Midtrimester maternal serum screening after multifetal pregnancy reduction in pregnancies conceived by in vitro fertilization

BACKGROUND: The rising incidence of esophageal adenocarcinoma in western countries requires a new strategy in the management of dysplasia in Barrett's esophagus. Esophagectomy, which has high morbidity and mortality rates, has been recommended to treat patients with severe dysplasia. Strictly superficial laser coagulation with tissue ablation therefore is a desirable option for the management of dysplasia in Barrett's esophagus because the tissue to be ablated is only about 2 mm thick. Potassium-titanyl-phosphate (KTP) laser light with a wavelength of 532 nm is preferentially absorbed by hemoglobin and therefore combines excellent coagulation with limited tissue penetration. We report first clinical results with KTP laser superficial vaporization of dysplasia and early cancer in Barrett's esophagus. METHODS: Eight men and 2 women 43 to 84 years of age with short segments of Barrett's esophagus or traditional Barrett's esophagus and histologically proved low-grade (n = 4) and high-grade (n = 4) dysplasia or early adenocarcinoma (n = 2) were selected for this pilot study. For all patients thermal endoscopic destruction was conducted with a frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG) KTP laser system. Laser therapy was performed by means of the free-beam method with coaxial insufflation of gas. An average of 2.4 sessions per patient were required for ablation of the Barrett's mucosa. RESULTS: Two to three days after laser treatment the response of the ablated mucosa was assessed with endoscopy and biopsy. Samples taken showed fibrinoid necrosis of the mucosal layer. A complete response was obtained for all 10 patients. Replacement by normal squamous cell epithelium was induced in combination with acid suppression therapy of up to 80 mg omeprazole daily. No complications occurred. In two patients biopsy showed specialized mucosa beneath the restored squamous cell epithelial layer. Follow-up times were as long as 15 months (mean value 10.6 months). CONCLUSIONS: KTP laser destruction of Barrett's esophagus induced mucosal regeneration with normal squamous cell epithelium in combination with acid suppression. Limitation of the depth of thermal destruction in Barrett's esophagus minimizes risk for perforation or stricture formation. KTP laser ablation of Barrett's esophagus seems to be feasible and safe in short segments of Barrett's esophagus with dysplasia or early cancer.     

Endoscopic treatment of Barrett esophagus

The purpose of the treatment of Barrett epithelium in the distal oesophagus is to reduce or even eliminate the increased risk of malignant degeneration in it. This can be achieved by removing the Barrett epithelium, whether or not dysplastic, and to have it replaced by normal squamous epithelium. Drug treatment or surgical antireflux treatment of Barrett epithelium has hardly any effect on the length of the Barrett epithelium or on the occurrence of malignancy. Various forms of endoscopic ablative therapy (laser coagulation, multipolar electrocoagulation, photodynamic therapy and argon plasma coagulation), in combination with antireflux treatment enable removal of the Barrett epithelium with regeneration of squamous epithelium. However, islets of Barrett epithelium may be found beneath the regenerated squamous epithelium and there is also the possibility of malignant potential of pluripotent stem cells left behind in the oesophagus. Future studies will have to afford insight into long-term results, the costs, the side effects of the various methods of treatment and the quality of life of patients during and after treatment of the Barrett oesophagus.     

K-ras point mutations are rare events in premalignant forms of Barrett's oesophagus

OBJECTIVE: In Barrett's adenocarcinomas, in contrast to squamous oesophageal carcinomas, K-ras point mutations are thought to be a frequent event. The frequency of K-ras point mutations in premalignant forms of Barrett's oesophagus (metaplasia, dysplasia) leading to adenocarcinoma with increased risk is currently not known. To establish the frequency of K-ras mutations in premalignant forms of Barrett's oesophagus, we investigated oesophageal biopsy specimens with Barrett's metaplastic and dysplastic epithelium for point mutations in the K-ras gene/codons 12, 13. DESIGN: A total of 412 biopsies from patients with Barrett's oesophagus were histologically classified into biopsies with metaplasia (n = 252), dysplasia (n = 105) and adenocarcinoma (n = 11), as well as biopsies distant from disease (normal, n = 37 and hyperplastic squamous epithelium, n = 7). METHODS: DNA from biopsy specimens was amplified by polymerase chain reaction (PCR) with a modified primer for generating a restriction site in the case of wild type in codon 12. Wild-type or point mutations in the K-ras gene/codons 12, 13 were detected by restriction fragment length analysis of the PCR products. RESULTS: Point mutations in K-ras/codon 12 were found in 9 biopsies (n = 1 in metaplasia, n = 4 in dysplasias, n = 4 in adenocarcinomas). All the other biopsies showed the wild type of K-ras/codon 12. No K-ras/codon 13 mutation (GGCgly-->GACasp) was observed. CONCLUSION: Mutations in K-ras/codon 12 were rarely found in premalignant forms of Barrett's oesophagus. Whereas the screening for K-ras point mutations in metaplastic sites of Barrett's epithelium seems not to be of practical value, the screening for mutations in dysplastic lesions might be helpful to estimate the individual risk for progression of Barrett's epithelium to adenocarcinoma. A further evaluation in larger numbers of patients is needed.     

Restoration of the normal squamous lining in Barrett's esophagus by argon beam plasma coagulation

OBJECTIVE: Barrett's esophagus is associated with significantly increased risk of development of esophageal adenocarcinoma. Replacing columnar epithelium with the normal squamous lining in this condition offers the possibility of decreasing the risk of degeneration to invasive adenocarcinoma. This study aimed to establish the feasibility of argon beam plasma coagulation (ABPC), in conjunction with control of gastroesophageal reflux, to restore the squamous lining. METHODS: Thirty patients with Barrett's esophagus (four low-grade dysplasia, three high-grade) were recruited from our surveillance program, and underwent endoscopic ABPC. RESULTS: Twenty-seven patients completed treatment, with macroscopic replacement of their columnar lining by squamous epithelium, histologically confirmed in all 27, and followed up for a median of 9 months (range, 6-18 months). Two patterns of squamous replacement were identified: 70% of patients showed squamous epithelium with no persistent intestinal metaplasia, and in 30% the new squamous epithelium covered areas of underlying intestinal metaplasia. One patient has withdrawn from the study. Two esophageal perforations, with one death, occurred early in the study. CONCLUSION: ABPC, in conjunction with control of gastroesophageal reflux, allows squamous regrowth in both benign and dysplastic Barrett's esophagus. Despite the theoretical safety advantages of ABPC over techniques such as laser, esophageal perforation may occur with this technique. It is too soon to recommend ABPC for dysplastic or nondysplastic Barrett's because follow-up is too short to show a decreased incidence of and mortality from adenocarcinoma.     

In vitro cell density-dependent clonal growth of EGF-responsive murine neural progenitor cells under serum-free conditions

BACKGROUND: Barrett's oesophagus is thought to be a complication of severe gastro-oesophageal reflux. AIM: To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus. METHODS: An 8-week, randomized, double-blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus. Erosive reflux oesophagitis was defined as grades 2-4 oesophagitis; Barrett's oesophagus, as specialized columnar epithelium obtained by biopsy from the tubular oesophagus; and healing, as a return to grade 0 or 1 oesophageal mucosa (complete re-epithelialization). One-hundred and five (105) patients from one centre were randomized to receive either lansoprazole 30 mg daily or ranitidine 150 mg twice daily. Unhealed or symptomatic lansoprazole patients at week 4 were randomized to receive the same 30 mg dose daily or an increased dose of 60 mg daily. Endoscopy was performed at baseline and at weeks 2, 4, 6 and 8. RESULTS: The treatment groups were similar in regards to baseline characteristics, erosive reflux oesophagitis grades and length of Barrett's oesophagus. At each 2-week interval, lansoprazole patients had significantly greater healing rates and less day and night heartburn and regurgitation than ranitidine patients. There were no significant differences between treatment groups in antacid use, quality of life parameters, or rate of reported adverse events. Median values for fasting serum gastrin levels remained within the normal range for both groups. CONCLUSION: In patients with both Barrett's oesophagus and erosive reflux oesophagitis, lansoprazole is significantly more effective than ranitidine in relieving reflux symptoms and healing erosive reflux oesophagitis.     

Prolonged survival follows resection of oesophageal SCC downstaged by prior chemoradiotherapy

BACKGROUND: The poor survival rate of surgically treated patients with oesophageal cancer has not improved substantially over the last 25 years, but combined modality therapy has shown early promising results. METHODS: A prospective study was undertaken to determine the effect of pre-operative synchronous chemoradiotherapy followed by oesophagectomy in 53 patients with squamous cell carcinoma (SCC) of the oesophagus. The patient group was unselected, other than by fitness for surgery. RESULTS: In 25% of patients, complete pathological regression of the tumour was achieved. All but one of the patients in this subgroup had T2 tumours on pre-operative clinical staging and two had evidence of lymph node involvement, but postoperative pathological examination revealed that pre-operative chemoradiotherapy had downstaged their disease to T0N0. There was no hospital mortality in this subgroup and the actuarial 7 year survival was 69%. CONCLUSIONS: For squamous oesophageal tumours deep to the submucosa this is an extremely good survival. For the present, this form of therapy for SCC of the oesophagus appears capable of achieving results comparable to, or better than, those reported for 3-field lymphadenectomy.     

Incidence of Barrett's adenocarcinoma in an Italian population: an endoscopic surveillance programme. Gruppo Operativo per lo Studio delle Precancerosi Esofagee (GOSPE)

BACKGROUND: Barrett's oesophagus is a premalignant condition leading to adenocarcinoma. The incidence of adenocarcinoma of the oesophagus and the gastrooesophageal junction is rapidly increasing in the USA, northern and central Europe. Data from southern Europe are still unavailable. OBJECTIVE: To evaluate the incidence of oesophageal adenocarcinoma in a large cohort of Italian patients with Barrett's oesophagus. METHODS: A total of 344 patients (253 males and 91 females, age range 19-75 years) with histologically proven Barrett's oesophagus (length of metaplasia > or = 3 cm) were enrolled from November 1987 to June 1995. Endoscopic and histological examinations were scheduled at yearly intervals. RESULTS: One hundred and eighty-seven patients complied with the follow-up. The mean duration of the follow-up period was 36 months (total follow-up 562 patient-years; range 12-90 months). Low grade dysplasia was found in five patients at the initial examination. During the surveillance period, dysplasia increased in frequency as well as in severity and was found exclusively in the intestinal type of Barrett's oesophagus. In all, dysplastic changes were found in seven patients (five low grade and two high grade) and adenocarcinoma developed in three patients during the follow-up. In a single case, both adenocarcinoma and specialized columnar epithelium developed without any evidence of dysplasia or intestinal metaplasia at the previous follow-up examination. This prospective study shows an incidence of adenocarcinoma in Barrett's oesophagus of 1/187 patient-years. When only patients with specialized columnar epithelium were considered, the risk of adenocarcinoma was 1/88 patient-years. CONCLUSION: The present report shows that the incidence of adenocarcinoma in Italian Barrett's oesophagus patients is in the range of that reported from other Western countries.     

Esophageal cancer on the increase. Is Barrett esophagus the cause?

At the Dept of Surgery, Lund University, during the 10-year period 1985-95, 54 patients with adenocarcinoma of the gastro-oesophageal junction (17 with Barrett's epithelium, and 37 without) underwent oesophageal resection: oesophagectomy and gastric pull-up (n = 10), extended total gastrectomy (n = 37), or oesophageal resection and interposition of colon (n = 2) or jejunum (n = 5). Hospital mortality was 3.7% (2/54), and the mean duration of hospitalisation 13 days (range, 9-42). Long-term survival was significantly better in the Barrett's oesophagus subgroup than in the carcinoma of the cardia (non-Barrett's oesophagus) subgroup, the respective rates being 50% vs. 10% (p = 0.0052; Log rank test). The better survival in the Barrett's oesophagus subgroup is probably to be explained by the earlier stage of disease among these patients, in turn due to a history of gastro-oesophageal reflux, whereas the predominant symptom in the cardia carcinoma subgroup was dysphagia.     

High-grade dysplasia in Barrett's oesophagus

BACKGROUND: The management of high-grade dysplasia (HGD) in Barrett's oesophagus is a controversial and challenging problem. METHODS: An up-to-date review of the literature has been made using Index Medicus, the Medline database, and cross-referencing of major articles on this subject. RESULTS: Diagnosis should be confirmed by a second expert pathologist. Repeat multiple jumbo biopsies and brushings need to be taken to reduce sample error and exclude associated invasive cancer. In young fit patients the advantages of surgery outweight the disadvantage of missing an early adenocarcinoma. Continued endoscopic surveillance may be more appropriate in elderly patients. New technology has increased the number of options. Early results of laser and multipolar electrocoagulation ablation of Barrett's epithelium are encouraging. Photodynamic therapy appears to be ideally suited to HGD and early cancers. CONCLUSION: A selective approach to the management of HGD on an individual patient basis should be adopted.     

Regression of childhood Barrett's esophageal mucosa by antireflux surgery and bipolar electrocoagulation

The authors report a case of a 13-year-old girl with Barrett's esophagus who underwent antireflux surgery and was subsequently treated with endoscopic thermal coagulation using bipolar electrocoagulation. Follow-up endoscopy 15 months after completion of the endoscopic therapy showed normal esophageal mucosa without intestinal metaplasia. Longer follow-up is needed to assess the long-term effects of endoscopic treatment of the Barrett's mucosa with thermal coagulation, and this procedure should still be considered under investigation.     

Restoration of squamous mucosa after ablation of Barrett's esophageal epithelium

BACKGROUND: Antireflux therapy has generally failed to induce regression of Barrett's epithelium. It was hypothesized that squamous epithelium could be restored if the columnar tissue was ablated while gastric acid secretion was suppressed. METHODS: Ten white men with Barrett's esophagus received 40 mg of omeprazole daily. Thereafter, every 2-5 weeks they underwent videotaped endoscopies to argon laser photoablate columnar tissue, obtain biopsy specimens, and assess results. Squamous re-epithelialization was assessed by correlation of videotapes and directed biopsies. RESULTS: Patients had one to eight areas ablated, totaling 0.5-12.0 cm2. Videotape assessments were corroborated by biopsy in all but one instance. Thirty-eight of 40 treatment locations partially or completely re-epithelialized with squamous tissue. Squamous regrowth appeared to occur by spread from contiguous squamous borders and de novo from glandular tissue. Regrowth was influenced by the extent of squamous borders and completeness of ablations. Nonablated glandular tissue persisted beneath squamous epithelium. CONCLUSIONS: Ablation of Barrett's epithelium and suppression of acid secretion facilitated squamous re-epithelialization. A progenitor cell within the metaplastic tissue has the potential to differentiate normally.     

Radiofrequency volumetric tissue reduction for treatment of turbinate hypertrophy: a pilot study

BACKGROUND: Apoptosis maintains cell homeostasis. Altered apoptosis is involved in carcinogenesis. It was our aim to investigate whether reflux esophagitis may alter apoptosis in the esophageal mucosa and whether antireflux surgery may restore normal apoptosis. METHODS: Apoptosis was studied preoperatively and postoperatively in esophageal biopsies of 39 patients with various grades of reflux esophagitis and in Barrett's mucosa using the TUNEL method. Biopsies were also taken from lesions of the squamous epithelium adjacent to the Barrett's mucosa. RESULTS: Apoptosis increased with the severity of esophagitis. Apoptosis was low in Barrett's epithelium. Squamous epithelium adjacent to Barrett's mucosa showed increased apoptosis. After surgery apoptosis decreased in squamous epithelium, and it remained low in Barrett's epithelium. CONCLUSIONS: Apoptosis in reflux esophagitis may be protective against increased proliferation. Low apoptosis following antireflux surgery indicates that surgery is effective to prevent reflux-induced cell proliferation. Inhibition of apoptosis in Barrett's may promote carcinogenesis. This may not change following surgery.     

The etiopathogenesis of esophageal cancer

Cancer of the oesophagus is a challenging clinical problem. Overall survival is poor, but patients who present early are eminently curable. Most cancers of the middle and upper oesophagus are squamous cell carcinoma. Adenocarcinoma is the most common cancer of the third of the oesophagus; this is not surprising when the usual distribution of Barrett's mucosa is considered. The geographical variation in the prevalence of oesophagus cancer is important. In most parts of the world, alcohol consumption and tobacco usage are the principal risk factors. Other risk factors have been identified in "the high-risk areas": a diet high in nitrosamines, deficient in trace elements, in vitamins (C.A, E) and the hereditary conditions like: Barrett's oesophagus, achalasia, caustic strictures.     

False positive MIBG scan

OBJECTIVE: An increased age-related incidence of oesophageal cancer in people with intellectual disability has been suggested by studies in the Netherlands. Gastro-oesophageal reflux disease (GORD), as documented by pH testing, occurs frequently in the intellectually disabled population, being found in nearly 50% of those with an IQ less than 50, while Barrett's oesophagus is found in about 15-26%. DESIGN: We compared the age-related incidence of oesophageal cancer in institutionalized, intellectually disabled individuals in the Netherlands with the age-related incidence in the general Dutch population. METHODS: Data were provided by the Netherlands Cancer Registry. The patient's institute physician was asked to complete a questionnaire about the diagnosis, which was endoscopically and histologically confirmed. RESULTS: The incidence of oesophageal carcinoma was 20 in 168,000 person-years. The expected incidence for oesophageal cancer, based on age-related incidence in the general population, was 7.0, resulting in a standardized morbidity ratio in the population with intellectual disability of 2.9 (confidence limits, 1.8-4.1; P < 0.001). Endoscopic findings were as follows: in 18/20 intellectually disabled carcinoma patients an adenocarcinoma was found; the remaining two patients had a squamous cell carcinoma. Barrett's epithelium was observed in nine patients (45%), eight (42%) of whom showed a peptic stricture as well. In 15 (75%) cancer patients reflux oesophagitis was found, accompanied in 14 cases by a hiatal hernia. CONCLUSION: A standardized morbidity ratio for oesophageal carcinoma of 2.9 was found in the intellectually disabled population as compared to the general population. Early detection and treatment of GORD in the population with intellectual disability is of paramount importance to prevent the development of Barrett's dysplasia and carcinoma.     

Gastro-oesophageal reflux associated with nocturnal gastric acid breakthrough on proton pump inhibitors

BACKGROUND: Nocturnal gastric acid breakthrough, defined as intragastric pH < 4 for more than 1 h in the overnight period, is observed in up to 70% of normal subjects on proton pump inhibitors taken twice daily. The frequency of this breakthrough in patients with gastro-oesophageal reflux and accompanying oesophageal reflux during this period has not been studied. AIM: To examine the frequency of nocturnal break-through and accompanying oesophageal acid exposure in patients with gastro-oesophageal reflux treated with proton pump inhibitors twice daily. METHODS: Prolonged ambulatory pH records from 76 patients on twice daily proton pump inhibitors between January 1991 and July 1997 were analysed for the presence of nocturnal gastric acid breakthrough and accompanying oesophageal pH < 4. Studies from 31 normal subjects on twice daily proton pump inhibitors constituted the control group. RESULTS: Nocturnal gastric acid breakthrough was seen in 70% of 61 patients with gastro-oesophageal reflux, 80% of 15 patients with Barrett's oesophagus and 67% of normal controls (P=N.S.). Oesophageal acid exposure was seen in 33% of gastro-oesophageal reflux patients, 50% of Barrett's oesophagus patients and 8% of normal controls (P < 0.03). No difference was found between patients taking omeprazole or lansoprazole. CONCLUSION: Nocturnal acid breakthrough is frequently seen on proton pump inhibitors twice daily and is often accompanied by oesophageal reflux. This has important implications for medical therapy in patients with severe gastro-oesophageal reflux and Barrett's oesophagus.     

Drug abuse in Japan

OBJECTIVE: Cis-platinum and 13-cis-retinoic acid have received much attention in the treatment of head and neck squamous cell cancer. Even though they have different mechanisms of action, little information is available on their interaction. This paper reviews experimental evidence for retinoic acid-cis-platinum synergy and presents toxicity data from patients with stage IV head and neck squamous cell cancer participating in a phase I trial combining 13-cis-retinoic acid and cis-platinum. METHODS: Patients were given 13-cis-retinoic acid orally daily for 7 days before and daily during high-dose (150 mg/m2 per week for 4 weeks) intraarterial cis-platinum treatment with concurrent radiation. Toxicity was scored with use of the cancer and leukemia group B scale. RESULTS: In the phase I clinical trial, 15 patients were treated to determine a maximum tolerated dosage for 13-cis-retinoic acid of 20 mg/day. Grade 4 hematologic toxicity was dose limiting in 3 of 8 patients treated with 40 mg/day and in 1 patient treated with 60 mg/day. There were no deaths caused by toxicity; 12 of the 15 patients received all four weekly doses and the remaining 3 received three doses. Of 10 patients with fully evaluable data, all achieved a complete response at the primary site and 9 had a complete response in the neck. One patient had persistent neck disease after chemoradiation, and this tumor was removed with neck dissection. CONCLUSIONS: 13-Cis-retinoic acid and cis-platinum are strongly synergistic against head and neck squamous cell cancer in vitro. Pretreatment with retinoic acid results in stronger synergy than concurrent drug exposure alone. Preliminary clinical experience with combined retinoic acid and cis-platinum in a design that parallels the in vitro study indicates that toxicity is acceptable with 13-cis-retinoic acid dosages of 20 mg/day in a high-dose-intensity intraarterial chemoradiation regimen.     

A gene for FG syndrome maps in the Xq12-q21.31 region

AIMS: An increased risk of adenocarcinoma of the oesophagus has been demonstrated in patients with long segments of Barrett's mucosa. The risk of cancer associated with short segments of metaplasia of the oesophagogastric junction is not known. METHODS AND RESULTS: We report a case of early adenocarcinoma of the oesophagus arising on short tongues of Barrett's mucosa associated with an oesophageal cyst. The patient was a 68-year-old man with no previous clinical history of gastro-oesophageal reflux disease. The fortuitous discovery of an oesophageal cyst lead to the diagnosis of short tongues of Barrett's mucosa with high-grade dysplasia. On pathological examination of the resected specimen, an early adenocarcinoma had developed in Barrett's mucosa, localized just above the oesophageal cyst. CONCLUSIONS: As oesophageal cysts can cause symptoms suggestive of reflux, we hypothesize that this association may not be fortuitous.     

Prevalence of metaplasia at the gastro-oesophageal junction

Specialised columnar epithelium (SCE), a form of intestinal metaplasia usually found in Barrett's oesophagus, cannot be distinguished endoscopically from normal gastric epithelium. Endoscopists seldom obtain biopsy specimens from a normal-appearing gastro-oesophageal junction, and therefore short segments of SCE in this region may go unrecognised. We studied patients who had short segments of SCE at the gastro-oesophageal junction. All patients scheduled for elective endoscopic examinations in our general endoscopy unit, irrespective of indication, were questioned for symptoms of gastro-oesophageal reflux disease. At endoscopy, severity of oesophagitis was graded, and biopsy specimens obtained from the squamocolumnar junction, irrespective of its appearance or location in the oesophagus. Among 142 patients without endoscopically apparent Barrett's oesophagus, 26 (18%) were found to have SCE. All patients with SCE were white, and the male/female ratio was 1.9. In contrast, non-whites accounted for 14% of the 114 patients without SCE and the male/female ratio was 0.8. The groups did not differ significantly in the frequency of symptoms and endoscopic signs of gastrooesophageal reflux. We conclude that adults frequently have unrecognised segments of SCE at the gastro-oesophageal junction; this may underlie the rising frequency of cancer of the gastrooesophageal junction in the USA and Europe.     

Histopathologic spectrum of vaginal adenosis and related changes in stilbestrol-exposed females

A total of 98 colposcopically directed biopsies were obtained from the vagina, cervix, and cervicovaginal ridge (hood) of 80 young women believed to have had intrauterine exposure to stilbestrol (DES). Specific investigation of the patient's medical records corroborated the history of maternal stilbestrol administration in 36 patients (45%), while in the remainder the drug history was regarded as presumptive since medical records were unavailable for review. The findings did not differ significantly in those biopsies taken from patients with confirmed or presumptive drug histories. Histologic evidence of vaginal adenosis was detected in vaginal biopsies from 43 patients. In 30 cases (70%) benign Müllerian-type glandular epithelium was in the superficial vaginal wall, residing on the mucosal surface and/or in the lamina propria. The glandular epithelium predominantly was of endocervical type, but in six instances it resembled endometrial or fallopian tubal epithelium. The glands were accompanied by varying degrees of squamous metaplasia in 22 cases. When extensive the metaplasia produced transformation zones similar to those seen in the normal cervix. Vaginal biopsies of adenosis from the other 13 patients (30%) revealed squamous metaplasia without demonstrable glands due to complete transformation of all antecedent glandular epithelium by squamous metaplasia. Our studies indicate that squamous metaplasia is a component of major importance in the natural history of adenosis and that the concept of adenosis should be broadened to include those examples comprised exclusively of metaplastic epithelium. In such examples metaplasia is identified by the immaturity and poor glycogenation of the squamous cells and their accompanying squamous pegs which often contain residual gland openings or squamous "eddies." Similar findings were present in biopsies of seven cervicovaginal ridges and in cervical biopsies from 37 patients, except for the absence of endometrial or tubal type glands in the latter site. Although no adenocarcinomas were detected, six patients had squamous dysplasia of the vagina and/or cervix. In no case were premalignant or dysplastic changes of glandular cells found. Our findings support the thesis that stilbestrol-associated adenosis represents anomalous embryologic localization of the original squamocolumnar junction in the vagina rather than in the cervix. It is closely related to so-called cervical "erosions." The development of squamous metaplasia accounts for modifications in the clinical and histologic appearances by producing transformation zones which then may be subject to the same oncogenic stimuli for squamous neoplasia as are their counterparts in the cervix.     

Spontaneous rupture of the oesophagus (author's transl)

During the last 4 years three so-called spontaneous perforations of the oesophagus were treated, twice by surgical intervention 12 anys after the rupture. Two patients survived. The classical history of retching or vomiting and retrosternal splitting pain is indicative, wht medium, amidotrizoate sodium (Gastrografin), from the oesophagus. Prognosis depends decisively on the time of operation after the rupture. Direct suture of the rupture with plastic coverage of the defect by sewing on of the gastric fundus or by plication of the fundus have proved valuable.