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Biomedical subjects

P Gunvén

Publications and source records attributed to P Gunvén.

At least 19 recordsLinked to original sources

[Regional medical care program in Stockholm-Gotland region: a first step toward a unified care of patients with stomach cancer].

Cancer treatment in Sweden is coordinated by regional oncology centers responsible for keeping registers of cancer cases and assisting the medical profession in establishing regional consensus on the treatment of specific cancer forms. The article describes the development of a regional multidisciplinary protocol for gastric cancer, with standardization of preoperative investigations and curative surgery. A follow-up procedure deals with postoperative problems and defines recurrence rates.

Follow-Up Studies↗

Six-year recurrence free survival after intraluminal iridium-192 therapy of human bilobar biliary papillomatosis. A case report.

BACKGROUND: Biliary papillomatosis is rare and often fatal. Liver resection or transplantation is recommended but may be impossible due to tumor or patient factors; furthermore, it appears to the authors of this study that no follow-up results after transplantation have been reported in previous studies. METHODS: Bilobar but limited biliary papillomatosis in a man age 54 years was mapped by cholangiopancreatography, cholecystectomy, and operative cholangioscopy. After cholangioscopic electrocoagulation, iridium-192 wires were temporarily inserted into the affected bile ducts, giving a dose of 60 grays at a 3-mm distance. Another percutaneous cholangioscopic electrocoagulation was performed 3 weeks later. RESULTS: The patient has been free of tumor and in good health for 80 months, but he has a long term stenting of a nonneoplastic stricture at the confluence of the bile ducts. CONCLUSIONS: Mechanical tumor reduction and intraluminal brachytherapy could possibly replace transplantation (which up to now has been suggested but not reported) when this life-threatening disease is bilobar, and also possibly replace liver resection for limited tumors in patients who are too frail for surgery.

Bile Duct Neoplasms↗

High-dose percutaneous ethanol injection therapy of liver tumors. Patient acceptance and complications.

PURPOSE: To study the safety of high-dose ethanol injections in liver tumors and their acceptability as out-patient procedures under local anesthesia. MATERIAL AND METHODS: Twenty-nine patients received 20-95 ml of 95% ethanol by 62 percutaneous injections under local anesthesia. Pain was assessed by a visual analogue scale from 1 to 10 for 33 of the sessions. Side effects, complications, post-treatment requirement of parenteral analgesics, and hospital stay (discharge the same day or later) were recorded. The sessions were compared to 80 injections of <20 ml of ethanol in 18 patients. RESULTS: High-dose injections with an average volume of 39 ml gave a mean pain score of 5.1, with a weak relationship between pain and volume. Other side effects and complications were unrelated to the ethanol dose. They comprised 1 syncopation, 1 occasion of hypoventilation requiring antidote to opiates, 12 short episodes of nausea or vomiting without need for i.v. fluids, 2 instances of sepsis, and 1 abscess that was drained percutaneously. Thirty-nine of the 62 sessions were performed in day care. Ethanol was given in high doses without apparent complications after or shortly before liver resections (3 patients in each group), and on 4 occasions in 2 HIV carriers. Low-dose injections resulted in a mean pain score of 4.7 with the same requirement of i.v. analgesics as high doses, fewer instances of nausea and no infectious complications. CONCLUSION: High-dose ethanol injections in patients with liver malignancy had no mortality and a reasonable complication rate. They could be given without general anesthesia, often in day care.

Abscess↗

Expression of the low-density lipoprotein receptor, HMG-CoA reductase, and multidrug resistance (Mdr1) genes in colorectal carcinomas.

Some malignant cells have elevated uptake of plasma low-density lipoprotein (LDL). We determined the expressions in colorectal cancers of the LDL receptor gene, of the gene for the rate-limiting enzyme in cholesterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and of the multidrug resistance gene (mdr1) by quantitative RNA-RNA solution hybridisation. LDL receptor RNA levels in tumor tissue exceeded those in normal mucosa in 20 of 23 patients (2-11-fold higher in 17 of 23 patients), with a mean +/- SD of 7.8 +/- 5.8 copies/cell in tumor tissue vs 3.5 +/- 2.5 in normal mucosa (P = 0.002). The HMG-CoA reductase gene was similarly expressed in tumor and normal tissue, with means and SD of 2.0 +/- 1.3 copies/cell versus 2.2 +/- 1.9 (pi = 21). Mdr1 RNA was undetectable ( < 0.15 copies/cell) in 5 of 20 tumors, with a mean +/- SD of 1.0 +/- 1.1 copies/cell vs 1.6 +/- 1.7 in normal mucosa. Expression of all three genes was, in most cases, higher in normal liver than in liver metastasis of colorectal carcinomas or normal colon mucosa. The results may form the basis for using LDL as a drug carrier for treatment of colorectal carcinomas, and may indicate that drug resistance in these tumors is not due to overexpression of the mdr1 gene.

Adolescent↗

Expression of deoxycytidine kinase and phosphorylation of 2-chlorodeoxyadenosine in human normal and tumour cells and tissues.

Deoxycytidine kinase (dCK) activates several clinically important drugs, including the recently developed antileukaemic compound 2-chlorodeoxyadenosine (CdA). The distribution of dCK in cells and tissues has previously been determined by activity measurements, which may be unreliable because of the presence of other enzymes with overlapping substrate specificities. Therefore we have measured dCK polypeptide levels in extracts of normal and malignant human peripheral blood mononuclear cells, gastrointestinal tissues and sarcomas, using a specific immunoblotting technique, as well as the phosphorylation of CdA in the same extracts. High levels of dCK were found in all major subpopulations of normal mononuclear leucocytes (120 +/- 19 ng dCK/mg protein) and in B-cell chronic lymphocytic leukaemia (81 +/- 30 ng/mg, n = 23). Hairy-cell leukaemia contained lower levels (28 +/- 23 ng/mg, n = 7), as did three samples of T-cell chronic lymphocytic leukaemia (18 +/- 14 ng/mg). Phytohaemagglutinin stimulation of normal lymphocytes did not lead to any substantial increase in either dCK activity or protein expression (less than 2.5-fold). The human CEM wt T-lymphoblastoid cell line contained 56 +/- 1 ng/dCK/mg protein, while in the CEM ddC50 and AraC8D mutants that lack dCK activity, no dCK polypeptide could be detected. In colon adenocarcinomas, the dCK content was significantly higher (20 +/- 9 ng/mg, n = 20) than in normal colon mucosa (8 +/- 3.5 ng/mg, n = 19, P < 0.05). A similar pattern of dCK expression was found in gastric adenocarcinomas (21 +/- 13 ng/mg, n = 5) and normal stomach mucosa (6 +/- 5 ng/mg, n = 5, P < 0.15). One leiomyosarcoma and one extra-skeletal osteosarcoma showed dCK levels comparable with those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg, respectively), while other sarcoma samples contained lower levels, comparable to the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). Thus, dCK is expressed constitutively and predominantly in lymphoid cells, but it is also found in solid non-lymphoid tissues, with increased levels in malignant cells. The phosphorylation of CdA in crude extracts showed a close correlation to the dCK polypeptide level.

Blotting, Western↗

Properties and levels of deoxynucleoside kinases in normal and tumor cells; implications for chemotherapy.

Deoxynucleoside kinases are key enzymes in deoxyribonucleoside salvage, activating several clinically important chemotherapeutic drugs. The four known kinases, cytosolic thymidine kinase (TK1) and deoxycytidine kinase (dCK) and the mitochondrial thymidine kinase (TK2) and deoxyguanosine kinase (dGK), have been purified and characterized as to the subunit structure as well as specificity with a large number of analogs. These results are summarized and used to establish selective assays for the four enzymes in crude extracts of normal and malignant human peripheral blood mononuclear cells, gastrointestinal tissues and sarcomas. TK2 and dGK activities were found at low levels in all tissues, possibly correlated to the content of mitochondria. TK1 activity was detected only in samples containing a significant number of S phase cells. We have measured dCK activity as well as dCK polypeptide level by immuno blotting in these extracts. High levels of dCK were found in normal mononuclear leukocytes (91-145 ng dCK/mg protein) and in B-cell chronic lymphocytic leukemia (80 +/- 30 ng/mg, n = 23). Hairy cell leukemia contained lower levels (28 +/- 23 ng/mg, n = 7), as did unexpectedly three samples of T-cell chronic lymphocytic leukemia (18 +/- 14 ng/mg). Phytohemaglutinine stimulation of normal lymphocytes did not lead to any substantial increase in either dCK activity or expression (less than 2.5-fold). In colon adenocarcinomas, the dCK content was significantly higher (21 +/- 9.3 ng/mg, n = 20) than in normal colon mucosa (8.2 +/- 3.7 ng/mg, n = 19, p < 0.05). A similar pattern of dCK expression was found in gastric adenocarcinomas (21 +/- 13 ng/mg, n = 5) and normal ventricular mucosa (6.2 +/- 5.4 ng/mg, n = 5, p < 0.15). One leiomyosarcoma and one extra-skeletal osteosarcoma showed a dCK levels comparable to those found in normal lymphocytes (84 +/- 6 and 109 +/- 4 ng/mg), while other sarcoma samples contained levels comparable to the gastrointestinal adenocarcinomas (20 +/- 7 ng/mg, n = 12). We confirm that dCK is expressed constitutively and predominantly in lymphoid cells, but conclude that a significant expression may be found in non-lymphoid tissues as well, with increased levels in the corresponding tumor tissue. 2-Chlorodeoxyadenosine (CdA), an antileukemic agent used in treatment of hairy cell leukemia and chronic lymphocytic leukemias (B-CLL), is phosphorylated by dCK which was used as the selective substrate for this enzyme. A study was performed to investigate if there was a correlation between the dCK levels and the response to CdA treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

Genetic rearrangements in sporadic and familial gastric carcinomas detected with microsatellite markers.

Ten gastric carcinomas were studied for loss of heterozygosity by analysis of 21 microsatellite markers from 14 different chromosomes. Four patients had a family history of gastro-intestinal cancer, and six tumours were considered sporadic. We also studied a new mechanism in tumourigenesis recently reported in hereditary non polyposis colon cancer, a defect in mismatch repair that is seen as gain of new bands by the use of dinucleotide repeat markers. Loss of heterozygosity was detected with two markers in one primary tumour and with the majority of markers in one metastasis from a sporadic gastric tumour. Gain of microsatellite bands was seen in one tumour from a gene carrier in a family with hereditary non-polyposis colon cancer and in one sporadic tumour. Two tumours from patients with a family history of gastric cancer showed no rearrangements. Our results suggest that different types of genes are involved in initiation and progression of gastric cancer in sporadic and familial gastric cancer.

Adult↗

Temporary redistribution of hepatic or pancreatic blood flow by vascular occluders during intra-arterial chemotherapy for carcinoma of the liver or pancreas.

Surgically placed inflatable vascular occluders temporarily increased or restricted the target volume for intra-arterial therapy for tumors in the liver and pancreas. Proximal occlusion of the common hepatic artery directed retrograde flow from the cannulated gastroduodenal artery into a variant left hepatic artery in one patient with carcinoma of the liver. Occlusion of the distal splenic artery and common hepatic artery after distal gastrectomy with cannulation of the left gastric artery gave selective perfusion of the tumor-bearing pancreatic head in three patients. The occlusions had no untoward effects and the regional infusions seemed to retard local tumor growth.

Catheterization↗

Debulking surgery and arterial embolization for unresectable liver cancer.

Hepatocellular carcinomas measuring less than 5 cm in diameter became completely necrotic after arterial chemoembolization with Lipiodol, doxorubicin, and gelfoam more often than larger lesions. In 60 patients, we surgically debulked large unresectable tumors, with the aim of subsequently embolizing residual small tumors transarterially. Forty-seven patients were actually embolized. The rate of major non-fatal complications was similar to that seen after radical resections, but the hospital mortality rate was 30%, as compared with 4%. Stage I disease, including non-embolized patients and hospital mortality, had an estimated 5-year survival rate of 27%. This result approached that obtained after curative resections, and was better than that seen after embolization only. Stage II disease had no five-year survivors and its survival curve was intermediate, lying between those of curatively resected and embolization patients. No stage I patients with tumor growth in the portal trunk or lobar branches survived for 2 years. The results warrant further study of this treatment strategy.

Adult↗

Non-ominous micrometastases of gastric cancer.

So-called R2 or wider meticulous node dissection was performed in 1368 patients with resected gastric cancer invading beyond the submucosa but without distant metastases. Survival rates were similar in subsets of patients with or without microscopic node metastases and macroscopically normal lymph nodes. The extent of node metastases has previously been shown to be one of the two most important prognostic factors in gastric cancer without distant metastases, and its lack of impact in these patient groups was not explained by the imbalance of other prognostic factors. The findings indicate that micrometastases of gastric cancer are curable by a wide node dissection made in the absence of palpable abnormality. They also offer the possibility that an extensive node dissection may yield good stage-specific survival rates, in part because of upstaging of patients. The findings should influence the recording of node metastases for evaluation of stage-specific treatment results and for research purposes.

Female↗

Extrahepatic division of the right hepatic vein in hepatectomy.

Extrahepatic division of the right hepatic vein, after division of the inferior vena cava ligament and, if necessary, of the adrenal gland, was performed during 87 liver resections, and the results compared with those of intraparenchymal division of the right hepatic vein in 32 similar hepatectomies. The selection of the method reflected the surgeon's preference, and was unrelated to the weight of the resected specimen. The incidences of injury to the adrenal gland, inferior vena cava and short hepatic veins were comparable with the two methods, 28 versus 26%, but massive bleeding occurred in 13 vs. 6%, and the mean operative bleeding was 3.8 vs. 1.8 liters (p less than 0.01) during intrahepatic and extrahepatic dissection, respectively. Tumors close to the junction of the right hepatic vein with the inferior vena cava cannot be removed radically with intraparenchymal division of the right hepatic vein. For these reasons, we prefer extrahepatic right hepatic vein division, which was technically possible in 75 of the 84 cases in whom it was attempted.

Adrenal Glands↗

Endoscopic laser coagulation through an optical laser balloon.

An endoscope was equipped with a saline-filled latex rubber balloon at its tip to displace contaminating blood, bile, or gastric contents during operative portoscopy, biliary endoscopy, or upper gastrointestinal endoscopy. A fiber with its tip inside the balloon transmitted energy from an Nd:YAG laser for coagulation of tumors in one bile duct cancer, in six portal vein growths from primary liver cancers, and in a superficially growing stomach cancer. The balloon increased the precision of irradiation by making lesions easier to identify through displacement of bile or blood and by keeping the fiber tip at a fixed position relative to the lesion. The technique, basic experimental studies, and clinical experiences are reported.

Animals↗