high index of clinical suspicion of tuberculous otitis media is required in patients who do not respond to standard antibiotic therapy for (nontuberculous) chronic middle-ear infection. Early diagnosis and treatment of tuberculous otitis media is important to avoid irreversible complications, surgical intervention and propagation of the disease.

Nasopharyngeal Carcinoma Database.

Nasopharyngeal carcinoma (NPC) is a cancer which is common in Asia. We report the establishment and early results of a multi-institutional prospective study of nasopharyngeal carcinoma, which seeks to systematically collect data as well as blood and tumour tissue samples from patients diagnosed with nasopharyngeal cancer at six centres in Malaysia. A total of 484 confirmed NPC cases were reported from the six participating centres between 1st July 2007 and 29th February 2008. Of these, 225 were newly diagnosed cases, 53 were recurrent cases and 206 were in remission at the time of reporting. Amongst the newly diagnosed cases, the most common presenting symptom was the presence of neck lumps (42%). Ophthalmo-neurologic symptoms were the presenting symptoms of 11% of the new cases. The majority of cases (75%) presented at stage III/IV.

Epithelial migration in open mastoidectomy cavities.

OBJECTIVE: To study the rate and pattern of epithelial migration in 18 dry, open mastoidectomy cavities. METHODS: This was a prospective study of 19 patients who had undergone mastoidectomy at a secondary (state) hospital and a tertiary referral centre at least 6 months previously and whose mastoid cavities were dry and not infected. Their mastoidectomy cavities were cleaned and India ink dots applied in its medial aspect under microscope. The patients were followed up at 1 or 2 weekly intervals for a minimum of 3 months or until the dots disappeared, whichever came first. On follow-up, the cavities were examined under microscope. If migration was observed, the rate and pattern were noted. RESULTS: Most (94.4%) of the cavities were noted to have epithelial migration laterally. No migration was observed in 5.6%. The start of migration of ink dots was noted in the 2nd week in 53% of the cavities, with a mean of 3.05 weeks. The mean rate of migration was 0.68 mm/week. CONCLUSION: Epithelial migration appears to be predominantly lateral (94.4%), with onset in the 2nd week (53%) at a rate of 0.68 mm/week. Epithelial migration might not play an important role in accumulation of wax in open mastoidectomy cavities.

Parotid duct mucocele.

Parotid swelling is a common presentation in ENT clinic. Most of the cases involve pathology of the gland. There are not many reported cases about parotid duct pathology. We describe a case of a large parotid duct mucocele with a calculus. Excision of the mucocele and superficial parotidectomy was performed. The post-operative recovery was uneventful.

Bilateral lacrimal sac mucocele with punctal and canalicular atresia.

Congenital absence of lacrimal puncta may be an isolated finding or associated with other developmental abnormality. Nasolacrirnal ducts can be absent thus predisposing to the formation of a congenital lacrimal mucocele. Punctal and canalicular agenesis is very rare. Four percent of new patients attending the lacrimal clinic at Moorfields Eye Hospital, London, UK. from 1981 to 1990 inclusive were diagnosed to have this condition. We describe a case of bilateral congenital absence of lacrimal puncta with lacrimal mucocele. Combined surgery was carried out by Ophthalmologist and Otolaryngologist with successful results.

Rice tungro bacilliform virus open reading frame 3 encodes a single 37-kDa coat protein.

Rice tungro bacilliform virus (RTBV) is a plant pararetrovirus and a member of the Caulimoviridae family and closely related to viruses in the Badnavirus genus. The coat protein of RTBV is part of the large polyprotein encoded by open reading frame 3 (ORF3). ORF3 of an RTBV isolate from Malaysia was sequenced (accession no. AF076470) and compared with published sequences for the region that encodes the coat protein or proteins. Molecular mass of virion proteins was determined by mass spectrometry (matrix-assisted laser desorption/ionization-TOF) performed on purified virus particles from three RTBV isolates from Malaysia. The N- and C-terminal amino acid sequences of the coat protein were deduced from the mass spectral analysis, leading to the conclusion that purified virions contain a single coat protein of 37 kDa. The location of the coat protein domain in ORF3 was reinforced as a result of immunodetection reactions using antibodies raised against six different segments of ORF3 using Western immunoblots after SDS-PAGE and isoelectrofocusing of proteins purified from RTBV particles. These studies demonstrate that RTBV coat protein is released from the polyprotein as a single coat protein of 37 kDa.

An enhanced NAS-RIF algorithm for blind image deconvolution.

We enhance the performance of the nonnegativity and support constraints recursive inverse filtering (NAS-RIF) algorithm for blind image deconvolution. The original cost function is modified to overcome the problem of operation on images with different scales for the representation of pixel intensity levels. Algorithm resetting is used to enhance the convergence of the conjugate gradient algorithm. A simple pixel classification approach is used to automate the selection of the support constraint. The performance of the resulting enhanced NAS-RIF algorithm is demonstrated on various images.

Near immunity to rice tungro spherical virus achieved in rice by a replicase-mediated resistance strategy.

ABSTRACT Rice tungro disease is caused by rice tungro bacilliform virus (RTBV), which is responsible for the symptoms, and rice tungro spherical virus (RTSV), which assists transmission of both viruses by leafhoppers. Transgenic japonica rice plants (Oryza sativa) were produced containing the RTSV replicase (Rep) gene in the sense or antisense orientation. Over 70% of the plants contained one to five copies of the Rep gene, with integration occurring at a single locus in most cases. Plants producing antisense sequences exhibited significant but moderate resistance to RTSV (60%); accumulation of antisense RNA was substantial, indicating that the protection was not of the homology-dependent type. Plants expressing the full-length Rep gene, as well as a truncated Rep gene, in the (+)-sense orientation were 100% resistant to RTSV even when challenged with a high level of inoculum. Accumulation of viral RNA was low, leading us to conclude that RTSV Rep-mediated resistance is not protein-mediated but is of the cosuppression type. Resistance was effective against geographically distinct RTSV isolates. In addition, RTSV-resistant transgenic rice plants were unable to assist transmission of RTBV. Such transgenic plants could be used in an epidemiological approach to combat the spread of the tungro disease.