The use of Human Subjects in Biomedical Research: A Problematic Scientific Past Shapes Present Ethical Challenges

The ethics of human experimentation is a relatively new phenomenon in medicine. The Nuremberg Code and the Helsinki Declaration focused on informed consent in human experimentation. More recently, ethicists have begun to emphasize that, beyond the need for consent, the \"content\" of the experiment also needs to be ethical. The method and process of the experiment must be humanizing and affirming of the subject as moral agent. The religious perspective has provided a comprehensive moral foundation, demanding respect for the subjects\' moral agency and their right to he treated as equally worthy members of the human community, thus ensuring the integrity of the subject as person

Accessing surgical care for pancreaticoduodenectomy: Patient variation in travel distance and choice to bypass hospitals to reach higher volume centers

BackgroundWhile better outcomes at high‐volume surgical centers have driven regionalization of complex surgical care, access to high‐volume centers often requires travel over longer distances. We sought to evaluate travel patterns of patients undergoing pancreaticoduodenectomy (PD) for pancreatic cancer to assess willingness of patients to travel for surgical care.MethodsThe California Office of Statewide Health Planning database was used to identify patients who underwent PD between 2005 and 2016. Total distance traveled, as well as whether a patient bypassed the nearest hospital that performed PD to get to a higher‐volume center was assessed. Multivariate analyses were used to identify factors associated with bypassing a local hospital for a higher‐volume center.ResultsAmong 23 014 patients who underwent PD, individuals traveled a median distance of 18.0 miles to get to a hospital that performed PD. The overwhelming majority (84%) of patients bypassed the nearest providing hospital and traveled a median additional 16.6 miles to their destination hospital. Among patients who bypassed the nearest hospital, 13,269 (68.6%) did so for a high‐volume destination hospital. Specifically, average annual PD volume at the nearest “bypassed” vs final destination hospital was 29.6 vs 56 cases, respectively. Outcomes at bypassed vs destination hospitals varied (incidence of complications: 39.2% vs 32.4%; failure‐to‐rescue: 14.5% vs 9.1%). PD at a high‐volume center was associated with lower mortality (OR = 0.46 95% CI, 0.22‐0.95). High‐volume PD ( > 20 cases) was predictive of hospital bypass (OR = 3.8 95% CI, 3.3‐4.4). Among patients who had surgery at a low‐volume center, nearly 20% bypassed a high‐volume hospital in route. Furthermore, among patients who did not bypass a high‐volume hospital, one‐third would have needed to travel only an additional 30 miles or less to reach the nearest high‐volume hospital.ConclusionMost patients undergoing PD bypassed the nearest providing hospital to seek care at a higher‐volume hospital. While these data reflect increased regionalization of complex surgical care, nearly 1 in 5 patients still underwent PD at a low‐volume center.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153129/1/jso25750.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153129/2/jso25750_am.pd

Hereditary Pancreatic and Hepatobiliary Cancers

Hereditary etiologies of pancreatic and hepatobiliary cancers are increasingly recognized. An estimated >10% of pancreatic and increasing number of hepatobiliary cancers are hereditary. The cumulative risk of hereditary pancreatic cancer ranges from measurable but negligible in cystic fibrosis to a sobering 70% in cases of hereditary pancreatitis. Candidates for pancreatic cancer surveillance are those with a risk pancreatic cancer estimated to be >10-fold that of the normal population. Screening for pancreatic cancer in high-risk individuals is typically performed by endoscopic ultrasound and should begin at least 10 years prior to the age of the youngest affected relative. Disease states known to be associated with increased risk of hepatocellular cancer include hereditary hemochromatosis, autoimmune hepatitis, porphyria, and α1-antitrypsin deficiency, with relative risks as high as 36-fold. Although much less is known about hereditary bile-duct cancers, Muir-Torre syndrome and bile salt export pump deficiency are diseases whose association with hereditary carcinogenesis is under investigation

What to expect when you're expecting a hepatopancreatobiliary surgeon: self‐reported experiences of HPB surgeons from different training pathways

BackgroundHepatopancreatobiliary (HPB) surgery fellowship training has multiple paths. Prospective trainees and employers must understand the differences between training pathways. This study examines self‐reported fellowship experiences and current scope of practice across three pathways.MethodsAn online survey was disseminated to 654 surgeons. These included active Americas Hepato‐Pancreato‐Biliary Association (AHPBA) members and recent graduates of HPB, transplant–HPB and HPB–heavy surgical oncology fellowships.ResultsA total of 416 (64%) surgeons responded. Most respondents were male (89%) and most were practising in an academic setting (83%). 290 (70%) respondents underwent formal fellowship training. Although fellowship experiences varied, current practice was largely similar. Minimally invasive surgery (MIS) and ultrasound were the most commonly identified areas of training deficiencies and were, respectively, cited as such by 47% and 34% of HPB‐, 49% and 50% of transplant‐, and 52% and 25% of surgical oncology‐trained respondents. Non‐HPB cases performed in current practice included gastrointestinal (GI) and general surgery cases (56% and 49%, respectively) for HPB‐trained respondents, transplant and general surgery cases (87% and 21%, respectively) for transplant‐trained respondents, and GI surgery and non‐HPB surgical oncology cases (70% and 28%, respectively) for surgical oncology‐trained respondents.ConclusionsFellowship training in HPB surgery varies by training pathway. Training in MIS and ultrasound is deficient in each pathway. The ultimate scope of non‐transplant HPB practice appears similar across training pathways. Thus, training pathway choice is best guided by the training experience desired and non‐HPB components of anticipated practice.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113167/1/hpb12430.pd

Colorectal Liver Metastases

The diagnosis and management of CRLM is complex and requires a multidisciplinary team approach for optimal outcomes. Over the past several decades, the 5-year survival following resection of CRLM has increased and the criteria for resection have broadened substantially. Even patients with multiple, bilateral CRLM, previously thought unresectable, may now be candidates for resection. Two-stage hepatectomy, repeat curative-intent hepatectomy, and even selected resection of extrahepatic metastases have further increased the number of patients who may be treated with curative intent. Multiple liver-directed therapies exist to treat unresectable, incurable patients with adequate survival benefit and morbidity rates

Phenotypic plasticity in the Caribbean sponge Callyspongia vaginalis (Porifera: Haplosclerida)

Sponge morphological plasticity has been a long-standing source of taxonomic difficulty. In the Caribbean, several morphotypes of the sponge Callyspongia vaginalis have been observed. To determine the taxonomic status of three of these morphotypes and their relationship with the congeneric species C. plicifera and C. fallax, we compared the spicule composition, spongin fiber skeleton and sequenced fragments of the mitochondrial genes 16S and COI and nuclear genes 28S and 18S ribosomal RNA. Phylogenetic analyses with ribosomal markers 18S and 28S rRNA confirmed the position of our sequences within the Callyspongiidae. None of the genetic markers provided evidence for consistent differentiation among the three morphotypes of C. vaginalis and C. fallax, and only C. plicifera stood as a distinct species. The 16S mtDNA gene was the most variable molecular marker for this group, presenting a nucleotide variability (π = 0.024) higher than that reported for COI. Unlike recent studies for other sponge genera, our results indicate that species in the genus Callyspongia maintain a high degree of phenotypic plasticity, and that morphological characteristics may not reflect reproductive boundaries in C. vaginalis

Plasticidad fenotípica de la esponja Callyspongia vaginalis (Porifera: Haplosclerida)

Sponge morphological plasticity has been a long-standing source of taxonomic difficulty. In the Caribbean, several morphotypes of the sponge Callyspongia vaginalis have been observed. To determine the taxonomic status of three of these morphotypes and their relationship with the congeneric species C. plicifera and C. fallax, we compared the spicule composition, spongin fiber skeleton and sequenced fragments of the mitochondrial genes 16S and COI and nuclear genes 28S and 18S ribosomal RNA. Phylogenetic analyses with ribosomal markers 18S and 28S rRNA confirmed the position of our sequences within the Callyspongiidae. None of the genetic markers provided evidence for consistent differentiation among the three morphotypes of C. vaginalis and C. fallax, and only C. plicifera stood as a distinct species. The 16S mtDNA gene was the most variable molecular marker for this group, presenting a nucleotide variability (π = 0.024) higher than that reported for COI. Unlike recent studies for other sponge genera, our results indicate that species in the genus Callyspongia maintain a high degree of phenotypic plasticity, and that morphological characteristics may not reflect reproductive boundaries in C. vaginalis.La gran plasticidad morfológica de ciertas esponjas dificulta una correcta clasificación taxonómica. En el Caribe, se han observado varios morfotipos de la esponja Callyspongia vaginalis a nivel de colores y formas. Con el fin de determinar su clasificación taxonómica, se muestrearon y analizaron tres morfotipos de C. vaginalis y sus especies congenéricas C. plicifera y C. fallax. Para cada muestra, se observó la composición espicular y del esqueleto dermal y se secuenciaron parte de los genes mitocondriales 16S y COI y parte de los genes ribosomales 28S y 18S. Los análisis filogenéticos con los genes ribosomales 18S y 28S confirmaron la posición taxonómica de las secuencias obtenidas. Ninguno de los marcadores genéticos utilizados reveló diferencias consistentes entre los tres morfotipos de C. vaginalis y C. fallax, y sólo C. pleicifera apareció en los análisis como una especie distinta. El gen mitocondrial 16S fue el marcador molecular más variable para este grupo, presentando una variabilidad nucleotídica (p = 0.024) superior a la descrita para COI. Nuestros resultados indican que las especies del género Callyspongia presentan una gran plasticidad fenotípica y que estas diferencias morfológicas no suponen barreras reproductivas para C. vaginalis

Synchronous primary colorectal and liver metastasis: impact of operative approach on clinical outcomes and hospital charges

AbstractObjectivesThe management of patients with colorectal cancer (CRC) and synchronous colorectal liver metastasis (CLM) remains controversial. The present study was conducted in order to assess the clinical and economic impacts of managing synchronous CLM with a staged versus a simultaneous surgery approach.MethodsA total of 224 patients treated for synchronous CLM during 1990–2012 were identified in the Johns Hopkins Hospital liver database. Data on clinicopathological features, perioperative outcomes and total hospital charges (inflation-adjusted) were collected and analysed.ResultsOverall, 113 (50.4%) patients underwent staged surgery and 111 (49.6%) were submitted to a simultaneous CRC and liver operation. At surgery, liver-directed therapy included hepatectomy (75.0%) or combined resection and ablation (25.0%). Perioperative morbidity (30.0%) and mortality (1.3%) did not differ between groups (both P > 0.05). Median total length of hospitalization was longer in the staged (13 days) than the simultaneous (7 days) surgery group (P < 0.001). Median total hospital charges were higher among patients undergoing staged surgery (US$61 938) than among those undergoing a simultaneous operation (US$34 114) (P < 0.01). Median (simultaneous, 32.4 months versus staged, 39.6 months; P = 0.65) and 5-year (simultaneous, 27% versus staged, 29%; P = 0.60) overall survival were similar between groups.ConclusionsPatients with synchronous CLM managed with either simultaneous or staged surgery have comparable perioperative and longterm outcomes. However, patients treated with simultaneous surgery spent an average of 6 days fewer in hospital, resulting in a reduction of median hospital charges of US$27 824 (55.1%). When appropriate and technically feasible, the simultaneous surgery approach to synchronous CLM should be preferred