Biomedical subjects

M Tomikawa

Publications and source records attributed to M Tomikawa.

At least 37 records · Page 2Linked to original sources

PubMed2000

Role of vascular endothelial growth factor in portal hypertensive gastropathy.

BACKGROUND AND AIMS: Portal hypertensive gastropathy (PHG) is now recognized as a distinct entity; however, the angiogenesis in the portal hypertensive gastric mucosa has yet to be elucidated. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in both physiological and pathological angiogenesis. The aim of this study was thus to examine the function of VEGF in the portal hypertensive and non-portal hypertensive gastric mucosa. METHOD: Forty-five cirrhotic patients were divided into 3 groups as follows. Group I included 15 patients without PHG who were treated with 1.5 g teprenone/day for 8 weeks: PHG(-)-t. Group II included 15 patients with PHG who were not treated with teprenone: PHG(+)-n. Group III included 15 patients with PHG who were treated with teprenone for 8 weeks: PGH(+)-t. The gastric mucosal blood flow (GMBF), the concentration of gastric mucosal VEGF and hexosamine and the endoscopic findings were studied both before and after medication. RESULTS: Before teprenone treatment, the GMBF in the antrum, fundus, fornix were significantly higher in PHG(+)-n than PHG(-)-t. After treatment, the GMBF in the fundus and fornix significantly decreased more than before treatment in the PHG(+)-t. After treatment, the GMBF in the antrum increased significantly more than before treatment in PHG(-)-t. The gastric VEGF and hexoxamine concentration in the antrum were significantly higher in PHG(+)-n than in PHG(-)-t. After treatment, the gastric VEGF and hexosamine concentration in the antrum significantly decreased in PHG(+)-t while no change in concentration was recognized in PHG(+)-n. In the endoscopic findings, a decrease in the PHG score was recognized in 2 patients in PHG(+)-t. CONCLUSION: Portal hypertensive gastric mucosal change was thus found to trigger a high concentration of VEGF and hexosamine. Such increased activity of VEGF and hexosamine may thus account for the presence of active congestion in PHG.

Adult↗

PubMed2000

[Epilepsy surgery for focal cortical dysplasia and dysembryoplastic neuroepithelial tumor].

We studied six patients with focal cortical dysplasia (CD) and four patients with dysembryoplastic neuroepithelial tumor (DNT) who had surgical resection for medically intractable epilepsy. In all CD patients, ictal single photon emission computed tomography (SPECT) using 99mTc-ECD revealed hyperperfusion in the regions where magnetic resonance (MR) imaging showed CD abnormalities. Interictal epileptiform activity and ictal seizure onset on electrocorticography using subdural strip or grid electrodes were demonstrated in the CD itself. In contrast, in all DNT patients, interictal SPECT disclosed hypoperfusion in the area of the lesions. Ictal SPECT in one DNT patient disclosed hyperperfusion in the superior area of the region where MR imaging showed cystic abnormalities. Interictal spiking in all DNT patients and ictal seizure onset in two DNT patients were demonstrated not in the lesions themselves but in the distinct zone from the region of the tumor-involved brain. All CD patients who underwent lesionectomy became seizure-free with a mean follow-up period of 33.5 months. All DNT patients who underwent lesionectomy and resection of the epileptogenic cortex became seizure-free or had their seizure significantly reduced a mean follow-up period of 41.5 months. We conclude that CDs have intrinsic epileptogenicity, while DNTs have epileptogenicity not intrinsically but in encompassed cortical surface areas.

Adolescent↗

PubMed2000

[Difficulty in using RP, PL, and EW factors in the Japanese classification of pancreatic carcinoma].

The classification of pancreatic carcinoma by the Japan Pancreas Society reflects the prognosis of each stage better than does the TMN classification. On the other hand, there are too many factors to examine in the Japanese system, some of which are difficult to use and have low accuracy in pre- and/or intraoperative diagnosis (RP and PL), and their analysis requires various specimen handling procedures (EW). We propose that: 1) a simple, easy decision flow chart be established for ew and 2) EW/ew be designated as (-) or (+) and for EW/ew (+) cases other factors (ly, v, pl, and direct tumor invasion) be added (for example, ew (+)-pl).

Humans↗

PubMed2000

Isolation and characterization of rat gastric microvascular endothelial cells as a model for studying gastric angiogenesis in vitro.

We have previously characterized morphologic features of wounding-induced angiogenesis that occurs in response to acute and chronic gastric mucosal injury. As a means of investigating the molecular mechanisms underlying gastric angiogenesis, microvascular endothelial cells were isolated from stomachs of normal (non-injured) rats. The isolation procedure adapted and combined aspects of previous methods and employed positive selection using magnetic beads coated with monoclonal antibody specific for rat CD31 (PECAM-1), a cell surface marker restricted to platelets, monocytes, T lymphocytes and endothelial cells. The isolated microvascular endothelial cells expressed vascular endothelium-specific antigen and the endothelial-specific receptors, Tie2 and flt-1 (VEGFR1). When plated on growth factor-reduced matrigel, the isolated microvascular endothelial cells formed capillary-like structures reflecting in vitro angiogenesis. These cells were also responsive to vascular endothelial growth factor, VEGF, further verifying their endothelial nature. The rat microvascular endothelial cells isolated by this procedure should be useful in delineating molecular mechanisms and regulation of the angiogenesis that is essential for the healing of acute and chronic gastric injury.

Animals↗

PubMed1999

Characterization of mast cell-committed progenitors present in human umbilical cord blood.

Human mast cells are derived from CD34(+) hematopoietic cells present in cord blood, bone marrow, and peripheral blood. However, little is known about the properties of the CD34(+) cells. We demonstrated here that mast cell progenitors that have distinct phenotypes from other hematopoietic cell types are present in cord blood by culturing single, sorted CD34(+) cells in 96-well plates or unsorted cells in methylcellulose. The CD34(+) mast cell-committed progenitors often expressed CD38 and often lacked HLA-DR, whereas CD34(+) erythroid progenitors often expressed both CD38 and HLA-DR and CD34(+) granulocyte-macrophage progenitors often had CD33 and sometimes expressed CD38. We then cultured single cord blood-derived CD34(+)CD38(+) cells under conditions optimal for mast cells and three types of myeloid cells, ie, basophils, eosinophils, and macrophages. Of 1,200 CD34(+)CD38(+) cells, we were able to detect 13 pure mast cell colonies and 52 pure colonies consisting of either one of these three myeloid cell types. We found 17 colonies consisting of two of the three myeloid cell types, whereas only one colony consisted of mast cells and another cell type. These results indicate that human mast cells develop from progenitors that have unique phenotypes and that committed mast cell progenitors develop from multipotent hematopoietic cells through a pathway distinct from myeloid lineages including basophils, which have many similarities to mast cells.

ADP-ribosyl Cyclase↗

PubMed1999

Gastrointestinal mucosal regeneration: role of growth factors.

Growth factors and their receptors play important roles in cell proliferation, migration, tissue injury repair and ulcer healing. In gastric mucosa, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) by activating their common receptor, control cell proliferation. TGF-alpha predominantly plays this role under normal conditions and after acute injury, while EGF exerts its actions mainly during healing of chronic ulcers. During regeneration of injured gastric mucosa, these growth factors serve predominantly to restore the epithelial component. Other growth factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) serve to promote restoration of the connective tissue and microvessels (angiogenesis) in injured mucosa. During healing of chronic ulcers, a new epithelial lineage secreting EGF and other growth peptides develops and the majority of cells lining the ulcer margin overexpress the EGF receptor. Activation of the EGF receptor induces dramatic increases in MAP (Erk -1 and -2) kinase activity and phosphorylation levels. Inhibition of this signaling pathway dramatically delays ulcer healing. Granulation connective tissue, which grows under the stimulation of bFGF and VEGF is the major source for regeneration of connective tissue lamina propria and microvessels within the ulcer scar. Other growth factors such as insulin - like growth factor, keratinocyte growth factor, hepatocyte growth factor and trefoil peptides have been implicated in gastrointestinal (gastric ulcers, colitis) regeneration following injury. This paper is intended to provide an overview of the role of growth factors in gastrointestinal mucosal regeneration.

Animals↗

PubMed1999

Activation of Raf-1 during experimental gastric ulcer healing is Ras-mediated and protein kinase C-independent.

Our previous study demonstrated increases in epidermal growth factor receptor (EGF-R) phosphorylation and receptor tyrosine kinase and extracellular signal-regulated kinase (ERK1 and ERK2) activities in the ulcer margin of experimental gastric ulcer during healing. However, the intermediate steps linking activated receptor tyrosine kinase to ERKs during ulcer healing are as yet unknown. Raf-1 is upstream of mitogen-activated protein kinases (MAPK/ERK) and can be activated by Ras-dependent and/or Ras-independent mechanisms. Therefore, we studied Raf-1 activity, its potential activators protein kinase C (PKC) and Ras, and expression and associations of adapter proteins Shc, Grb2, and Sos during experimental gastric ulcer healing. To investigate if Raf-1-ERK activation is attributable to the epithelial component of ulcer margins, we studied the effect of EGF on PKC, Ras, and ERK activities in a rat gastric epithelial cell line (RGM1). Our results demonstrate that gastric ulceration significantly increases Raf-1 kinase activity, Grb2 and Ras protein, and Shc-Grb2 and Grb2-Sos complex levels. In contrast, PKC activity and protein level were significantly decreased in the ulcer margins. In RGM1 cells, EGF significantly increased Ras and ERK2 activities without affecting PKC activity. These findings indicate that Raf-1 activation during gastric ulcer healing is Ras mediated, involves Shc-Grb2-Sos, and is PKC-independent.

Animals↗

PubMed1999

Ethanol injury triggers activation of adrenomedullin and its receptor genes in gastric mucosa.

Adrenomedullin (AM) is a potent vasodilatory peptide, which is present in the stomach. However, its precise function in the gastric mucosa is unknown. The expression and localization of AM and its receptor in gastric mucosa injured by ethanol also have not been explored, forming the basis for this study. Gastric samples of rats were obtained at 0 and 8 hr and 1, 2, and 4 days after intragastric administration of 100% ethanol. By RT-PCR, AM mRNA expression in gastric mucosa at 8 and 24 hr following ethanol injury was increased by 2-fold and by 2.5-fold (both P<0.01), respectively, and returned to normal at two days. AM receptor mRNA expression was increased by 2.7-fold, 2.3-fold, and 2.4-fold at 8, 24, and 48 hr, respectively (all P<0.01), and returned to normal at four days. By in situ hybridization, AM and AM receptor mRNAs were present in normal gastric mucosa and up-regulated in gastric mucosa following ethanol injury. The immunohistochemical signal for AM was significantly increased in the mucosa bordering erosion sites. We conclude that ethanol injury up-regulates the expression of both AM and AM receptor in gastric mucosa.

Adrenomedullin↗

PubMed1999

A selective cyclo-oxygenase-2 inhibitor, NS-398, may improve portal hypertension without inducing gastric mucosal injury.

BACKGROUND AND AIMS: Prostacyclin has been shown to play a role in hyperdynamic circulation in portal hypertension. Recently, a new subtype of cyclo-oxygenase (COX), COX-2, which acts as an inducible synthase in response to various stimuli. The aim of this study was to investigate whether COX-2 contributes to portal hypertension and whether a COX-2 blockade induces the same sort of gastric mucosal injury as a COX-1 blockade. METHODS: Portal hypertension (PHT) in rats was induced by a two-step ligation of the portal vein. The mean arterial pressure (MAP), portal pressure (PP), visceral blood flow volume (BFV), serum levels of 6-keto-prostaglandin F1alpha (PGF1alpha), thromboxane B2 (TXB2) and gastric mucosal injury induced by pure ethanol were all measured in PHT rats receiving different inhibitors (indomethacin, a highly selective COX-1 inhibitor; NS-398, a highly selective COX-2 inhibitor). Control rats treated by a sham operation were also studied. RESULTS: The NS-398 administration significantly decreased PP to the same extent as indomethacin at doses of 5 and 10 mg/kg in PHT rats after a 60 min administration, while neither inhibitor affected the control rats. Both inhibitors significantly increased PP after a 30 min administration in the PHT and control rats at a dose of 5 mg/kg while both inhibitors significantly decreased PP after 60 min administration only in the PHT rats. Portal vein ligation treatment induced a significant increase in PP and BFV of the portal vein, gastric mucosa, oesophageal mucosa and the serum levels of 6-keto-PGF1alpha and TXB2, while portal vein ligation treatment induced a significant decrease in BFV of the liver. Both blockades increased MAP and decreased PP and BFV in the splanchnic area and decreased the serum level of 6-keto-PGF1alpha and TXB2 in the PHT rats, while neither blockade modified any parameters in the control rats, except that indomethacin administration significantly decreased the BFV of the gastric mucosa. Indomethacin administration significantly increased the ulcer index (UI). The NS-398 had no effect on UI in either the PHT or control rats. Only indomethacin significantly increased the number of rats demonstrating gastric mucosal long lesions (> 2 cm) in the PHT rats. CONCLUSION: In the PHT rats, prostaglandin seemed to contribute to portal hypertension. Both COX blockades reduced PP and BFV of the portal vein and gastric mucosa. NS-398, a selective COX-2 inhibitor, may, therefore, improve portal hypertension without inducing gastric mucosal injury.

6-Ketoprostaglandin F1 alpha↗

PubMed1999

Reduced adrenomedullin expression in gastric mucosa of portal hypertensive rats after ethanol-induced injury.

OBJECTIVE: To determine the expression and localization of adrenomedullin (AM) and its receptor (AM-R) in portal hypertensive (PHT) gastric mucosa after intragastric ethanol administration. SUMMARY BACKGROUND DATA: The repair of gastric mucosal injury requires reestablishment of the microvascular network. The authors previously demonstrated impaired angiogenesis of PHT gastric mucosa after ethanol-induced injury. Because AM, a potent vasodilatory peptide, is also a novel growth and angiogenic factor, the authors hypothesized that AM is involved in the impaired repair of PHT gastric mucosa and its microvasculature after damage. METHODS: Either PHT or sham-operated rats received intragastrically 100% ethanol, and the stomachs were excised at 1, 6, and 24 hours later. Expression and localization of AM and AM-R mRNA were examined by competitive reverse transcription-polymerase chain reaction and in situ hybridization. AM protein expression was examined by Western blot analysis. RESULTS: One hour after ethanol administration, AM mRNA expression in PHT gastric mucosa was significantly decreased by 81%, especially in the superficial mucosa, compared with the gastric mucosa in sham-operated rats. The significant decrease lasted for 24 hours. AM protein expression was significantly decreased by 43% compared with the sham-operated gastric mucosa. Although AM-R mRNA expression in both groups was significantly increased 1 hour after ethanol administration and lasted for 24 hours compared with baseline, there were no differences between the two groups. CONCLUSIONS: The expression of AM in PHT gastric mucosa after ethanol-induced injury is significantly decreased compared with controls. This finding could explain one mechanism for the impaired angiogenesis after injury of PHT gastric mucosa.

Adrenomedullin↗

PubMed1999

Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury.

Our previous studies demonstrated that ethanol injury triggers the angiogenic response in gastric mucosa bordering necrosis. The present study was aimed to determine whether vascular endothelial growth factor (VEGF) (a potent angiogenic peptide selectively acting on endothelial cells) and Ras (a mediator of cell proliferation and a putative regulator of VEGF expression) are involved in gastric angiogenesis after ethanol injury. We studied the angiogenic response and expression of VEGF and Ras in gastric mucosa after ethanol injury. Ethanol damage triggered 1) angiogenesis in the gastric mucosa bordering necrosis, 2) significant increases in VEGF mRNA and protein expression, and 3) significant increases in the expression of Ki-ras mRNA and Ras proteins. Neutralizing anti-VEGF antibody significantly reduced (by greater than threefold) the angiogenic response to ethanol-induced injury. Moreover, mevastatin, an inhibitor of Ras activation, completely blocked the induction of VEGF expression in cultured primary endothelial cells. Because, in other tissues, VEGF is one of the most potent angiogenic factors and VEGF expression is dependent on Ras, our data indicate that Ras and VEGF are involved in gastric mucosal angiogenesis after ethanol injury.

Animals↗

PubMed1998

Tumor necrosis factor alpha regulates nitric oxide synthase expression in portal hypertensive gastric mucosa of rats.

Anti-tumor necrosis factor alpha (TNF-alpha) treatment decreases nitric oxide (NO) synthesis and ameliorates the hyperdynamic circulation in portal hypertensive rats. We have recently demonstrated that nitric oxide synthase isoform 3 (NOS3) is overexpressed in portal hypertensive gastric mucosa and that resultant NO overproduction probably is responsible for the increased susceptibility of the mucosa to damage. In the present study, we examined whether TNF-alpha is overexpressed in portal hypertensive gastric mucosa and whether anti-TNF-alpha treatment affects gastric NOS3 messenger RNA (mRNA) and protein expression. We examined plasma concentrations of TNF-alpha and its protein expression in gastric specimens from portal hypertensive and sham-operated rats using Western blotting and immunohistochemistry. We also measured gastric mucosal blood flow, gastric expression of NOS3 mRNA and protein, and NOS3 enzyme activity in rats with and without TNF-alpha-neutralizing antibody treatment. The TNF-alpha protein levels in portal hypertensive stomachs were significantly increased by 57% compared with levels in sham-operated controls. TNF-alpha antibody treatment normalized gastric mucosal blood flow in portal hypertensive stomachs and significantly reversed overexpression of gastric NOS3 mRNA, protein, and its enzyme activity in portal hypertensive rats by 48%, 45%, and 33%, respectively. These results suggest that TNF-alpha may regulate NOS3 expression in the portal hypertensive stomach and that anti-TNF-alpha treatment may ameliorate the pathophysiological abnormalities of portal hypertensive gastric mucosa.

Animals↗

PubMed1998

Laparoscopic gastric devascularization and splenectomy for sclerotherapy-resistant esophagogastric varices with hypersplenism.

BACKGROUND: The combination of sclerotherapy with surgical salvage for sclerotherapy-resistant esophagogastric varices has recently received much attention, however, the longterm results after such an operation have yet to be reported. This is a preliminary report of a laparoscopic adaptation of a previously described surgical procedure for the treatment of refractory esophagogastric varices. STUDY DESIGN: Laparoscopic gastric devascularization and splenectomy (Hassab's operation) was successfully performed to treat recurrent sclerotherapy-resistant giant esophageal varices (n=4) and recurrent rebleeding gastric varices (n=6). The patients included 8 men and 2 women who ranged in age from 35 to 67 years (average, 54.2 years). The procedure and clinical results were evaluated from various viewpoints. RESULTS: The duration of the operation ranged from 200 to 400 minutes (mean+/-standard deviation; 287.5+/-66.0 minutes) and blood loss from 10 to 1,500 mL (average, 515.5+/-507.9 mL). The weight of the spleen ranged from 500 to 850 g (average 608.0+/-126.6 g). Conversion to minimal open operation with a gasless lifting method was done in 1 patient because of uncontrolled bleeding from the splenic vein. There were no other major complications either intraoperatively or postoperatively. All patients had hypersplenism; preoperative platelet counts ranged from 1.6 to 6.8 x 10(4)/microL (average, 4.5+/-2.7 x 10(4) microL) and the postoperative count was from 5.9 to 36.0 x 10(4)/microL (average, 21.7+/-11.5 x 10(4) microL). Postoperative endoscopy revealed that varices disappeared, and no patient had recurrence of the varices after operation during the mean followup period of 12.8+/-4.1 months (average, 8 to 20 months). CONCLUSIONS: The combination of laparoscopic gastric devascularization and splenectomy for sclerotherapy-resistant esophagogastric varices is considered a feasible and relatively safe surgical method for patients with hypersplenism.

Adult↗

PubMed1998

Decreased endothelial nitric oxide synthase in gastric mucosa of rats with chronic renal failure.

According to recent reports, chronic renal failure (CRF) increases the susceptibility of gastric mucosa to injury. Since nitric oxide plays a major role in gastric mucosal defense and injury, we investigated, in rats with CRF produced by five-sixths nephrectomy and in control rats, the expression of nitric oxide synthase(NOS) in the stomach and measured mucosal and submucosal gastric blood flow. In CRF rats, gastric mucosal blood flow was significantly reduced compared with control rats, whereas submucosal and serosal blood flow was significantly increased. CRF significantly decreased endothelial NOS (eNOS) mRNA abundance by 53% (P < 0.01) and reduced expression of eNOS protein by 42% (P < 0.01) compared with the controls. Enzyme activity of eNOS was significantly reduced in gastric mucosa of CRF rats (P < 0.05). These data are consistent with reduced gastric mucosal blood flow in CRF rats and can explain altered susceptibility of gastric mucosa to injury in CRF rats.

Animals↗

PubMed1998

Translocation of MAP (Erk-1 and -2) kinases to cell nuclei and activation of c-fos gene during healing of experimental gastric ulcers.

We examined localization of extracellular signal regulated kinases (Erk) 1 and 2, and c-fos mRNA expression in normal and ulcerated gastric mucosa in rats at 1, 3 and 7 days after gastric ulcer induction. In normal gastric mucosa immunofluorescence signal for Erk-1 and Erk-2 was detectable in surface epithelial, neck and some glandular cells. In gastric mucosa of the ulcer margin, almost all epithelial cells displayed strong Erk-1 and Erk-2 immunoreactivity in the basolateral membranes and the cytoplasm. In addition 19+/-3% of cells showed nuclear localization of the Erk-1 and -2 signal. The c-fos mRNA expression was increased by 790+/-14% and 220+/-10%, respectively in gastric ulcer at 3 and 7 days after ulcer induction. Since in in vitro models nuclear translocation of Erk-1 and -2 triggers cell proliferation, our finding indicates relevance of this mechanism to gastric ulcer healing.

Animals↗

PubMed1998

Expression of adrenomedullin in portal hypertensive gastric mucosa of rats.

We examined the expression and localization of adrenomedullin (AM) mRNA, AM receptor (AM-R) mRNA and AM protein in normal and portal hypertensive (PHT) rat gastric mucosa. Methods included competitive reverse transcription-polymerase chain reaction (RT/PCR), in situ hybridization and Western blot analysis. Both AM mRNA and AM-R mRNA were strongly expressed not only in normal rat gastric mucosa but also PHT rat gastric mucosa. While total AM and AM-R mRNA abundance was similar in both normal and PHT stomachs, in the superficial mucosa-where major defense mechanisms are located-their expression was significantly reduced in PHT rats by 33% (AM mRNA) and 25% (AM-R mRNA) (both p .0.05). AM protein was also expressed similarly in both normal and PHT gastric mucosa. We conclude that AM and its receptor play a role in regulation of gastric mucosal microcirculation and thus gastric mucosal defense.

Adrenomedullin↗

PubMed1997

Cold stimulation test and histamine release in primary acquired cold urticaria.

The patient was a 10-year-old boy who complained of urticaria upon exposure to cold air and after swimming in the pool. He also had seasonal asthma and wheezing after strenuous activities. To determine whether he had primary acquired cold urticaria, we performed a cold stimulation test twice. We likewise wanted to know whether a difference in response with regard to histamine release existed between blood samples taken from the challenged and the unchallenged sites. We obtained blood samples for histamine release initially at the site opposite the challenged forearm, and then on the same side on two separate occasions. We noted the appearance of constitutional signs and symptoms and correlated the time of their appearance with the result of histamine levels. The patient complained of pruritus and wheals appeared at the 5 minute in both tests. Results of plasma histamine release in the two measurements showed the highest releasability at 15 min. Our findings revealed that histamine is released systemically in response to cold stimulation regardless of the site where the blood sample was obtained.

Asthma↗

PubMed1997

[Surgical treatment for the upper and middle bile duct cancer].

A total of 45 patients with bile duct cancer, 13 patients predominantly with Bs bile duct cancer, 14 with Bm cancer, and 18 with Bim cancer, were chosen from 104 patients with bile duct cancer, not including gallbladder cancer or cancer of the papilla of Vater, who underwent surgical resection in our department between Sep 1974 and Nov 1996, and were evaluated with respect to surgical procedure, pathological findings, and outcome. The patients with Bs cancer were compared with 39 patients with cancer of the main hepatic duct junction who underwent hepatectomy, and the patients with Bim cancer were compared with another 20 patients with Bi bile duct cancer. The effect of combined resection of the vessels and hepatopancreatoduodectomy (HPD) on patients with advanced cancer was assessed. To attain a hw (-) margin, hepatectomy should be performed in patients with Bs bile duct cancer, unless localized. Bm and Bim bile duct cancer patients with negative margins had a relatively favorable outcome irrespective of surgical procedure. Resection of the vessels and HPD were useful in improving the resectability rate, but not in attaining longer survival.

Aged↗