Endoscopic submucosal tunnel dissection vs conventional endoscopic submucosal dissection for large colorectal neoplasms: a single-centre retrospective study.

BACKGROUND: Colorectal endoscopic submucosal dissection (ESD) is still not widely used due to its technical difficulty and the risk of complications. Several techniques, such as traction techniques, pocket techniques and others, have been proposed to facilitate it. One modified pocket technique especially suitable for large lesions is endoscopic submucosal tunnel dissection (ESTD). The aim of this study was to evaluate the safety and efficacy of ESTD and compare ESTD to the conventional ESD (CESD) for treating large colorectal lesions. METHODS: The charts of consecutive patients referred to the Arcispedale Santa Maria Nuova (Reggio Emilia, Italy) for colorectal ESD between January 2014 and February 2021 for colorectal neoplasms > 40 mm were retrospectively analysed. The primary outcome of the study was the en bloc resection rate. Secondary outcomes were complete and curative resection rates, procedure speed, the adverse events rate and the recurrence rate. RESULTS: There were 59 patients (M:F ratio 29:30, median age 70 years [range 50-93 years]). Of 59 colorectal lesions > 40 mm, 25 were removed by ESTD and 34 by CESD. The en bloc resection rate was 100% in both groups and the complete resection rate was similar (ESTD 92% vs CESD 97.1%, p = 0.569), while the curative resection rate was higher in the CESD group, but not significantly (94.1% vs 76%, p = 0.061). Procedure speed was significantly faster with ESTD (22 vs 17 mm2/min, p = 0.045), and the overall incidence of adverse events was low (6.8%). Eight patients were referred to surgery due to non-curative resection. During follow-up, no recurrence was observed in either treatment group. CONCLUSION: ESTD achieves a very high en bloc resection rate and is faster than CESD.

The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast.

Background: Tumor-infiltrating lymphocytes (TILs) are a robust prognostic adjunct in invasive breast cancer, but their clinical role in ductal carcinoma in situ (DCIS) has not been ascertained. Patients and methods: We evaluated the prevalence and clinical relevance of TILs in a well annotated series of 1488 consecutive DCIS women with a median follow-up of 8.2 years. Detailed criteria for TILs evaluation were pre-defined involving the International Immuno-Oncology Biomarker Working Group. TILs percentage was considered both as a continuous and categorical variable. Levels of TILs were examined for their associations with ipsilateral breast event (IBE), whether in situ or invasive. Results: Of the 1488 patients with DCIS under study, 35.1% had <1%, 58.3% 1-49% and 6.5% ≥50% peri-ductal stromal lymphocytes. The interobserver agreement in TILs evaluation, measured by the intraclass correlation coefficient (ICC) was 0.96 (95% CI 0.95-0.97). At univariable analysis, clinical factors significantly associated with TILs (P ≤0.001) were intrinsic subtype, grade, necrosis, type of surgery. Her-2 positive DCIS were more frequently associated with TILs (24% of patients with TILs ≥50%), followed by the triple negative (11%), Luminal B/Her-2 positive (9%) and Luminal A/B subtypes (1%) (P < 0.0001). We did not find any association between TILs as a continuous variable and the risk of IBEs. Likewise, when patients were stratified by TILs percentage (<1%, between 1% and 49.9%, and ≥50%), no statistically significant association was observed (10-year cumulative incidence of IBEs: 19%, 17.3%, and 18.7% respectively, P = 0.767). Conclusion: TILs occur more frequently in the Her-2 positive DCIS. Although we did not find a significant association between TILs and the 10-year risk of IBE, our data suggest that immunotherapies might be considered in subsets of DCIS patients.

Tailoring treatment for ductal intraepithelial neoplasia of the breast according to Ki-67 and molecular phenotype.

BACKGROUND: The post-surgical management of ductal intraepithelial neoplasia (DIN) of the breast is still a dilemma. Ki-67 labelling index (LI) has been proposed as an independent predictive and prognostic factor in early breast cancer. METHODS: The prognostic and predictive roles of Ki-67 LI were evaluated with a multivariable Cox regression model in a cohort of 1171 consecutive patients operated for DIN in a single institution from 1997 to 2007. RESULTS: Radiotherapy (RT) was protective in subjects with DIN with Ki-67 LI ≥ 14%, whereas no evidence of benefit was seen for Ki-67 LI <14%, irrespective of nuclear grade and presence of necrosis. Notably, the higher the Ki-67 LI, the stronger the effect of RT (P-interaction <0.01). Hormonal therapy (HT) was effective in both Luminal A (adjusted hazard ratio (HR)=0.56 (95% CI, 0.33-0.97)) and Luminal B/Her2neg DIN (HR 0.51 (95% CI, 0.27-0.95)). CONCLUSION: Our data suggest that Ki-67 LI may be a useful prognostic and predictive adjunct in DIN patients. The Ki-67 LI of 14% could be a potential cutoff for better categorising this population of women at increased risk for breast cancer and in which adjuvant treatment (RT, HT) should be differently addressed, independent of histological grade and presence of necrosis.

Radiation hybrid QTL mapping of Tdes2 involved in the first meiotic division of wheat.

Since the dawn of wheat cytogenetics, chromosome 3B has been known to harbor a gene(s) that, when removed, causes chromosome desynapsis and gametic sterility. The lack of natural genetic diversity for this gene(s) has prevented any attempt to fine map and further characterize it. Here, gamma radiation treatment was used to create artificial diversity for this locus. A total of 696 radiation hybrid lines were genotyped with a custom mini array of 140 DArT markers, selected to evenly span the whole 3B chromosome. The resulting map spanned 2,852 centi Ray with a calculated resolution of 0.384 Mb. Phenotyping for the occurrence of meiotic desynapsis was conducted by measuring the level of gametic sterility as seeds produced per spikelet and pollen viability at booting. Composite interval mapping revealed a single QTL with LOD of 16.2 and r (2) of 25.6 % between markers wmc326 and wPt-8983 on the long arm of chromosome 3B. By independent analysis, the location of the QTL was confirmed to be within the deletion bin 3BL7-0.63-1.00 and to correspond to a single gene located ~1.4 Mb away from wPt-8983. The meiotic behavior of lines lacking this gene was characterized cytogenetically to reveal striking similarities with mutants for the dy locus, located on the syntenic chromosome 3 of maize. This represents the first example to date of employing radiation hybrids for QTL analysis. The success achieved by this approach provides an ideal starting point for the final cloning of this interesting gene involved in meiosis of cereals.

Objective assessment of mandibular motor control using a 'reach-and-hold' task.

Mandibular motor function is well known to be impaired in the presence of temporomandibular disorders. However, while a vast literature is available concerning accuracy of motor control in limbs, quantitative and objective assessment of mandibular motor control has been seldom performed, also because of the lack of adequate investigative tools. Aim of this work is to present a technique for reliable evaluation of the motor performance of the mandible based on a kinesiography-monitored reach-and-hold task. Nineteen healthy subjects were engaged in a task in which they had to drive a cursor on a screen by corresponding movements of the mandible in the frontal plane and reach 30 random targets sequentially displayed on the screen. The whole task was repeated three times per session in two different days. The individual performance was assessed by different indices evaluating precision and steadiness of target matching. The performance progressively improved in the three trials of the first session, further improved and stabilised in the second session, with an average positioning error of 0·59 ± 038 mm and was slightly correlated with the horizontal dimension of the mandible border movement (r = 0·55). Intraclass correlation coefficient ranged between 0·76 and 0·94 for the different indices indicating good repeatability. The kinesiographic technique allowed for objective and reliable assessment of the voluntary control of the mandible position. Its potential applications include support to the characterisation of temporomandibular disorders and to motor training and progress monitoring in rehabilitation treatments.

Observed and estimated prevalence of Covid-19 in Italy: How to estimate the total cases from medical swabs data.

During the Covid-19 pandemic in Italy, official data are collected with medical swabs following a pure convenience criterion which, at least in an early phase, has privileged the exam of patients showing evident symptoms. However, there are evidences of a very high proportion of asymptomatic patients. In this situation, in order to estimate the real number of infected (and to estimate the lethality rate), it should be necessary to run a properly designed sample survey through which it would be possible to calculate the probability of inclusion and hence draw sound probabilistic inference. Unfortunately, the survey run by the Italian Statistical Institute encountered many field difficulties. Some researchers proposed estimates of the total prevalence based on various approaches, including epidemiologic models, time series and the analysis of data collected in countries that faced the epidemic in earlier times. In this paper, we propose to estimate the prevalence of Covid-19 in Italy by reweighting the available official data published by the Istituto Superiore di Sanità so as to obtain a more representative sample of the Italian population. Reweighting is a procedure commonly used to artificially modify the sample composition so as to obtain a distribution which is more similar to the population. In this paper, we will use post-stratification of the official data, in order to derive the weights necessary for reweighting the sample results, using age and gender as post-stratification variables, thus obtaining more reliable estimation of prevalence and lethality. Specifically, for Italy, we obtain a prevalence of 9%. The proposed methodology represents a reasonable approximation while waiting for more reliable data obtained with a properly designed national sample survey and that it could be further improved if more data were made available.

Low-dose tamoxifen in the treatment of breast ductal intraepithelial neoplasia: results of a large observational study.

BACKGROUND: Tamoxifen's cost-benefit ratio for breast ductal intraepithelial neoplasia (DIN) is unclear. Since low-dose tamoxifen showed a favorable modulation of breast cancer biomarkers in phase II trials, a monoinstitutional cohort of women with DIN treated with low-dose tamoxifen or no systemic treatment was analyzed. PATIENTS AND METHODS: A total of 309 patients with DIN received low-dose tamoxifen as part of institutional guidelines and were compared with 371 patients with DIN who received no systemic treatment after surgery. RESULTS: Women with estrogen receptor (ER)/progesterone receptor (PgR) >50% DIN who were not treated had a higher incidence of breast events than women on tamoxifen [hazard ratio (HR) 1.76; 95% confidence interval (CI) 1.00-3.12] or women with ER/PgR <50% DIN (HR 1.72; 95% CI 1.14-2.58). Among untreated patients with ER >50% DIN, recurrence was higher in PgR > or =50% DIN than in PgR <50% DIN, whereas it was similar among low PgR (<50%) DIN against which tamoxifen had no effect. No difference in endometrial cancer incidence was noted. CONCLUSIONS: High ER and especially high PgR expression is a significant adverse prognostic indicator of DIN, and low-dose tamoxifen appears to be an active treatment. Women with low-expression ER or PgR DIN do not seem to benefit from tamoxifen. A definitive clinical trial is warranted.

Frequency and severity of dental caries in foster care children of Turin, Italy: a retrospective cohort study.

AIM: Aim of this retrospective cohort study was to assess the frequency and severity of dental caries (DC) among foster care children in the city of Turin, in North West Italy, and to compare these data with those of a general paediatric population. MATERIALS AND METHODS: From May 2016 to September 2018, 75 paediatric subjects between the age of 4 and 12, located in 11 residential child care communities were recruited. Instructions were provided concerning oral health, caries and correlation with dietary habits. Oral and dental examination were carried out to establish frequency and severity of caries (not-penetrating, nPC, corresponding to the International Caries Detection and Assessment System (ICDAS) codes: 1-4, vs. penetrating, PC, corresponding to ICDAS codes: 5-6). Decayed, missed, filled teeth (DMFT) index was used. Data for comparison were acquired from the WHO Collaboration Center For Epidemiology and Community Dentistry of Milan (WHO-CCOMS), belonging to a nationwide sample of 2,141 Italian children. RESULTS: Only 13 subjects (17%) were caries-free; 187 caries were identified: 133 were PC, whereas 54 were nPC. Overall, 76% of the caries were found in deciduous teeth. Mean DMFT was 3.43 (D = 2.97; M = 0.24; F = 0.22). When the study data were compared to those from WHO-CCOMS, a significantly higher DMFT (3.43 vs 0.96; p <0.00001) and D (2.97 vs 0.62; p <0.00001) was detected. CONCLUSION: A significant higher frequency of caries in foster care children in Turin, Italy compared to the general population was detected.

Development of glass-ceramic scaffolds for bone tissue engineering: characterisation, proliferation of human osteoblasts and nodule formation.

Glass-ceramic macroporous scaffolds for tissue engineering have been developed using a polyurethane sponge template and bioactive glass powders. The starting glass (CEL2) belongs to the system SiO(2)-P(2)O(5)-CaO-MgO-Na(2)O-K(2)O and has been synthesised by a conventional melting-quenching route. A slurry of CEL2 powder, polyvinyl alcohol and water has been prepared in order to coat, by impregnation, the polymeric template. An optimised thermal treatment was then use to remove the sponge and to sinter the glass powders, leading to a glass-ceramic replica of the template. Morphological observations, image analyses, mechanical tests and in vitro tests showed that the obtained devices are good candidates as scaffolds for bone-tissue engineering, in terms of pore-size distribution, pore interconnection, surface roughness, and both bioactivity and biocompatibility. In particular, a human osteoblast cell line (MG-63) seeded onto the scaffold after a standardised preconditioning route in simulated body fluid showed a high degree of cell proliferation and a good ability to produce calcium nodules. The obtained results were enhanced by the addition of bone morphogenetic proteins after cell seeding.

[Conservative approach for breast cancer. The experience of the European Institute of Oncology]. / L'approccio conservativo al carcinoma mammario.L'esperienza dell'Istituto Europeo di Oncologia.

Conservative surgery represents the standard care for patients with early breast cancer. The aim of this review was to discuss the extension of conservative surgery in controversial fields such as after primary chemotherapy for large tumours or the possibility to repeat conservative surgery for a local reappearance. The project of a conservative approach to breast cancers continues with sentinel node biopsy which is worldwide performed more and more frequently. In our institute sentinel node biopsy is the standard procedure in the axillary staging of breast cancer even in those clinical scenarios which were previously considered either controversial or a contraindication such as in multicentric breast cancer, during pregnancy, in intra-ductal neoplasias, after primary chemotherapy, and male breast cancer. This conservative approach is completed by the possibility to deliver a partial breast irradiation and to provide patients with more personalized adjuvant treatments tailored on the biological features of the tumour.

Internal adaptation of fixed prosthodontics at shoulder preparation level evaluated by horizontal sections.

AIM: The precision of fixed prosthodontic restorations is fundamental for clinical success: well-fitting crowns reduce the risk of recurrent caries and periodontal disease. The aim of this study is to evaluate the internal fit of fixed prosthodontics at the shoulder preparation level by examining horizontal sections. METHODS: Twenty-four extracted teeth were resin-embedded and prepared on the platform of an iso-parallelometer with a 90 degrees shoulder with a rounded internal angle. Auro Galva Crown (AGC) copings were cemented in place. The preparations were observed by 3 different assessors at 8 points, first externally and then internally at 2 levels by grinding the specimen perpendicular to the long axis at 0.5 mm and at 0.2 mm from the margin of the preparation. A correction factor was calculated to derive real values from measured values. The results were analyzed using a linear regression with robust standard errors, accounting for within-subject correlation introduced by multiple measurements. Shrout-Fleiss Intraclass Correlation Coefficient (ICC) for Inter-Rater Reliability were calculated at each stage. RESULTS: Internal measurements at 0.5 and 0.2 mm from the margin provided data similar to the external margin data. Average inter-assessor differences were in the range of 2 mm. ICC ranged from 0.93 for the 0.5 mm level to 0.97 for the external level. CONCLUSIONS: External measurements effectively predict the internal precision at the shoulder level. Horizontal perimarginal sections allow the fit to be studied through the evaluation of a great number of points. Traditional vertical sections for the evaluation of internal fit enable only a few points to be observed. This internal observation method may be suitable for testing new materials.

Spermatic and peripheral venous plasma concentrations of progesterone, 17 alpha-hydroxyprogesterone, and 20 alpha-dihydroprogesterone in prepubertal boys.

Testosterone, progesterone, 17 alpha-hydroxyprogesterone, and 20 alpha-dihydroprogesterone have been measured in the spermatic and peripheral venous blood of 17 prepubertal boys undergoing surgery for undescended testis or inguinal hernia repair. Mean (+/-SE) spermatic testosterone and progesterone (538 +/- 212 and 704 +/- 110 pg/ml, respectively) were significantly higher (P less than 0.005) than peripheral levels (91 +/- 11 and 419 +/- 71 pg/ml, respectively). No significant spermatic-peripheral gradient was found for 17 alpha-hydroxyprogesterone and 20 alpha-dihydroprogesterone. These in vivo studies demonstrate that the secretory pattern of the prepubertal testis is different from the adult testis.

Spermatic and peripheral plasma concentrations of testosterone and androstenedione in prepubertal boys.

Spermatic and peripheral plasma concentrations of testosterone (T) and androstenedione (A) have been measured in prepubertal boys affected by inguinal hernia (group I; n = 7) and unilateral undescended testis (group II; n = 18). Mean (+/- SE) spermatic T concentrations (47.7 +/- 14.8 ng/dl in group I; 36.3 +/- 3.4 ng/dl in group II) were significantly different from mean peripheral T concentrations (9.8 +/- 2.1 ng/dl in group I; 9.3 +/- 0.9 ng/dl in group II) in both groups (P less than 0.05 and P less than 0.0005, respectively). Mean spermatic A concentration (59.7 +/- 4.9 ng/dl) was significantly higher than mean peripheral A concentration (49.8 +/- 4.9 ng/dl) in group II (P less than 0.05) but not in group I. Mean spermatic and peripheral T and A values found in boys of group I were not significantly different from those found in group II. The mean spermatic/peripheral T ratio was higher (5.01 in group I; 4.42 in group II) than the corresponding mean spermatic/peripheral A ratio (1.27 in group I; 1.32 in group II) in both groups. Our data suggest that 1) although testicular T secretion is present in all prepubertal boys, A secretion is not constant and often negligible; 2) the contribution of testicular secretion to the circulating T is much more important than the contribution to the circulating A; 3) no significant differences were found between the testicular secretory pattern of prepubertal boys with inguinal hernia and unselected boys with unilateral undescended testis.

Prediction of myotonic dystrophy clinical severity based on the number of intragenic [CTG]n trinucleotide repeats.

We carried out a genotype-phenotype correlation study, based on clinical findings in 465 patients with myotonic dystrophy (DM), in order to assess [CTG] repeat number as a predictive test of disease severity. Our analysis showed that the DM subtypes defined by strict clinical criteria fall into three different classes with a log-normal distribution. This distribution is useful in predicting the probability of specific DM phenotypes based on triplet [CTG] number. This study demonstrates that measurement of triplet expansions in patients' lymphocyte DNA is highly valuable and accurate for prognostic assessment.

Clinical and surgical relevance of the progressive phases of intrathoracic migration of the gastroesophageal junction in gastroesophageal reflux disease.

OBJECTIVE: The pathophysiologic influence of progressive intrathoracic migration of the gastroesophageal junction axial to the esophagus on gastroesophageal reflux disease was investigated. METHODS: A radiologic-manometric study was performed on hiatal insufficiency, concentric hiatus hernia, and short esophagus, the three radiologic steps of intrathoracic gastroesophageal junction migration, and on healthy volunteers. The distances between inferior and superior margins of the lower esophageal sphincter and the diaphragm were measured. Endoscopic, manometric, and pH-metric evaluations were performed after barium swallow in 38 patients with severe gastroesophageal reflux disease and sliding hiatus hernia with intraabdominally reducible gastroesophageal junction, in 35 patients with hiatal insufficiency, in 40 with concentric hiatus hernia, and in 19 with short esophagus. RESULTS: The distance from the lower esophageal sphincter inferior margin to the diaphragm was different in healthy volunteers (-2.6 +/- 0.9 cm [standard deviation]) versus that in patients with hiatal insufficiency (-1.0 +/- 0.7 cm; p = 0.02), concentric hiatus hernia (-0.8 +/- 1.0 cm; p = 0.02), and short esophagus (4.0 +/- 2.5 cm; p = 0.0002), and in patients with short esophagus versus hiatal insufficiency (p = 0.0002) and concentric hiatus hernia (p = 0.0002). Lower esophageal sphincter tone was reduced between healthy volunteers (19 +/- 9.1 mm Hg [standard deviation]) and patients with sliding hiatus hernia (12 +/- 7.2 mm Hg;p = 0.02), hiatal insufficiency (10 +/- 5.9 mm Hg; p = 0.0001), concentric hiatus hernia (7 +/- 3.1 mm Hg; p = 0.00002), and short esophagus (7 +/- 3.7 mm Hg; p = 0.00003) and between concentric hiatus hernia versus sliding hiatus hernia (p = 0.007). Acid gastroesophageal reflux total time percent was increased between healthy volunteers (2.4% +/- 1.8% [standard deviation]) and patients with sliding hiatus hernia (12.8% +/- 7.8%;p = 0.02), hiatal insufficiency (17.2% +/- 15.8%; p = 0.0001), concentric hiatus hernia (24.0% +/- 19.6%;p = 0.00002), and short esophagus (26.1% +/- 19.6%;p = 0.00002) and between sliding hiatus hernia versus concentric hiatus hernia (p = 0.002) and short esophagus (p = 0.01). CONCLUSIONS: Permanent gastroesophageal junction orad migration axial to the esophagus has greater pathophysiologic relevance on gastroesophageal reflux disease than sliding hiatus hernia with an intraabdominally reducible gastroesophgeal junction. Hiatal insufficiency, concentric hiatus hernia, and short esophagus are markers of progressively increasing irreversible cardial incontinence and therefore indications for surgical therapy.

Pathophysiology and natural history of acquired short esophagus.

The choice of therapy--whether medical or surgical--for patients with gastroesophageal reflux (GER) is often a subject of debate. After a period in which surgery was almost the exclusive mode of treatment in patients with severe complications resulting from GER or in patients who did not respond to medical therapy, long-term follow-up showed that in 20 cases of GER in which only medical treatment was given, a progressive shortening of the esophagus--frequently in the absence of esophagitis--had developed. To investigate the pathophysiology of acquired short esophagus, we studied 34 patients--20 from the initial group and 14 who already had this condition. Clinical assessment consisted of interview, radiologic examination of the upper digestive tract, endoscopic and histologic examinations, and 24-hour home esophagogastric pH monitoring. We noted that acid GER causes shortening in the presence of severe mucosal lesions, while "nonacid" GER--a combination of gastric, pancreatic, and hepatic secretions--causes shortening of the esophagus even without evident mucosal lesions. Symptom evaluation, acid GER pH recording, and endoscopy are not sufficient for determination of the current choice of therapy. It is also important to quantify GER that results from the mixing of gastric and biliopancreatic secretions with use of the esophagogastric pH recording. This should reduce the possibility of silent shortening of the esophagus.

Morphological response to positive end expiratory pressure in acute respiratory failure. Computerized tomography study.

Ten patients with acute respiratory failure (ARF), (4 pneumonia, 4 sepsis, 2 polytrauma), underwent computerized tomography (CT) of the lungs, (apex, hilum, base), at 5, 10, 15 cm H2O positive end expiratory pressure (PEEP). The ARF lungs, on CT scan, appeared as a patchwork of normal and dense areas with generally well defined boundaries. Most of the densities were found in the dependent regions. The areas of density were correlated with PaO2 (r = 0.51). The PEEP increase resulted in a significant expansion of total cross-sectional lung surface area. The dense areas decreased significantly at the hilum and base when increasing PEEP while the changes at the apex were not significant. The changes of density with PEEP were highly correlated with the changes in oxygenation (r = 0.91). In the individual patient, however, the modifications of gas exchange can not be entirely predicted from morphological changes, possibly due to a diversion of pulmonary blood flow.

Onset timing of delayed complications and criteria of follow-up after operation for esophageal achalasia.

BACKGROUND: The purpose of this study was to define the length of follow-up necessary to obtain definitive results of the Heller myotomy for the therapy of esophageal achalasia and the modalities of long-term follow-up. Insufficient myotomy, periesophageal scarring, and gastroesophageal reflux esophagitis are the most common late complications of operation for achalasia. Columnar-lined esophagus with or without dysplasia and cancer can further complicate postoperative reflux esophagitis. Because progressive worsening of results with time has been reported, we assessed the timing of appearance of these complications. METHODS: Since 1973, 129 patients submitted to Heller myotomy were clinically and objectively followed up. Mean follow-up was 97.4 months (range, 12 to 268 months). Of 129 patients, 42 were followed up for less than 5 years (17 voluntary drop outs, 10 reoperations, 3 deaths, 12 in follow-up), 47 more than 5 years, 26 more than 10 years, 12 more than 15 years, and 2 more than 20 years. The timing of onset of symptoms and complications related to the myotomy were evaluated as was the development of dysplasia and cancer. RESULTS: In 11 patients, severe dysphagia due to insufficient myotomy reappeared a mean of 12.4 months after the operation (range, 3 to 30 months). In 7 patients with periesophageal scarring, dysphagia recurred a mean of 18.8 months (range, 6 to 28 months) after the operation. Postoperative reflux esophagitis appeared in 22 patients a mean of 76.5 months (range 21 to 168 months) after the operation. Columnar-lined esophagus was detected in 8 patients a mean of 143.1 months (range, 85 to 230 months) after the operation. Mild to moderate dysplasia was found in 5 of 8 patients with columnar-lined esophagus a mean of 191.6 months after the operation (range, 152 to 287 months), and intramucosal adenocarcinoma was found in 1 patient with columnar-lined esophagus after 8 years. CONCLUSIONS: Dysphagia secondary to insufficient myotomy and periesophageal scarring recurs early, not later than 3 years. Conversely, abnormal gastroesophageal reflux with related complications can appear more than 10 years postoperatively. Five years after the operation the follow-up should be primarily endoscopic and histologic. Results should withstand a follow-up of at least 10 years.

Cytokine production and bone remodeling in patients wearing overdentures on oral implants.

The stability of titanium dental implants is determined by osseointegration. Bone is a dynamic tissue continuously remodeled through resorption and formation, processes controlled by local cytokine production. This study investigated osseotropic cytokine expression in gingival mucosa, in the intraforamina and inferior first molar zones, during rehabilitation with implant-retained overdentures. Specimens were taken from six patients prior to placement of implants in the intraforamina bone; at connection of healing abutments; and 4, 8, and 12 months after prosthetic anchorage. Through semi-quantitative reverse-transcriptase polymerase chain-reaction, the following constitutively expressed cytokines were found at first surgical stage: interleukin-1, -6, and -8; small amounts of interleukin-11; stem cell factor; and transforming growth factor-beta1, -beta2, and -beta3. From the connection of healing abutments to 12 months after prosthetic anchorage, transforming growth factor-beta1, -beta2, and -beta3 were markedly higher than initial values. Expression of interleukin-6 and -8 decreased 8 months after prosthetic anchorage, while that of interleukin-1 increased at 12 months. In cultured gingival fibroblasts, modulation of cytokine secretion was also time-dependent. Cell culture supernatants influenced osteoclast-like multinucleated cell formation in long-term human marrow culture or osteoblast function, depending on the cytokine profile produced. These results are consistent with functional contributions of cytokines to osseointegration and minimization of posterior edentulous zone bone resorption.