Unilamellar suspensions of dimyristoylphosphatidylcholine (DMPC) can be utilized to remove Photofrin from the erythrocyte. This enables correlation of the Photofrin membrane-binding processes with Photofrin-sensitized photolysis. The observed rates of erythrocyte biding as well as the observed rates of removal of PHotofrin from the erythrocyte membrane suggest the existence of two Photofrin species that differ in their rates of exchange between the erythrocyte and buffer phases. Selective depletion and readdition of these Photofrin species to the erythrocyte membrane permits evaluation of their separate and joint photolytic efficiencies. These rapidly and slowly exchanging membrane-bound Photofrin species are separately much less efficient photosensitizers than the two species together. The two Photofrin species exhibit essentially identical fluorescence emission spectra in the presence of DMPC. Nevertheless, models consistent with the results involve partitioning by chemically distinct Photofrin components or partitioning of chemically similar Photofrin components into distinct membrane environments, or a combination of these.

Anomalies of the biliary ductal system are not uncommon, and are of variable clinical significance. A case is reported of an extremely unusual variation, with the cystic duct entering the left hepatic duct. Preoperative delineation of the anomaly in this patient by endoscopic retrograde cholangiography assisted in the subsequent performance of a safe laparoscopic cholecystectomy. Awareness of potential biliary variations is one factor in avoidance of ductal injuries during laparoscopic surgery.

Anomalies of the biliary ductal system are not uncommon, and are of variable clinical significance. A case is reported of an extremely unusual variation, with the cystic duct entering the left hepatic duct. Preoperative delineation of the anomaly in this patient by endoscopic retrograde cholangiography assisted in the subsequent performance of a safe laparoscopic cholecystectomy. Awareness of potential biliary variations is one factor in avoidance of ductal injuries during laparoscopic surgery.

Evaluation 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.

Evaluation 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.

The ability of a photosensitizer to partition into membrane is determined by its structure and physical properties. Partitioning behavior can be quantitated as the partition coefficient (Kp) for a particular drug. This property may be an important determinant of cytocidal efficacy in photodynamic therapy. The Kp of five photoactive drugs--13,17-ditetraammonium protoporphyrin (PH1008), photofrin II (PII), hematoporphyrin (Hp), benzoporphyrin derivative monoacid (BPD-MA), coproporphyrin (Cp), and uroporphyrin (Up)--was determined using a simple liposome system composed of sonicated egg phosphatidylcholine single bilayer vesicles. The cytocidal efficacy of each drug was compared by determining the concentration of drug resulting in 50% maximal lysis (C50) obtained by measuring the hemoglobin absorbance at 414 nm released from lysed human red blood cells. The percentage lysis at 1 microM final drug concentration was also determined. An argon-dye laser was used to administer light of 630-nm wavelength for a total exposure of 5 J/cm2. Porphyrins with a greater tendency to partition into phosphocholine bilayer membranes demonstrated a greater lytic efficacy in the rbc system utilized. The comparison of physical properties with lytic ability may be useful in understanding the mechanism by which PDT exerts its effects and in predicting the clinical efficacy of different drugs.

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.

The primary role of the neodymium yttrium aluminum garnet (Nd:YAG) laser has been to relieve obstruction and to control hemorrhage associated with malignant neoplasms throughout the gastrointestinal tract. In an initial series (IS), the authors demonstrated the efficacy of the Nd:YAG laser as initial preresectional therapy (PR) in 11 patients with obstructing and resectable left colonic or rectal tumors obviating initial operative diversion and allowing for primary resection and anastomosis. In addition, the authors have illustrated the benefit of the Nd:YAG laser in relieving obstruction and arresting bleeding in those patients with either widely metastatic or nonresectable (NR) locoregional disease. Their cumulative experience from 1985 to the present includes 53 patients (PR: 29 and NR: 24). In the PR group, 25 lesions were above the peritoneal reflection and 4 below. Twenty-five patients underwent low anterior resection and four abdominoperineal resection. In the NR group, 17 patients were treated for imminent obstruction and 7 for bleeding. Ten lesions were above and 14 below the peritoneal reflection. There was one laser-related complication in the series (1.8%). There was no significant morbidity or mortality in the PR group. The reduction in length of stay (LOS) and total hospital costs (THC), when compared to the IS has continued to be significant. Laser therapy for those patients in the NR groups is a safe and acceptable alternative to permanent colostomy with its accompanying morbidity and mortality.

Hemorrhage of the upper gastrointestinal tract (UGI) remains a serious clinical problem. Age of the patient, the presence of shock, transfusion requirements and concurrent serious illnesses are predictors of outcome. Operative intervention is promulgated if a visible vessel in an ulcer crater is identified because most will rebleed. From 1986 to 1988, 40 patients with 46 actively bleeding upper gastrointestinal lesions were treated with endoscopic intervention (EI). The Nd:YAG (neodymium yttrium aluminum garnet) laser using the noncontact method was used exclusively. All patients had orthostatic hypotension on admission and had serious intercurrent illnesses. Admission hematocrit ranged from 13 per cent to 36 per cent (median, 24%) and patients had been transfused an average of 4 units of blood before EI. Gastric and duodenal ulcers were the most common bleeding sites. All gastric and duodenal ulcers had visible vessels and 19 were actively bleeding. Endoscopic intervention was initially successful in 35 of 40 (87.5%) patients. The five patients who did not respond required urgent operation with a mortality rate of 40 per cent. Four patients rebled after EI but responded to repeat EI. The mortality rate in the EI group was 8.6 per cent. These results suggest that EI is a useful alternative in UGI bleeding for a select group of those patients at high risk for operative intervention.

Surgical resection remains the therapy of choice for the treatment of potentially curable gastrointestinal tract (GI) malignancies. Many of these tumors are incurable at the time of diagnosis and therapy should be directed towards palliation with the intent of minimizing pain, bleeding, obstruction, and potential morbidity. Endoscopic laser therapy is uniquely applicable for the palliation of GI tumors and in selective instances may be appropriate for the treatment of early lesions. Eighty-six patients with GI malignancy have been treated at our institution since 1985. Thirty-one patients had advanced upper GI lesions (esophagus: 26, gastric: 3, duodenal: 1, and pancreatic: 1) and 55 patients had lower GI tumors (colon: 37 and rectal: 18). Pre-resectional recanalization for obstructing colorectal carcinomas obviating initial operative diversion was performed in 31 (56%) of 55 patients. Twenty-four patients had palliative laser therapy (obstruction: 17 and hemorrhage: 7) with resolution of their symptoms. There was 1 laser related perforation in the pre-resectional group and the overall complication rate was 1.2%. Endoscopic Nd:YAG and currently photodynamic laser therapy for GI tumors has proven to be an effective mode of therapy for advanced GI neoplasms with minimal morbidity. The utility of photodynamic therapy for the treatment of early stage esophageal and gastric cancers remains controversial.

American Society of Colon and Rectal Surgeons 91st Annual Convention Podium and Poster abstracts: PDF Only

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.

A neodymium yittrium aluminum garnet (Nd:YAG) laser inserted through an operating arthroscope was used to introduce applied energy to synovial tissues, articular discs, and bone in the temporomandibular joint of mongrel dogs. Arthroscopic inspection of the wounds was performed at 1 and 2 weeks postoperatively. The animals were killed and the temporomandibular joints were examined grossly and histologically to determine the extent of injury and healing. The results show that laser wounds of bone and articular disc undergo no repair, whereas laser wounds of symovium show rapid repair. Laser damage to condylar marrow under an articular disc wound was unexpectedly found.

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.

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.

The principal role of the Neodymium yttrium aluminum garnet (Nd-YAG) laser has been to alleviate obstruction and to arrest hemorrhage secondary to metastatic or locally unresectable malignant lesions throughout the gastrointestinal (GI) tract. Between June 1985 and December 1988, 26 patients have been treated for advanced upper GI malignancy: 20 obstructing esophageal carcinomas (three proximal, eight middle, and nine distal third); two prepyloric obstructing and one bleeding gastric lesion; one bleeding pancreatic carcinoma eroding into the duodenum; and two primary duodenal lesions (one partially obstructing and one bleeding). The dysphagia grade improved in all patients with esophageal carcinoma, but less so for those with proximal tumors. The obstructing gastric lesions were recanalized and bleeding was arrested. The pancreatic and duodenal lesions were successfully managed with one treatment. There were no perforations or other laser-related complications. The approaches to palliation must be conceived in a fashion to improve the quality of life with minimal risk and discomfort. Although ultimate survival is determined by the stage of the disease, the Nd:YAG laser can restore gastrointestinal continuity and, in so doing, significantly palliate the patient.

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.

Thirty-seven patients with either bleeding or obstructive metastatic gastrointestinal malignant neoplasms were treated with the neodymium-YAG laser between June 1985 and December 1988. The age range for the group was 55 to 99 years, with a mean of 71 years. There were 25 upper gastrointestinal lesions, including 22 obstructive lesions (20 esophageal and two prepyloric gastric) and three bleeding lesions (one metastatic melanoma to the stomach, one duodenal, and one pancreatic carcinoma). Of the esophageal tumors, three were proximal, eight were middle, and nine were distal third. The mean number of laser treatments was 2.6, and the overall survival ranged from 1 to 20 months, with a median of 8 months. The dysphagia grade was improved overall but depended on the site of the tumor. All bleeding lesions were successfully photocoagulated. Twelve colorectal malignant neoplasms were treated palliatively, six for obstruction (three intraperitoneal colon and three rectal) and six for bleeding (three intraperitoneal and three rectal). The mean number of treatments for the group was 1.5, and the overall survival ranged from 2 to 38 months, with a median survival of 15 months. The neodymium-YAG laser was found to be effective as a palliative mode of therapy for the management of malignant gastrointestinal lesions.