Frontal sinus variation in large samples of extant species of the genera Pan, Gorilla and Homo

Frontal pneumatisation is not present in all primates, and among extant species, ethmoidally-derived frontal sinuses are present only in the genera Pan, Gorilla and Homo. A simple and repeatable method is described here to quantify variation in the shape, size and bilateral variation of the frontal sinuses. This has allowed the first large study of these variables, including analyses of large samples of P. paniscus, P. troglodytes, G. gorilla and of several geographically diverse populations of H. sapiens. Frontal sinus shape and size are potential phylogenetic markers in primate systematics. We suggest that, in contrast to an allometric relationship between endocranial and frontal sinus form in Pan and Gorilla, H. sapiens is autapomorphic in having highly variable, supero-inferiorly large frontal sinuses, whose size is unrestricted by variation in cranial form. However, we also describe differences in frontal pneumatisation between those taxa. H. sapiens differs from the other taxa in having relatively smaller frontal sinuses that are more variable in shape and size. In P. troglodytes, P. paniscus and G. gorilla, the shape and size of frontal pneumatisation correlates positively with the overall size of the braincase. This suggests that the large space available in the bone structures of the non-human primates analysed allows the sinuses to develop under only slight constraint (if any) from surrounding structures. In H. sapiens, a significant correlation is observed between the asymmetry in the anterior extension of the frontal lobes of the brain and the shape and extension of the frontal sinuses. We suggest that the more vertical orientation of the H. sapiens frontal bone, its reduced thickness, the reduction of the supraorbital tori and the increased influence of the frontal lobes appear to have modified the integration between the skull, brain and sinuses in the frontal region in our species compared to our nearest extant relatives. Our results reduce the possibility of a strong functional origin for the variation in size and shape of the frontal sinuses in the primates analysed

Frontal sinuses and human evolution

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species’ holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of Homo erectus. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species

Frontal sinuses and human evolution.

The frontal sinuses are cavities inside the frontal bone located at the junction between the face and the cranial vault and close to the brain. Despite a long history of study, understanding of their origin and variation through evolution is limited. This work compares most hominin species' holotypes and other key individuals with extant hominids. It provides a unique and valuable perspective of the variation in sinuses position, shape, and dimensions based on a simple and reproducible methodology. We also observed a covariation between the size and shape of the sinuses and the underlying frontal lobes in hominin species from at least the appearance of 'Homo erectus'. Our results additionally undermine hypotheses stating that hominin frontal sinuses were directly affected by biomechanical constraints resulting from either chewing or adaptation to climate. Last, we demonstrate their substantial potential for discussions of the evolutionary relationships between hominin species

Frontal sinus variation in extant species of the genera Pan, Gorilla and Homo

Frontal pneumatisation is not present in all primates, and among extant species, ethmoidally-derived frontal sinuses are present only in the genera Pan, Gorilla and Homo. A simple and repeatable method is described here to quantify variation in the shape, size and bilateral variation of the frontal sinuses. This has allowed the first large study of these variables, including analyses of large samples of P. paniscus, P. troglodytes, G. gorilla and of several geographically diverse populations of H. sapiens. Frontal sinus shape and size are potential phylogenetic markers in primate systematics. We suggest that, in contrast to an allometric relationship between endocranial and frontal sinus form in Pan and Gorilla, H. sapiens is autapomorphic in having highly variable, supero-inferiorly large frontal sinuses, whose size is unrestricted by variation in cranial form. However, we also describe differences in frontal pneumatisation between those taxa. H. sapiens differs from the other taxa in having relatively smaller frontal sinuses that are more variable in shape and size. In P. troglodytes, P. paniscus and G. gorilla, the shape and size of frontal pneumatisation correlates positively with the overall size of the braincase. This suggests that the large space available in the bone structures of the non-human primates analysed allows the sinuses to develop under only slight constraint (if any) from surrounding structures. In H. sapiens, a significant correlation is observed between the asymmetry in the anterior extension of the frontal lobes of the brain and the shape and extension of the frontal sinuses. We suggest that the more vertical orientation of the H. sapiens frontal bone, its reduced thickness, the reduction of the supraorbital tori and the increased influence of the frontal lobes appear to have modified the integration between the skull, brain and sinuses in the frontal region in our species compared to our nearest extant relatives. Our results reduce the possibility of a strong functional origin for the variation in size and shape of the frontal sinuses in the primates analysed

Adjuvant treatment of resectable biliary tract cancer with cisplatin plus gemcitabine: A prospective single center phase II study

BACKGROUND Biliary tract cancer (BTC) is a dismal disease, even after curative intent surgery. We conducted this prospective, non-randomized phase II study to evaluate the feasibility and efficacy of cisplatin and gemcitabine as adjuvant treatment in patients with resected BTC. METHODS Patients initially received gemcitabine 1000 mg/m2 alone on days 1, 8 and 15 every 28-days for a total of six cycles (single agent cohort), and after protocol amendment a combination therapy with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 was administered every 21 days for a total of eight cycles (combined regimen cohort). Treatment was planned to start within eight weeks after curative intent resection. Adverse events, disease-free survival and overall survival were assessed. RESULTS Overall 30 patients were enrolled in the study from August 2008 and last patient was enrolled at 2nd December 2014. The follow-up of the patients ended at 31st December 2016. The first 9 patients received single-agent gemcitabine. The interim analysis met the predefined feasibility criteria and, from September 2010 on, the second group of 21 patients received the combination of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the median relative dose intensity (RDI) was 100% (IQR 88.3-100). Patients treated with the combination cisplatin-gemcitabine received an overall median RDI of 100% (IQR 50-100) for cisplatin and 100% (IQR 75-100) for gemcitabine respectively. The most significant non-hematological adverse events (grade 3 or 4) were fatigue (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%). Abnormal liver function was seen in 10% of the patients. One patient died due to infectious complications during treatment with cisplatin and gemcitabine. The median disease-free survival (DFS) was 14.9 months (95% CI 0-33.8) with a corresponding 3-year DFS of 43.1 ± 9.1%. The median overall survival (OS) was 40.6 months (95% CI 18.8-62.3) with a 3-year OS of 55.7 ± 9.2%. No statistically significant differences in survival were seen between the two treatment cohorts. CONCLUSION Adjuvant chemotherapy with gemcitabine with or without cisplatin was well tolerated and resulted in promising survival of the patients. TRIAL REGISTRATION The study was retrospectively registered on 25th June 2009 at clinicaltrials.gov ( NCT01073839 )