The impact of age on post-operative liver function following right hepatectomy: a retrospective, single centre experience.

BACKGROUND: An increasing number of patients undergoing liver resection are of advancing age. The impact of ageing on liver regeneration and post-operative outcomes following a major resection are uncertain. We aimed to investigate risk factors for patients who developed Post Hepatectomy Liver Failure (PHLF) following right hepatectomy with age as the primary risk-factor. METHOD: Patients undergoing right hepatectomy between July 2004-July 2018 were included. ROC analysis was performed to identify at which age PHLF development-risk increased. Secondary endpoints were length of stay (LOS), complications, and cost. RESULTS: 332-patients were included. ROC demonstrated a cut-off age of 75-years in which PHLF risk increased. >75 there was an increased risk of PHLF (35% >75yrs vs. 7% <75yrs (p = <0.001), OR = 8.8 (95% CI = 3.6-21)) There was no difference between the age groups for any other PHLF risk factor. Patients >75yrs had longer LOS (11-days vs. 7-days (p = 0.04). Patients who developed PHLF had increased hospital costs: £10,987.50 (£6175-£46,050) vs. £2575 (£900-£46,050 p = 0.01). CONCLUSIONS: Patients >75yrs have increased risk of developing PHLF after right hepatectomy, contributing to increased mortality and economic burden. Pre-operatively identifying patients at-risk of PHLF is important to consider liver volume optimization strategies and improve outcomes.

Solvent-free synthesis of heteroannulated carbazoles: a novel class of anti-tumor agents.

A series of novel carbazole analogues that hold pyrido, isoxazolo, pyrimido and pyrazolo templates were designed and synthesised in good yield by grinding conditions. All the synthesised compounds were screened for their anti-tumor activity and displayed enviable selective growth inhibition on HeLa cell line compared to AGS cell line. Among these compounds, compound 2-(3',4'-diethoxy-benzylidene)-6-methyl-2,3,4,9-tetrahydro-carbazol-1-one,6-chloro-2-(3',4'-diethoxy-benzylidene)-2,3,4,9-tetrahydro-carbazol-1one, 2-(3',4'-diethoxy-benzylidene)-8-methyl-2,3,4,9-tetrahydro-carbazol-1-one, 3-(3',4'-diethoxyphenyl)-7-methyl-4,5-dihydro-10H-isoxazolo[3,4-a]carbazole, 7-chloro-3-(3',4'-diethoxyphenyl)-4,5-dihydro-10H-isoxazolo[3,4-a]carbazole, 4-(3',4'-diethoxyphenyl)-2-ethoxy-8-methyl-6,11-dihydro-5H-pyrido[2,3-a]carbazole-3-nitrile, 8-chloro-4-(3',4'-diethoxyphenyl)-2-ethoxy-6,11-dihydro-5H-pyrido[2,3-a]carbazole-3-nitrile, 4-(3',4'-diethoxyphenyl)-2-ethoxy-10-methyl-6,11-dihydro-5H-pyrido[2,3-a]carbazole-3-nitrile were found to have promising anti-tumor properities with reference to the standard ellipticine against the HeLa cancer cell line. All these intermediates showed IC50 outranged the standard ellipticine. The same compounds showed moderate activity against AGS cancer cell lines. The efforts were undertaken to optimize potency and selectivity of this class of compounds.

10-Methyl-2-oxo-4-phenyl-2,11-di-hydro-pyrano[2,3-a]carbazole-3-carbo-nitrile.

In the title mol-ecule, C23H14N2O2, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1018 (8) Å]. The pyrrole ring makes dihedral angles of 4.44 (5), 3.84 (5), 2.18 (5) and 56.44 (5)° with the pyran, fused benzene rings and phenyl ring, respectively. In the crystal, pairs of N-H⋯O hydrogen bonds generate R 2 (2)(14) loops and a C-H⋯N inter-action is also found. Mol-ecules are further linked by a number of π-π interactions [centroid-centroid distances vary from 3.5702 (5) to 3.7068 (6) Å], forming a three-dimensional network.

(E)-2-[(Furan-2-yl)methyl-idene]-7-methyl-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

In the title mol-ecule, C(18)H(15)NO(2), the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1317 (12) Å]. The pyrrole ring makes dihedral angles of 1.01 (8) and 18.56 (10)° with the benzene and furan rings, respectively. The cyclo-hexene ring adopts a half-chair conformation. In the crystal, pairs of N-H⋯O hydrogen bonds form an R(2) (2)(10) ring. Mol-ecules are further linked by C-H⋯O and C-H⋯π inter-actions, forming a three-dimensional network.

7-Methyl-1-phenyl-1,10-di-hydro-pyrazolo-[3,4-a]carbazole.

In the title mol-ecule, C20H15N3, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1082 (15) Å]. The pyrrole ring makes dihedral angles of 3.17 (8)/4.10 (9), 7.20 (9) and 44.62 (9)° with the fused benzene, pyrazole and phenyl rings, respectively. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming an infinite chain along [010]. Mol-ecules are further linked by nine π-π [centroid-centroid distances vary from 3.6864 (11) to 3.9802 (11) Å] and one C-H⋯π inter-action, forming a three-dimensional network.

2-Chloro-7,8,9,10-tetra-hydro-cyclo-hepta-[b]indol-6(5H)-one.

In the title mol-ecule, C(13)H(12)ClNO, the dihedral angle between the benzene and pyrrole rings is 1.38 (9)°. The cyclo-heptene ring adopts a distorted twist chair and sofa conformation. Inter-molecular N-H⋯O hydrogen bonds form an R(2) (2)(10) loop in the crystal packing. Further, weak C-H⋯O and C-H⋯π (involving the benzene ring) inter-actions are found in the crystal structure.

Shotgun proteomics of human bile in hilar cholangiocarcinoma.

The need to find biomarkers for hepatobiliary diseases including cholangiocarcinoma (CCA) has led to an interest in using bile as a proximal fluid in biomarker discovery experiments, although there are inherent challenges both in its acquisition and analysis. The study described here greatly extends previous studies that have started to characterise the bile proteome. Bile from four patients with hilar CCA was depleted of albumin and immunoglobulin G and analysed by GeLC-MS/MS. The number of proteins identified per bile sample was between 378 and 741. Overall, the products of 813 unique genes were identified, considerably extending current knowledge of the malignant bile proteome. Of these, 268 were present in at least 3 out of 4 patients. This data set represents the largest catalogue of bile proteins to date and together with other studies in the literature constitutes an important prelude to the potential promise of expression proteomics and subsequent validation studies in CCA biomarker discovery.

6-Methyl-2,3,4,9-tetra-hydro-1H-carbazole-1-thione.

In the title mol-ecule, C(13)H(13)NS, the dihedral angle between the benzene ring and the fused pyrrole ring is 0.71 (8)° and the cyclo-hexene ring is in an envelope form. The (CH(2))(3) atoms of the cyclo-hexene ring are disordered over two positions; the site-occupancy factor for the major component refined to 0.862 (4). In the crystal, inter-molecular N-H⋯S hydrogen bonds lead to the formation of centrosymmetric aggregates via an R(2) (2)(10) ring.

9-Ethyl-N-(3-nitro-benzyl-idene)-9H-carbazol-3-amine.

The title compound, C(21)H(17)N(3)O(2), crystallizes with two mol-ecules in the asymmetric unit. The carbazole groups show relatively small deviations from planarity [maximum displacements from the mean carbazole plane are 0.077 (7) and 0.101 (7) Å]. The dihedral angles between the 3-nitro-benzyl-idene-amine and carbazole groups are 37.9 (1) and 37.0 (1)° in the two mol-ecules.

5-Methyl-7,8,9,10-tetra-hydro-cyclo-hepta-[b]indol-6(5H)-one.

In the title mol-ecule, C(14)H(15)NO, the dihedral angle between the benzene and pyrrole rings is 1.99 (12)°. The cyclo-heptene ring adopts a slightly distorted boat conformation.

Synthesis and crystal structure of 1-hy-droxy-8-methyl-9H-carbazole-2-carbaldehyde.

Two crystallographically independent mol-ecules are present in the asymmetric unit of the title compound, C14H11NO2, with virtually identical geometries. The carbazole units are planar. The hy-droxy group at position 1, carbaldehyde group at position 2, and methyl group at position 8 (with the exception of two H atoms) are coplanar with the attached benzene rings. The dihedral angle between the two benzene rings is 2.20 (9)° in mol-ecule A and 2.01 (9)° in mol-ecule B. The pyrrole ring makes dihedral angles of 0.82 (10) and 1.40 (10)° [0.84 (10) and 1.18 (10)° in mol-ecule B] with the (-CH3)-substituted and (-OH and -CHO) substituted benzene rings, respectively. The mol-ecular structure is stabilized by the intra-molecular O-H⋯O hydrogen bonds, while the crystal structure features N-H⋯O and C-H⋯O hydrogen bonds. A range of π-π contacts further stabilizes the crystal structure.

2-(2,3,4,9-Tetra-hydro-1H-carbazol-1-ylidene)propane-dinitrile.

In the title mol-ecule, C(15)H(11)N(3), the dihedral angle between the benzene ring and the fused pyrrole ring is 1.07 (5)°. The cyclo-hexene ring adopts an envelope conformation: the dicyano-methyl-ene group at position 1 has a coplanar orientation. An intra-molecular N-H⋯N hydrogen bond generates an S(7) ring motif. Inter-molecular N-H⋯N hydrogen bonds form an R(2) (2)(14) ring in the crystal. A C-H⋯π inter-action involving the benzene ring is also found in the structure.

8-Methyl-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

In the title compound, C(13)H(13)NO, the dihedral angle between the benzene ring and the fused pyrrole ring is 0.96 (7)°. The cyclohexenone ring adopts an envelope conformation. Inter-molecular N-H⋯O hydrogen bonds form R(2) (2)(10) ring motifs in the crystal structure. Weak C-H⋯π inter-actions involving the benzene ring also occur.

2,5-Dimethyl-7,8,9,10-tetra-hydro-cyclo-hepta-[b]indol-6(5H)-one.

In the title mol-ecule, C(15)H(17)NO, the dihedral angle between the benzene and pyrrole rings is 1.45 (13)°. The cyclo-heptene ring adopts a slightly distorted boat conformation. In the crystal structure, inter-molecular C-H⋯O hydrogen bonds are found.

(E)-2-(Furan-2-yl-methyl-idene)-8-methyl-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

In the title mol-ecule, C(18)H(15)NO(2), the carbazole unit is not planar [maximum deviation from mean plane = 0.236 (2) Å]. The pyrrole ring makes dihedral angles of 1.21 (10) and 16.74 (12)° with the benzene and the furan rings, respectively. The cyclo-hexene ring adopts a half-chair conformation. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(10) loops.

1-(1-Hy-droxy-8-methyl-9H-carbazol-2-yl)ethanone.

The title compound, C(15)H(13)NO(2), crystallizes with four independent mol-ecules (A, B, C and D) in the asymmetric unit. The carbazole units are almost planar [maximum deviations = 0.015 (3) for A, 0.024 (3) for B, 0.026 (3) for C and 0.046 (3) Šfor D]. In all four mol-ecules, there is an O-H⋯O hydrogen bond involving the hy-droxy substituent and the carbonyl O atom of the adjacent acetyl group, which forms a six-membered ring. In the crystal, the four independent mol-ecules are linked via N-H⋯O and C-H⋯O inter-actions.

(E)-6-Chloro-2-(furan-2-yl-methyl-idene)-2,3,4,9-tetra-hydro-1H-carbazol-1-one.

In the title compound, C(17)H(12)ClNO(2), the carbazole unit is nearly planar [maximum deviation = 0.052 (1) Å]. The pyrrole ring makes dihedral angles of 1.92 (8) and 4.71 (11)° with the benzene and furan rings, respectively. Inter-molecular N-H⋯O hydrogen bonds form R(2) (2)(10) rings in the crystal structure.

4-Methyl-7,8,9,10-tetra-hydro-cyclo-hepta-[b]indol-6(5H)-one.

In the title compound, C(14)H(15)NO, the seven-membered ring exhibits a slightly distorted twist-boat conformation. The pyrrole ring forms a dihedral angle of 1.44 (10)° with the fused benzene ring. N-H⋯O hydrogen bonds form a centrosymmetric dimer and weak C-H⋯π inter-actions are also found in the crystal structure.

4,8-Dimethyl-pyrano[2,3-a]carbazol-2(11H)-one.

The mol-ecule of the title compound, C(17)H(13)NO(2), is nearly planar, the r.m.s. deviation for all non-H atoms excluding the two methyl C atoms being 0.089 Å. Inter-molecular N-H⋯O and C-H⋯O hydrogen bonds are found in the crystal structure. C-H⋯π inter-actions are also found. The H atoms of the methyl group attached to the benzene ring are disordered equally over two positions.

3-Methyl-3,4-dihydro-9H-carbazol-1(2H)-one.

In the title mol-ecule, C(13)H(13)NO, the dihedral angle between the benzene ring and the fused pyrrole ring is 2.03 (5)°. The methyl group at the 3-position has an equatorial orientation. The cyclo-hexene ring adopts an envelope conformation. Three C atoms of the cyclo-hexene ring, with their attached H atoms, and all atoms of the methyl group are disordered over two positions, the site-occupancy factors being 0.883 (2) and 0.117 (2). In the crystal structure, mol-ecules are stabilized by inter-molecular N-H⋯O hydrogen bonds. A C-H⋯π inter-action, involving the benzene ring, is also found.