Wyniki wyszukiwania - Biblioteka Nauki

1

Rak trzustki – podsumowanie sesji szóstych Międzynarodowych Dni Trzustki w Gdyni w dniach 27–30 października 2016

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Verbeke C. , Dobosz M. , Buchler M. , Hać S.

Polish Journal of Surgery

|

2018

|

tom 90(6)

43-45

PL

W sesji uczestniczyli prof. Caroline Verbeke z Zakładu Patologii Uniwersytetu w Oslo oraz prof. Marcus Wolfgang Büchler z Kliniki Chirurgii Ogólnej, Gastroenterologicznej i Transplantacyjnej Szpitala Uniwersyteckiego w Heidelberg w Niemczech. Uczestnicy omawiali zagadnienie chirurgii raka trzustki w odniesieniu do radykalności leczenia.

2

Patient with disseminated malignant tumor of the pancreas. Application of liposomal irinotecan as a new option of palliative treatment

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Galińska B. , Becht R.

OncoReview

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2021

|

tom 11

|

nr 3

73-76

EN

In palliative treatment of pancreatic neoplasms, chemotherapy regimens with gemcitabine, nab-paclitaxel, oxaliplatin, irinotecan, 5-fluorouracil or combinations of these drugs are used. The registration of liposomal irinotecan in the treatment of stage IV disease in patients with progression after gemcitabine creates new options for the treatment choice. The described case concerns a relatively young patient in whom the use of liposomal irinotecan in the registration indication turned out to be a safe and well-tolerated treatment.

3

Endoscopic ultrasound for differential diagnosis of malignant pancreatic cystic lesions: case report and review of literature

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Janiszewski J. , Woźniak J. , Kot-Gromuł I. , Michalak M. , Kozielec Z. , Zadrożny D. , Grabysa R.

OncoReview

|

2020

|

tom 10

|

nr 3

103-107

EN

A 63-year-old female patient was admitted to the hospital for an in-depth diagnosis of accidentally found pancreatic cystic lesion. The lesion was detected by computed tomography scan and magnetic resonance imaging of the abdomen and identified as potentially malignant mucinous cystic neoplasm (MCN). Endoscopic ultrasound-guided fine-needle aspiration biopsy with the analysis of the fluid from the cyst was performed as well and it confirmed the malignancy of the cystic lesion. The patient was qualified for surgery and the final diagnosis based on histopathological examination of the surgical material confirmed MCN with the accompanying invasive pancreatic adenocarcinoma.

4

Surgical treatment of pancreatic cancer

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Masiak-Segit W. , Rawicz-Pruszyński K. , Skórzewska M. , Polkowski W. P.

Polish Journal of Surgery

|

2018

|

tom 90(2)

45-53

EN

The only way to cure the patient with adenocarcinoma of the pancreas (RT) is surgical excision of the tumor. The standard surgical treatment of resectable pancreatic carcinoma is considered the classic pancreatoduodenectomy (PD) with the Kausch-Whipple procedure, or the pylorus-preserving PD with the Traverso-Longmire method. The most difficult technically and at the same time the most important PD stage from an oncological point of view is the separation of the head of the pancreas from the superior mesenteric artery. Over the last decades several PD modifications have been developed, focusing on this maneuver in the early phase of the operation, i.e. before the pancreas is cut (an irreversible stage of the procedure). These procedures in the English literature are called “artery-first approach” or “SMA-first approach”. The term “mesopancreas” was created. Complete removal of the mesopancreas together with the proximal part of the jejunum is considered an R0 resection in the case of a tumor of the head of the pancreas with direct or indirect vascular invasion, or metastases to regional lymph nodes, and in English literature it is referred to as pancreatoduodenectomy with systematic mesopancreas dissection (SMDPD). Distal resection of the pancreas (DRT) due to cancer, is associated with a high percentage of positive margins, insufficient number of removed lymph nodes, low survival rates. A new technique was developed - a radical proximal-distal modular pancreatosplenectomy (RAMPS). In RAMPS, surgical operations proceed from the side of the pancreas head towards the tail, the pancreas is cut early, and the splenectomy is performed at the final stages of the procedure. Currently, following the PD model, attempts are made to further modify the original RAMPS technique, especially in the direction of SMA-first approach. In patients with borderline resectable pancreatic tumors or locally advanced tumors, after neoadjuvant treatment, a technique of radical resection with preservance of arterial vessels - “the TRIANGLE operation” has been elaborated. Despite the tremendous progress of surgical techniques, RT is still detected too late in the phase preventing effective resection.

5

Pancreatic cancer – summary of the session of 6th International Pancreatic Days in Gdynia 27-30 October 2016

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Verbeke C. , Dobosz M. , Buchler M. , Hać S.

Polish Journal of Surgery

|

2018

|

tom 90(6)

43-45

EN

The session participants were Prof. Caroline Verbeke from The Department of Pathology of Oslo University and Prof. Marcus Wolfgang Büchler from the Department of General, Visceral and Transplantation Surgery at the University Hospital Heidelberg. The participants discussed the problem of surgical treatment of pancreatic cancer with regard to radicality.

6

Young Patient Age as the Cause of Delayed Diagnosis of Gastrointestinal Carcinoma

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Zaręba K. , Bandurski R. , Kędra B.

Polish Journal of Surgery

|

2012

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tom 84

|

nr 6

317-321

EN

Most patients diagnosed with gastrointestinal carcinomas are older people. The above-mentioned fact may lead to an erroneous finding that the problem does not concern patients aged between 20 and 30 years. Unfortunately, this assumption is often the reason for late diagnosis and delayed treatment of these malignancies. The study presented an example of three patients subject to surgical management of gastrointestinal carcinomas at the II Department of General and Gastroenterological Surgery, Medical University in Białystok.

7

Abdominal Ultrasonography in Detecting and Surgical Treatment of Pancreatic Carcinoma

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Kulig P. , Pach R. , Pietruszka S. , Banaś B. , Sierżęga M. , Kołodziejczyk P.

Polish Journal of Surgery

|

2012

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tom 84

|

nr 6

285-292

EN

The aim of the study was to asses the clinical value of percutaneous abdominal ultrasonography in diagnosis, staging and surgical treatment of patients with pancreatic carcinoma.Material and methods. Prospective clinical trial on diagnostic accuracy of percutaneous abdominal ultrasonography was conducted in 409 consecutive patients with pancreatic cancer which were operated on at the I Dept. of General Surgery in Cracow between 2000 and 2010.Results. Diagnostic accuracy of percutaneous abdominal ultrasonography in pancreatic cancer was 91,1%. The accuracy in detecting different stages of local advancement according to TNM classification was assessed respectively 92.3%-T1, 91.3%-T2, 89.4%-T3, 92.1%-T4, a whole T1-T4 on 91.3%. Diagnostic accuracy of percutaneous abdominal ultrasonography in diagnosis of metastasis to lymph nodes, vascular infiltration, and resectability was respectively 80.7%, 86%, 91.4%.Conclusions. Percutaneous abdominal ultrasonography has high diagnostic accuracy in diagnosis, staging and predicting surgical treatment of patients with pancreatic carcinoma.

8

Metalloproteinase 2 and 9 Activity in the Development of Pancreatic Cancer

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Durlik M. , Gardian K.

Polish Journal of Surgery

|

2012

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tom 84

|

nr 8

377-382

EN

Pancreatic adenocarcinoma is the fourth most common cancer occurring in both women and men. In Poland, within the past ten years the number of deaths from pancreatic cancer increased by 29%.The aim of the study was to determine the correlation between the activity of metalloproteinase (MMP) 2 and 9 and progression and aggressiveness of pancreatic cancer.Material and methods. Tissue samples were collected from 36 patients with diagnosed pancreatic adenocarcinoma who underwent Whipple resection. Tumor tissues were analyzed by gel zymography, zymography in situ and immunohistochemistry.Results. The activity of MMPs was found mainly in cancer cells. Active form of MMP2 (62 kDa) was present in 88% of cases and MMP9 (83 kDa) in 38% of cases. By contrast, immunohistochemical staining revealed the presence of metalloproteinase 9 in all studied tissues. MMP activity was assessed against histological grade of the tumor. In the case of group G1 there was no activity of matrix metalloproteinase 9. By comparing the activity we concluded that the activity of MMPs in tumors with the highest degree of differentiation is significantly lower than in G2 and G3. Metalloproteinase 9 expression analysis revealed no significant differences between the groups of various degrees of histological maturity. The level of expression did not differ between the groups N0 and N1.Conclusion. Lack of metalloproteinase 9 activity in group G1 may indicate that MMP9 is activated only in higher tumor grades. We have shown that an active form of MMP2 is found in all histological grades, which supports its involvement in the development of pancreatic cancer. Metalloproteinases are attractive target of anticancer therapy but not only the level of expression of metalloproteinases should be taken into account but also their level of activity and factors associated with their activation.

9

Very High Concentration of D-Dimers in Portal Blood in Patients with Pancreatic Cancer

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Durczyński A. , Szymański D. , Nowicki M. , Hogendorf P. , Poznańska G. , Strzelczyk J.

Polish Journal of Surgery

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2012

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tom 84

|

nr 10

521-525

EN

Nowadays, increasing attention has been focused on relation between increased D-dimer levels and cancer among patients without detectable thrombosis. was to measure plasma D-dimer levels in portal and peripheral blood in pancreatic cancer patients with absence of venous thromboembolism. Material and methods. Fifteen consecutive patients hospitalized in the Department of General and Transplant Surgery of Medical University in Łódź, from January to March 2012 who underwent surgery due to a pancreatic cancer were enrolled. At laparotomy, portal and peripheral blood were sampled concurrently. D-dimer and fibrinogen levels were measured. Moreover, to investigate overall coagulation function prothrombin time (PT), prothrombin index (PI), international normalized ratio (INR), thrombin time (TT), activated partial thromboplastin time (APTT), TT and APTT index were evaluated. Results. Peripheral plasma D-dimmer levels above normal range were found in 10/15 patients (66,67%), whereas D-dimer above normal values were confirmed in all portal blood samples. Mean D-dimer values were higher in portal than in peripheral blood (3279.37 vs 824.64, by 297%, p=0,025). These discrepancies were accompanied by normal limits of portal and peripheral levels of fibrinogen and comparable coagulation function indexes. Conclusion. Our preliminary study showed the close relation between activation of hemostasis, reflected by elevated D-dimers in portal blood and presence of pancreatic cancer. These data suggest that measurement of portal blood D-dimer levels may be a potentially useful technique for screening the pancreatic cancer.

10

Comparison of Early Results of Surgical Treatment in Patients with Pancreatic Cancer

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Śmigielski J. , Piskorz Ł. , Kutwin L. , Brocki M.

Polish Journal of Surgery

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2012

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tom 84

|

nr 1

1-5

EN

Pancreatic tumours are a serious medical and social issue. Patients come to the doctor too late, when the disease is well advanced. The most frequently applied method of surgical treatment is pancreatoduodenectomy (Whipple procedure). The most frequently used technique of pancreatoduodenectomy is the Child-Waugh method. The procedure can be performed in a classic way or as modified by Traverso (with preservation of the pylorus).Material and methods. Between August 2008 and June 2011, in the Department of Thoracic, General and Oncologic Surgery of Medical University in Łódź, a total of 79 patients with pancreatic tumours were hospitalized. In 61, pancreatoduodenectomy was performed. The patients were divided into two groups, depending on the diagnosis and the procedures performed: group 1 comprised patients in whom the pylorus was resected (n = 43); group 2 comprised patients in whom the pylorus was preserved (Traverso-Longmire procedure; n = 18).Results. Mean duration of surgery was about 3 hours and 50 minutes in both groups. Mean duration of hospitalization after the procedure was 15.6 days in group 1 and 12.2 days in group 2 (p < 0.05). Early complications (within 30 days of the procedure) were observed in 33.2% of patients in both groups. Blood transfusion was necessary in 21% of patients in group 1 and 28% of patients in group 2 (p>0.05).Conclusions. There are specific indications for each method of surgical treatment, however, it seems that both techniques of pancreatic resection can be recommended as standard surgical treatment, and the number of complications after both procedures is similar.

11

Prolongation of survival time and improvement of the quality of life after treatment with irinotecan liposomal in the patient with metastatic pancreatic adenocarcinoma

100%

Rogowski W. , Będkowski P.

OncoReview

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2021

|

tom 11

|

nr 3

77-79

EN

Pancreatic cancer is one of the malignant neoplasms with the worst prognosis. It is most often diagnosed at an advanced stage, which relates to unsatisfactory results of the therapy. Only about 15–20% of patients with pancreatic cancer qualify for surgery. The remaining patients are diagnosed with locally advanced disease or much more frequently in the generalized stage. Systemic treatment (chemotherapy) remains the mainstay of therapy in these patients, but both the response rate and progression-free time are unsatisfactory [1, 2]. This paper presents a case of a patient with metastatic pancreatic cancer, in whom three lines of systemic treatment were applied sequentially, which allowed to extend the survival time and improve the quality of life.

12

CA 19-9 Concentration in Peripheral and Portal Blood of Patients Operated on for Pancreatic Tumor

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Szwedziak K. , Strzelczyk J.

Polish Journal of Surgery

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2013

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tom 85

|

nr 1

20-28

EN

Pancreatic cancer is one of the most common malignant diseases in the world. Morbidity rate increases and now reaches around 200 000 new cases yearly. Poor prognosis mainly results from usually late diagnosis and non-specific symptoms. Despite of advances in radiological diagnosis of pancreatic diseases, differentiation between malignant and inflammatory pancreatic tumors still remains difficult. The aim of the studywas the assessment of clinical utility of CA 19-9 in peripheral and portal blood of patients with pancreatic tumor. Material and methods.66 patients were hospitalized at the Department of General and Transplant Surgery between October 2010 nad July 2012 due to pancreatic tumor. Blood samples were collected from peripheral vein before surgery and intraoperatively from the portal vein to measure CA 19-9 concentration. 57 patients were diagnosed with malignant tumor and 9 with inflammatory lesion. Metastases to the liver were present in 7 of all patients. Radical surgery (Whipple’s procedure in 27 cases) were performed in 34 patients. Results.Significantly higher CA 19-9 concentration in the peripheral blood and in the portal blood as well was found in the pancreatic cancer group than in the inflammatory lesions group (51.2 vs <3 and 52.1 vs 6.3 respectively). Marker concentration in case of malignant lesions was significantly higher in the portal blood than in the peripheral blood (52.1 vs 51.2; p<0.05). CA 19-9 concentration of patients with malignant pancreatic tumors but without metastases to the liver was significanlty higher in the portal blood than in the peripheral blood (19.32 vs 18.65; p<0.01). Conclusions.Determination of the CA 19-9 concentration not only in the peripheral blood but in the portal blood as well might be a useful diagnostic tool in order to differentiate between the malignant and inflammatory pancreatic tumors. We did not see any statistically significant dependency between the CA 19-9 concentrations in the peripheral blood and portal blood and if the surgery was radical or not, but significantly higher concentrations of CA 19-9 in the portal blood than the peripheral blood among the patients suffering from the malignant pancreatic tumor without metastases to the liver might be useful tool when decisions on performing pancreatoduodenectomy are being made since this surgery is forborne from when metastases are present.

13

Assessment of changes in body composition measured with bioelectrical impedance in patients operated for pancreatic, gastric and colorectal cancer

88%

Dzierżek P. , Kurnol K. , Hap W. , Frejlich E. , Diakun A. , Karwowski A. , Kotulski K. , Rudno-Rudzińska J. , Kielan W.

Polish Journal of Surgery

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2020

|

tom 92(2)

8-11

EN

ntroduction: A proper level of nutrition is significant in the period of convalescence in patients subject to major surgical procedures, particularly due to neoplastic disease. Bioelectrical Impedance Analysis, or BIA is a widely used method in assessing body mass composition. BIA measurement is easy, quick, cheap and repetitive. Material and methods: We assessed the body composition of 56 patients (25 women and 31 men) hospitalized and operated at the Department of General and Oncological Surgery of the Wroclaw Medical University in the years 2017–2018 using bioelectric impedance. Results: The average body weight loss in the 4th postoperative day was 1.32% of body mass and on the day of release from hospital – 4.23% of body mass in relation to body mass upon admission. The percentage of body fat (FM – Fat Mass) in patients admitted to the department is above the normal range. The change in body composition in hospitalized patients mainly concerns the amount of adipose tissue and the amount of extracellular and intracellular water (ECW – Extracellular Water; ICW – Intracellular Water). Conclusions: Bioelectrical impedance can be an easy and effective method of assessing body composition and its change in patients undergoing major surgery. Amongst the analyzed groups, patients operated for pancreatic cancer lose the largest percentage of body weight until discharge from the department. Loss of body mass mainly occurs as loss of fat mass (FM).

14

Assessment of the presence of pancreatic intraepithelial neoplasia in various diseases of this organ

88%

Zińczuk J. , Zaręba K. , Konarzewska-Duchnowska E. , Guzińska-Ustymowicz K. , Kędra B. , Kemona A. , Pryczynicz A.

Progress in Health Sciences

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2017

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tom 7(2)

43-49

EN

Purpose: Pancreatic intraepithelial neoplasia (PanIN) is one of the most commonly occurring precancerous lesion in pancreas which leads to development of pancreatic ductal adenocarcinoma (PDAC). We assessed the presence and grade of pancreatic intraepithelial neoplasia in the course of various diseases of the pancreas and its correlations with chosen clinicopathological parameters. null Results: A total of 276 foci of PanIN were identified in 94 patients. The most common lesions were PanIN 1a and PanIN 1b which together constituted 68.2 % of all lesions, whereas the PanIN 2 was present in 21.7% and PanIN 3 in 10.1% of patients. No statistical differences were observed in gender tendency for the development of PanINs. There was correlation between age of patients and degree of PanIN (p=0.034). There is no statistical difference in PanIN frequency among patients with pancreatic ductal adenocarcinomas, neuroendocrine tumors, chronic pancreatitis and pancreatic cysts (p=0.592). Conclusions: Our study showed that important factor in development of pancreatic intraepithelial neoplasia is age and the presence of PanIN in nonneoplastic diseases in older people should be included to the group with increased risk of cancer development.

15

The favourable effect of catechin in electrochemotherapy in human pancreatic cancer cells

88%

Michel O. , Przystupski D. , Saczko J. , Szewczyk A. , Niedzielska N. , Rossowska J. , Kulbacka J.

Acta Biochimica Polonica

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2018

|

tom 65

|

nr 2

173-184

EN

Until recently, green tea polyphenols were considered strong antioxidants. However, the latest reports have revealed that bioflavonoids can play a multiple role in anticancer therapy, including the inhibition of cell proliferation and generation of the oxidative stress in a dose-dependent manner. The presented research was designed to examine the potential of the green tea (±)-catechin as a reinforcement of the electrochemotherapy (ECT) with cisplatin in pancreatic cancer in vitro. The study was performed on two cell lines of the pancreatic ductal adenocarcinoma (PDA) - parental EPP85-181P and multidrug-resistant EPP85-181RNOV. Prior to the ECT protocol the cells were preincubated with high or low concentration of catechin for 2 or 24 hours, respectively. We assessed the influence of preincubation on the cisplatin toxicity with and without electroporation (EP), the electrosensitivity of PDA cell lines and the uptake of the daunorubicin and propidium iodide. Additionally, we evaluated the antioxidative properties of catechin by the measurement of the ROS-related fluorescence and the immunoreactivity of the oxidative stress-related enzymes superoxide dismutase (SOD2) and glutathione S-transferase (GST). We found that co-treatment with catechin can firmly enhance the efficacy of electroporation with cisplatin in vitro. More favorable effect was obtained for 2-hour incubation, which indicates the involvement of the transcriptional-independent mechanisms of catechin action. The effect may be partially explained by the increased oxidative stress level, which was higher in multidrug-resistant cells. However, further studies on cisplatin-catechin interplay and the thorough examination of the catechin-cell membrane interaction need to be performed.

16

Concentration of Gelatinases and Their Tissue Inhibitors in Pancreatic Inflammatory and Neoplastic Tumors and Their Influence on the Early Postoperative Course

88%

Lekstan A. , Olakowski M. , Jabłońska B. , Łabuzek K. , Olakowska E. , Filip I. , Lampe P.

Polish Journal of Surgery

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2013

|

tom 85

|

nr 2

65-72

EN

Pancreatic cancer (PC) is the fourth leading cause of death in the world, due to neoplastic disease. Chronic pancreatitis (CP) is a progressive disease leading towards pancreatic fibrosis. The aim of the study was to assess the impact of matrix metalloproteinases 2 and 9 (MMP2 and 9) and their tissue inhibitor (TIMP 1 and 2) concentrations in case of PC and CP tissue homogenates on early treatment results of patients subject to pancreatic resections. Material and methods. The study group comprised 63 patients, including 25 (39.68%) female and 38 (60.32%) male patients. Group 1 (CP) consisted of 31 patients with CP (F: M = 10/21). Group 2 (PC) consisted of 32 patients with PC (F: M = 15:17). The pancreatic tumor samples were collected from the resected pancreas, being subject to electrophoresis and immunoenzymatic studies. After confirming their activity, MMP2, MMP9, TIMP1, TIMP2 concentrations were determined. Correlation analysis of MMPs and TIMPs concentrations was performed in relation to the following: tumor diameter, age, BMI, hospitalization, duration of symptoms and surgery, blood loss, incidence of perioperative complications. Results. Group differences were presented in terms of: age, BMI, ASA, duration of symptoms, jaundice, tumor diameter, time of operation. There were no differences considering weight loss, blood loss, extent of resection, and hospitalization. Significant MMPs and TIMPs concentration differences between groups were demonstrated. Conclusions. Comparison of PC to CP tissue samples showed significantly higher levels of metalloproteinases and TIMPs in the former. Positive correlations of MMP1, TIMP1 and 2 with tumor diameter (CP) were observed, and MMP2 with the duration of surgery and blood loss (PC). There was no MMPs and TIMPs concentration levels influence on the incidence of postoperative complications.

17

Signal transduction in human pancreatic cancer: roles of transforming growth factor beta, somatostatin receptors, and other signal intermediates

88%

Li M. , Becnel L. S. , Li W. , Fisher W. E. , Chen C. , Yao Q.

Archivum Immunologiae et Therapiae Experimentalis

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2005

|

tom 53

|

nr 5

18

Mini-review on the glucose metabolism modifications after pancreatic resection

75%

Timofte D. , Ionescu L. , Ochiuz L.

International Letters of Natural Sciences

|

2016

|

tom 53

EN

Pancreatic cancer is one of the most severe malignant disease, with an extreme degree of lethality, considering that the survival rate at 5 years is up to 4%. In addition, a major disadvantage of this disease is the fact that the diagnosis is determined very late in the evolution of the disorder, despite the development of new technologies. In this way, the main symptoms are occurring later on, when the tumour is well to advanced and totally unresectable. Up to now surgery is the only modality that can provide a greater chance of survival, but unfortunately the pancreatic resection has many unknowns and controversies around it. Moreover, the studies on endocrine pancreatic function after resection are very few and somehow controversial. In this way, in the present minireview we will describe the most relevant experimental data regarding the post-resection pancreatogenic diabetes, the pancreatic polypeptide PP and the pancreatic glucose metabolism after resection or the glucose metabolism after partial or total pancreatectomy.

19

Exocrine pancreatic cancer and living near to waste sites containing hazardous organic chemicals, New York State, USA – an 18-year population-based study

75%

Weinstein B. , da Silva A. , Carpenter D. O.

International Journal of Occupational Medicine and Environmental Health

|

2022

|

tom 35

|

nr 4

459-471

EN

ObjectivesThe etiology of exocrine pancreatic cancer (EPC) remains unknown except for family history and smoking. Despite recent medical advances, rates of pancreatic cancer incidence and mortality are increasing. Although existing evidence suggests a potentially causal relationship between environmental chemical exposures and pancreatic cancer, whether residential exposure impacts pancreatic cancer rates remains unknown.Material and MethodsThe authors identified 28 941 patients diagnosed with exocrine pancreatic cancer in New York State exclusive of New York City for the years 1996–2013. Descriptive statistics and negative binomial regression were used in this ecological study to compare pancreatic cancer hospitalization rates among patients who lived in zip codes with hazardous waste sites (HWSs) containing persistent organic pollutants (POPs) and volatile organic pollutants (VOCs) compared with clean zip codes with no identified hazardous waste sites. The authors assessed the effect of selected known and suspected human carcinogens on the EPC hospitalization rates by subgroup analyses.ResultsCompared with the clean sites, the pancreatic cancer hospital discharge rate in the “VOCs without POPs” and “VOCs and POPs” sites, after adjustment for potential confounders were 1.06 (95% CI: 1.03–1.09) and 1.05 (95% CI: 1.01–1.08), respectively. In the analysis by specific chemicals, rate ratios (RR) for the benzene (RR = 1.12) and ethylbenzene (RR = 1.34) in the non-chlorinated VOCs group, trichloroethylene (RR = 1.07) and tetrachloroethylene (RR = 1.11) in the chlorinated VOCs group, chlorinated pesticides (RR = 1.11) and PCBs (RR = 1.05) in the POPs groups were statistically significant (p-values <0.05) compared with clean sites.ConclusionsCompared with the clean sites, the pancreatic cancer hospital discharge rate in the “VOCs without POPs” and “VOCs and POPs” sites, after adjustment for potential confounders were 1.06 (95% CI: 1.03–1.09) and 1.05 (95% CI: 1.01–1.08), respectively. In the analysis by specific chemicals, rate ratios (RR) for the benzene (RR = 1.12) and ethylbenzene (RR = 1.34) in the non-chlorinated VOCs group, trichloroethylene (RR = 1.07) and tetrachloroethylene (RR = 1.11) in the chlorinated VOCs group, chlorinated pesticides (RR = 1.11) and PCBs (RR = 1.05) in the POPs groups were statistically significant (p-values <0.05) compared with clean sites.

20

Use of cell therapy as a means of targeting chemotherapy to inoperable pancreatic cancer

75%

Günzburg W. H. , Salmons B.

Acta Biochimica Polonica

|

2005

|

tom 52

|

nr 3

601-607

EN

Although approved for the treatment of pancreatic cancer, the chemotherapeutic agent ifosfamide is not an effective therapy for this type of tumour. Ifosfamide must be activated by cytochrome P450 (P450) enzymes in the liver, initially to a short lived intermediate and then to toxic metabolites that are subsequently distributed by the circulatory system. Particularly for pancreatic cancer, this liver-mediated conversion results in relatively high systemic toxicities and poor therapeutic concentrations at the liver-distant site of the tumour. Activation of ifosfamide at the site of the tumour may allow lower doses to be used, while increasing the therapeutic index due to the resultant active concentrations generated locally. A cell-based therapy has been conceived where encapsulated, 293-derived cells genetically modified to overexpress a cytochrome P450 enzyme, are implanted near solid tumours. The cells are encapsulated in polymers of cellulose sulphate in order to provide a means of immunoprotection in vivo as well as to physically constrain them to the vicinity of the tumour. A major advantage of this strategy is that it allows one standard cell line to be applied to all patients and this approach can be extended to the treatment of other tumour types. After proof of principle studies in animal models, a phase I/II clinical trial was initiated in patients with stage III/IV nonresectable pancreatic cancer. Encapsulated cells were angiographically placed into the tumour vasculature of 14 patients and followed by systemic low dose ifosfamide treatment. Angiographic delivery of encapsulated cells proved feasible in all but one patient, and was well tolerated with no capsule or ifosfamide treatment-related adverse events. Four of the treated patients showed tumour regressions after capsule delivery and ifosfamide treatment in computer-tomography scans. The other 10 patients showed no further tumour growth (i.e. stable disease) during 20 weeks observation period. The median life expectancy of the patient collective was extended two fold as compared to age and status matched historical controls, with a 3-fold improvement in one year survival being attained. Evidence for a clinical benefit of the treatment was also obtained on the basis of standard parameters for quality of life. This approach has been evaluated by the European Medicines Evaluation Agency (EMEA) and orphan drug status has been granted. A pivotal clinical trial is now being planned with the help of the EMEA. Taken together, the data from this clinical trial suggest that encapsulated cytochrome P450-expressing cells combined with chemotherapy may be useful for the local treatment of a number of solid tumours and support the performance of further clinical studies of this new treatment.