Marc L. Eckhauser

Photodynamic therapy for multiple primary bronchogenic carcinoma

In recent years, multiple primary lung cancers have been reported with greater frequency, partly as a result of technologic advances in the detection of lung cancer and therapeutic achievements in its management. Photodynamic therapy (PDT) is a relatively new therapy used with increasing frequency in the treatment of a wide variety of malignancies, including central lung cancers. In PDT, the differential retention of an injected photosensitizer by malignant tissue is exploited by treatment with a low‐power laser beam delivered endoscopically. Since 1980, 145 patients with central lung cancers, including 35 cases of endoscopically evaluated early‐stage lesions were treated with PDT at Tokyo Medical College. Thirteen of these 145 patients had multiple primary bronchogenic carcinomas, five cases of which were synchronous with the rest, metachronous. Three of 13 patients with multiple tumors had early‐stage lesions and were treated with endoscopic PDT alone. In the other ten cases, PDT was used to treat accessible early‐stage foci although operative excision was required for advanced lesions. Mean survival after PDT, alone or in combination with surgery, was 38 months (range, 14 to 87 months), and seven patients remain alive to date. It was concluded that PDT is useful in extending the therapeutic options for, and improving the prognosis of patients with, multiple primary bronchogenic carcinomas.

Diagnostic laparoscopy in the intensive care patient

SummaryEvaluation of a potential acute abdomen in patients who require intensive care for concurrent medical/surgical problems is often difficult due to ambiguities in the physical exam and ancillary diagnostic tests. Between August 1990, and February 1992, 25 ICU patients underwent diagnostic laparoscopy to evaluate a suspected acute intraabdominal process. Thirteen laparoscopies were negative, and 12 were positive. The overall accuracy for laparoscopy was 96% as confirmed by subsequent laparotomy, autopsy, or clinical course. Laparoscopic findings led to a change in management in nine patients (36%), leading to earlier exploration in four patients, and avoidance of laparotomy in five. No significant hemodynamic effects were noted during laparoscopy, and the procedure-related morbidity was low (8.0%).Diagnostic laparoscopy is a safe and accurate guide for managing the ICU patient with a suspected acute surgical abdomen. The use of laparoscopy can help avoid nontherapeutic laparotomy or confirm the need for operative intervention in these complex cases.

Percutaneous endoscopic gastrostomy: another cause of “benign” pneumoperitoneum

most often involved with adenocarcinoma. The patient we have described was noted on barium esophagogram to have an incompetent LES following esophagomyotomy for achalasia. Barretts esophagus developed and, 24 years after the surgical procedure, she presented with metastatic adenocarcinoma. Her chief complaint at the time of presentation was pelvic bone pain related to metastases. The absence of symptoms from the esophageal carcinoma was due to the widely dilated esophagus. There are no established recommendations on the frequency or type of evaluation needed for patients following surgical treatment for achalasia. Through serial biopsies of the esophagus, we demonstrated changes of columnar metaplasia, dysplasia, carcinoma in situ, and invasive adenocarcinoma in this patients esophagus. Endoscopic evaluation with biopsy of areas of suspicious mucosa may result in the early detection of Barretts esophagus and aid in the diagnosis of a malignancy at a curable stage.

Biodistribution of the photosensitizer dihaematoporphyrin ether

Prior investigations describing the biodistribution of haematoporphyrin derivative (HpD) failed to substantiate a tumour-specific localization. Earlier optimism that dihaematoporphyrin ether (DHE), the active component of HpD, would demonstrate tumour specificity has also failed to be substantiated. The major sites of deposition for DHE are the same as those for HpD (liver, kidney and spleen) while the remaining organs show varying accumulation of DHE, depending on the dose given. Smaller doses of DHE, however, result in biodistribution patterns similar to those for HpD. The pharmacokinetics suggest that DHE binds to plasma proteins and, to some extent, to tissue. The optimal time for photodynamic therapy appears to be between 48 and 72 hours since the greatest mean tumour:muscle concentrations are found during this period.

Laser Therapy of Colorectal Carcinoma

A plethora of literature is available demonstrating the efficacy of Nd:YAG laser therapy for obstructing or bleeding colorectal cancers. The in-hospital mortality and morbidity rates can be reduced when Nd:YAG laser therapy is used to avoid operative diversion prior to resection and anastomosis. The Nd:YAG laser used to control bleeding or obstruction in those patients with either widely metastatic or unresectable locoregional disease has been successful in the majority of patients and has been associated with minimal morbidity and mortality rates. This laser may be the only treatment modality that may substitute for operative diversion in hopeless clinical situations such as hemorrhage or obstruction in patients with advanced disease. The utility of photodynamic therapy for colorectal cancer will require definition in further controlled trials.

DIHEMATOPORPHYRIN ETHER‐PHOSPHOLIPID INTERACTIONS. THE ROLES OF SURFACE CHARGE and LATERAL PHASE SEPARATIONS

Abstract Fluorescence spectroscopy was utilized to investigate the equilibrium interaction of dihem‐atoporphyrin ether(s) (DHE) with binary and ternary phospholipid mixtures of defined composition in order to define the roles of net negative surface charge and lateral phase separations in DHE‐membrane partitioning. Binary phospholipid mixtures employed were composed of dimyristoyl‐phosphatidylcholine (DMPC) mixed with increasing weight percentages of dimyristoylphosphatidylgly‐cerol (DMPG) providing controlled variation of net membrane surface charge. Two types of ternary phospholipid mixtures were utilized. Ternary acid mixtures contained various percentages of palmitoyl‐lysophosphatidyl choline (LPC) + palmitic acid (PA) dispersed in DMPC. Ternary alcohol mixtures contained various percentages of LPC + hexadecanol (OL) dispersed in DMPC. The ternary phospholipid mixtures are known to be phase separated. At total DHE concentrations of 0.33 μA/ and using 100% DMPC, the DHE partition coefficient (P) is 250 000. This partition coefficient is to some extent dependent on the DHE concentration. The observed partition coefficients show little dependence on surface charge in DMPC‐DMPG mixtures. However, P decreases markedly with increasing phase separation in the ternary lipid mixtures. The fluorescence of membrane‐bound DHE is dependent on the composition of the ternary mixtures in a manner suggesting micropartitioning of DHE into the phospholipid bulk phase as well as into the disordered regions between laterally phase separated phospholipid domains.

Biodistribution of55Fe (II) phthalocyanine tetrasulphonate (55Fe (II)-TsPc)

Phthalocyanines may be an alternative group of macrocycles applicable for use in photodynamic therapy (PDT) of cancer. Although as a class, phthalocyanines localize in tumours, efficacy of cytotoxicity appears to depend to some degree on the specific compound. Biodistribution patterns of the phthalocyanines are similar to those for dihaematoporphyrin ether (DHE); the major sites of deposition being liver, kidney and spleen while the remaining organs show varying degrees of accumulation. The optimal time for PDT when using phthalocyanine appears to be between 24 and 48 h.

Focal Fatty Infiltration of the Liver Appearing as a Defect on a Liver-Spleen Scintigram: Case Report

The authors present a biopsy-proven case of focal fatty infiltration of the liver that appeared as a focal defect on a liver/spleen scintigram, matching a defect seen on a CT scan.

A New Porphyrin Photosensitizer (PH1008) in Model Membranes, Normal Cells, and Bladder Cancer Cells

Newer photosensitizers continue to be sought for photodynamic therapy of bladder cancer particularly since local rather than systemic application is desired. Recent studies have indicated that a cationic dye, PH1008, a 13,17-N,N,N-dimethylethylethanolamine ester of protoporphyrin, sensitizes the photolysis of red blood cells. The study described in this report was designed to investigate the plasma membrane partitioning of PH1008 model lipid system and to compare partitioning of PH1008 in normal transitional cells and bladder cancer cells in vitro. Partition coefficient (Kp) values characterizing the distribution of PH1008 between aqueous buffer and normal and malignant transitional cells were 3.4 +/- 0.7 x 10(4) (CRL-7881) and 9.5 +/- 1.4 x 10(4) (HTB-9), resulting in a 20% difference in membrane photosensitizer concentration at a particular photosensitizer concentration. Significantly higher (2-5 fold) differences are observed between tumor and surrounding normal tissue for systemically delivered photofrin II. Cell-bound drug was 30-fold (CRL-7881) and 80-fold (HTB-9) more fluorescent when compared to aqueous buffer. The combined effects of partitioning and bound fluorescence suggest that a 3.2-fold increase in fluorescence of transformed vs. normal bladder urothelium exists. This difference in fluorescence suggests that PH1008 might be more useful as a diagnostic tool than as a phototherapeutic agent.

Detection of experimental atheroma in atherosclerotic rabbits: The fluorescence spectrum of haematoporphyrin derivative obtained in situ by angioscopic fluorescence spectrophotometry

An endoscopic laser fluorescence spectrophotometer has been developed to measure the fluorescence spectrum of haematoporphyrin derivative (HPD) in situ. In this study the demonstration of HPD accumulation in experimentally induced atheroma within the aortas of atherosclerotic rabbits is reported. Atheromas were induced in rabbit aortas after aortic intimai injury by balloon catheterization and hypercholesterolemic diets. Subsequently, an ultra-thin diagnostic angioscopic catheter was introduced into the descending aortas of these rabbits under anaesthesia, 24 h after the intravenous injection of 5 mg kg−1 HPD. Characteristic red-shifted peaks of the fluorescence of HPD at 630 nm, 665 nm and 690 nm were detected in the fibrous plaques. In fatty streaks, however, the 630 nm and the 690 nm emission intensities were lower and the 665 nm peak was notably absent. Red-shifted HPD fluorescence was not detectable in normal areas of diseased aorta and in control animals. In addition, the emission spectra of HPD incubated with various lipid components representing the constituents of these atheromas were obtained. The resemblance of the emission spectrum of HPD incubated with sphingomyelin and cholesterol to that of the atheromatous lesions suggest that HPD may interact with these lipids in order to produce the red-shifted fluorescence maxima seen within atheromas. The possibility of future applications with this equipment for the diagnosis of atheroma is supported by this investigation.