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Photodynamic therapy of superficial squamous cell cancer and severe dysplasia of the esophagus: Preli-minary results using 5-aminolaevolinic acid
ESOPHAGUS "P181
183
ENDOSCOPIC SUTURING OF A NOVEL GASTROESOPHAGEAL ANTIREFLUX DEVICE (GARD) A PRELIMINARY REPORT..NJ Godin*. C P Swain, F. Gong, S S Kadirkamanathan, C C Hepworth. Geneva University Hospital*, Switzerland, Royal London Hospsital, London, UK. A tubular shaped gastro-esophageal anti reflux device (GARD) was designed to allow food to pass freely from the esophagus into the stomach but to prevent acid and gastric contents refluxing into the esophagus. It is formed from lightweight compliant biocompatible plastic material. In bench experiments in which this device was sewn to the gastro-esophageal (GE) junction in postmortem human and porcine tissue it was shown to increase yield pressure. The device is compressed by small rises in intragastric or abdominal pressure and collapses. It prevents reflux by forming a rico-esophagus thus elongating the intra-abdominal esophagus, by increasing the angle of His and acting when collapsed as a one way valve.The length of the device can be easily adjusted to ensure exposure to intra-abdominal pressure. For insertion the GARD was tightly folded and secured with tape and then passed down to the gastro-esophageal junction through an pro-esophageal overtube once the threads had been passed through holes in the proximal end of the device. Multiple interrupted nylon stitches were placed at the GE junction held outside the mouth using an endoscopic sewing machine. They were sequentially placed through holes formed in the device which was "parachuted" through overtube and oesophagus to the GE junction and each stitch was knotted with 4 half hitches and the threads were cut. The tapes holding the device in its folded configuration were released to allow the device to regain its tubular shape. In survival experiments in pigs 4 anti-reflux devices were sewn at the gastro-esophageal junction with multiple separate stitches. There were no deaths, perforations, bleeding or other complications, eating was normal immediately after insertion without weight loss and the devices remained in situ at follow up endoscopies. Further studies are in progress to study long term efficacy and safety. This preliminary study describes the endoscopic attachment of a new prosthetic device to treat gastro esophageal reflux disease at flexible endoscopy using stitches. Sewing attachment of prosthetic tubular structures to the gastrointestinal wall by means of endoscopic sewing machine technology using a parachuting technique is feasible.
I N T E S T I N A L M E T A P L A S I A IN B A R R E T T ' S E S O P H A G U S (BE) IS NOT R E L A T E D TO I N T E S T I N A L M E T A P L A S I A IN T H E STOMACH. O. Gut!6rrez, H. Cardona, 0 Ricaurte. Department of Gastroenterology and Pathology, Hospital San Juan de Dios Universidad Nacional de Colombia, Bogot/t, Colombia.
Background: BE is considered a premalignant condition and is associated to chronic G E R disease. Intestinal metaplasia (IM) and dysplasia may accompany BE but whether there is an increased frequency of IM in the stomach in patients with BE has not yet been evaluated. The high background frequency o f IM in st6machs in Colombia provided an excellent opportunity to evaluate this question. Aim: To investigate the prevalence of IM in the stomach in patients with and without BE. Methods: Patients with endoscopic criteria of B E were studied. Biopsies were taken from the esophagus every 2 cm, starting 2 cm proximal to Z line. 4 biopsies from the body and 4 from the antrum were taken also for histological evaluation. A control group with 29 NUD patients with chronic gastritis and I M but without GER and/or hiatal hernia was also investigated with 3 biopsies from the cardia, 4 from the body, and 4 from the antrum. Results: 33 out of 63 patients, with the endoscopic diagnosis of BE had specialized columnar epithelium in the esophagus. In the control group the prevalence of IM in the stomach was 48%, 69%, and 90% for the cardia, corpus, and antrum, respectively. The frequency p r i m in the stomach was slightly higher in B E patients with specialized epithelium than those without (12% vs. 3% and 15% vs. 7% for corpus and antrum respectively) but the differences were not significant. Conclusions: IM in the cardia reflects the severity of the underlying chronic gastritis and is not related to B E nor is it related to the presence of gastric IM in general.
"/'182
"P184
PHOTODYNAMIC THERAPY OF SUPERFICIAL SQUAMOUS CELL CANCER AND SEVERE DYSPLASIA OF THE ESOPHAGUS: PRELIMINARY RESULTS USING $-AMINOLAEVOLINIC ACID. L.Gosmer, R. Smka, M. Stoltel, G. Seitz2, E.G. Hahn, C. Ell. Department of Medicine L University of Edangen - Nuremburg, Eflangen, 1Institute of Pathology, Bayreuth, 2Institute of Pathology, Baml~erg, FRG. So far esophagactomy which is associated with a significant morbidity and mortality is recommended for superficial squamous cell carcinomas (SCC). First reports of photodynamic therapy (PDT) with hematoporphyrins as a nonoperati~e treatment medality of SCC are encouraging. In contrast to the conventional photosensitizers like hematopozphyrins 5-aminolaevulinie acid (ALA), a naturally occurring intermediary in the hem synthetic pathway which is metabolized to the active compound protoporphyrin IX ~ IX) as an endogenous photosensitizer, causes no clinically relevant skin photosensitivity. We report on the therapeutic u,sr of ALA in severe dysplasia or superficial squamous cell carcinomas (SCC) of the esophagus in a prospective study of 15
ENDOSCOPIC EARLY DETECTION WITH IODINE STAINING OF ESOPHAGEAL CANCER IN ALCOHOLICS H.Harada, A.Toyonaga, S.Ban, K.Sakamoto, S.Kameo, T.Minetoma, M.Watanabe, H.Ohnishi, O.Tsuruta, N.lkejiri, C.D.Hugo, K.Tanikawa. Department of Internal Medicine II, Division of Gastroenterology and Endoscopy, Kurume University Hospital, Fukuoka, Japan (830)
~ e t h o d : 12 male and 3 female patients (aged 54 to 77 years) with histologically proven and inoperable severe dysplasia (n = i) and/or SCC (n = 14; normal endoscopic ultrasound or uT1NOM0) were included in this clinical pilot study. The patients were given a solution of ALA in a dose of 60 mg/kg b.w. orally. They were irradiated 6 hours after oral ingestion with red light of 635 run. PDT was conduct~xl with a 2.0 a n cylindrical diffuser and a light dose of 150 J/cm2 using a dye laser (XP 800 KTP/'YAG, Laserscope, San Jose, CA) with an output of 100 mW/cm2 was administered. Results: All tumours responded to the ALA-PDT with a superficial fibrinoid necrosis of the mucoSal layer 2-3 days after PDT. 8 patients with histologically proven carcinoma in site and I patient with severe dysplasia showed a complete mspanse (60 %) and are biopsy proven dyspiasia/tumor-free for 1 - 21 months after an average of 2.8 treatments. In 6 patients with superficial cancer and endosonographically diagnosed thickening of the musosa up to 5 m m - 3 up to 10 cm in tumor length - a reduction of the tumor length was observed, but the lesions were not completely eradicated. Only minor side effects occurred, 9 patients had a mild nausea or vomiting. One third of the patients showed a transient rise in hcpadc enzymes, hot the values normalized within 3-4 days and had local pain dudng light therapy. Conclusions: ALA-PDT may be a promising minimal invasive technique for the complete destruction of severe epithelial dysplasia and carcinoma in situ in > 50 % of all patients. Tumors infiltrating to the submucosa or with a mucosal thickening > 2 mm however, cannot successfully be treal~l with the used ALA-PDT. Therefore, improved dosimetry and light application including more powerful serksitizcrs arc nec~sary to enhance the rate of complete remissions.
336
GASTROINTESTINAL ENDOSCOPY
I n t r o d u c t i o n ; Alcohol abuse is a major risk factor for esophageal cancer. Other investigator are certain that two thirds of superficial esophageal cancer would have been missed by conventional endoscopy only. (Cancer 1995;Vol 76;928-934) . However, prospective endoscopic screening study of early detection is not fully available in alcoholics at present. A i m ; It is to evaluate the usefulness of screening esophagoscopy with iodine staining in alcoholics. Method: During 1 year, 244 alcoholics (56_+8 years old)were included in a prospective study. They were consecutively screened by esophagoscopy with iodine staining and targeted biopsy. R e s u l t s ; The mean consumption of alcohol was 110 g/day. Iodineunstained lesions ( greater than 5ram in diameter) were observed on the esophageal wall in 87patients (35.7%) .9 patients {3.7%) withl2 lesions found to have esophageal cancer and had no symptoms. Relationship between alcohol intake and incidence of esophageal cancer. (Table} Alcoholintake (R/day) ~70g 71g~120g 121g-Inciclenceofesophage~lcancer(%) 0/19 (0%) 1/103 {0.96%) 8/12216-6%) Twelve such unstained lesions in 9 of 244 patients turned out to be squamous cell carcinoma of the superficial type. The cancer invasion was confined within the epithelium in three patients, to the proper mucosal layer in seven, and to the submucosa in two. Endoscopic esophageal mucosal resection was performed in 10 of these patients. Esophagecmmy was performed in two patients. C o n c l u s i o n ; 1) Incidence of esophageal cancer increases with total alcohol intake.2) Screening esophugoscopy with iodine staining is of great advantage to detect early esophageal cancer in alcoholics.
VOLUME 43, NO. 4, 1996
183
ENDOSCOPIC SUTURING OF A NOVEL GASTROESOPHAGEAL ANTIREFLUX DEVICE (GARD) A PRELIMINARY REPORT..NJ Godin*. C P Swain, F. Gong, S S Kadirkamanathan, C C Hepworth. Geneva University Hospital*, Switzerland, Royal London Hospsital, London, UK. A tubular shaped gastro-esophageal anti reflux device (GARD) was designed to allow food to pass freely from the esophagus into the stomach but to prevent acid and gastric contents refluxing into the esophagus. It is formed from lightweight compliant biocompatible plastic material. In bench experiments in which this device was sewn to the gastro-esophageal (GE) junction in postmortem human and porcine tissue it was shown to increase yield pressure. The device is compressed by small rises in intragastric or abdominal pressure and collapses. It prevents reflux by forming a rico-esophagus thus elongating the intra-abdominal esophagus, by increasing the angle of His and acting when collapsed as a one way valve.The length of the device can be easily adjusted to ensure exposure to intra-abdominal pressure. For insertion the GARD was tightly folded and secured with tape and then passed down to the gastro-esophageal junction through an pro-esophageal overtube once the threads had been passed through holes in the proximal end of the device. Multiple interrupted nylon stitches were placed at the GE junction held outside the mouth using an endoscopic sewing machine. They were sequentially placed through holes formed in the device which was "parachuted" through overtube and oesophagus to the GE junction and each stitch was knotted with 4 half hitches and the threads were cut. The tapes holding the device in its folded configuration were released to allow the device to regain its tubular shape. In survival experiments in pigs 4 anti-reflux devices were sewn at the gastro-esophageal junction with multiple separate stitches. There were no deaths, perforations, bleeding or other complications, eating was normal immediately after insertion without weight loss and the devices remained in situ at follow up endoscopies. Further studies are in progress to study long term efficacy and safety. This preliminary study describes the endoscopic attachment of a new prosthetic device to treat gastro esophageal reflux disease at flexible endoscopy using stitches. Sewing attachment of prosthetic tubular structures to the gastrointestinal wall by means of endoscopic sewing machine technology using a parachuting technique is feasible.
I N T E S T I N A L M E T A P L A S I A IN B A R R E T T ' S E S O P H A G U S (BE) IS NOT R E L A T E D TO I N T E S T I N A L M E T A P L A S I A IN T H E STOMACH. O. Gut!6rrez, H. Cardona, 0 Ricaurte. Department of Gastroenterology and Pathology, Hospital San Juan de Dios Universidad Nacional de Colombia, Bogot/t, Colombia.
Background: BE is considered a premalignant condition and is associated to chronic G E R disease. Intestinal metaplasia (IM) and dysplasia may accompany BE but whether there is an increased frequency of IM in the stomach in patients with BE has not yet been evaluated. The high background frequency o f IM in st6machs in Colombia provided an excellent opportunity to evaluate this question. Aim: To investigate the prevalence of IM in the stomach in patients with and without BE. Methods: Patients with endoscopic criteria of B E were studied. Biopsies were taken from the esophagus every 2 cm, starting 2 cm proximal to Z line. 4 biopsies from the body and 4 from the antrum were taken also for histological evaluation. A control group with 29 NUD patients with chronic gastritis and I M but without GER and/or hiatal hernia was also investigated with 3 biopsies from the cardia, 4 from the body, and 4 from the antrum. Results: 33 out of 63 patients, with the endoscopic diagnosis of BE had specialized columnar epithelium in the esophagus. In the control group the prevalence of IM in the stomach was 48%, 69%, and 90% for the cardia, corpus, and antrum, respectively. The frequency p r i m in the stomach was slightly higher in B E patients with specialized epithelium than those without (12% vs. 3% and 15% vs. 7% for corpus and antrum respectively) but the differences were not significant. Conclusions: IM in the cardia reflects the severity of the underlying chronic gastritis and is not related to B E nor is it related to the presence of gastric IM in general.
"/'182
"P184
PHOTODYNAMIC THERAPY OF SUPERFICIAL SQUAMOUS CELL CANCER AND SEVERE DYSPLASIA OF THE ESOPHAGUS: PRELIMINARY RESULTS USING $-AMINOLAEVOLINIC ACID. L.Gosmer, R. Smka, M. Stoltel, G. Seitz2, E.G. Hahn, C. Ell. Department of Medicine L University of Edangen - Nuremburg, Eflangen, 1Institute of Pathology, Bayreuth, 2Institute of Pathology, Baml~erg, FRG. So far esophagactomy which is associated with a significant morbidity and mortality is recommended for superficial squamous cell carcinomas (SCC). First reports of photodynamic therapy (PDT) with hematoporphyrins as a nonoperati~e treatment medality of SCC are encouraging. In contrast to the conventional photosensitizers like hematopozphyrins 5-aminolaevulinie acid (ALA), a naturally occurring intermediary in the hem synthetic pathway which is metabolized to the active compound protoporphyrin IX ~ IX) as an endogenous photosensitizer, causes no clinically relevant skin photosensitivity. We report on the therapeutic u,sr of ALA in severe dysplasia or superficial squamous cell carcinomas (SCC) of the esophagus in a prospective study of 15
ENDOSCOPIC EARLY DETECTION WITH IODINE STAINING OF ESOPHAGEAL CANCER IN ALCOHOLICS H.Harada, A.Toyonaga, S.Ban, K.Sakamoto, S.Kameo, T.Minetoma, M.Watanabe, H.Ohnishi, O.Tsuruta, N.lkejiri, C.D.Hugo, K.Tanikawa. Department of Internal Medicine II, Division of Gastroenterology and Endoscopy, Kurume University Hospital, Fukuoka, Japan (830)
~ e t h o d : 12 male and 3 female patients (aged 54 to 77 years) with histologically proven and inoperable severe dysplasia (n = i) and/or SCC (n = 14; normal endoscopic ultrasound or uT1NOM0) were included in this clinical pilot study. The patients were given a solution of ALA in a dose of 60 mg/kg b.w. orally. They were irradiated 6 hours after oral ingestion with red light of 635 run. PDT was conduct~xl with a 2.0 a n cylindrical diffuser and a light dose of 150 J/cm2 using a dye laser (XP 800 KTP/'YAG, Laserscope, San Jose, CA) with an output of 100 mW/cm2 was administered. Results: All tumours responded to the ALA-PDT with a superficial fibrinoid necrosis of the mucoSal layer 2-3 days after PDT. 8 patients with histologically proven carcinoma in site and I patient with severe dysplasia showed a complete mspanse (60 %) and are biopsy proven dyspiasia/tumor-free for 1 - 21 months after an average of 2.8 treatments. In 6 patients with superficial cancer and endosonographically diagnosed thickening of the musosa up to 5 m m - 3 up to 10 cm in tumor length - a reduction of the tumor length was observed, but the lesions were not completely eradicated. Only minor side effects occurred, 9 patients had a mild nausea or vomiting. One third of the patients showed a transient rise in hcpadc enzymes, hot the values normalized within 3-4 days and had local pain dudng light therapy. Conclusions: ALA-PDT may be a promising minimal invasive technique for the complete destruction of severe epithelial dysplasia and carcinoma in situ in > 50 % of all patients. Tumors infiltrating to the submucosa or with a mucosal thickening > 2 mm however, cannot successfully be treal~l with the used ALA-PDT. Therefore, improved dosimetry and light application including more powerful serksitizcrs arc nec~sary to enhance the rate of complete remissions.
336
GASTROINTESTINAL ENDOSCOPY
I n t r o d u c t i o n ; Alcohol abuse is a major risk factor for esophageal cancer. Other investigator are certain that two thirds of superficial esophageal cancer would have been missed by conventional endoscopy only. (Cancer 1995;Vol 76;928-934) . However, prospective endoscopic screening study of early detection is not fully available in alcoholics at present. A i m ; It is to evaluate the usefulness of screening esophagoscopy with iodine staining in alcoholics. Method: During 1 year, 244 alcoholics (56_+8 years old)were included in a prospective study. They were consecutively screened by esophagoscopy with iodine staining and targeted biopsy. R e s u l t s ; The mean consumption of alcohol was 110 g/day. Iodineunstained lesions ( greater than 5ram in diameter) were observed on the esophageal wall in 87patients (35.7%) .9 patients {3.7%) withl2 lesions found to have esophageal cancer and had no symptoms. Relationship between alcohol intake and incidence of esophageal cancer. (Table} Alcoholintake (R/day) ~70g 71g~120g 121g-Inciclenceofesophage~lcancer(%) 0/19 (0%) 1/103 {0.96%) 8/12216-6%) Twelve such unstained lesions in 9 of 244 patients turned out to be squamous cell carcinoma of the superficial type. The cancer invasion was confined within the epithelium in three patients, to the proper mucosal layer in seven, and to the submucosa in two. Endoscopic esophageal mucosal resection was performed in 10 of these patients. Esophagecmmy was performed in two patients. C o n c l u s i o n ; 1) Incidence of esophageal cancer increases with total alcohol intake.2) Screening esophugoscopy with iodine staining is of great advantage to detect early esophageal cancer in alcoholics.
VOLUME 43, NO. 4, 1996