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P S Bhathal

Publications and source records attributed to P S Bhathal.

At least 19 recordsLinked to original sources
PubMed2006

Liver fluke-associated and sporadic cholangiocarcinoma: an immunohistochemical study of bile duct, peribiliary gland and tumour cell phenotypes.

AIM: To compare cell phenotypes displayed by cholangiocarcinomas and adjacent bile duct lesions in patients from an area endemic in liver-fluke infestation and those with sporadic cholangiocarcinoma. METHODS: 65 fluke-associated and 47 sporadic cholangiocarcinomas and 6 normal livers were studied. Serial paraffin-wax sections were stained immunohistochemically with monoclonal antibodies characterising a Brunner or pyloric gland metaplasia cell phenotype (antigens D10 and 1F6), intestinal goblet cells (antigen 17NM), gastric foveolar apomucin (MUC5AC), a gastrointestinal epithelium cytokeratin (CK20) and the p53 protein. RESULTS: 60% of the 112 cholangiocarcinomas expressed antigen D10, 68% MUC5AC, 33% antigen 17NM and 20% CK20; 37% showed overexpression of p53. When present together in a cholangiocarcinoma, cancer cells expressing D10 were distinct from those displaying 17NM or MUC5AC. Many more fluke-associated cholangiocarcinomas than sporadic cholangiocarcinomas displayed 17NM and p53 expression. Most cases of hyperplastic and dysplastic biliary epithelium expressed D10 strongly. Pyloric gland metaplasia and peribiliary glands displayed D10 and 1F6, with peribiliary gland hyperplasia more evident in the livers with fluke-associated cholangiocarcinoma; goblet cells in intestinal metaplasia stained for 17NM. No notable association of expression between any two antigens (including p53) was found in the cancers. CONCLUSIONS: Most cases of dysplastic biliary epithelium and cholangiocarcinoma display a Brunner or pyloric gland cell phenotype and a gastric foveolar cell phenotype. The expression of D10 in hyperplastic and dysplastic epithelium and in cholangiocarcinoma is consistent with a dysplasia-carcinoma sequence. Many more fluke-associated cholangiocarcinomas than sporadic cholangiocarcinoma display an intestinal goblet cell phenotype and overexpress p53, indicating differences in the aetiopathology of the cancers in the two groups of patients.

Adult↗
PubMed2002

Liver failure complicating non-alcoholic steatohepatitis following allogeneic bone marrow transplantation for Shwachman-Diamond syndrome.

Bone marrow transplantation is potentially curative therapy for the hematologic complications associated with Shwachman-Diamond syndrome (SDS). This syndrome is, however, also associated with significant pancreatic and hepatic dysfunction, which may complicate BMT. We report a case of liver failure due to non-alcoholic steatohepatitis (NASH) following BMT for SDS. This case illustrates the need for assessing liver dysfunction pre-BMT in these patients, in addition to highlighting the potential risk posed by pre-existing steatosis for the development of rapidly progressive hepatic failure following transplantation.

Adult↗
PubMed2001

Local recurrence after curative anterior resection with principally blunt dissection for carcinoma of the rectum and rectosigmoid.

PURPOSE: The aim of this study was to determine the incidence of local pelvic recurrence of carcinoma of the rectum and rectosigmoid (tumors where the lower edge is 18 cm or less from the anal verge) in a consecutive series of patients operated on by a single surgeon. All patients underwent curative anterior resection and a formal anatomic dissection of the rectum where mobilization was achieved through a principally careful blunt manual technique along fascial planes, preserving an oncologic package. METHOD: During the period April 1986 to December 1997, 157 consecutive anterior resections for carcinoma of the rectum and rectosigmoid were performed by one surgeon (ALP). One hundred thirty-eight (87.9 percent) were curative, and 19 (12.1 percent) were palliative. The mean follow-up period was 46 +/- 31.6 (range, 2-140) months. Data were retrospectively collated and computer coded by an independent contracted medical research team. Follow-up data were available on all patients. RESULTS: Four (3.1 percent) of the 131 patients undergoing curative anterior resection had local recurrence. Local recurrences occurred between 16 and 38 months from the time of resection, and the cumulative risk of developing local recurrence at five years was 5.2 percent. All tumors in which pelvic recurrence occurred were high grade, and the probability of developing local recurrence at five years for this group was 13.9 percent, which is significantly higher compared with patients who had average or low-grade tumors (P = 0.01). The probability of developing local recurrence at five years for Stage I tumors was 0, Stage II was 5.9 percent, and Stage III was 8.9 percent. In addition, there was a significantly higher incidence of local recurrence in the group of patients undergoing ultralow anterior resection (between 3 and 6 cm from the anal verge) as compared with patients undergoing low or high anterior resection (P = 0.03). Local recurrence developed in 3 of 28 (10.7 percent) patients having ultralow anterior resection, 1 of 57 (1.8 percent) patients having low anterior resection (between 6 and 10 cm from the anal verge), and no patients having high anterior resection (above 10 cm from the anal verge). The clinical anastomotic leak rate for curative anterior resection was 7 of 131 patients (5.3 percent). Thirty-seven of the 131 (28.2 percent) required a proximal defunctioning stoma; 35 (41.2 percent) of these were established for low or ultralow anterior resections and 2 for high anterior resection. The overall five-year cancer-specific survival rate of the entire group of 131 patients was 81.8 percent, and the overall probability of being disease free at five years including both local and distal recurrence was 72.9 percent. Three local recurrences occurred in the 101 patients (77 percent) who did not receive any form of adjuvant therapy. One local recurrence occurred in the 18 patients (13.7 percent) who had adjuvant chemoradiation. No recurrence occurred in the 12 patients (9.2 percent) who had adjuvant chemotherapy alone. CONCLUSION: Curative anterior resection for carcinoma of the rectum and rectosigmoid with principally blunt dissection of the rectum in this study is associated with a 3.1 percent incidence and a 5.2 percent probability at five years of developing local recurrence. Evidence from this study indicates that, as with sharp pelvic dissection, a low incidence and probability of local recurrence can be achieved by a principally blunt mobilization technique through careful attention to preservation of fascial planes in the pelvis and removal of an oncologic package with selective rather than routine adjuvant or neoadjuvant chemoradiation.

Aged↗
PubMed2001

Overexpressed growth hormone (GH) synergistically promotes carcinogen-initiated liver tumour growth by promoting cellular proliferation in emerging hepatocellular neoplasms in female and male GH-transgenic mice.

BACKGROUND/AIMS: Growth hormone (GH), when overexpressed in male and female GH-transgenic mice, is known to induce liver tumours within 1 year. This study aimed to gain a clearer understanding of the interaction between GH and tumour cells in vivo. METHODS/RESULTS: The carcinogen diethylnitrosomine (DEN) was administered to neo-natal transgenic and non-transgenic mice maintained in a "hepatocarcinogenesis resistant" genetic background (C57BL/6J). Macroscopic, microscopic and liver weight/body weight ratio analyses revealed that carcinogen-induced hepatocarcinogenesis was dramatically accelerated in young GH-transgenic mice compared to non-transgenic counterparts. Image analysis of microscopic hepatocellular neoplasms showed rapidly increasing tumour burdens, and neoplastic foci size over time in young adult GH-transgenic mice. The magnitude of enhanced tumour growth was equivalent in both male and female transgenic mice, whereas much lower and sexually dimorphic tumour growth rates (males>females) were observed in non-transgenic mice treated with DEN. BrdU labelling experiments demonstrated that rapid tumour growth in carcinogen-treated GH-transgenic mice was due to the promotion of cell proliferation in emerging lesions. Tumour cell proliferation in young GH-transgenic mice was 2.6- and 4-fold higher, respectively, than that observed in similar age male and female non-transgenic mice. Interestingly, both GH-transgenic and non-transgenic mice displayed progressively slower tumour growth rates in older animals. CONCLUSION: Overall, GH synergistically promotes carcinogen-induced hepatocarcinogenesis in both sexes of GH-transgenic mice by stimulating tumour cell proliferation.

Animals↗
PubMed2001

Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is common in severely obese subjects and can progress to cirrhosis and liver failure. Predicting advanced or progressive disease may help in selecting patients for liver biopsy and assist the development of therapeutic options. METHODS: Liver biopsies were taken at laparoscopic obesity surgery in 105 consecutive patients. The clinical and biochemical variables were analyzed for correlation with specific histologic features. RESULTS: Twenty-six patients (25%) were found to have nonalcoholic steatohepatitis (NASH), and 11 (42%) of these had advanced fibrosis. A raised index of insulin resistance (odds ratio [OR] 9.3, 95% confidence interval [CI] 3.4-26), systemic hypertension (OR 5.2, 95% CI 2.0-13.5), and raised alanine aminotransferase (OR 8.6, 95% CI 3.1-23.5) were independent predictors of NASH. A combination of 2 or 3 of these predictors allows a sensitivity of 0.8 and specificity of 0.89 for NASH. Alcohol consumption was associated with a reduction in NASH (OR 0.35, 95% CI 0.12-1.00) and diabetes (OR 0.18, 95% CI 0.047-0.67). CONCLUSION: Insulin resistance and systemic hypertension, features of the metabolic syndrome, are independently associated with advanced forms of NAFLD. Moderate alcohol consumption seems to reduce the risk of NAFLD in the severely obese, possibly by reducing insulin resistance.

Adult↗
PubMed2001

Compound heterozygosity for haemochromatosis gene mutations and hepatic iron overload in allogeneic bone marrow transplant recipients.

Iron overload has been proposed as a cause of liver dysfunction after BMT Factors which could be relevant to iron overload include the number of red cell transfusions and mutations within the haemochromatosis gene (HFE). Two point mutations, Cys282Tyr and His63Asp, have been described within HFE. Cys282Tyr homozygosity is associated with haemochromatosis; the effect of compound heterozygosity, Cys282Tyr/His63Asp, on iron status is variable. We analysed HFE status in 52 allograft patients surviving more than 6 months. Compound heterozygosity was identified in three patients (Cases 1-3). Iron status and liver function were evaluated and, in Cases 1 and 2, liver histology and iron content as well. Case 3 who received 12 units of red cells had a normal ferritin and liver function. Cases 1 and 2 received 29 and 59 units, respectively, and had high serum ferritins and transferrin saturations, abnormal liver function and significant hepatic iron overload on biopsy. Iron overload in Case 1 patient progressed in the context of GVHD and in the absence of further transfusion, suggesting that liver GVHD may increase hepatic iron accumulation. These cases demonstrate the variable phenotypic expression of HFE compound heterozygosity in BMT recipients, which may be only partly explained by transfusional iron loading. Venesection or chelation therapy should be considered in patients with coexistent hepatic GVHD and iron overload.

Adult↗
PubMed2000

Vertebrate phylogeny of antigen D10: identification of a conserved foregut cell lineage.

The monoclonal antibody 5HL-5D11-D10 to antigen D10 identifies a cell lineage that is restricted to certain tissues of the human foregut. We investigated the tissue distribution of antigen D10 in mammals, birds, reptiles, amphibians and fish by immunohistochemical staining. Tissue from human and each of ten other mammalian species showed staining of gastric mucous neck cells and glands of the cardia and antrum, Brunner's glands, peribiliary glands and periductal glands of the pancreas. Six of the mammalian species also expressed antigen D10 in mucosa of the larger bronchi, and five expressed it to varying degree in small bowel distal to the duodenum and in colon (three of these five species). Antigen was not detected in any of the three species of bird studied. Both reptiles and amphibians showed strong staining for antigen D10 in the gastric mucous neck cells and pyloric glands, and in a subpopulation of secretory cells in the oesophagus, with the amphibian also expressing antigen in some epithelial cells of the mouth and lung. Although absent from two species of bony fish, antigen D10 was expressed by small groups of epithelial cells of the intestine of a shark, and generally by the epithelial and connective tissue cells of the gut and gills, and hepatocytes of one species of ray. The presence of antigen D10 in different tissues and species was confirmed by both an indirect ELISA and immunoblot analysis of tissue extracts. Our observations suggest that the D10 epitope characterises a subpopulation of mucus-secreting cells, predominantly of the foregut and associated organs, which has been conserved throughout terrestrial vertebrate evolution.

Animals↗
PubMed2000

A study of graft versus host disease using bile duct implants under the kidney capsule.

BACKGROUND/AIMS: Graft versus host disease (GVHD) following histoincompatible bone marrow transplantation may be modelled experimentally using irradiated metallothionein promoter-H-2Kb transgenic mice (MET-Kb mice), reconstituted with syngeneic non-transgenic spleen and lymph node (LN) cells. In this model, inflammation peaks at 3 weeks post-reconstitution, but resolves by 3 months, and is focussed on portal tracts and bile ducts (BD). The aim of this study was to determine if transgene-expressing hepatocytes play a role in the immune response, why portal tracts are selectively targeted, and which cell types are involved. METHODS: Intrahepatic BD (IHBD) with attached hepatocytes, or extrahepatic BD (EHBD) devoid of hepatocytes, were isolated from MET-Kb mice and implanted under the kidney capsule of transgenic (syngeneic) and congenic (allogeneic) mice. Three weeks post-implantation, BD were scored histologically for rejection or survival, and stained for various cell-surface molecules. RESULTS: Generally, IHBD survived better than EHBD, and T cells were the predominant infiltrating cell type in both implants. Both types of implants undergoing rejection expressed intercellular adhesion molecule-1 (ICAM-1) and leukocyte function antigen-1 (LFA-1) at high density; BD and the underlying kidney parenchyma also expressed class I and II major histocompatibility complex (MHC). CONCLUSIONS: The rejection of both groups of implants by congenic recipients suggests that BD from MET-Kb mice express the transgene, but the reason for the selective targeting of portal tracts rather than transgene-expressing hepatocytes remains unclear. One possible explanation is that dendritic cells/antigen-presenting cells (DC/APC) in portal tracts, which express high levels of MHC and co-stimulatory molecules, are the primary targets, and that BD are infiltrated and destroyed as 'bystanders'.

Animals↗
PubMed1999

High, persistent hepatocellular proliferation and apoptosis precede hepatocarcinogenesis in growth hormone transgenic mice.

AIMS/BACKGROUND: Growth hormone (GH) transgenic mice are known to develop hepatocellular adenomas and carcinomas. In order to understand more about hepatocarcinogenesis in the GH-transgenic mouse model we quantitated the rates of hepatocellular proliferation and apoptosis in these mice. METHODS: Two lines of GH-transgenic mice and non-transgenic control mice were generated and sacrificed at regular intervals between one and nine months. Hepatocellular replication was measured by in vivo incorporation of bromodeoxyuridine (BrdU) and counting BrdU-positive nuclei in histological liver sections. Serial sections taken from these mouse livers were also assessed for rates of hepatocellular apoptosis using the in situ end-labelling of fragmented DNA (TUNEL) method. RESULTS: High levels of hepatocellular replication were sustained life-long in this model. Increased rates of hepatocellular proliferation preceded the onset of hepatic inflammation, a prominent feature in the liver pathology of GH-transgenic mice. In tumour tissue, cellular proliferation was up to 17-fold greater than in surrounding non-tumour tissue. Apoptosis rates were also elevated in non-tumour regions of GH-transgenic mouse livers compared to controls. Interestingly, large dysplastic hepatocytes were common in the fraction of cells undergoing apoptosis, especially in older mice with inflamed livers. The increase in the rate of hepatocellular apoptosis in GH-transgenic animals largely balanced the augmented levels of proliferation seen in these mice. In tumour tissue, however, the profound increase in the number of proliferating tumour cells outstripped the increase in apoptosis. CONCLUSION: Relatively high and enduring levels of hepatocellular replication and apoptosis precede hepatocarcinogenesis in GH-transgenic mice. Increased cellular proliferation and resistance to apoptosis were evident in tumour growth in older animals.

Adenoma↗
PubMed1998

The effect of hepatocyte enlargement on the hemodynamic characteristics of the isolated perfused rat liver preparation.

The influence of hepatocyte enlargement on intrahepatic hemodynamics was assessed in the isolated perfused rat liver preparation (IPRL) using two experimental models: hypotonic liver cell swelling and phenobarbitone-induced hepatocyte hypertrophy. The analysis of pressure-flow data obtained from the portal vascular bed over a flow range of 0 to 70 mL/min in the presence of a maximally-effective concentration of the vasodilator agent papaverine hydrochloride (6 x 10(-4) mol/L) enabled the calculation of P0, an estimate of the pressure required to passively distend the intrahepatic vasculature, and Gmax, the maximal portal vascular conductance. By comparison with an isotonic perfusion medium (Krebs-Henseleit buffer [KH] containing 2.5% bovine serum albumin [BSA]), perfusion with a hypotonic medium induced a significant increase in mean hepatocyte cross-sectional area (H(A)) (590 +/- 21 vs. 324 +/- 23 microm(-2), p < .05), a fall in Gmax (0.39 +/- 0.08 vs. 2.02 +/- 0.18 mL/min/g/mm hg, P < .001), and an increase in P0 (2.96 +/- 0.38 vs. 1.58 +/- 0.07 mm hg, P < .001). Phenobarbitone administered in drinking water (0.5 g/L) over a period of 60 days also induced a significant degree of hepatocyte enlargement (HA, 510 +/- 29 microm2, P < .05). On day 7, portal pressure measured in vivo in this group was significantly elevated compared with untreated controls (10.5 +/- 0.3 vs. 8.4 +/- 0.2 mm hg, P < .001), while in the IPRL Gmax was reduced (0.48 +/- 0.01 mL/min/g/mm hg, P < .001), and P0 was increased (2.23 +/- 0.17 mm hg, P < .05). However, with continued phenobarbitone treatment portal pressure, Gmax and P0 returned toward control values. The results confirm that hepatocyte enlargement is associated with a significant disturbance of intrahepatic hemodynamics but also that some adaptation occurs if hepatocyte enlargement is sustained over a prolonged period of time.

Animals↗
PubMed1998

Effect of interferon gamma on intrahepatic haemodynamics of the cirrhotic rat liver.

Sublethal injury of the liver with carbon tetrachloride (CCl4) induces the modulation of hepatic stellate cells to their myofibroblast (MFB) phenotype. Pretreatment or concomitant treatment with interferon gamma (IFNgamma) has been shown to inhibit this phenomenon. The aim of this study was to investigate the influence of IFNgamma treatment (50000 IU s.c. each day for 5 days) in rats with an established cirrhosis. Cirrhosis was induced with nine doses of CCl4. Comparison of biopsies before and after treatment with IFNgamma showed that the number of MFB present, identified by their alpha-smooth muscle actin immunoreactivity, was markedly reduced. Pressure-flow curves were constructed in isolated perfused liver preparations from IFNgamma-treated and saline-treated cirrhotic rats and analysed to obtain the extrapolated zero-flow intercept (Po, an index of hepatic vascular distensibility) and the vasodilator-induced change in resistance at a flow rate of 1 mL/min per g (deltaR1, an indication of the level of intrinsic vascular tone). In IFNgamma-treated rats, portal venous pressure measured in vivo was significantly reduced compared with controls (11.9+/-1.2 vs 16.0+/-0.5 mmHg, P< 0.05), Po was lower (2.03+/-0.18 vs 2.87+/-0.32 mmHg, P<0.05) and deltaR1 was decreased (0.39+/-0.15 vs 1.02+/-0.19 mmHg/mL per min per g, P< 0.05). The findings indicate that treatment with IFNgamma is effective in reducing MFB density in established CCl4-cirrhosis in the rat and results in a marked improvement in intrahepatic haemodynamics.

Animals↗
PubMed1997

Colonoscopy and biopsy.

The place of colonoscopy in the management of ulcerative colitis is restricted to clinical situations where the information provided will change clinical management. The information provided will be answers to the questions?inflammatory bowel disease, o r, in the patient with known colitis: inflammatory bowel disease?type?activity extent?dysplasia. Biopsy is pivotal to the diagnosis and provides the certainty of tissue diagnosis, assessment of activity and detection of dysplasia. Sigmoidoscopy is sufficient for providing information for clinical management in most circumstances, but colonoscopy is important where clinical features are disproportionate to sigmoidoscopic findings and systemic parameters of inflammatory activity; to determine type and extent of inflammatory bowel disease and when surveillance needs to start; and for biopsy to detect dysplasia. Ileoscopy is an important aspect of colonoscopy for differential diagnosis, and is the unique definer of total colonoscopy.

Biopsy↗
PubMed1997

Comparison of intrahepatic lymphocytes from normal and growth hormone transgenic mice with chronic hepatitis and liver cancer.

Mice expressing an ovine growth hormone-mouse metallothionein promoter fusion gene (METoGH mice) develop chronic hepatitis which becomes progressively more severe over time, hepatocellular adenomas, and eventually carcinoma in the oldest animals. T-lymphocyte expression of activation/memory-associated markers was compared between liver and blood lymphocytes isolated from METoGH and non-transgenic mice at 7, 10 and 12 months of age. The percentage of intrahepatic lymphocytes (IHL) which were CD4+ was markedly diminished in METoGH mice at all times. CD4+ and CD8+ IHL in METoGH mice expressed Ly-6A/6D at increased density, and were CD45RBlo at later time-points. Ly-6C+ and NK1.1+ CD4+ cells, which are common in normal mouse liver, were found at decreased frequency in METoGH livers. Further analysis demonstrated that, as a proportion of total T-cell receptor (TCR) alpha beta cells, NK1.1+ TCR alpha beta int CD4+ cell numbers (NKT cells) were diminished in the livers of METoGH mice. Observations made in METoGH mice support the hypothesis that sustained liver inflammation and hepatocellular injury may be linked to liver cancer. Additionally, it is possible that the relative lack of NKT cells may create an environment permissive for the growth of liver tumours.

Animals↗
PubMed1997

Endothelin-induced vasoconstriction in isolated perfused liver preparations from normal and cirrhotic rats.

Isolated, perfused rat liver preparations (IPRL), obtained from rats with carbon tetrachloride-induced cirrhosis and normal controls, were used to investigate responses to the vasoactive peptide endothelin-1 (ET-1). The mean perfusion resistance (R) of cirrhotic IPRL was significantly greater than that of controls (2.63 +/- 0.24 vs 1.54 +/- 0.14 mmHg/mL per min per g; P < 0.01). Both control and cirrhotic IPRL demonstrated a concentration-related increase in resistance (delta R) in response to ET-1, with a minimum effective concentration of approximately 3 x 10(-11) mol/L. The EC50 (-log of the 50% effective concentration) was not significantly different between cirrhotic and control IPRL (8.48 +/- 0.19 and 8.79 +/- 0.11, respectively); however, the maximum response to ET-1 was significantly greater in cirrhotic preparations (R: 10.4 +/- 2.2 vs 4.4 +/- 0.5 mmHg/mL per min per g, P < 0.01; DR, 7.8 +/- 2.1 vs 2.8 +/- 0.4 mmHg/mL per min per g, P < 0.01). Following maximal stimulation by ET-1, the mean portal-hepatic venous pressure gradient at a physiological flow rate of 1 mL/min per g was approximately 90% greater across cirrhotic IPRL than that across normal IPRL (11.2 +/- 2.0 vs 5.9 +/- 0.9 mmHg, respectively; P < 0.05). These results support the hypothesis that endogenously released ET-1 has a significant influence on the portal vascular resistance of cirrhotic liver in vivo and has an important role in the pathogenesis of portal hypertension.

Animals↗
PubMed1997

Gastric mucous neck cell and intestinal goblet cell phenotypes in gastric adenocarcinoma.

AIM: To investigate the phenotype of cells comprising diffuse and intestinal-type gastric cancers using monoclonal antibodies to two antigens. One antigen (designated D10) is characteristic of gastric mucous neck cells, cardiac glands, pyloric glands, and Brunner's glands. The second antigen (designated 17NM) is specific to the mucous vacuole of intestinal goblet cells. METHODS: Thirty two gastrectomy specimens with adenocarcinoma were studied. Serial paraffin sections were stained immunohistochemically for D10 and 17NM and histochemically for acid and neutral mucins. The cancers were classified histologically as of either diffuse or intestinal type according to Lauren. RESULTS: Of 15 diffuse-type gastric carcinomas, 11 showed the majority of cancer cells staining for D10 while four were typical signet ring cell cancers staining predominantly for 17NM; five tumours displayed both phenotypes with the two phenotypes segregated in different areas of the tumours. In contrast, of 16 intestinal-type cancers, six expressed 17NM, three D10, five neither antigen, and two expressed both antigens. One indeterminate-type cancer expressed both antigens. The staining of individual cells for D10 and 17NM was mutually exclusive in both diffuse and intestinal types. In contrast to the diffuse cancers, intestinal-type cancers typically expressed either antigen only in occasional small groups of cells and individual cells. CONCLUSIONS: In disease, the gastric stem cell can assume the capacity of the duodenal stem cell for divergent differentiation into either intestinal goblet cells (for example, as in intestinal metaplasia) or Brunner's gland cells (for example, as in pyloric gland/Brunner's gland metaplasia). With neoplastic transformation, this potential for divergent differentiation is maintained and gives rise to diffuse-type cancers that display either the D10 phenotype, the 17NM phenotype, or the clonal expression of both phenotypes. In the more cell cohesive (intestinal-type) tumours, differentiation for antigen expression is poorly developed and more frequently directed towards the intestinal goblet cell phenotype.

Adenocarcinoma↗
PubMed1996

The so-called bile duct adenoma is a peribiliary gland hamartoma.

The cell phenotype of so-called bile duct adenoma (BDA) was investigated immunohistochemically using monoclonal antibodies to two recently identified antigens (designated D10 and 1F6) extracted from human liver and cultured biliary epithelium. The acini and tubules of BDA consisted of serous and mucous cells that expressed D10 and 1F6. The intrahepatic peribiliary glands of normal liver, comprising intramural mucous glands and extramural tubuloalveolar seromucinous glands, similarly expressed D10 and 1F6 antigens. Antigen 1F6 was present in the cells forming the canals of Hering and normal bile ductules but not in interlobular and larger bile ducts. Proliferating bile ductules associated with large bile duct obstruction and alcoholic cirrhosis or the epithelia of the von Meyenberg complex and polycystic liver did not exhibit this combined profile of D10 and 1F6 expression and mucous cells. These findings suggest an origin of BDA from peribiliary glands rather than from bile ductules or ducts. Consistent with this view was our finding that 18 of the 30 BDA were spatially related to a large-calibre bile duct. Therefore, BDA, well known for its benign behavior is a small mass of disorganized but mature peribiliary gland acini and tubules within a variable amount of stroma and should properly be called a peribiliary gland hamartoma.

Adenoma↗