Jens-Christian Kröger

Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma

Pancreatic cancer can seldom be resected, and chemotherapy has only a limited effect on survival or tumour load. We did a phase I/II trial in 14 patients with pancreatic cancer to assess the safety of local activation of low-dose ifosfamide. We encapsulated genetically modified allogeneic cells, which expressed a cytochrome P450 enzyme, in cellulose sulphate and delivered them by supraselective angiography to the tumour vasculature. These cells locally activated systemically administered ifosfamide. The tumours of four patients regressed after treatment, and those of the other ten individuals who completed the study remained stable. Median survival was doubled in the treatment group by comparison with historic controls, and 1-year survival rate was three times better. Further studies of this cell-therapy-based treatment combined with chemotherapy for inoperable pancreatic cancer are warranted.

Cell therapy using microencapsulated 293 cells transfected with a gene construct expressing CYP2B1, an ifosfamide converting enzyme, instilled intra-arterially in patients with advanced-stage pancreatic carcinoma: a phase I/II study.

Matthias Lohr (principal investigator) · Zoltan Tibor Bago · Helga Bergmeister · Manfred Ceijna · Mathias Freund · Wolfgang Gelbmann · Walter H. Gunzburg · Ralf Jesnowski · Johannes Hain · Karlheinz Hauenstein Wolfgang Henninger · Anne Hoffmeyer · Peter Karle · Jens-Christian Kroger · Gunther Kundt · Stefan Liebe Udo Losert · Petra Muller · Alexander Probst · Katrin Puschel · Matthias Renner · Renate Renz · Robert Saller Brian Salmons · Maximilian Schuh · Ilse Schwendenwein · Kerstin von Rombs · Thomas Wagner · Ingrid Walter (coinvestigators)

Low frequency of p53 and ras mutations in bile of patients with hepato-biliary disease : a prospective study in more than 100 patients

The diagnosis of biliary disease, namely malignant disorders, is frequently hampered by the inconclusive cytology. We investigated prospectively the frequency of molecular changes in p53 and ras compared with cytology in patients with primary or secondary hepato‐biliary disease.

Intra-arterial instillation of microencapsulated, ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting

Background: The therapeutic efficacy of intratumoral instillation of genetically engineered, CYP2B1-expressing, microencapsulated cells in combination with ifosfamide had been previously demonstrated in xenografted human pancreatic ductal carcinomas [Gene Ther 1998;5:1070–1078]. Prior to a clinical study, the feasibility of an intra-arterial application of microencapsulated cells to the pancreas and its consequences to the organ had to be evaluated. Material and Methods: Microencapsulated, CYP2B1-producing cells were instilled both in vivo (transfemoral angiographical access) and in vitro (perfusion model) in the splenic lobe of the pig pancreas. In vivo, animals were monitored clinically for 7 days, then treated with ifosfamide and sacrificed. In vitro, ifosfamide was administered intra-arterially. Results: In all animals, 100 microcapsules could be instilled safely via the femoral route without clinical, biochemical or histological signs of pancreatitis. Histological examination revealed partial obstruction of small arteries by the capsules, without causing any parenchymal damage. In vitro, instillation reduced blood flow by half. Ifosfamide, also in combination with the capsules, did not add any damage to the pancreas. Conclusion: Intra-arterial instillation of microencapsulated cells to the pig pancreas is feasible and safe. Neither pancreatitis, foreign body reactions nor circulatory disturbances were observed. Clinical application of this genetically enhanced chemotherapeutic method seems possible.

Superficial arm arteries revisited: Brother and sister with absent radial pulse

Atypical or superficial courses of arteries of the arm may cause accidents in therapeutic and surgical procedures. Magnetic resonance imaging (MRI) was performed in a female patient and her brother. In addition, 109 cadaver arms were evaluated for superficial arm arteries and relevant vessels were measured with a calliper. In the patient and her brother the distal radial artery was absent in the normal position. Magnetic resonance imaging showed an artery surrounding the distal radius that nourished the dorsal and palmar hand. In addition, a strongly developed median artery was expressed in the patients brother. It is noteworthy that the female patient suffered from occasional hand pain while her brother did not, which is likely due to the additional expression of a median artery. A high origin of radial artery is found 3.67% of the examined cadavers and can be followed by additional vessels nourishing the biceps brachii or by connections to the brachial artery in the cubital fossa. Superficial ulnar arteries were detected in 1.83% of the cadavers, in both instances accompanied by an absent palmaris longus. Additionally, in one case the fork of the median nerve has moved distally and took its lateral fork from musculocutaneous nerve. In conclusion, family members can bear identical arterial variations as has been observed in the patients brother. High origin of radial artery and superficial ulnar artery can be accompanied by additional variations concerning vessels, muscles or nerves which have to be considered in the context of invasive and surgical procedures.

Akute mesenteriale Ischämie: Management und radiologische Interventionen in der Therapie akuter arterieller Verschlüsse und venöser Thrombosen

Die akute intestinale Ischämie (AMI) stellt trotz der in den letzten Jahren verbesserten diagnostischen Methoden auch heute ein Krankheitsbild mit hoher Mortalitätsrate dar. Die vorgestellte optimierte interdisziplinäre Therapie der AMI unter Einbeziehung aller interventionell-radiologischen Möglichkeiten ist nur bei Patienten mit frühzeitiger Diagnosestellung oder nach primärer chirurgischer Versorgung einsetzbar. In Abhängigkeit vom Typ der AMI kann sie die Bedingungen für eine Operation und letztendlich die Ergebnisse des chirurgischen Eingriffs verbessern. 22 Patienten mit unterschiedlichen Typen der AMI wurden mit verschiedenen radiologischen Interventionen behandelt, bei 13 Patienten erfolgte die Behandlung als Ersteingriff und bei 9 nach chirurgischer Resektion. Sechs Patienten hatten eine arterielle Embolie, 3 eine arterielle Thrombose, 5 eine nonokklusive mesenteriale Ischämie, 6 eine venöse Thrombose und 2 ein dissezierendes Aortenaneurysma. Trotz der positiven Selektion lag die Mortalität bei 27%, da der Zeitpunkt irreversibler ischämischer Veränderungen der Darmwand nicht exakt zu bestimmen ist und eine verspätete Revaskularisation schwere oder letale Komplikationen verursacht. Die beste Prognose weisen Patienten auf, bei denen die AMI als Komplikation einer mesenterikoportalen Thrombose auftritt. Unser an den radiologischen Möglichkeiten orientiertes Konzept des diagnostischen und therapeutischen Managements optimiert die interdisziplinäre Zusammenarbeit und die Kombination chirurgischer und interventioneller Behandlungsformen.

Laparoscopic treatment of renal artery entrapment

Renal artery entrapment by the diaphragmatic crus is a very infrequent cause of renovascular hypertension. We present the case of a young man who was assigned to our hospital with arterial hypertension and stenosis of the left renal artery. Extrinsic compression was diagnosed by duplex ultrasound and magnetic resonance angiography. We performed laparoscopic decompression using the transperitoneal retrorenal approach. Antihypertensive medication could be stopped thereafter and duplex ultrasound revealed a normal blood flow to the left renal artery. We therefore propose laparoscopic treatment of left renal artery entrapment as a minimally-invasive alternative to open surgery.