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Background Bariatric surgery can influence the presentation, diagnosis, and management of gastrointestinal cancers. Oesophago-Gastric (OG) malignancies in patients who have had a prior bariatric procedure have not been fully characterised. Objective To characterise OG malignancies after bariatric procedures. Setting University Hospital, United Kingdom. Methods We performed a retrospective, multi-centre observational study of patients with OG malignancies after bariatric surgery to characterise this condition. Results This study includes 170 patients from 75 centres in 25 countries who underwent bariatric procedures between 1985 and 2020. At the time of the bariatric procedure, the mean age was 50.2 ± 10 years and the mean weight 128.8 ± 28.9 kg. Females comprised 57.3% (n=98) of the population. Most (n=64) patients underwent a Roux-en-Y Gastric Bypass (RYGB) followed by Adjustable Gastric Band (AGB) (n = 46) and Sleeve Gastrectomy (SG) (n = 43). Time to cancer diagnosis after bariatric surgery was 9.5 ± 7.4 years and mean weight at diagnosis was 87.4 ± 21.9 kg. The time lag was 5.9 ± 4.1 years after SG compared to 9.4 ± 7.1 years after RYGB and 10.5 ± 5.7 years after AGB. One-third of patients presented with metastatic disease. The majority of tumours were adenocarcinoma (82.9%). Approximately 1 in 5 patients underwent palliative treatment from the outset. Time from diagnosis to mortality was under one year for most patients who died over the intervening period. Conclusions The OGMOS (Oesophago-Gastric Malignancies after Obesity/ Bariatric Surgery) study presents the largest series to date of patients developing OG malignancies after bariatric surgery and attempts to characterise this condition.

Tumor lysis syndrome is a life-threatening complication comprising hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia attributed to release of intracellular contents. Although traditionally associated with leukemia and lymphoma after chemotherapy, it is known to occur in solid malignancies. We herein report a rare case of this syndrome after resection of bulky carcinoid tumor of the lung.

Due to the strong relationship between the Human Papillomavirus (HPV) "high-risk" subtypes and cervical cancers, most HPV-related studies have been focusing on the "high-risk" HPV subtypes 16 and 18. However, it has been suggested that the "low-risk" subtypes of HPV, HPV6 and HPV11, are the major cause of recurrent respiratory papillomatosis and genital warts. In addition, HPV 6 and 11 are also associated with otolaryngologic malignancies, carcinoma of the lung, tonsil, larynx and low-grade cervical lesions. Therefore, development of HPV therapeutic vaccines targeting on subtypes 6 and 11 E6 or E7 are in great need. In this report, we describe two novel engineered DNA vaccines that encode HPV 6 and 11 consensus E6/E7 fusion proteins (p6E6E7 and p11E6E7) by utilizing a multi-phase strategy. Briefly, after generating consensus sequences, several modifications were performed to increase the expression of both constructs, including codon/RNA optimization, addition of a Kozak sequence and a highly efficient leader sequence. An endoproteolytic cleavage site was also introduced between E6 and E7 protein for proper protein folding and for better CTL processing. The expressions of both constructs were confirmed by western blot analysis and immunofluorescence assay. Vaccination with these DNA vaccines could elicit robust cellular immune responses. The epitope mapping assay was performed to further characterize the cellular immune responses induced by p6E6E7 and p11E6E7. The HPV 6 and 11 E6 or E7-specific immunodominant and subdominant epitopes were verified, respectively. The intracellular cytokine staining revealed that the magnitude of IFN-γ and TNF-α secretion in antigen-specific CD8(+) cells was significantly enhanced, indicating that the immune responses elicited by p6E6E7 and p11E6E7 was heavily skewed toward driving CD8(+) T cells. Such DNA immunogens are interesting candidates for further studies on HPV 6 and 11-associated diseases.

DNA vaccines require significant engineering in order to generate strong CTL responses in both non-human primates and humans. In this study, we designed a clade C env gene (EY3E1-C) to decrease the genetic distances of virus isolates within clade C and focus the induced T cell responses to conserved clade C epitopes. After generating a consensus sequence by analyzing full-length clade C env early transmitter sequences, several modifications were performed to increase the expression of the EY3E1-C, including codon/RNA optimization, addition of Kozak sequence and addition of an IgE leader sequence. We also shortened the V1 and V2 loops to approximate early transmitter isolate sequences and the cytoplasmic tail was truncated to prevent envelope recycling. When studied as a DNA vaccine in Balb/c mice, compared to a primary codon-optimized clade C envelope DNA vaccine (p96ZM651gp140-CD5), this novel construct is up to three times more potent in driving CTL responses. Importantly this construct not only induces stronger cross-reactive cellular responses within clade C, it also induces stronger immune responses against clade B and group M envelope peptide pools than p96ZM651gp140-CD5. Epitope mapping demonstrated that EY3E1-C was able to induce clade C envelope-specific immune responses against 15 peptide pools, clade B envelope-specific immune responses against 19 peptide pools and group M envelope-specific immune responses against 16 peptide pools out of 29, respectively, indicating that a significant increase in the breadth of induced immune responses. The analysis of antibody responses suggested that vaccination of pEY3E1-C could induce a clade C envelope-specific antibody response. The cellular immune responses of pEY3E1-C could be further enhanced when the DNA was delivered by using electroporation (EP). Thus, the synthetic engineered consensus EY3E1-C gene is capable of eliciting stronger and broader CTL responses than primary clade C envelopes. This finding suggests that such synthetic immunogens could be important for examination of their potential as part of an efficient HIV DNA vaccine.

It was discovered almost 20 years ago that plasmid DNA, when injected into the skin or muscle of mice, could induce immune responses to encoded antigens. Since that time, there has since been much progress in understanding the basic biology behind this deceptively simple vaccine platform and much technological advancement to enhance immune potency. Among these advancements are improved formulations and improved physical methods of delivery, which increase the uptake of vaccine plasmids by cells; optimization of vaccine vectors and encoded antigens; and the development of novel formulations and adjuvants to augment and direct the host immune response. The ability of the current, or second-generation, DNA vaccines to induce more-potent cellular and humoral responses opens up this platform to be examined in both preventative and therapeutic arenas. This review focuses on these advances and discusses both preventive and immunotherapeutic clinical applications.