Phylogeny,taxonomy and diversification events in the Caliciaceae

Although the high degree of non-monophyly and parallel evolution has long been acknowledged within the mazaediate Caliciaceae (Lecanoromycetes, Ascomycota), a natural re-classification of the group has not yet been accomplished. Here we constructed a multigene phylogeny of the Caliciaceae-Physciaceae clade in order to resolve the detailed relationships within the group, to propose a revised classification, and to perform a dating study. The few characters present in the available fossil and the complex character evolution of the group affects the interpretation of morphological traits and thus influences the assignment of the fossil to specific nodes in the phylogeny, when divergence time analyses are carried out. Alternative fossil assignments resulted in very different time estimates and the comparison with the analysis based on a secondary calibration demonstrates that the most likely placement of the fossil is close to a terminal node rather than a basal placement in the Calicium clade. Our dating analysis show two successive events giving rise to main clades of mazaediate taxa within the Caliciaceae, in the Upper-Lower Cretaceous boundary and in the Paleocene. As a result of this study, Cyphelium is synonymized with Calicium, Acolium is resurrected, and the new genera Allocalicium and Pseudothelomma are described. Twelve new combinations are proposed: Acolium karelicum, Acolium marcianum, Allocalicium adaequatum, Calicium carolinianum, Calicium lecideinum, Calicium lucidum, Calicium notarisii, Calicium pinicola, Calicium trachyliodes, Pseudothelomma occidentale, Pseudothelomma ocellatum and Thelomma brunneum. A key for the mazaedium-producing Caliciaceae is included.     

Walking the thin line… ten years later: the dilemma of above- versus below-ground features to support phylogenies in the <Emphasis Type="Italic">Russulaceae</Emphasis> (Basidiomycota)

For the very first time, morpho-anatomical features of both fruiting bodies as well as below-ground structures have been confronted with a newly produced multigene phylogeny of root symbiotic basidiomycetes using one of the most speciose genera of ectomycorrhizal fungi (Russula, Russulales) as an example. In this first of two papers, the authors focus more specifically on below-ground structures. Our five-gene phylogeny divides the genus in five main clades, here interpreted as representing seven subgenera, all significantly supported. Although more conserved than features of fruiting bodies, the anatomy of ectomycorrhiza does not allow for an unambiguous characterization of the main clades resolved by phylogenetic analysis, but the anatomy of ectomycorrhiza performs better to naturally classify the species of this genus. Features of fruiting bodies remain much more adequate for the delimitation of terminal clades and are irreplaceable for morphological species identification. Tropical taxa mostly nest in ancient lineages, but are also present in some terminal clades of otherwise temperate species groups. The shift from plectenchymatic to pseudoparenchymatic ECM outer mantle structures happened most likely already in the paleotropics, and is here hypothesized to have facilitated a major diversification of the genus with new hosts in the northern hemisphere. Available data as well as our own observations on below ground structures of several Lactifluus species suggests that this genus shares with Russula the absence of lactifers in ECM mantles and rhizomorphs, contrary to species of Lactarius where lactifers are always present. First observations on rhizomorphs of species in Multifurca confirm the presence of vessel-like and ladder-like hyphae, also found in the other agarioid genera of this family, while distinct lactifers are only present in the lactarioid, but not in russuloid members of this genus.     

Evidence for the polyphyly of <Emphasis Type="Italic">Encoelia</Emphasis> and <Emphasis Type="Italic">Encoelioideae</Emphasis> with reconsideration of respective families in Leotiomycetes

This study focuses on the genus Encoelia and the subfamily Encoelioideae in the morphologically and ecologically diverse Helotiales. The 28S and 18S rDNA as well as tef1, rpb1 and rpb2 were sequenced for 70 species. Phylogenetic analyses revealed Encoelia and Encoelioideae to be highly polyphyletic, with species distributed among eight major lineages. Encoelia fascicularis and E. pruinosa belonged to Sclerotiniaceae and were combined in a new genus, Sclerencoelia. Rutstroemiaceae comprised E. tiliacea and Dencoeliopsis johnstonii, both accepted in Rutstroemia. The type of Encoelia, E. furfuracea, was closely related to species of Velutarina, Cenangiopsis and Crumenulopsis. These species together with members of Hemiphacidiaceae formed a clade conforming to the emended concept of Cenangiaceae, introduced here. Another resurrected family, Cordieritidaceae, comprised E. fimbriata, E. heteromera and species of Ameghiniella, Cordierites, Diplocarpa and Ionomidotis, characterised by inamyloid asci and a positive ionomidotic reaction. Encoelia glauca showed closest affinities with Chlorociboria species in Chlorociboriaceae. A new genus, Xeropilidium, with sporodochial and pycnidial synanamorphs, was described for the distinct encoelioid member of the Chaetomellaceae, previously known as E. fuckelii. Morphological and ecological synapomorphies were distinguished from convergent characters to delimit monophyletic taxa including encoelioid fungi. Incorporation of public sequences from various biological samples in ITS rDNA analyses allowed identification of sequenced organisms at species, genus, or family level and added information on the ecology of seversal taxa. Members of Cenangiaceae appeared to be widespread as endophytes. Inclusion of encoelioid genera in Chaetomellaceae and Sclerotiniaceae added xylicolous saprotrophs to these families.     

A six-gene phylogenetic overview of <Emphasis Type="Italic">Basidiomycota</Emphasis> and allied phyla with estimated divergence times of higher taxa and a phyloproteomics perspective

In this paper, we provide a phylogenetic overview of Basidiomycota and related phyla in relation to ten years of DNA based phylogenetic studies since the AFTOL publications in 2007. We selected 529 species to address phylogenetic relationships of higher-level taxa using a maximum-likelihood framework and sequence data from six genes traditionally used in fungal molecular systematics (nrLSU, nrSSU, 5.8S, tef1-α, rpb1 and rpb2). These species represent 18 classes, 62 orders, 183 families, and 392 genera from the phyla Basidiomycota (including the newly recognized subphylum Wallemiomycotina) and Entorrhizomycota, and 13 species representing 13 classes of Ascomycota as outgroup taxa. We also conducted a molecular dating analysis based on these six genes for 116 species representing 17 classes and 54 orders of Basidiomycota and Entorrhizomycota. Finally we performed a phyloproteomics analysis from 109 Basidiomycota species and 6 outgroup taxa using amino-acid sequences retrieved from 396 orthologous genes. Recognition of higher taxa follows the criteria in Zhao et al (Fungal Divers 78:239–292, 2016): (i) taxa must be monophyletic and statistically well-supported in molecular dating analyses, (ii) their respective stem ages should be roughly equivalent, and (iii) stem ages of higher taxa must be older than those of lower level taxa. The time-tree indicates that the mean of stem ages of Basidiomycota and Entorrhizomycota are ca. 530 Ma; subphyla of Basidiomycota are 406–490 Ma; most classes are 358–393 Ma for those of Agaricomycotina and 245–356 Ma for those of Pucciniomycotina and Ustilaginomycotina; most orders of those subphyla split 120–290 Ma. Monophyly of most higher-level taxa of Basidiomycota are generally supported, especially those taxa introduced in the recent ten years: phylum Entorrhizomycota, classes Malasseziomycetes, Moniliellomycetes, Spiculogloeomycetes, Tritirachiomycetes and orders Amylocorticiales, Golubeviales, Holtermanniales, Jaapiales, Lepidostromatales, Robbauerales, Stereopsidales and Trichosporonales. However, the younger divergence times of Leucosporidiales (Microbotryomycetes) indicate that its order status is not supported, thus we propose combining it under Microbotryales. On the other hand, the families Buckleyzymaceae and Sakaguchiaceae (Cystobasidiomycetes) are raised to Buckleyzymales and Sakaguchiales due to their older divergence times. Cystofilobasidiales (Tremellomycetes) has an older divergence time and should be amended to a higher rank. We however, do not introduce it as new class here for Cystofilobasidiales, as DNA sequences from these taxa are not from their respective types and thus await further studies. Divergence times for Exobasidiomycetes, Cantharellales, Gomphales and Hysterangiales were obtained based on limited species sequences in molecular dating study. More comprehensive phylogenetic studies on those four taxa are needed in the future because our ML analysis based on wider sampling, shows they are not monophyletic groups. In general, the six-gene phylogenies are in agreement with the phyloproteomics tree except for the placements of Wallemiomycotina, orders Amylocorticiales, Auriculariales, Cantharellales, Geastrales, Sebacinales and Trechisporales from Agaricomycetes. These conflicting placements in the six-gene phylogeny vs the phyloproteomics tree are discussed. This leads to future perspectives for assessing gene orthology and problems in deciphering taxon ranks using divergence times.     

Botryosphaeriaceae and Diaporthaceae associated with panicle and shoot blight of pistachio in California,USA

Botryosphaeria panicle and shoot blight was considered as one of the single greatest threats to the California pistachio industry in the last two decades. A large number of fungi with typical morphological characteristics of Botryosphaeriaceae and Diaporthe were collected from pistachios in 18 counties in California and deposited in our culture collection. The aims of this study were to identify these isolates, recognize the distribution of these fungal species and test their pathogenicity to pistachio cultivars. A total of 304 California isolates were identified based on comparisons of DNA sequence data of the ITS, TEF-1α and β-tubulin gene regions, and combined with the morphological features of the cultures and conidia. Research results showed that California isolates represent eight species of Botryosphaeriaceae and one species of Diaporthe. These species include Botryosphaeria dothidea, Diplodia seriata, Dothiorella iberica, Dot. sarmentorum, Lasiodiplodia citricola, L. gilanensis, Neofusicoccum mediterraneum, Neof. vitifusiforme and Diaporthe chamaeropis. Of the Botryosphaeriaceae, 86 % of the isolates were identified as Neof. mediterraneum, which distributed in all the sampled counties. On pistachio trees, in addition to isolates from California, Neof. mediterraneum from Arizona, Neof. australe from Australia, B. dothidea, Neof. parvum and Dia. viticola from Greece were also identified. Pathogenicity of the California fungi on pistachio cultivars, Kerman (female) and Peters (male), using a mycelium plug and conidial suspension inoculation methods showed that all these species are pathogenic to the two tested pistachio cultivars, with L. citricola, L. gilanensis being the most pathogenic species, followed by Neof. mediterraneum. This study represents the first comprehensive work on the species identification, distribution and pathogenicity of Botryosphaeriaceae and Diaporthe on pistachio in California.     

The family Amanitaceae: molecular phylogeny,higher-rank taxonomy and the species in China

Mushrooms in the basidiomycete family Amanitaceae are very important both economically and ecologically. However, the delimitation of the family is still controversial, in part due to limited taxon sampling and in part because of insufficient gene fragment employed for molecular phylogenetic analyses. Furthermore, species diversity in the family is likely to have been largely underestimated, due to morphological similarity between taxa and phenotypic plasticity. In this study, we examined 1190 collections, including 1008 Chinese and 182 external ones, and performed the first comprehensive phylogenetic analyses of Amanitaceae using multi-locus sequence data. To test the monophyly of the Amanitaceae, a concatenated (nrLSU, rpb1, and rpb2) dataset of 200 taxa of the order Agaricales was analyzed. To infer the phylogeny of Amanitaceae, a concatenated nrLSU, tef1-α, rpb2 and β-tubulin dataset (3010 sequences from ca. 890 samples with 2309 newly generated sequences) was used. In this dataset, 252 sequences from the types of 77 species were provided. Our results indicate that Amanitaceae is a monophyletic group, and consists of five genera, namely Amanita, Catatrama, Limacella, Limacellopsis and Myxoderma. It is clear that Catatrama is closely related to Limacella, however, the phylogenetic relationships among these genera remain largely unresolved. Amanita contains 95% of the species in the family, and is here divided into three subgenera and eleven sections (subgen. Amanita, containing: sect. Amanita, sect. Amarrendiae, sect. Caesareae and sect. Vaginatae; subgen. Amanitina, containing: sect. Amidella, sect. Arenariae, sect. Phalloideae, sect. Roanokenses, sect. Strobiliformes and sect. Validae; and subgen. Lepidella, containing sect. Lepidella). Subgen. Lepidella occupies the basal position in the genus. One-hundred and sixty-two species of Amanitaceae known from China are treated in this study, including 50 novel species and 112 known taxa. Amanita gleocystidiosa, A. pyriformis, A. atrofusca, A. subjunquillea var. alba and A. areolata are treated as synonyms of A. sychnopyramis f. subannulata, A. orientigemmata, A. umbrinolutea, A. subjunquillea and A. zangii, respectively. 26 extralimital taxa including a novel species, namely Catatrama indica, were included in our study to allow us to make comparisons between these and the Chinese taxa. DNA sequence data for all the species of Amanitaceae in China and keys for identification of the species are provided.     

High levels of endemism among Galapagos basidiolichens

This study is a re-assessment of basidiolichen diversity in the Galapagos Islands. We present a molecular phylogenetic analysis, based on 92 specimens from Galapagos, using two nuclear ribosomal DNA markers (ITS and nuLSU). We also re-examined the morphology and anatomy of all sequenced material. The molecular results confirm our previous assessment that all Galapagos basidiolichens belong to the Dictyonema clade, which in Galapagos is represented by four genera: Acantholichen, Cora, Cyphellostereum, and Dictyonema. Most species previously reported from Galapagos in these genera were at the time believed to represent widely distributed taxa. This conclusion, however, has changed with the inclusion of molecular data. Although almost the same number of species is distinguished, the phylogenetic data now suggest that all are restricted to the Galapagos Islands. Among them, six species are proposed here as new to science, namely Cora galapagoensis, Cyphellostereum unoquinoum, Dictyonema barbatum, D. darwinianum, D. ramificans, and D. subobscuratum; and four species have already been described previously, namely Acantholichen galapagoensis, Cora santacruzensis, Dictyonema pectinatum, and D. galapagoense, here recombined as Cyphellostereum galapagoense. Our analysis is set on a very broad phylogenetic framework, which includes a large number of specimens (N = 826) mainly from Central and South America, and therefore strongly suggests an unusually high level of endemism previously not recognized. This analysis also shows that the closest relatives of half of the basidiolichens now found in Galapagos are from mainland Ecuador, implying that they reached the islands through the shortest route, with all species arriving on the islands through independent colonization events.     

Complications in hepatic arterial infusion chemotherapy: retrospective comparison of catheter tip placement in the right/left hepatic artery vs. the gastroduodenal artery

Purpose

To compare the complication rates associated with hepatic arterial infusion chemotherapy (HAIC) for unresectable hepatocellular carcinoma (HCC) using two different catheter tip locations, the right/left hepatic artery (group 1) and the gastroduodenal artery (group 2).

Methods

Between April 2001 and March 2015, 88 patients (group 1, n?=?36; group 2, n?=?52) with unresectable HCC, underwent HAIC via a transfemorally placed infusion catheter. The incidence of complications related to catheter placement (including hepatic arterial occlusion, catheter dislocation, non-target embolization and port-catheter system infection) as well as catheter patency and patient survival were evaluated.

Results

The technical success rate was 100%. The overall complication rate was 17% (15/88 patients). The specific complications were as follows: hepatic artery occlusion, n?=?1 (group 2, n?=?1), gastroduodenal ulcer, n?=?6 (group 1, n?=?2; group 2, n?=?4); catheter dislocation, n?=?1 (group 2, n?=?1); port-catheter system infection, n?=?3 (group 2, n?=?3); and bleeding at the puncture site, n?=?4 (group 1, n?=?1; group 2, n?=?3).

Conclusions

The complication rates in groups 1 and 2 did not differ to a statistically significant extent.

     

The world’s ten most feared fungi

An account is provided of the world’s ten most feared fungi. Within areas of interest, we have organized the entries in the order of concern. We put four human pathogens first as this is of concern to most people. This is followed by fungi producing mycotoxins that are highly harmful for humans; Aspergillus flavus, the main producer of aflatoxins, was used as an example. Problems due to indoor air fungi may also directly affect our health and we use Stachybotrys chartarum as an example. Not everyone collects and eats edible mushrooms. However, fatalities caused by mushroom intoxications often make news headlines and therefore we include one of the most poisonous of all mushrooms, Amanita phalloides, as an example. We then move on to the fungi that damage our dwellings causing serious anxiety by rotting our timber structures and flooring. Serpula lacrymans, which causes dry rot is an excellent example. The next example serves to represent all plant and forest pathogens. Here we chose Austropuccinia psidii as it is causing devastating effects in Australia and will probably do likewise in New Zealand. Finally, we chose an important amphibian pathogen which is causing serious declines in the numbers of frogs and other amphibians worldwide. Although we target the top ten most feared fungi, numerous others are causing serious concern to human health, plant production, forestry, other animals and our factories and dwellings. By highlighting ten feared fungi as an example, we aim to promote public awareness of the cost and importance of fungi.     

Image-based monitoring of targeted biopsy-proven prostate cancer on active surveillance: 11-year experience

Purpose

To report our 11-year experience of Active Surveillance (AS) program focusing on modern transrectal ultrasound (TRUS)-based monitoring of targeted biopsy-proven cancer lesion.

Methods

Consecutive patients on AS, who had targeted biopsy-proven lesion followed by at least a repeat surveillance biopsy and three times TRUS monitoring of the identical visible lesion, were included. Doppler grade of blood flow signal within the lesion was classified from grade 0 to 3. Biopsy-proven progression was defined as upgrade of Gleason score or 25 % or greater increase in cancer core involvement.

Results

Fifty patients were included in this study. Clinical variables (median) included age (61 years), clinical stage (T1c, 42;T2, 8), PSA (4.6 ng/ml), and Gleason score (3 + 3, n = 41;3 + 4, n = 9). Of the 50 patients, 34 demonstrated pathological progression at a median follow-up of 4.4 years. In comparing between without (n = 16) and with (n = 34) pathological progression, there were significant differences in cancer core involvement at entry (p = 0.003), the major axis diameter (p = 0.001) and minor axis diameter (p = 0.001) of the visible lesion at entry, increase in the major axis diameter (p = 0.005) and minor axis diameter (p = 0.013), and upgrade of Doppler grade (p < 0.0001). In multivariate analysis for predicting pathological progression, the increase (≥25 %) in diameter of biopsy-proven lesion (hazard ratio, 15.314; p = 0.023) and upgrade of Doppler grade (hazard ratio, 37.409; p = 0.019) were significant risk factors.

Conclusions

Longitudinal monitoring of the TRUS-visible biopsy-proven cancer provides a new opportunity to perform per-lesion-based AS. The increase in diameter and upgrade of Doppler grade of the lesion were significant risk factors for biopsy-proven progression on AS.

     

Minimalinvasive Unfallchirurgie

Arthroscopic operations on the major joints account for a large proportion of those described as ‘minimally invasive trauma surgery’. The frequency of such operations in the different joints varies with the frequency with which they are injured. The joints onwhich the most frequent arthroscopic procedures and the greatest number of different arthroscopic techniques are performed are the knee and the shoulder, followed in order by the ankle, the elbow and the wrist. Implants and surgical techniques have been developed to allow minimally invasive plate osteosynthesis (MIPO) and minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of metaphyseal fractures. These techniques have made it possible to significantly improve final outcomes and to reduce the incidence of major complications substantially. Continuous development of arthroscopic and minimally invasive surgical techniques, instruments and implants means that in the near future the treatment of joint injuries and metaphyseal fractures will be synonymous with minimally invasive trauma surgery.     

Detrusor pressures in urodynamic studies during voiding in women

Introduction and hypothesis

To investigate detrusor pressure during voiding in women using urodynamic studies (UDS).

Methods

The study group comprised 57 women with non-neurogenic lower urinary tract symptoms. All patients underwent UDS between January 2010 and December 2014. UDS included filling cystometry, pressure flow study (PFS), uroflowmetry for the maximum flow rate (Qmax) and mean flow rate, and postvoid residuals. Existence of voluntary detrusor contraction was defined as a continuous and smooth increase in detrusor pressure (Pdet) after the instruction to micturate in the PFS. The bladder contractility index (BCI) was calculated as Pdet at Qmax?+?5 × Qmax. Statistical analyses were performed using the Mann–Whitney U test and p?<?0.05 was considered statistically significant.

Results

The PFS showed that 23 patients had detrusor contraction (Pdet+ group) and 34 patients had no detrusor contraction (Pdet? group) during voiding. There were no significant differences in urodynamic parameters between the Pdet+ and Pdet? groups except in Pdet at Qmax and BCI. In the Pdet??group, 21 patients showed an increase in abdominal pressure during voiding (Pabd+ group), while the other 13 patients did not (Pabd? group). There were no differences in any of the urodynamic parameters between the Pabd+ and Pabd? groups.

Conclusions

Based on UDS, an increase in detrusor or abdominal pressure may not be necessary in micturition in women. The present study suggests that relaxation of pelvic floor muscles including normal urethral function are important for micturition in women.

     

Suture to wound length ratio in abdominal wall closure: how well are we doing?

Purpose

Research has established that a ≥4:1 suture to wound (S:W) length ratio decreases incisional hernias. We evaluated our ability to obtain a 4:1 S:W length ratio in a surgery residency program.

Methods

Consecutive abdominal wall closures from 12/1/2013 through 4/9/2015 were reviewed. The length of the incisions and amount of suture used were measured. Patient demographics and operative variables were documented and compared related to inability to obtain a 4:1 ratio.

Results

One hundred patients underwent abdominal closure with S:W length measurements. Average wound length was 18.3 cm; average suture length used was 84.5 cm; and average S:W length ratio was 4.6:1. An S:W length ratio of ≥4:1 was achieved in 76% of cases. There was no difference in race, age, gender, BMI, type of procedure, or resident level in obtaining a 4:1 S:W length ratio. There was a significantly higher rate of not achieving a 4:1 ratio when two residents closed. Postoperative infection rate and hernia rate increased when a 4:1 S:W length ratio was not achieved compared with an adequate S:W length ratio.

Conclusions

Despite the known importance of achieving a 4:1 S:W length ratio for abdominal closure, it was only achieved in 76% of study patients. Improved education on the importance of fascial closure is needed.

     

Increased Bile Acids and FGF19 After Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Correlate with Improvement in Type 2 Diabetes in a Randomized Trial

Background

Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are both effective bariatric procedures to treat type 2 diabetes (T2DM) and obesity. The contribution of changes in bile acids (BAs) and fibroblast growth factor19 (FGF19) to such metabolic improvements is unclear.

Methods

We examined associations between changes in BAs, FGF19 (fasting and prandial), with changes in body weight, glycemia, and other metabolic variables in 61 obese patients with T2DM before and 1 year after randomization to SG or RYGB.

Results

Weight loss and diabetes remission (defined by HbA1c <?39 mmol/mol [<?5.7%] in the absence of glucose-lowering therapy) after RYGB and SG was similar (mean weight loss ??29 vs ??31 kg, p?=?0.50; diabetes remission proportion 37.5 vs 34%, p?=?1.0). Greater increments in fasting and prandial levels of total, secondary, and unconjugated BAs were seen after RYGB than SG. Fasting and prandial increases in total (r?=???0.3, p?=?0.01; r?=???0.2, p?=?0.04), secondary (r?=???0.3, p?=?0.01; r?=???0.4, p?=?0.01) and unconjugated BA (r?=???0.3, p?=?0.01; r?=?0.4, p?<?0.01) correlated with decreases in HbA1c, but not weight. Changes in 12α-OH/non 12α-OH were positively associated with prandial glucose increments (r?=?0.2, p?=?0.03), HbA1c (r?=?0.3, p?=?0.01), and negatively associated with changes in insulinogenc index (r?=???0.3, p?=?0.01). Only changes in prandial FGF19 were negatively associated with HbA1c (r?=???0.4, p?<?0.01) and visceral fat (r?=???0.3, p?=?0.04).

Conclusions/interpretation

The association between increases in secondary, unconjugated BAs and improvements in HBA1c (but not weight) achieved after both RYGB and SG suggest manipulation of BA as a potential strategy for controlling T2DM through weight-independent means.

     

Intra-pancreatic Distal Bile Duct Carcinoma is Morphologically,Genetically, and Clinically Distinct from Pancreatic Ductal Adenocarcinoma

Purpose

Differentiating intra-pancreatic distal bile duct carcinoma invading the pancreas from pancreatic ductal adenocarcinomas (PDAC) surrounding the distal common bile duct (CBD) can be challenging. Our aim is to identify clinical, morphological, and genetic features characteristic of intra-pancreatic distal bile duct carcinoma.

Methods

Clinicopathologic data of 550 patients undergoing a pancreaticoduodenectomy between September 1990 and May 2008 were reviewed. KRAS status was assessed with mass-spectrometric genotyping.

Results

Ninety-seven patients with intra-pancreatic adenocarcinomas surrounding the CBD were identified; slides were available for 80. Two relationships with the CBD were recognized as follows: type I (n?=?42): cancer grew concentrically around the CBD and type II (n?=?38): cancer grew asymmetrically around the CBD. Type I adenocarcinomas were associated with high-grade biliary dysplasia (45 vs. 13 %; p?=?0.003); type II were associated with high-grade pancreatic intra-epithelial neoplasia (PanIN-2 or -3) (39 vs. 9 %; p?=?0.003). Type I tumors had a better median survival (46 months) compared to type II (23 months) or other PDAC (20 months) (p?<?0.001). Mutated KRAS was identified in 3/26 (11 %) type I and 20/21 (95 %) type II cancers (p?<?0.001). There may be poorer survival in the presence of a KRAS mutation than wild-type KRAS (22.9 vs. 41.6 months; p?=?0.3).

Conclusions

Distal periductal adenocarcinomas fall into two distinct groups with biologic, morphologic and genetic differences. Those growing symmetrically around the CBD are more likely to be intra-pancreatic distal bile duct carcinomas and are associated with improved survival whereas cancers with asymmetric growth are more likely to have KRAS mutations and to be PDACs. These findings facilitate a more accurate histopathological diagnosis, which could improve patient selection for therapeutic trials.