Hepato-bronchial fistula secondary to perforated sigmoid diverticulitis: a case report

Abstract Background Patients with diverticulitis are predisposed to hepatic abscesses via seeding through the portal circulation. Hepatic abscesses are well-documented sequelae of diverticulitis, however instances of progression to hepato-bronchial fistulization are rare. We present a case of diverticulitis associated with hepatic abscess leading to hepato-bronchial fistulization, which represents a novel disease course not yet reported in the literature. Case Presentation A 61-year-old Caucasian man presented with a history of unintentional weight loss and dyspnea both at rest and with exertion. He had a significant tobacco and alcohol misuse history. A massive right-sided pleural effusion was found on chest X-ray, which responded partially to chest tube insertion. A computed tomography scan of his thorax confirmed the presence of innumerable lung abscesses as well as a complex pleural effusion. An indeterminate tiny air pocket at the dome of the liver was also noted. A follow-up computed tomography scan of his abdomen revealed a decompressed hepatic abscess extending into the right pleural space and the right lower lobe. A sigmoid-rectal fistula was also revealed with focal colonic thickening, presumed to be the sequelae of remote or chronic diverticulitis. An interventional radiologist inserted a percutaneous drain into the decompressed hepatic abscess and the instillation of contrast revealed immediate filling of the right pleural space, lung parenchyma, and bronchial tree, confirming a hepato-bronchial fistula. After two concurrent chest tube insertions failed to drain the remaining pleural effusion completely, surgical lung decortication was conducted. Markedly thickened pleura were seen and a significant amount of gelatinous inflammatory material was debrided from the lower thoracic cavity. He recovered well and was discharged 10 days post-thoracotomy on oral antibiotics. The percutaneous liver abscess tube was removed 3 weeks post-discharge from hospital after the drain check revealed that the fistula and abscess had entirely resolved. Conclusions Refractory right-sided pleural effusion combined with constitutional symptoms should alert clinicians to search for possible hepatic abscess, especially in the context of diverticulitis. The rupture of an untreated hepatic abscess could lead to death from profound sepsis or rarely, as in this case, a hepato-bronchial fistula. Timely investigation and a multidisciplinary treatment approach can lead to improved patient outcomes

ShatterProof:Operational detection and quantification of chromothripsis

BackgroundChromothripsis, a newly discovered type of complex genomic rearrangement, has been implicated in the evolution of several types of cancers. To date, it has been described in bone cancer, SHH-medulloblastoma and acute myeloid leukemia, amongst others, however there are still no formal or automated methods for detecting or annotating it in high throughput sequencing data. As such, findings of chromothripsis are difficult to compare and many cases likely escape detection altogether.ResultsWe introduce ShatterProof, a software tool for detecting and quantifying chromothriptic events. ShatterProof takes structural variation calls (translocations, copy-number variations, short insertions and loss of heterozygosity) produced by any algorithm and using an operational definition of chromothripsis performs robust statistical tests to accurately predict the presence and location of chromothriptic events. Validation of our tool was conducted using clinical data sets including matched normal, prostate cancer samples in addition to the colorectal cancer and SCLC data sets used in the original description of chromothripsis.ConclusionsShatterProof is computationally efficient, having low memory requirements and near linear computation time. This allows it to become a standard component of sequencing analysis pipelines, enabling researchers to routinely and accurately assess samples for chromothripsis. Source code and documentation can be found at http://search.cpan.org/~sgovind/Shatterproof

ShatterProof: operational detection and quantification of chromothripsis

Abstract Background Chromothripsis, a newly discovered type of complex genomic rearrangement, has been implicated in the evolution of several types of cancers. To date, it has been described in bone cancer, SHH-medulloblastoma and acute myeloid leukemia, amongst others, however there are still no formal or automated methods for detecting or annotating it in high throughput sequencing data. As such, findings of chromothripsis are difficult to compare and many cases likely escape detection altogether. Results We introduce ShatterProof, a software tool for detecting and quantifying chromothriptic events. ShatterProof takes structural variation calls (translocations, copy-number variations, short insertions and loss of heterozygosity) produced by any algorithm and using an operational definition of chromothripsis performs robust statistical tests to accurately predict the presence and location of chromothriptic events. Validation of our tool was conducted using clinical data sets including matched normal, prostate cancer samples in addition to the colorectal cancer and SCLC data sets used in the original description of chromothripsis. Conclusions ShatterProof is computationally efficient, having low memory requirements and near linear computation time. This allows it to become a standard component of sequencing analysis pipelines, enabling researchers to routinely and accurately assess samples for chromothripsis. Source code and documentation can be found at http://search.cpan.org/~sgovind/Shatterproof

ShatterProof: operational detection and quantification of chromothripsis.

BackgroundChromothripsis, a newly discovered type of complex genomic rearrangement, has been implicated in the evolution of several types of cancers. To date, it has been described in bone cancer, SHH-medulloblastoma and acute myeloid leukemia, amongst others, however there are still no formal or automated methods for detecting or annotating it in high throughput sequencing data. As such, findings of chromothripsis are difficult to compare and many cases likely escape detection altogether.ResultsWe introduce ShatterProof, a software tool for detecting and quantifying chromothriptic events. ShatterProof takes structural variation calls (translocations, copy-number variations, short insertions and loss of heterozygosity) produced by any algorithm and using an operational definition of chromothripsis performs robust statistical tests to accurately predict the presence and location of chromothriptic events. Validation of our tool was conducted using clinical data sets including matched normal, prostate cancer samples in addition to the colorectal cancer and SCLC data sets used in the original description of chromothripsis.ConclusionsShatterProof is computationally efficient, having low memory requirements and near linear computation time. This allows it to become a standard component of sequencing analysis pipelines, enabling researchers to routinely and accurately assess samples for chromothripsis. Source code and documentation can be found at http://search.cpan.org/~sgovind/Shatterproof

Spatial genomic heterogeneity within localized, multifocal prostate cancer

Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis

Appui aux travaux conduits sur les systèmes avec semis direct et couvert végétal en Haute Guinée et en Guinée forestière : mission réalisée du 30 juin au 13 juillet 2002

Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates