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Onno T Terpstra

Publications and source records attributed to Onno T Terpstra.

15 recordsLinked to original sources

Necrosis of a large hepatic tumor after hemorrhage and subsequent selective arterial embolization.

This case report describes a young female patient presenting with acute intra-abdominal hemorrhage originating from a large tumor in the liver, most likely a hepatocellular adenoma. The bleeding was stopped by selective embolization of right hepatic artery branches. Subsequently, partial hepatectomy was performed after 6 mo. Macro- and microscopic examination showed complete necrosis and absence of tumorous tissue. The patient was discharged without complications, and subsequent follow-up until 22 mo after resection did not reveal any new lesions in the liver. This case emphasizes the significance of selective arterial embolization in the management of bleeding liver tumors and questions the need for (partial) hepatectomy after this procedure in selective cases.

Adenoma, Liver Cell↗

Persistent portal venous gas.

This case report describes a patient diagnosed with ongoing portal venous gas, initiated by a rather common Campylobacter enterocolitis and maintained by septic thrombophlebitis and possibly by chronic cholecystitis. Cholecystectomy attenuated the patient's septic condition. The etiology of portal venous gas determines both the patient's prognosis and the choice for either conservative or surgical treatment. This report describes persistence of portal venous gas for a long period and a possible role for chronic cholecystitis as a cause.

Campylobacter↗

Pretransplant culture selects for high-quality porcine islets.

OBJECTIVES: The pig is generally considered a suitable alternative donor for clinical islet transplantation. However, adult pig islets are difficult to isolate and culture, often behave variably in in vitro assays, and do not consistently cure diabetic nude mice. In this study, we compared the in vivo function of freshly isolated and cultured adult porcine islets by transplantation in diabetic nude mice. METHODS: Freshly isolated and cultured islets were transplanted in different doses to diabetic nude mice (N = 48). RESULTS: Average islet yield was 1924 islet-equivalents per gram of pancreas, purity 96%, and the viability that was measured by acridine orange and propidium iodide was greater than 80% in all freshly isolated islet preparations. Grafts of freshly isolated islets failed to reduce hyperglycemia in 17 of 18 recipients. Although after 1 day of culture islet recovery was only 21%, grafts of these islets cured 12 of 17 mice. After 7 to 14 days of culture, the recovery had decreased to 11%; however, these islets reversed hyperglycemia in all mice (13/13) and showed shorter time-to-normoglycemia and more tightly regulated blood glucose. CONCLUSIONS: Although freshly isolated adult porcine islets survive culture and transplantation poorly, islets selected by prolonged culture are of high potential.

Animals↗

Photodynamic therapy with 5,10,15,20-tetrakis(m-hydroxyphenyl) bacteriochlorin for colorectal liver metastases is safe and feasible: results from a phase I study.

BACKGROUND: The prognosis for patients with liver metastases from colorectal carcinoma is limited because of the low number of patients who are eligible for curative hepatic resection. In this phase I study, 31 liver metastases in 24 patients with nonresectable metastases from colorectal carcinoma were treated with photodynamic therapy (PDT). METHODS: The photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC) was intravenously administered in a dose of .6 mg/kg (n = 12) or .3 mg/kg (n = 12). After 120 hours (n = 18) or 48 hours (n = 6), tumors were illuminated for 300 to 600 seconds through percutaneously inserted optical fibers with a light dose of 60 J/cm of diffuser (740 nm). RESULTS: Tumor necrosis at 1 month after PDT was achieved in all treated lesions. Laser treatment was associated with mild pain (n = 8) and transient subclinical hepatotoxicity (n = 21). In one patient, PDT damage to the pancreas was inflicted, and in another patient, PDT damage of the skin occurred, but no serious clinical complications from PDT were reported. Administration of .6 mg/kg of mTHPBC led to transient phlebitis in 10 patients, and 3 patients experienced mild skin phototoxicity after excess light exposure. CONCLUSIONS: Colorectal liver metastases that are ineligible for resection can be safely and effectively treated with interstitial mTHPBC-based PDT.

Adult↗

Heterotopic vs. orthotopic liver transplantation for chronic liver disease: a case-control comparison of short-term and long-term outcomes.

Between 1986 and 1990 we performed heterotopic liver transplantation (HLT) in 17 patients with chronic liver disease. In spite of theoretical advantages and favorable short-term results, we abandoned HLT because of doubts about the long-term outcome and the improved results of standard orthotopic liver transplantation (OLT). There are, however, no studies comparing the long-term survival after HLT and OLT for chronic liver disease. We performed a case-control study of HLT vs. OLT, with long-term patient and graft survival as the main outcome measures. Known confounders and differences in baseline characteristics between HLT and OLT patients were corrected for. At 1 year, 5 of the 17 HLT patients had died, compared with 9 of the 34 OLT patients (relative risk [RR], 1.15; 95% confidence interval [CI], 0.33-4.02; P = 0.83). After correction for confounders, the long-term risk of graft failure (RR, 18.0; 95% CI, 1.5-223.5; P = 0.02) and of death (RR, 5.2; 95% CI, 0.8-34.8; P = 0.09) was higher after HLT than after OLT. The main causes of graft loss and death at more than 1 year after HLT were de novo malignancies and a variety of biliary complications. In conclusion, our data, from 1 of the largest single-center series of HLTs available, showed no significant difference between HLT and OLT in 1-year survival. However, the long-term outcome of HLT was inferior. HLT cannot be recommended as an alternative to OLT for any of the indications we studied, even though only 1 of the late deaths was definitely related to the heterotopic technique.

Adult↗

Mannose binding lectin gene polymorphisms confer a major risk for severe infections after liver transplantation.

BACKGROUND & AIMS: Infection is the primary cause of death after liver transplantation. Mannose binding lectin (MBL) is a recognition molecule of the lectin pathway of complement and a key component of innate immunity. MBL variant alleles have been described in the coding region of the MBL gene, which are associated with low MBL serum concentration and impaired MBL structure and function. The aims of our study were to establish the role of the liver in production of serum MBL and to evaluate the effect of MBL variant alleles on the susceptibility to infection after liver transplantation. METHODS: We investigated 49 patients undergoing orthotopic liver transplantation. MBL exon 1 and promoter polymorphisms were determined in patients and in liver donors. MBL serum concentration was determined before and during 1 year after transplantation. The incidence of clinically significant infections during this period was assessed. RESULTS: Transplantation of MBL wildtype recipients with donor livers carrying MBL variant alleles resulted in a rapid and pronounced decrease of serum MBL levels. This serum conversion was associated with the disappearance of high molecular weight MBL. No indication for extrahepatic production of serum MBL could be obtained. The presence of MBL variant alleles in the MBL gene of the donor liver, but not in the recipient, was associated with a strongly increased incidence of clinically significant infections after transplantation. CONCLUSIONS: Serum MBL is produced by the liver under strong genetic control. After liver transplantation, the MBL genotype of the donor liver is a major risk determinant for life-threatening infections.

Adult↗

Elevated levels of mannose-binding lectin at clinical manifestation of type 1 diabetes in juveniles.

Mannose-binding lectin (MBL) is a recognition molecule of the lectin pathway of complement and a key component of innate immunity. MBL polymorphisms have been described that are associated with MBL serum concentration, impaired function, and diabetic complications. We investigated 86 new-onset juvenile type 1 diabetic patients and compared these with their nondiabetic siblings and healthy unrelated control subjects. Polymorphisms of MBL exon 1 and promoter were determined, and serum concentration and MBL-complex activity were measured. Although the genetic polymorphisms of MBL were not different between patients and control subjects, MBL serum concentration as well as MBL complex activity was significantly higher in new-onset diabetic patients compared with their siblings matched for high-producing MBL genotypes (P = 0.0018 and P = 0.0005, respectively). The increase in MBL complex activity in high-MBL-producing patients could only partially be explained by high MBL production, as demonstrated by an increased MBL complex activity-to-MBL concentration ratio (P = 0.004). We conclude that MBL serum concentration and complex activity are increased in early-onset diabetic patients upon manifestation independently of genetic predisposition to high MBL production, indicating a possible role in the immunopathogenesis of type 1 diabetes, in addition to the adaptive islet autoimmunity.

Adolescent↗

Combined donor leucocyte administration and immunosuppressive drug treatment for survival of rat heart allografts.

BACKGROUND: Donor leucocytes (DL) play an important role in rat liver transplant tolerance and their postoperative administration can convert rejection to tolerance. They appear to induce early activation, altered patterns of infiltration and death of recipient alloreactive T cells. The ability of immunosuppressive drugs to combine with DL administration was examined in a rat heart transplant model. METHODS: Immediately after PVG to DA heterotopic heart transplantation, 6 x 10(7) spleen DL were injected. Cyclosporine A (CsA), 1.5 mg/kg/day, or methotrexate (MTX), 0.1 or 0.2 mg/kg/day, were given from day (d) 0 to d4 (early) or from d3 to d7 (delayed). Castanospermine (CAST) was administered from d0 to d7 at 100 or 300 mg/kg/day. In a separate experiment, transplanted hearts and recipient spleens were collected from treatment groups for analysis of infiltrate and cytokine mRNA expression. RESULTS: Delayed treatment with CsA or early treatment with MTX but not CAST combined with DL to result in prolonged graft survival. Recipients treated with DL and delayed CsA had a reduced level of intra-graft interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-4R mRNA expression and reduced infiltrate compared to DL alone. Early MTX plus DL led to almost complete inhibition of all markers of inflammation during treatment followed by a rapid increase after cessation. In combination with DL, CsA was more effective than MTX for induction of donor-specific tolerance at the dose and administration regimens tested. CONCLUSIONS: Delayed CsA or early MTX combine with DL to prolong heart allograft survival. Early and extensive inhibition of rejection by MTX was less effective than delayed and partial inhibition of the response by CsA for induction of transplant tolerance.

Adoptive Transfer↗

A systemic antitumor immune response prevents outgrowth of lung tumors after i.v. rechallenge but is not able to prevent growth of experimental liver tumors.

Although a systemic antitumor immune response by antibodies or T cells is often detected in cancer patients, this response mostly does not result in tumor rejection. The beneficial effect of tumor vaccination on survival rates is limited as tumor response is low. In contrast to solid tumors, circulating tumor cells may be more easily accessible and therefore destroyed by the immune system and thus prevent metastases. This discrepancy is further clarified in our study, by assessing the effect of a systemic immune response on established liver tumors and circulating tumor cells. Male Wag/Rij rats were inoculated with CC531 colorectal tumor cells subcapsulary in the liver, with or without immune suppression (60 mg/kg cyclophosphamide). To study the effect of a systemic immune response, rats received CC531 tumor cells intravenously and three weeks later the number of lung tumors was assessed. Presence of specific anti-CC531 antibodies in serum was determined by flow cytometric analysis at times of inoculation, i.v. tumor cell administration and sacrifice. Rats with liver tumors and subsequent rechallenge produced anti-CC531 IgG antibodies and did not develop lung tumors, whereas without existing liver tumors, rats developed lung tumors upon i.v. administration of CC531 tumor cells. Liver tumors in rats with and without i.v. CC531 tumor cell administration were equal in size. These results showed that a systemic immune response, induced upon liver tumor induction and rechallenge, prevented formation of lung tumors but did not affect tumor growth in the liver. Possibly the immune response lacked the ability to penetrate the protective extracellular matrix surrounding the established liver tumors, which prevented the tumor cells from recognition by and contact with cells of the immune system.

Animals↗

Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: a prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors.

OBJECTIVE: A prospective randomized multicenter study was performed to assess whether the results of pylorus-preserving pancreaticoduodenectomy (PPPD) equal those of the standard Whipple (SW) operation, especially with respect to duration of surgery, blood loss, hospital stay, delayed gastric emptying (DGE), and survival. SUMMARY BACKGROUND DATA: PPPD has been associated with a higher incidence of delayed gastric emptying, resulting in a prolonged period of postoperative nasogastric suctioning. Another criticism of the pylorus-preserving pancreaticoduodenectomy for patients with a malignancy is the radicalness of the resection. On the other hand, PPPD might be associated with a shorter operation time and less blood loss. METHODS: A prospective randomized multicenter study was performed in a nonselected series of 170 consecutive patients. All patients with suspicion of pancreatic or periampullary tumor were included and randomized for a SW or a PPPD resection. Data concerning patients' demographics, intraoperative and histologic findings, as well as postoperative mortality, morbidity, and follow-up up to 115 months after discharge, were analyzed. RESULTS: There were no significant differences noted in age, sex distribution, tumor localization, and staging. There were no differences in median blood loss and duration of operation between the 2 techniques. DGE was observed equally in the 2 groups. There was only a marginal difference in postoperative weight loss in favor of the standard Whipple procedure. Overall operative mortality was 5.3%. Tumor positive resection margins were found for 12 patients of the SW group and 19 patients of the PPPD group (P < 0.23). Long-term follow-up showed no significant statistical differences in survival between the 2 groups (P < 0.90). CONCLUSIONS: The SW and PPPD operations were associated with comparable operation time, blood loss, hospital stay, mortality, morbidity, and incidence of DGE. The overall long-term and disease-free survival was comparable in both groups. Both surgical procedures are equally effective for the treatment of pancreatic and periampullary carcinoma.

Adenocarcinoma↗

Hepatocyte survival depends on beta1-integrin-mediated attachment of hepatocytes to hepatic extracellular matrix.

BACKGROUND: A major drawback of allogeneic hepatocyte transplantation is the lack of sustained survival of the transplanted cells in the recipient liver parenchyma. The purpose of this study was to determine the effect of the presence or absence of hepatic extracellular matrix (ECM) molecules on hepatocyte survival and function following hepatocyte isolation for transplantation purposes, and the role of beta1-integrin molecules therein. METHODS: Hepatocytes, either untreated or treated with anti-beta1 integrin antibodies or RGD peptides, were seeded on wells precoated with collagen type I, type IV, laminin, fibronectin or polyhydroxyethylmehacrylate. The extent of attachment and apoptosis was evaluated. RESULTS: When hepatocytes were added into wells precoated with either fibronectin, or collagen type IV, rapid spreading and prolonged survival occurred, in contrast to hepatocytes that were seeded in wells precoated with collagen type I or polyhydroxyethylmehacrylate. Pretreatment of the cells with anti-beta1-integrin antibodies resulted in reduction of cell attachment to laminin, fibronectin, collagen I, and collagen IV. Synthetic RGD (arginine-glycine-aspartate)-peptides and anti-beta1 antibodies inhibited apoptosis of cultured hepatocytes. CONCLUSIONS: Our findings indicate that embedding of hepatocytes within their normal liver ECM surroundings maintains their survival. When detached from their natural surrounding hepatocytes enter into apoptosis, unless treated with anti-beta1-integrin antibodies or RGD peptides. This knowledge will allow improvement of hepatocyte transplantation efficiency.

Animals↗

Plasma MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 during human orthotopic liver transplantation. The effect of aprotinin and the relation to ischemia/reperfusion injury.

Uncontrolled activation of matrix metalloproteinases (MMPs) can result in tissue injury and inflammation, yet little is known about the activation of MMPs during orthotopic liver transplantation (OLT). OLT is associated with increased fibrinolytic activity due to elevated plasmin generation. The serine-protease plasmin not only causes degradation of fibrin clots but is also thought, amongst others, to play a role in the activation of some matrix metalloproteinases. We therefore studied the evolution of MMP-2 and -9 plasma concentrations during OLT and the effect of serine-protease inhibition by aprotinin on the level and activation of these MMPs. In a group of 24 patients who participated in a randomized, double-blind, placebo-controlled study we determined serial MMP-2 and MMP-9 plasma levels during transplantation using ELISA (total MMP), activity assays (activatable MMP) and zymography. In addition, the MMP-inhibitors TIMP-1 and TIMP-2 were assessed by ELISA. The putative regulating factors tumor necrosis factor alpha (TNF-alpha) and tissue-type plasminogen activator (t-PA) were assessed as well. Patients were administered high-dose aprotinin, regular-dose aprotinin or placebo during surgery. Plasma TIMP-1, TIMP-2 and MMP-2 level gradually decreased during transplantation. Approximately two-thirds of total MMP-2 appeared to be in its activatable proMMP form. No release of MMP-2 from the graft could be detected. In contrast, plasma levels of MMP-9 increased sharply during the anhepatic and postreperfusion periods. Peak MMP-9 levels of about eight times above baseline were found at 30 minutes after reperfusion. Most MMP-9 appeared to be in its active/inhibitor-complexed form. No significant differences were observed between the three treatment groups. However, in patients with more severe ischemia/reperfusion (I/R) injury the MMP-9 concentration, particularly of the active/inhibitor-complexed form, remained high at 120 minutes postreperfusion compared to patients with no or mild I/R injury. The decrease in plasma levels of MMP-2, TIMP-1 and TIMP-2 during OLT occurred irrespective of the severity of the I/R injury. There was a significant correlation between MMP-9 and t-PA levels, but not with TNF-alpha. In conclusion, OLT is associated with a sharp increase of MMP-9 during the anhepatic and postreperfusion periods, which coincided with the changes in t-PA. MMP-2, TIMP-1 and TIMP-2 gradually decreased during OLT. The composition of these MMPs was not altered by the use of aprotinin, suggesting that serine-protease/plasmin-independent pathways are responsible for MMP regulation during OLT. In addition, only MMP-9 seems to be involved in I/R injury during human liver transplantation.

Adolescent↗

The immunological consequences of photodynamic treatment of cancer, a literature review.

In this review we discuss the effect of photodynamic treatment (PDT) of solid tumors on the immune response. The effect on both the innate and adapted immune response is discussed. We have summarized the evidence that PDT causes or enhances an anti-tumor response. PDT is a local treatment in which the treated tumor remains in situ while the immune system is only locally affected and still functional in contrast with e.g. after systemic chemotherapy. We conclude that PDT of cancer is a way of in situ vaccination to induce a systemic antitumor response. In general, immune cells are found in the tumor stroma, separated from tumor cells by extracellular matrix and basal membrane-like structures. We hypothesize that PDT destroys the structure of a tumor, thereby enabling direct interaction between immune cells and tumor cells resulting in the systemic anti-tumor immune response.

Animals↗

Immunological aspects of photodynamic therapy of liver tumors in a rat model for colorectal cancer.

We have investigated tumor immunological effects of photodynamic therapy (PDT) of liver metastases. Livers of Wag/Rij rats were inoculated with three tumors of a syngeneic rat colon carcinoma cell line, CC531. One tumor in each rat was illuminated, with or without previous administration of the photosensitizer metatetrahydroxyphenylchlorin (mTHPC). PDT was effective in causing necrosis of tumors, but it did not affect the growth rate of nearby, nonilluminated tumors in the liver. Immunological staining of tumors showed natural killer (NK) cells to be significantly lower in PDT-treated tumors than in control tumors (P < 0.05). T cells in PDT-treated tumors and in their margins were lower than in tumors that received only sensitizer or only illumination (P = 0.015) at day 2 after treatment but reappeared at the tumor margins from day 7 after treatment. For macrophages, a similar pattern was found. NK cells, T cells or macrophages in nonilluminated tumors in mTHPC-treated rats did not increase significantly when compared with tumors in rats without mTHPC treatment. These findings indicated that no antitumor effect of a systemic immune response was present, as measured by the effect of PDT on growth of distant tumors and the number of T lymphocytes, NK cells and macrophages in these tumors.

Animals↗