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Karel Caca

Publications and source records attributed to Karel Caca.

30 records · Page 2Linked to original sources
PubMed2003

Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma: a phase II pilot study.

BACKGROUND: Only 20-30% of patients with hilar cholangiocarcinomas (CC) are candidates for potentially curative resection. However, even after curative (R0) resection, these patients have a disease recurrence rate of up to 76%. The current prospective Phase II study investigated photodynamic therapy (PDT) as a neoadjuvant treatment for CC. METHODS: Seven patients with advanced proximal bile duct carcinoma were evaluated. Patients were treated with PDT at the area of tumor infiltration and 2 cm beyond and underwent surgery after a median period of 6 weeks (range, 3-44 weeks). RESULTS: One patient had a Bismuth-Corlette Type II tumor, two patients had Type IIIa, one patient had Type IIIb, and three patients had Type IV. Cholestasis parameters after PDT decreased significantly. No relevant adverse events from PDT occurred except for minor intraoperative phototoxicity in one patient. Three patients underwent right-sided liver resections, two patients underwent left-sided liver resections, and one patient received a combined hilar resection with partial pancreatoduodenectomy (PD) due to tumor extension into the distal bile duct. Liver transplantation and PD were performed in another patient. In all patients, R0 resection was achieved. Four patients developed minor surgical complications, even though the bilioenteric anastomoses were sewn to PDT-pretreated bile ducts. No viable tumor cells were found in the inner 4 mm layer of the surgical specimens. The PDT-pretreated epithelium of the tumor-free proximal resection margins exhibited only minimal inflammatory infiltration. Tumors recurred in 2 patients 6 and 19 months after surgery. The 1-year recurrence free survival rate was 83%. CONCLUSIONS: Neoadjuvant PDT for hilar CC is a low-risk procedure with efficient selective destruction of the superficial 4 mm layer of bile duct tumor without complications exceeding series without neoadjuvant PDT. Neoadjuvant PDT should be evaluated prospectively to determine whether it reduces the rate of local disease recurrence after potentially curative resection.

Adult↗
PubMed2003

Successful photodynamic therapy for nonresectable cholangiocarcinoma: a randomized prospective study.

BACKGROUND & AIMS: In nonrandomized trials, photodynamic therapy (PDT) had a promising effect on nonresectable cholangiocarcinoma (NCC). This prospective, open-label, randomized, multicenter study with a group sequential design compared PDT in addition to stenting (group A) with stenting alone (group B) in patients with NCC. METHODS: In patients with histologically confirmed cholangiocarcinoma, endoscopic or percutaneous double stenting was performed. Patients fulfilling inclusion criteria were randomized to group A (stenting and subsequent PDT) and group B (stenting alone). For PDT, Photofrin 2 mg/kg body wt was injected intravenously 2 days before intraluminal photoactivation (wavelength, 630 nm; light dose, 180 J/cm(2)). Further treatments were performed in cases of residual tumor in the bile duct. The primary outcome parameter was survival time. Secondary outcome parameters were cholestasis and quality of life. RESULTS: PDT resulted in prolongation of survival (group A: n = 20, median 493 days; group B: n = 19, median 98 days; P < 0.0001). It also improved biliary drainage and quality of life. CONCLUSIONS: PDT, given in addition to best supportive care, improves survival in patients with NCC. The study was terminated prematurely because PDT proved to be so superior to simple stenting treatment that further randomization was deemed unethical.

Bile Duct Neoplasms↗
PubMed2003

Diagnosis and phenotypic classification of Wilson disease.

Wilson disease is an inherited autosomal recessive disorder of hepatic copper metabolism leading to copper accumulation in hepatocytes and in extrahepatic organs such as the brain and the cornea. Originally Wilson disease was described as a neurodegerative disorder associated with cirrhosis of the liver. Later, Wilson disease was observed in children and adolescents presenting with acute or chronic liver disease without any neurologic symptoms. While diagnosis of neurologic Wilson disease is straightforward, it may be quite difficult in non-neurologic cases. Up to now, no single diagnostic test can exclude or confirm Wilson disease with 100% certainty. In 1993, the gene responsible for Wilson disease was cloned and localized on chromosome 13q14.3 (MIM277900) (1, 2). The Wilson disease gene ATP7B encodes a P-type ATPase. More than 200 disease causing mutations of this gene have been described so far (3). Most of these mutations occur in single families, only a few are more frequent (like H1069Q, 3400delC and 2299insC in Caucasian (4-6) or R778L in Japanese (7), Chinese and Korean patients). Studies of phenotype-genotype relations are hampered by the lack of standard diagnostic criteria and phenotypic classifications. To overcome this problem, a working party discussed these problems in depth at the 8th International Meeting on Wilson disease and Menkes disease in Leipzig/Germany (April 16-18, 2001). After the meeting, a preliminary draft of a consensus report was mailed to all active participants and their comments were incorporated in the final text.

Adolescent↗
PubMed2003

Defective cellular localization of mutant ATP7B in Wilson's disease patients and hepatoma cell lines.

BACKGROUND & AIMS: Wilson's disease, a hereditary disorder caused by mutations in the Wilson's disease gene (ATP7B), leads to hepatic and/or neurological pathology resulting from cellular copper overload. In vitro studies showed that ATP7B, located in the trans-Golgi network, traffics to a cytoplasmic vesicular compartment in response to increased copper concentration. Mislocalization and failed intracellular trafficking of ATP7B mutants are suggested to be among disease-causing mechanisms; however, the effect of mutations on ATP7B localization in human tissues has not been directly shown. Therefore, we characterized the subcellular localization of normal and mutant ATP7B in human livers and in hepatoma cell lines. METHODS: Subcellular distribution of ATP7B in liver tissue from 3 control individuals and 3 Wilson's disease patients harboring a homozygous H1069Q-ATP7B mutation was analyzed by using immunogold electron microscopy. In addition, 14 ATP7B mutants tagged to green fluorescent protein were generated and expressed in HuH-7 and HepG2 cells; intracellular localization of these mutants was characterized by confocal microscopy. RESULTS: In hepatocytes, ATP7B was localized in trans-Golgi vesicles, whereas H1069Q-ATP7B was trapped in the endoplasmic reticulum. Similar results were observed for wild-type ATP7B and H1069Q-ATP7B expressed in hepatoma cells. Most ATP7B proteins harboring missense mutations were distributed similarly to wild-type ATP7B. In contrast, truncated ATP7B mutants showed a diffuse, clustered, cytoplasmic pattern, distinct from the trans-Golgi network or endoplasmic reticulum. CONCLUSIONS: These results provide a detailed demonstration of the ATP7B distribution in control and diseased human livers and indicate that several Wilson's disease mutations lead to incorrect localization of ATP7B to distinct cell compartments.

Adenosine Triphosphatases↗
PubMed2003

Self-expandable metallic stents for malignant duodenal obstruction caused by biliary tract cancer.

BACKGROUND: Malignant duodenal obstruction is a common event in patients with advanced biliary tract cancer. Because bypass surgery is accompanied by significant morbidity, self-expandable metallic stents have emerged as a possible alternative for palliation. METHODS: Twenty patients with biliary tract cancer (7 gallbladder, 13 Klatskin tumors) and duodenal obstruction were treated with metallic stents at a single institution between 1999 and 2001. Survival, morbidity, and stent function were studied prospectively. The ability to eat was assessed by using a scoring system. RESULTS: Stent placement was technically successful in all patients. An additional stent was required in 6 cases (4 occlusions, 2 dislocations). Median survival was 20.5 weeks; there was no treatment-related death. Twenty-eight biliary stent exchanges were performed in 13 (65%) patients. Erosive reflux esophagitis improved in 11 of 12 (92%) cases. After 4 weeks, all 17 surviving patients tolerated soft or solid food, whereas 13 of 17 (77%) tolerated a more solid diet (p < 0.001, gastric outlet obstruction scoring system). Twelve of 17 (71%) patients gained a median of 1.5 kg of body weight (p = 0.001). The median Karnofsky scale increased from 50% to 60% in 13 of 17 (77%) patients. CONCLUSIONS: Self-expandable metallic stents are a safe, efficacious, and minimally invasive treatment option for palliation of patients with duodenal obstruction from biliary tract cancer. Technical complications can be managed endoscopically and the bile duct remains accessible for endoluminal treatment.

Aged↗
PubMed2003

Outcome after duodenum-preserving pancreatic head resection is improved compared with classic Whipple procedure in the treatment of chronic pancreatitis.

BACKGROUND: There is no consensus in the surgical management of chronic pancreatitis (cP) as to whether techniques preserving the duodenum are superior to pancreatoduodenectomy. This prospective study compared the outcome of standard pancreatoduodenectomy (PD) and duodenum-preserving pancreatic head resection (DPPHR) in treatment of selected patients with cP. METHODS: Inclusion criteria for this prospective controlled, nonrandomized study were patients suffering from cP centered in the head and with severe pain. Seventy consecutive patients underwent DPPHR (n = 38) or, if there was suspicion of malignancy, classic PD (n = 32). A multidimensional, psychometric questionnaire was used to measure the quality of life (QoL). QoL was compared with that of the general German population. Pain intensity was evaluated on the basis of the frequency of pain attacks, analgesic medication, and self-assessed pain score. Assessment of endocrine and exocrine function as well as nutritional status included oral glucose tolerance test, fecal elastase, stool frequency, and body mass index. The median follow-up was 34 months. RESULTS: Multiple clinical characteristics did not differ between the two groups except for age (P =.04), the tumor marker carbohydrate antigen 19-9 (P =.02), and the parameter suspicion of malignancy. There was no hospital mortality. Surgical morbidity was 19% in the PD group and 8% in the DPPHR group (P =.60). PD resulted in a longer median hospital stay than DPPHR (19 vs 15 days, P =.04). Complications of adjacent organs were definitively treated in 100% after PD and in 97% after DPPHR. Postoperative pain intensity as self-assessed by the patients was significantly less in the DPPHR group (P <.001), whereas the frequency of acute episodes (P =.27) and analgesic medication (P =.43) did not differ between the two groups. After surgery, symptom and functional scales of the DPPHR group were significantly better than those in the PD group and were similar to those of the overall German population. No significant difference was found between the two groups with regard to endocrine and exocrine function. Postoperative increase of body mass index was significantly higher in the DPPHR group (P <.001). CONCLUSIONS: DPPHR provides better results in the treatment of cP than PD in terms of QoL, pain intensity as self-assessed by the patients, nutritional status, and length of hospital stay.

Adult↗
PubMed2003

Imatinib mesylate (STI571; Glivec)--a new approach in the treatment of biliary tract cancer?

Non-resectable biliary tract cancer is associated with poor prognosis due to widespread resistance to chemotherapeutic agents and radiotherapy. It is therefore essential to explore new therapeutic approaches like the inhibition of tyrosine kinases. The aim of this study was to determine the expression of c-kit and platelet-derived growth factor (PDGF) receptors (PDGFRs) and the effects of the tyrosine kinase inhibitor imatinib +/- 5-fluorouracil (5-FU) on proliferation and apoptosis in biliary tract cancer cell lines. The expression of c-kit and PDGFR mRNA was examined in 12 biliary tract cancer cell lines using RT-PCR. Cells were treated with imatinib (1, 10, 20 and 50 micromol/l) +/- 5-FU (0.1 microg/ml) for 6 days and inhibition of cell growth was assessed by manual cell counting. Cell proliferation and apoptosis were analyzed by flow cytometry of BrdU and Annexin-V/propidium iodide-stained cells. c-kit and PDGF mRNA expression was detected in 50 and 75%, respectively. Imatinib (10 and 20 micromol/l) alone inhibited cell growth significantly higher in c-kit+ cell lines (p<0.02) and inhibition was independent of PDGFR status. The combination with 5-FU increased the effect of imatinib mesylate in all cell lines. Treatment of cells with imatinib +/- 5-FU was associated with a significant induction of apoptosis, but no inhibition of proliferation. We conclude that imatinib alone exerts marked effects on c-kit+ biliary tract cancer cell lines only at intermediate and high concentrations, but there is a potential role of low-dose imatinib in combination with 5-FU for the treatment of biliary tract cancers.

Antineoplastic Agents↗
PubMed2002

Inactivation of the INK4a/ARF locus and p53 in sporadic extrahepatic bile duct cancers and bile tract cancer cell lines.

The tumor-suppressor genes p14(ARF), p16(INK4a) and Tp53 are commonly inactivated in many tumors. We investigated their role in the pathogenesis of 9 bile tract cancer cell lines and 21 primary sporadic extrahepatic bile duct carcinomas. p53 and p16 protein expression was examined by Western blot analysis and immunohistochemistry. Mutation screening of p53 was done by SSCP and direct sequencing. Inactivating mechanisms of p14 and p16 were addressed by screening for mutations, homozygous deletions, chromosomal loss of 9p21 (loss of heterozygosity [LOH] analysis) and promoter hypermethylation of the p14/p16 genes. p53 overexpression could be detected in 7 of 9 cell lines and 7 of 21 primary tumors, but mutations were found in 3 cell lines only. p16 expression was absent in all cell lines, due to homozygous deletion of the gene in 8 of 9 cell lines and hypermethylation of the p16 promoter in one cell line (CC-LP-1). p14 exon 1beta was homozygously deleted in 6 of 9 cell lines, while retained in CC-LP-1 and 2 additional lines. No p14 promoter hypermethylation could be detected. p16 expression was lost in 11 of 21 primary tumors. p16 promoter hypermethylation was present in 9 of 21 primary tumors, all with lost p16 expression. Allelic loss at 9p21 was detected in 13 of 21 primary tumors, 10 of 11 with lost p16 expression and 8 of 9 with methylated p16 promoter. No p14 promoter hypermethylation or p14/p16 mutations could be detected. Neither Tp53 nor p16 alterations showed obvious association with histopathologic or clinical characteristics. In conclusion, inactivation of the p16 gene is a frequent event in primary sporadic extrahepatic bile duct cancers, 9p21 LOH and promoter hypermethylation being the principal inactivating mechanisms. Therefore, p16, but not p14, seems to be the primary target of inactivation at the INK4a locus in bile duct cancers. Other mechanisms than Tp53 mutations seems to be predominantly responsible for stabilization of nuclear p53 protein in bile duct cancers.

Bile Duct Neoplasms↗
PubMed2002

Genotype correlation with fine motor symptoms in patients with Wilson's disease.

Wilson's disease, an autosomal recessive disorder of copper metabolism, is caused by about 200 different mutations of the ATP7B gene. Using a genotype-phenotype correlation, 36 patients were examined to see whether the disorder of the automatic handwriting movement depends on the genotype. The findings of this study indicated that no such link exists. Neither the profile of the impairment of the fine motor parameters nor the severity and frequency of pathological findings were different among the three genotype groups (homozygous for H1069Q, compound homozygous for H1069Q and other mutations). By contrast, fine motor disorders were found to correlate with the clinical symptoms recorded when therapy began. The pathophysiology of the basal ganglia and the cerebellar loop therefore cannot be directly attributed to the genotype of the mutation in the ATP7B gene.

Adenosine Triphosphatases↗
PubMed2001

Neuroendocrine tumours of the duodenum. Clinical aspects, pathomorphology and therapy.

BACKGROUND AND AIMS: Neuroendocrine tumours (NTs) of the duodenum are uncommon neoplasms. They represent a heterogeneous spectrum of subtypes and may be associated with von Recklinghausen's disease type I (VRD) and multiple endocrine neoplasia type I. There are few studies concerning the biological characteristics and adequate therapy of these tumours. PATIENTS AND METHODS: We report on a retrospective analysis of 12 patients with NTs of the duodenum: six non-ampullary (naNTs) and six ampullary tumours (aNTs). These patients were treated between January 1992 and January 2001. Clinical and histopathological features, therapy and follow-up were evaluated retrospectively and compared with the literature. RESULTS: All tumours were located in the first and second portions of the duodenum. Three of six aNTs presented with jaundice, and four of six naNTs were incidental findings. Two patients with naNTs showed Zollinger-Ellison syndrome and two with aNTs VRD. Of the six patients with naNTs, four were treated by local excision (two endoscopically, two surgical resection), one by Kausch-Whipple operation and in one patient the tumour was an incidental finding in the Billroth II specimen. Four of the six patients with aNTs underwent Kausch-Whipple procedure, one patient ampullectomy (gangliocytic paraganglioma) and one patient palliative chemotherapy. The size of the naNTs were less than 0.6 cm, whereas the size of the aNTs ranged from 1.5 cm to 4 cm. Tumour size of aNTs had no correlation with depth of invasion and metastases. Metastases were found in two aNTs and none of the naNTs. Immunohistochemically tumour cells expressed somatostatin in 5 of 6 aNTs and gastrin in 1 of 6 aNTs and in two gastrinomas. There was no hospital mortality. Two patients died for reasons not related to the tumour. Tumour excision of both patients with gastrinomas was not curative. Three patients with naNTs and four with aNTs are alive without disease. One patient with palliative treatment of a metastasising aNT is alive 66 months after diagnosis. CONCLUSION: Non-ampullary duodenal NTs differ clinically, histologically and immunohistochemically as well as with respect to the extent of resection from NTs of the ampulla of Vater.

Adult↗
PubMedDate not supplied

Endoscopic treatment of duodenal obstruction due to a gallstone ("Bouveret's syndrome").

We describe the case of a 73-year-old woman was admitted to our hospital because of constant abdominal pain in her right upper quadrant and postprandial bloating and fullness for several months. On abdominal x-ray the extrahepatic bile ducts were positive for gas and on ultrasound a gallstone in the duodenum was suspected whereas the gallbladder was not detectable. An upper gastrointestinal endoscopy confirmed a large gallstone that was impacted in the duodenal bulb ("Bouveret's syndrome"). The gallstone was fragmented employing mechanical lithotripsy and removed. Duodenoscopy revealed a cholecystoduodenal fistula and a second gallstone in the gallbladder. The patient underwent open cholecystectomy with closure of the cholecystoduodenal fistula and made a full recovery. We conclude that in patients with upper abdominal pain and pneumobilia on x-ray the unusual complication of cholelithiasis with an impacted gallstone in the duodenal bulb should be suspected. In those rare cases of Bouveret's syndrome endoscopic removal of the gallstone should be attempted to minimize the necessary surgical procedure whenever possible.

Aged↗