Intestinal GLP-1 and satiation: from man to rodents and back.

In response to luminal food stimuli during meals, enteroendocrine cells release gastrointestinal (GI) peptides that have long been known to control secretory and motor functions of the gut, pancreas and liver. Glucagon-like peptide-1 (GLP-1) has emerged as one of the most important GI peptides because of a combination of functions not previously ascribed to any other molecule. GLP-1 potentiates glucose-induced insulin secretion, suppresses glucagon release, slows gastric emptying and may serve as a satiation signal, although the physiological status of the latter function has not been fully established yet. Here we review the available evidence for intestinal GLP-1 to fulfill a number of established empirical criteria for assessing whether a hormone inhibits eating by eliciting physiological satiation in man and rodents.

[Sealing of the hepatic resection area using hemostat devices does not improve results of adequate surgery]. / Versiegelung der Leberresektionsfläche mit Gewebsklebematerialien bewirkt keine weitere Verbesserung adäquater Chirurgie.

PURPOSE: In hepatic resections, there has been a high quality demand. The aim of this systematic clinical, prospective, unblinded unicenter observational study with two arms in an unselected patient cohort was to investigate whether hemostat device can significantly improve outcome in resective liver surgery, in particular, in high risk patients. METHODS: All consecutive patients (mean age, 60.5 [range, 17 - 96] years) who underwent hepatic resection (ntotal = 770) were prospectively documented in a computer-based registry at a university hospital (tertiary center) over a time period of 10 years and retrospectively evaluated specifically with regard to the use (-/+; in daily practice and intraoperative decision-making) of hemostat device (Tissucol(®), n = 59/Tachocomb(®), n = 202/combination, n = 55) indicated (among others) by drainage volume, inflammatory parameters and rate of specific complications (nvalidated = 541 [100 %]). RESULTS: Most frequently, (a-)/typical segmental resections were used: n = 192/90 (3-segment resection, only n = 38). 1) For the assignment of patients to the two different groups (-/+ hemostat device), weight loss and type of resection were found as significant factors (trend: ASA, cirrhosis), for the amount of drainage volume, ASA, sex, Karnofsky Performance Scale and also type of resections using independent distributed statistical tests (such as χ(2), U test [Mann/Whitney]; H test [Kruskal-Willis]; correlation coefficient by Spearman) - no impact: smoking, diabetes, BMI, ethanol. 2) Not taking into account these parameters, the use of hemostat device was characterized by an increased drainage volume (negative control < Tissucol = Tachocomb < combination). 3) Using multifactorial analysis of variance, it was found even under correction by the factors with significant impact elucidated in the single test that the application of hemostat device onto the hepatic resection area resulted unexpectedly rather in an increase than a decrease of the drainage volume but 4) under accompanying more pronounced increase of the white blood cell count (leucocytosis). 5) General and specific complications such as postoperative bleeding, biliary fistula and subhepatic abscess were not further lowered in a significant manner using hemostat device. CONCLUSION: Adequate surgery in the operative management of hepatic resection area cannot further be improved or optimized using hemostat device. In this context, drainage volume may not be considered a sufficient rather an orienting parameter. However, there is an inflammatory response detectable most likely indicated by a(n un-)specific effusion and increase of white blood cell count, which can be interpreted as a) being characteristic for the problematic group of patients, in whom hemostat device was decided to be useful and was finally used in daily prectice, or b) reactive inflammation to foreign material.

Effect of inulin on breath hydrogen, postprandial glycemia, gut hormone release, and appetite perception in RYGB patients: a prospective, randomized, cross-over pilot study.

BACKGROUND AND OBJECTIVE: Large intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients. METHOD: Eight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales. RESULTS: Surgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3-5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations. CONCLUSION: RYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin.

[Surgical treatment of carcinomas of the oesophagogastric junction - results achieved in multicentre studies]. / Multizentrische Ergebnisse der chirurgischen Therapie der Karzinome des ösophagogastralen Übergangs.

BACKGROUND: Adenocarcinomas of the oesophagogastric junction are increasingly being considered as a separated tumour entity. The prognosis is rather poorer compared with that for distal gastric cancer. Data from a multicentre study as part of research on clinical care aim to reflect the current situation in surgical treatment after inauguration of neoadjuvant modalities. PATIENTS AND METHOD: As part of the ongoing prospective multicentre observational study QCGC 2 (German Gastric Cancer Study 2), 544 adenocarcinomas of the oesophagogastric junction (AEG 1-3) were registered from 01/01/2007 to 12/31/2009. RESULTS: Patients underwent surgical intervention in 108 (76.6 %) of the 141 surgical departments which provided data to the study. In 391 patients (82.5 %), R0 resection was achieved. Almost 60 % of the carcinomas of the oesophagogastric junction were approached in departments with no more than 10 of these tumour lesions through the whole study period (3 years). Endoscopic ultrasonography was performed in 283 cases (53 %); the rate of neoadjuvant treatment was 34.4 % (n = 187). Intraoperative fresh frozen section was only included in intraoperative decision-making in 242 patients (60.8 %). In the revealed heterogeneous spectrum of surgical interventions, a limited number of transthoracic approaches (20 %) and a mediastinal lymphadenectomy rate of only 47 % were found. Hospital lethality was 6.6 %. In the adenocarcinomas of the oesophagogastric junction, a significantly lower median survival (25 months) compared with distal gastric cancer (38 months) was observed depending on the tumour stage. In addition, 5-year survival rate of AEG patients (33.1 %) was distinctly lower than for patients with distal gastric cancer (41.4 %). There was no significantly better survival by neoadjuvant treatment in the group of investigated patients. CONCLUSION: The results in the treatment of carcinomas of the oesophagogastric junction in the multicentre setting including surgical departments of each profile and region even after introduction of multimodal therapeutic concepts are not satisfying. In particular, modern diagnostic and surgical strategies need to be widely used or their percentage has to be increased. In this context, centralisation of the surgical care of this specific tumour entity appears reasonable.

The role of the gut sweet taste receptor in regulating GLP-1, PYY, and CCK release in humans.

The recent identification of sweet taste receptors in the gastrointestinal tract has important implications in the control of food intake and glucose homeostasis. Lactisole can inhibit the sweet taste receptor T1R2/T1R3. The objective was to use lactisole as a probe to investigate the physiological role of T1R2/T1R3 by assessing the effect of T1R2/T1R3 blockade on GLP-1, PYY, and CCK release in response to 1) intragastric administration of nutrients or 2) intraduodenal perfusion of nutrients. The study was performed as a randomized, double-blind, placebo-controlled crossover study that included 35 healthy subjects. In part I, subjects received intragastrically 75 g of glucose in 300 ml of water or 500 ml of a mixed liquid meal with or without lactisole. In part II, subjects received an intraduodenal perfusion of glucose (29.3 g glucose/100 ml; rate: 2.5 ml/min for 180 min) or a mixed liquid meal (same rate) with or without lactisole. The results were that 1) lactisole induced a significant reduction in GLP-1 and PYY but not CCK secretion in both the intragastric and the intraduodenal glucose-stimulated parts (P ≤ 0.05), 2) comparison of the inhibitory effect of lactisole showed a significantly greater suppression of the hormone response in the intragastric part (P = 0.023), and 3) lactisole had no effect on liquid meal-stimulated parameters. We conclude that T1R2/T1R3 is involved in glucose-dependent secretion of satiation peptides. However, the results of the liquid meal-stimulated parts show that the receptor alone is not responsible for peptide secretion.

[Minimal Residual Disease (MRD) in gastric carcinoma--an overview]. / Minimale Resterkrankung beim Magenkarzinom - eine Übersicht.

Despite recent developments in therapy for gastric cancer, the prognosis of this disease remains poor in advanced stages. In many cases even curatively treated patients without any residual tumour develop metachronous metastases. As in other solid tumours, adjuvant therapies can reduce the metastatic risk, which implies that some of these patients harbour isolated tumour cells or micrometastases (minimal residual disease, MRD) that are undetectable by radiological imaging and conventional histopathology but can still be the cause of tumour recurrence. Therefore, reliable methods for diagnosing MRD would be desirable for individually tailoring therapy for these patients. Unfortunately, testing methods for MRD and interpretation of their results are not standardised and studies published on this topic are difficult to interpret due to methodological differences and small sample sizes. As of now, testing for MRD has not become relevant in clinical routine for any of the anatomic compartments lymph nodes, peritoneal lavage fluid, peripheral blood, and bone marrow in the Western hemisphere. Most reliable data on MRD in gastric cancer patients have been reported for peritoneal lavage fluid. In some centres in Japan, this test is routinely being used for making therapeutic decisions, e. g., on the use of intraperitoneal chemotherapy. MRD in resected lymph nodes will be further evaluated in the context of the sentinel lymph node concept and possibly be employed for designing individualised therapy for patients in early disease stages who are not routinely candidates for multimodal treatment. As for tumour cells in peripheral blood and in bone marrow, studies suggest that these cells are only able to form metastases in the presence of certain molecular factors. Therefore, rather than simply confirming the existence of isolated tumour cells in blood or bone marrow, future studies should concentrate on defining their molecular characteristics and the conditions required for their metastatic potential. This may gain relevance in diagnostics and prognostic evaluation of individual patients as well as in the development of targeted therapies directly interfering with the metastatic process.

[Clinical value of laparoscopic surgery for colon cancer]. / Stellenwert der laparoskopischen Chirurgie des Kolonkarzinoms in der klinischen Routine.

BACKGROUND: Using data and analysis compiled in the nationwide German Colon/Rectal Cancer qualitative multicenter study, the aim of this study was to determine the value of laparoscopic surgery for colon cancer in clinical routine. METHODS: From 1 January 2000 to 31 December 2003, patients with colon cancer resections were evaluated for short-term postoperative and long-term oncologic results associated with operative approach (laparoscopic vs conversion vs open). RESULTS: Of 21,721 patients with colon cancer, 949 (4.4%) underwent laparoscopic resection. These patients were younger (P<0.001) with lower ASA risk factors (P<0.001) and earlier UICC tumor stages (P<0.001) than open resected patients. They also showed reduced overall morbidity (P<0.001), in-hospital mortality (P=0.001), and shorter hospital stays (P<0.001). The rates of intraoperative and specific complications remained unchanged. Nineteen percent of the patients had resections converted to open approaches. These had the highest overall morbidity and longest hospital stays. Their mortality was three times that of the group with complete laparoscopic resection. CONCLUSIONS: The open approach remained the standard of surgical care in colon cancer for the study duration. Laparoscopic surgery was used in only a small number of patients. By virtue of preferential patient selection, better early postoperative and long-term results could be achieved for the laparoscopic group than with the open approach. Conversions were shown to be associated with inferior results at the high rate of 19%. To ensure optimal results, laparoscopic surgery for colon carcinoma should be conducted by an experienced surgeon in an appropriately selected patient pool.

[Gender-specific differences of the early postoperative and oncosurgical long-term outcome in rectal cancer-data obtained in a prospective multicenter observational study]. / Genderspezifische Unterschiede im frühpostoperativen und onkochirurgischen Langzeitoutcome nach Rektumkarzinomresektion.

BACKGROUND: Gender-specific aspects have been increasingly considered in clinical medicine, also in oncological surgery. AIM: To analyze gender-specific differences of early postoperative and oncological outcomes after rectal cancer resection based on data obtained in a prospective multicenter observational study. PATIENTS AND METHODS: As part of the multicenter prospective observational study "Quality assurance in primary rectal cancer", data on tumor site, exogenic and endogenic risk factors, neoadjuvant treatment, surgical procedures, tumor stage, intraoperative and postoperative complications of patients with the histological diagnosis of rectal cancer were registered. Data from the years 2005-2006 and 2010-2011 were investigated with respect to gender-specific differences of postoperative morbidity, hospital mortality, local recurrency rate, disease-free and overall survival by univariable and multivariable analyses. RESULTS: Overall, data from 10,657 patients were evaluated: 60.9% of the patients were male, who were significantly younger (p < 0.001). Men had a significantly higher rate of alcohol (p < 0.001) and nicotine abuse (p < 0.001) as well as a trend to a higher body mass index (BMI) compared with women. Although, there was no significant difference in the distribution of various tumor stages comparing men and women, neoadjuvant radiochemotherapy was used significantly more often in male patients (p < 0.001). In addition, male patients underwent an abdominoperineal rectum exstirpation more often, whereas creation of an enterostoma and Hartmann's procedure were more frequently used in women (p < 0.001 each). Multivariate analysis revealed that male patients developed a higher overall morbidity (odds ratio, OR: 1.5; p < 0.001) during both study periods and from 2010-2011 a higher hospital mortality (OR: 1.8; p < 0.001). After a median follow-up period of 36 months, gender did not have a significant impact on overall survival, disease-free survival or on the local tumor recurrency. The 5­year overall survival was 60.5%, disease-free survival 63.8% and local recurrency rate was 5%. CONCLUSION: Independent of other variables, gender differences were found with respect to early postoperative outcome but not to oncological long-term results after surgery of rectal cancer.

Palliative stent implantation in the treatment of malignant colorectal obstruction.

BACKGROUND: Palliative surgical interventions for the management of colonic obstruction in cases of metastasized or locally irresectable colorectal carcinoma show remarkable morbidity and mortality rates for mostly older and multimorbid patients. For manifest obstruction, placement of a self-expanding metal stent (SEMS) is considered to be a suitable minimally invasive therapeutic option. This study aimed to investigate the efficacy of stent-based treatment for malignant large bowel obstruction. METHODS: From January 1999 to June 2005, consecutive patients who had undergone placement of a SEMS for malignant colorectal obstruction were enrolled and monitored. Manifest incontinence and rectum carcinoma within 5 cm above the anocutaneous line were contraindications for SEMS implantation. For all further locations of tumor-induced stenosis, a stent was implanted using endoscopy and fluoroscopy. This case series was characterized in terms of age, carcinoma localization, complications, morbidity and mortality, and the necessity for further interventions. RESULTS: For 44 of 48 patients (92%), stents were placed successfully and obstruction was abolished. The four remaining patients experienced stent dislocation. The median of age of the patients was 77.7 years (range, 47-96 years). The distribution of malignant stenoses was as follows: rectum (n = 16, 33.3%), sigmoideal colon (n = 21, 43.8%), descending colon (n = 4, 8.3%), splenic flexure (n = 2, 4.2%), transversal colon (n = 3, 6.2%), hepatic flexure (n = 1, 2.1%), and ascending colon (n = 1, 2.1%). There was no peri-interventional morbidity or mortality. The median in situ time for the stents was 251 days (mean, 422 days), with 13 of 44 patients treated with palliative therapy showing complications (29.5%). Six patients were treated endoscopically, and three individuals underwent surgical intervention. For four patients, no further intervention was required. Overall, there was no treatment-related mortality. CONCLUSIONS: For palliative treatment of malignancy-induced colorectal obstruction, SEMS is an efficient tool associated with low morbidity and minimal mortality. From a technical point of view, all tumor locations are accessible.

[Long-term oncological results after laparoscopic, converted and primary open procedures for rectal carcinoma. Results of a multicenter observational study]. / Operative Behandlung von Rektumkarzinomen im Vergleich. Onkologische Langzeitergebnisse einer multizentrischen Beobachtungsstudie nach laparoskopisch-assistierter, konvertierter und primär offener Operation.

BACKGROUND: The laparoscopic resection of rectal cancer shows morbidity and oncological safety comparable to the open approach, but morbidity increases after conversion to open resection. No oncological long-term results are available for the latter patients. METHODS: From 01/01/2000-31/12/2002, patients with curatively resected rectal cancer enrolled in a observational study were evaluated for morbidity, mortality, tumor- and local recurrence rate, paying attention to patients with conversion from laparoscopic to open resection. RESULTS: 237 (3.3%) of 7,189 patients underwent laparoscopic resection (ITT). These patients showed significantly more T1/2 tumors (P<0.001) in earlier UICC stages (P<0.001) than open resected patients. 35 (14.8%) of 237 laparoscopic procedures were converted. Compared with patients receiving complete laparoscopic or open resection, these patients showed significantly higher frequencies of intraoperative (P<0.001) and general postoperative complications (P=0.003) as well as the highest overall morbidity (P=0.031). After a median follow-up of 30.1 months, the highest 5-year local recurrence rate was found in the converted group (16.0%). The laparoscopically resected patients showed a local recurrence rate of 3.3%, patients with open resection of 12.4% (P=0.082). The disease-free survival rate did not differ between the groups (P=0.585). CONCLUSION: Laparoscopic resection of rectal cancer provides oncological results similar to open resection. After conversion, the short and oncological long-term outcomes were worse. Considering a conversion rate of 15%, only a strict indication for the laparoscopic approach can be allowed, and laparoscopic resection should be performed at centers.

The prebiotic concept and human health: a changing landscape with riboflavin as a novel prebiotic candidate?

Emerging evidence suggests that the gut microbiota has a critical role in both the maintenance of human health and the pathogenesis of many diseases. Modifying the colonic microbiota using functional foods has attracted significant research effort and product development. The pioneering concept of prebiotics, as introduced by Gibson and Roberfroid in the 1990s, emphasized the importance of diet in the modulation of the gut microbiota and its relationships to human health. Increasing knowledge of the intestinal microbiota now suggests a more comprehensive definition. This paper briefly reviews the basics of the prebiotic concept with a discussion of recent attempts to refine the concept to open the door for novel prebiotic food ingredients, such as polyphenols, minerals and vitamins.

Discordance between K-ras mutations in bone marrow micrometastases and the primary tumor in colorectal cancer.

PURPOSE: To study bone marrow micrometastases from colorectal cancer patients for the presence of K-ras mutations and to compare their genotype with that of the corresponding primary tumor. PATIENTS AND METHODS: Bilateral iliac crest aspiration was performed in 51 patients undergoing surgery for colorectal cancer, and bone marrow micrometastases were detected by immunohistochemistry. The presence of K-ras mutations was determined by single-strand conformation polymorphism analysis on both primary tumors and paired bone marrow samples and was confirmed by sequencing. RESULTS: In six patients with primary tumor mutations, it was possible to amplify a mutated K-ras gene also from the bone marrow sample. In three of those patients the pattern of K-ras mutations differed between both samples, in two patients the mutation was identical between the bone marrow and its primary tumor, and in one patient the same mutation plus a different one were found. Fifteen of 17 K-ras mutations found in primary tumors were located in codon 12, whereas in bone marrow, five of seven mutations were found in codon 13 (P =.003). CONCLUSION: Our results demonstrate that, at least for K-ras mutations, disseminated epithelial cells are not always clonal with the primary tumor and they question the malignant genotype of bone marrow micrometastases. They also indicate that different tumoral clones may be circulating simultaneously or sequentially in the same patient. Analysis of the type of mutations suggests that cell dissemination might be an early event in colorectal carcinogenesis.

[Palliative treatment of advanced gastric cancer from surgical point of view]. / Palliative Behandlung des fortgeschrittenen Magenkarzinoms aus chirurgischer Sicht.

Data are available on two multicenter observational studies, the East German Gastric Cancer Study (EGGCS) '02 (surgical interventions only) and the German Gastric Cancer Study II (QCGC) from 2007 to 2009 (after inauguration of multimodal therapeutic concepts) with regard to palliative treatment of advanced gastric cancer. Through the first investigation period from January to December 2002 (EGGCS) overall 1139 patients with primary gastric cancer were registered and evaluated and then from 2007 to 2009 (QCGC) another 2897 patients were included. Comparing both time periods, there were no significant changes in the distribution of tumor sites and stages according to the Union Internationale Contre le Cancer (UICC) classification, in particular, there was no significant reduction of advanced tumor stages. From 2007 to 2009 in total 521 patients (18 %) received neoadjuvant therapy, 401 patients (13.9 %) out of the group with curative intention and 120 (4.1 %) out of the group of patients with palliative intention. The proportion of palliative patients who underwent chemotherapy (with neoadjuvant intention and/or postoperatively) was 32.5 % (n = 223). Thus, the rate of palliative treatment (rate of no R0 resection status 29.6 %, rate of patients who did not undergo surgical intervention at all 9.5 %) could be diminished from almost 40 % in 2002 to 24.5 % through the time period from 2007 to 2009. Taking all patients together (with curative and palliative intention) an increase of the 4-year survival probability from 40.0 % to 48.5 % was observed after inauguration of multimodal therapy. After a 5-year follow-up median survival time was 34 months during the investigation period from 2007 to 2009 considering all study subjects. Patients who had undergone palliative surgical interventions benefited from postoperative palliative chemotherapy; however, as expected this was of greater benefit to patients with resecting surgical interventions than those with non-resecting operations. Palliative tumor resection (even R2 resection status) should be part of a concept of multimodal palliative therapy in cases of acceptable perioperative risk.

Time-resolved studies of Nd:YAG laser-induced breakdown. Plasma formation, acoustic wave generation, and cavitation.

The use of high intensity ultrashort pulsed laser radiation to produce optical breakdown is an important approach for the surgical treatment of intraocular structures. We have investigated the transient properties of Nd:YAG laser induced breakdown in a saline model using time-resolved spectroscopic techniques. Spatially resolved pump and probe techniques are applied to study the dynamic behavior of the plasma formation, acoustic wave generation, and cavitation processes which accompany the optical breakdown. Measurements of plasma shielding and luminescence indicate that the laser induced plasma forms on a subnanosecond time scale and has a lifetime of several nanoseconds. An acoustic transient is generated at the breakdown site and propagates spherically outward with an initial hypersonic velocity, then loses energy and propagates at sound velocity. Transient heating following the plasma formation produces a liquid-gas phase change and gives rise to cavitation or gas bubble formation. This gas bubble expands rapidly for several microseconds, then slows to reach its maximum size and finally collapses.

Proteomic prediction of disease outcome in cancer : clinical framework and current status.

Better than gene sequencing or quantitative amplification, proteomics tools allow the study of tumor phenotype. Indeed, most current prognostic tests in cancer (carcinoembryonary antigen [CEA], prostate-specific antigen [PSA], CA 19-1, CA 125, alpha-fetoprotein [AFP], etc.) are based on the detection and quantification of single proteins in body fluids. However, a common characteristic of these tests is their relatively low predictive value, so that they are usually complemented with other procedures such as biopsy and/or endoscopy. Recently, improved analytical and bioinformatics tools have driven the attention on pattern recognition approaches rather then single-marker tests for prognostic forecasting. It is expected that predicting metastasization on the basis of tumoral protein patterns will soon be a reality. However, currently available technologies either limit the number of proteins that can be analyzed simultaneously or they are expensive, difficult, and time-consuming. Moreover, the tools adapted for expression proteomics might not be the same as those for prognostic studies that require investigation of protein function over time. We believe that clinical proteomics research designed within a precise clinical and pathology framework should be strongly supported, since many prognostic factors are determined not by the tumor itself, but by the patient, the treatment and the environment.

Intrinsic stability of 'self-sealing' unsutured cataract wounds.

Many operative and postoperative factors can influence cataract wound stability and postoperative astigmatism. The final outcome is fundamentally dependent on the intrinsic biomechanical stability of the corneal dome in the presence of the wound. We determined the stability of the central and peripheral cornea with computer-assisted topographic analysis of six freshly enucleated human globes. Self-sealing, unsutured, scleral tunnel wounds 4.0 mm in length were dissected, with widths varying from 1.4 to 6.0 mm. Intraocular pressure was elevated in 5-mm increments from 15 to 40 mm Hg without measurable topographic change in the visual axis or superior cornea. We conclude that these long scleral tunnel wounds do not necessarily destabilize the cornea within the usual range of intraocular pressure. Postoperative-induced astigmatism is therefore due to other operative and postoperative factors. Some of these factors may be identifiable with this model and controlled or eliminated.

Long-term comparison of epikeratoplasty and penetrating keratoplasty for keratoconus.

The results of epikeratoplasty for keratoconus in ten patients with long-term follow-up (mean, 25 months; range, 19 to 31 months) vs ten patients with contemporaneous penetrating keratoplasty for keratoconus (mean, 33 months; range, three to 81 months) indicate a similar level of postoperative spectacle visual acuity (20/32 vs 20/27, respectively) and similar refractive and keratometric results. The healing period until achieving best corrected visual acuity averaged 12 months for epikeratoplasty vs three months for penetrating keratoplasty. Compared with penetrating keratoplasty, epikeratoplasty offers the advantages of maintaining an intact globe surgically and postoperatively in a young, active population, while avoiding potential immune rejection. The major disadvantages are a prolonged healing period and undefined limits in the extent of the cone that would define suitable candidates preoperatively.

One-year results of excimer laser photorefractive keratectomy for low to moderate myopia.

OBJECTIVE: Excimer photorefractive keratectomy is a promising method to reduce myopia. We evaluated the effectiveness, predictability, stability, and safety of photorefractive keratectomy performed by two surgeons at a single site with a 1-year follow-up. METHODS: An excimer laser (Summit Excimed UV200, Summit Technology, Waltham, Mass) was used to treat 47 eyes. Preoperative uncorrected visual acuity averaged 20/277 and ranged from 20/60 to 20/500. Spherical equivalent averaged -3.9 diopters and ranged from -1.5 to -6.1 D. RESULTS: One year postoperatively, best corrected visual acuity averaged 20/13 and ranged from 20/10 to 20/20. No patients lost any of best corrected visual acuity. The uncorrected visual acuity at 1 year averaged 20/20 and ranged from 20/10 to 20/200. Ninety-four percent of eyes had an uncorrected visual acuity of 20/40 or better; 83%, 20/25 or better; and 74%, 20/20 or better. An initial hyperopic overcorrection is followed by gradual regression to emmetropia during a 12-month period. Refractive spherical equivalent averaged 0.44 D and ranged from -3 to +2.6 D at 1 year. The proportion of eyes within 1 D of emmetropia was 80% at 1 year. The most significant shifts in refraction occurred between the first and second months, but small shifts occurred up to 12 months. Subgrouping the results according to age revealed a significantly greater effect with larger residual hyperopia in those older than 40 years. Patient satisfaction with the procedure was high. CONCLUSION: During a 1-year period, excimer photorefractive keratectomy appears to be an effective, predictable, stable, and safe method to reduce myopia. Age may play a role in the effectiveness of the procedure, with greater hyperopia resulting in those older than 40 years.

A comparative study of masking fluids for excimer laser phototherapeutic keratectomy.

Several fluids of different viscosity were used to mask deeper tissues while exposing protruding irregularities during therapeutic keratectomy of an irregular anterior corneal surface with the 193-nm argon fluoride excimer laser. A model of an irregular anterior corneal surface was developed in deepithelialized calf eyes using grade 8-0 sandpaper. Therapeutic keratectomy was then performed on 28 eyes at a fluence of 180 mJ/cm2, a repetition rate of 10 Hz, and 500 pulses per eye. Solutions of 0.3% hydroxypropylmethylcellulose 2910 and a 0.1% dextran 70 solution, 1% carboxymethylcellulose sodium solution, or 0.9% saline solution were applied to the corneal surface of 21 eyes. Seven control eyes underwent ablation without the addition of fluid. Scanning electron microscopy demonstrated that corneas treated with dextran 70 had the least surface irregularity, and those treated with carboxymethylcellulose or saline solution had intermediate surface irregularity. Corneas that were ablated without additional fluid had the greatest surface irregularity. The application of a moderately viscous solution during therapeutic excimer laser keratectomy enhances the smoothing effect of surface ablation.