[Multiparametric prostate MRI for follow-up monitoring after radiation therapy]. / Multiparametrische MRT der Prostata zum Therapiemonitoring nach Strahlentherapie.

CLINICAL/METHODICAL ISSUE: Radiation therapy is a therapeutic option with curative intent for patients with prostate cancer. Monitoring of prostate-specific antigen (PSA) values is the current standard of care in the follow-up. Imaging is recommended only for symptomatic patients and/or for further therapeutic options. STANDARD RADIOLOGICAL METHODS: For detection of local recurrence magnetic resonance imaging (MRI) of the prostate is acknowledged as the method of choice. PERFORMANCE: Good results for primary diagnosis were found especially in combination with functional techniques, whereas in recurrent prostate cancer only few studies with heterogeneous study design are available for prostate MRI. Furthermore, changes in different MRI modalities due to radiation therapy have been insufficiently investigated to date. PRACTICAL RECOMMENDATIONS: As the initial results were promising prostate MRI and available therapeutic options for detection of local recurrence should be considered in patients with increased PSA.

Medical analysis of the contribution of sialendoscopy in managing non-tumoral main salivary gland pathology in Reunion Island: Observational study following STROBE guidelines.

GOALS: To perform a medical analysis of the contribution of sialendoscopy in the treatment of non-tumoral pathologies of the main salivary glands, in Reunion Island, a French overseas territory. MATERIAL AND METHOD: A multicenter retrospective observational study was conducted for an 8-year period, before and after introduction of sialendoscopy (2011-2014 and 2015-2018), following STROBE guidelines. OBJECTIVES: To compare populations treated before (period A) and after (period B) the introduction of sialendoscopy in terms of clinical characteristics, and analyze the characteristics of patients treated by sialendoscopy. RESULTS: Two hundred and sixty-five patients were included: 74 in 2011-2014 and 191 in 2015-2018; 139 had sialendoscopy. Populations A and B were comparable except for the proportion of parotids treated (9% vs. 31%, respectively; P<0.0001), and smaller stones (11mm vs. 7.4mm, respectively; P=0.003). One hundred and ten pure sialendoscopies and 29 combined routes (20.8%) were performed: 63% submandibular and 37% parotid. Median age was 46 years. The M/F sex ratio was 0.96. Thirty-seven patients presented stenosis. There were 10 cases of papillary catheterization failure (7.1%), and 16 false routes or creation of false channels (11.5%), including 9 during the learning period. The rate of crossover to gland resection decreased: 10.45% for 2015-2016 and 5.56% for 2017-2018. CONCLUSION: Although follow-up ranged between 12 and 55months (median, 30months), sialendoscopy appeared to be a useful and reliable technique, with a role in therapeutic strategy for the management of non-tumoral salivary pathologies in Reunion Island.

Economic analysis of the contribution of sialendoscopy in managing non-tumoral principal salivary gland pathology in the Réunion Island: Economic evaluation following the CHEERS methodology.

GOALS: Cost analysis of the contribution of sialendoscopy in the treatment of non-tumoral pathologies of the main salivary glands, in Réunion Island, a French overseas territory. OBJECTIVES: Calculation and comparison of median pricing (i.e., median payment to the healthcare establishment) per patient before and after the introduction of sialendoscopy, in the only regional establishment practicing sialendoscopy and in the whole of Réunion Island. Material and method A multicenter retrospective cost study was conducted over an 8-year period, before and after the introduction of sialendoscopy (period A: 2011-2014 and period B: 2015-2018), according to the CHEERS guidelines for economic studies, and included inpatients with non-tumoral pathology of the main salivary glands, whether treated by sialendoscopy or not. RESULTS: Two hundred sixty-five patients were included, 139 of whom were treated by sialendoscopy: 74 in 2011-2014 and 191 in 2015-2018. Between the two periods, median pricing in the only center practicing sialendoscopy did not vary significantly: €3468 vs. €3368 (i.e., +2.9% (P=0.1)). In the Island as a whole, pricing increased significantly: €598 vs. €2332, (i.e., +390% (P<0.0001)). CONCLUSION: Sialendoscopy is cost-effective in France in the public healthcare sector if outpatient management is optimal, but significantly increases the public health budget. It makes it possible to recruit and manage previously untreated patients (small stones, salivary strictures, etc.).

Risk factors associated with severe perineal tears: A five-year study.

OBJECTIVE: Our aim was to describe risk factors associated with 34DPT in operative and non-operative vaginal deliveries, over a five-year period. STUDY DESIGN: This was a retrospective cohort study including 39,227 vaginal deliveries from 2013 to 2017 in a single French University Hospital. Annual characteristics of the analyzed population were recorded. Univariate logistic regression was used to evaluate the association between these characteristics and 34DPT. Multivariate analysis was used to identify combinations of risk factors associated with instrumental delivery. RESULTS: The rate of perineal tears was constantly rising but rate of 34DPT was stable, ranging between 0.8 and 1.4% over the study period. Cesarean section rate was stable between 18.8% and 19.6%. Rate of diabetes, preeclampsia and obesity (BMI < 40) was increasing and episiotomy rate decreasing (from 19.8% to 11.8%). Operative deliveries rate remained stable between 11 and 12.8%. Multivariate regression showed that gestational age over 39 weeks (aOR 1.18, 95% CI [1.02; 1.35]), birth weight over 3500 g (aOR 1.62, 95% CI [1.05; 2.49]) were associated with 34DPT in patients without operative vaginal deliveries but not episiotomy. Gestational age (aOR 1.71, 95% CI [1.18; 2.47]), episiotomy (aOR 0.55, 95% CI [0.38; 0.79]) and diabetes (aOR 1.73, 95% CI [1.15; 2.61]) were associated with 34DPT among patients with operative vaginal deliveries. CONCLUSION: In a tertiary medical center model with low cesarean section rate, factors associated with 34DPT were different among patients with or without operative vaginal delivery. The question of the protective effect of mediolateral episiotomy against 34DPT in case of operative delivery deserves further investigations.

[30 year-old patient with multiple pelvic lesions and fecal incontinence]. / Multiple Raumforderungen bei einem 30-Jährigen mit Stuhlinkontinenz.

In a 30 year-old patient with subacute loss of bowel control and perianal anesthesia radiologic examination showed multiple bone lesions. The results of a bone marrow aspiration showed acute myeloid leukemia M2 with translocation t(8,21) associated with granulocytic sarcoma. The patient was treated with high dose chemotherapy and had a complete remission after autologous stem cell transplantation.

Permselectivity of the glomerular capillary wall. Facilitated filtration of circulating polycations.

To examine the electrostatic effects of fixed negative charges on the glomerular capillary wall, polydisperse [(3)H]DEAE dextran, a polycationic form of dextran, was infused into 10 Munich-Wistar rats. Fractional clearances of DEAE ranging in radius from 18 to 44A were determined in these rats, together with direct measurements of the forces and flows governing the glomerular filtration rate of water. These results were compared with data previously obtained in Munich-Wistar rats receiving tritiated neutral dextran (D) and polyanionic dextran sulfate (DS). Measured values for the determinants of the glomerular filtration rate of water in rats given DEAE were found to be essentially identical to those in rats given either D or DS. In addition, DEAE was shown to be neither secreted nor reabsorbed. Fractional clearances of polycationic DEAE were increased relative to both D and DS, the increase relative to D being significant for effective molecular radii ranging from 24 to 44A. Fractional DEAE clearances were also measured in a separate group of six Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). Fractional DEAE clearances in NSN rats were reduced significantly, relative to values measured in normal rats, for effective DEAE radii ranging from 18 to 42A. Moreover, in NSN rats, fixed negative charges on the glomerular capillary wall were greatly reduced, relative to non-NSN rats, as evidenced by a reduction in intensity of colloidal iron staining. Thus, in NSN rats, DEAE clearances were essentially indistinguishable from values obtained with both neutral D and polyanionic DS.

Mechanisms of the puromycin-induced defects in the transglomerular passage of water and macromolecules.

To investigate the mechanism(s) of increased filtration of serum proteins after glomerular injury, polydisperse samples of uncharged [(3)H]dextran (D) or anionic [(3)H]dextran sulfate (DS) were infused into 14 control and 16 puromycin aminonucleoside- (PAN) treated Munich-Wistar rats. Fractional clearances of D or DS ranging in radius from 18 to 42A were determined in these rats, together with direct measurements of the forces governing the glomerular filtration rate of water. Whole kidney and single nephron glomerular filtration rates were approximately 40% lower in PAN-treated rats, relative to controls, due mainly to a marked reduction in the glomerular capillary ultrafiltration coefficient and, to a lesser extent, to a small reduction in glomerular plasma flow rate as well. In PAN-treated rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and both D and DS were shown to be neither secreted nor reabsorbed. Fractional clearances of uncharged D were reduced after PAN administration, falling significantly for effective D radii from 22 to 38A. Utilizing a theory based on macromolecular transport through pores, these results indicate that in PAN-treated rats, effective pore radius is the same as in controls, approximately 44A. In PAN nephrosis, however, the ratio of total pore surface area/pore length, a measure of pore density, is reduced to approximately one-third that of control, due very likely to a reduction in filtration surface area. In contrast to the results with uncharged D, fractional clearances of DS were found to increase after PAN administration for all DS radii studied. These results with D and DS suggest that proteinuria in PAN nephrosis is due, not to an increase in effective pore radius or number of pores, but rather to a diminution of the electrostatic barrier function of the glomerular capillary wall, thereby allowing increased passage of polyanions such as DS and albumin.

Influence of molecular configuration on the passage of macromolecules across the glomerular capillary wall.

The influence of molecular configuration on the filtration of macromolecules across glomerular capillary walls was examined by comparing fractional clearances of two uncharged polysaccharides of distinctly different molecular configuration in the Munich-Wistar rat. The macromolecules employed were dextran, a slightly branched polymer of glucopyranose, and ficoll, a highly cross-linked copolymer of sucrose and epichlorohydrin. Differences in effective shape between these two polymers were determined from measurements of several physical properties of aqueous solutions containing either dextran or ficoll. It was found that dextran is best represented as a prolate ellipsoid with axial ratios of 4, 9, and 16 for molecules with Stokes-Einstein radii of 22, 32, and 40 A, respectively. On the other hand, ficoll is more closely approximated as spherical since the axial ratio was found to be between 1 and 2 for all molecular sizes. Fractional clearances of dextran and ficoll ranging in effective radius from 18 to 44 A were determined in each of seven Munich-Wistar rats. Fractional clearances of dextran were found to be greater than those of ficoll, the difference being significant for molecular radii ranging from 24 to 44 A. In addition, as shown previously for dextran, ficoll was found to be neither secreted nor reabsorbed by the renal tubules. These results, therefore, suggest that in addition to molecular size and charge, molecular configuration is also a determinant of the filtration of macromolecules across the glomerular capillary wall.

Does Cytokeratin7/20 immunoreactivity help to distinguish Barrett's esophagus from gastric intestinal metaplasia? Results of a prospective study of 75 patients.

Barrett's esophagus is a recognized risk factor for the development of esophageal dysplasia and carcinoma. Unfortunately, gastric incomplete intestinal metaplasia arising in Short Segment Barrett's esophagus can be indistinguishable histologically on hematoxylin/eosin stains. Distinct patterns of CK 7 and CK 20 immunohistochemical expression have been demonstrated to be both highly sensitive and specific for Barrett's esophagus, but have not been found in gastric metaplasia. The aim of our study was to test whether immunostaining with CK 7/20 helps to distinguish between Barrett's epithelium and gastric incomplete metaplasia. Cases of long segment Barrett's esophagus, short segment Barrett's esophagus, and cases with a normal gastroesophageal junction, as well as specimens with gastric antral intestninal metaplasia, were examined: three patterns were defined. Barrett's pattern (superficial CK 20 staining; superficial and crypt CK 7 staining); gastric pattern (superficial and crypt staining of both markers); other patterns (different from Barrett and gastric types). Seventy-five patients were enrolled in this study, 26 with long segment Barrett's esophagus, 21 with short segment esophagus, 13 with intestinal metaplasia of the cardia, and 18 with antral intestinal metaplasia. The Barrett pattern showed a high specificity of 97%, but a sensitivity of only 30% in patients with short segment Barrett esophagus. Our results do not confirm the hypothesis that CK 7/20 immunostaining can be used for a reliable differentiation between incomplete intestinal metaplasia and Barrett's epithelium.

Transmural [125I]albumin concentration in the rabbit aorta during acute hypoxia.

We have quantified the concentration profile of 125I-labeled rabbit albumin in the avascular intima and media of the rabbit descending thoracic aorta following intravenous injection under control and acute hypoxic conditions in vivo. Our purpose was to determine if alterations occurred in the transmural concentration profiles which could be attributed to hypoxia-induced changes in the permeability of the intimal endothelium to plasma-borne macromolecules. The profiles were obtained with frozen serial sections of the aorta from experiments of 30 min duration. Acute hypoxia was induced by addition of nitrogen to the breathing mixture. The hypoxia resulted in arterial pO2 values of 23--32 mm Hg while the arterial pO2 in the control animals ranged from 80 to 88 mm Hg. All animals were under sodium pentobarbital anesthesia. The results revealed no detectable changes in the concentration profile in the inner media accompanying hypoxia. However, increases in the label concentration in the outer media of the hypoxic animals suggested either dilation or increased permeability of the adventitial blood vessels.

Relationship of DNA ploidy to hormone receptor status and proliferation in invasive breast carcinoma.

PURPOSE: In 247 primary invasive breast carcinomas, DNA ploidy was related to hormone receptor status, proliferation, and clinical/histopathologic factors. METHODS: DNA ploidy analysis was performed by image analysis using imprints. Estrogen (ER) and progesterone (PR) receptor status was determined immunohistochemically. The proliferative activity of the tumours was assessed by Ki-67 antigen labelling. Total observation time was 3.5 years. RESULTS: DNA ploidy analysis revealed a high fraction of tumours with non-peridiploid patterns (78%). Significant correlations between DNA ploidy and ER/PR receptor status (P < 0.01) were found with increased frequencies of peridiploid DNA results in receptor positive tumours. A significant relationship became manifest between DNA ploidy and Ki-67 index showing high frequencies of non-peridiploid DNA patterns in tumours with Ki-67 index > 20% (P < 0.01). There was a strong correlation (P < 0.001) between DNA ploidy and histopathologic grading, while tumour size and lymph node status were not correlated to DNA ploidy. CONCLUSIONS: The results of our study on invasive breast carcinoma demonstrate that DNA ploidy measured by image analysis is predominantly associated with markers of cell differentiation. Preliminary outcome data reveal a risk-indicating potential of DNA ploidy primarily in cases with favourable results for other prognostic factors.

Recurrent cervical pregnancy after assisted reproduction by intrafallopian transfer.

BACKGROUND: Cervical pregnancy is an uncommon, yet potentially catastrophic form of ectopic pregnancy. Early diagnosis and intervention are important in avoiding short-term and long-term morbidity. Although transcervical embryo transfer is thought to increase the incidence of this phenomenon in patients undergoing in vitro fertilization, its occurrence after intrafallopian transfer is rarely seen. CASE: A 43-year-old nulliparous white female with a history of unexplained infertility experienced recurrent cervical pregnancy after two consecutive gamete/zygote intrafallopian transfer cycles. Abnormally rising beta-hCG levels combined with transvaginal sonography helped establish the diagnosis in each case. Intramuscular (IM) methotrexate combined with intra-amniotic potassium chloride successfully treated this condition initially, and IM methotrexate alone was sufficient for successful treatment in the second case. CONCLUSION: Cervical pregnancy may occur with assisted reproductive techniques involving intrafallopian transfer. Early diagnosis may be important for successful treatment of cervical pregnancy with conservative measures. Even in the case of recurrence, prompt intervention may allow for preservation of a patient's future fertility potential.

The utility of a home urinary LH immunoassay in timing the postcoital test.

OBJECTIVE: To evaluate whether a urinary LH immunoassay improves timing of the postcoital test compared to traditional timing methods in normally ovulating women. METHODS: Subjects included 37 infertile couples evaluated in a tertiary care setting. A randomized, prospective trial was performed of two methods of postcoital test timing: urinary LH assay or the traditional timing by cycle-averaging and/or review of basal body temperature graphs. RESULTS: Similar serum estradiol, progesterone, LH, number of motile sperm per high-power field, cervical mucus scores, and postcoital test scores were identified in both groups. CONCLUSION: Urinary LH immunoassays do not appear to improve timing of the postcoital test as compared with traditional timing methods.

Serum progesterone as a predictor of methotrexate success in the treatment of ectopic pregnancy.

OBJECTIVE: To determine the prognostic value of a single serum progesterone measurement for resolution of ectopic pregnancy following methotrexate therapy. METHODS: All patients attending our infertility clinic had quantitative beta-hCG and serum progesterone measured prospectively within the first week of missed menses. Ectopic pregnancy was diagnosed nonsurgically by poorly rising beta-hCG levels and lack of evidence of intrauterine gestation by transvaginal sonography. Once diagnosed, candidates received a single intramuscular injection of methotrexate, 50 mg/m2. Treatment outcome was categorized as either resolved or requiring surgery, and interpreted with respect to serum progesterone measured within 24 hours of methotrexate administration. RESULTS: Twenty-one patients were treated for ectopic pregnancy. Eleven had serum progesterone levels greater than 10 ng/mL and ten patients had levels of 10 ng/mL or less. The two groups did not differ significantly with respect to age, weight, hCG at the time of methotrexate administration, or amount of methotrexate administered. Of the 11 patients with serum progesterone levels above 10 ng/mL, only five had pregnancies that resolved following methotrexate. All ten patients with levels less than 10 ng/mL had resolution. This difference is significant (P = .009, 95% confidence interval 0.26-0.84). There was no improvement in the prediction of outcome when either the absolute or daily percentage increase of hCG was determined before methotrexate administration. CONCLUSION: A single serum progesterone measurement above or below 10 ng/mL is useful for predicting resolution of tubal pregnancy with methotrexate treatment.

Risk factors for spontaneous abortion in menotropin-treated women.

Women who conceive with human gonadotropins have a high rate of spontaneous abortions. The causes for this poor outcome are unknown. In a retrospective analysis, the authors analyzed potential factors in 45 menotropin-treated patients with spontaneous first-trimester miscarriages. Data were compared with 119 menotropin-treated patients who conceived and delivered viable infants. Patient factors that were analyzed included the following: age, history of past miscarriages, duration of infertility, diagnostic category, weight, body surface area, duration and weight-corrected dose of menotropin administration, maximum estradiol level, estradiol pattern, human chorionic gonadotropin (hCG) dose, presence or absence of hCG support in the luteal phase, results of postcoital testing, methods of insemination, and results of husband's semen analysis. There was a significant difference between the miscarriage group and the control group in regard to age and weight distribution. All other characteristics were not significantly different. Patients over 81.8 kg as well as patients aged 35 years and older were both significantly (P less than 0.01) at increased risk to have a spontaneous first-trimester miscarriage. The data suggest that obesity and advanced age contribute to the high miscarriage rate in menotropin-treated patients. It appears reasonable to suggest that women weighing more than 81.8 kg should make every effort to lose weight before beginning menotropin therapy.

A prospective, randomized study of the chorionic gonadotropin-time relationship in early gestation: clinical implications.

OBJECTIVE: To investigate the hCG-time relationship in early pregnancy. DESIGN: Prospective, randomized study. SETTING: Pregnant human volunteers in a university-based clinical research environment. PATIENTS: Normal pregnant women with viable singleton pregnancies, conceived spontaneously or after ovulation induction. INTERVENTIONS: Vaginal ultrasound was performed, and blood samples were obtained for hormone parameters between 20 and 30 days after conception. The timing of the tests was determined by random assignment using sealed envelopes. MAIN OUTCOME MEASURE: Serum hCG. RESULTS: The log hCG-time relationship was linear, both during the first 20 days and between 20 and 30 days after conception. The inclusion of a quadratic term in either regression was not statistically significant. The slopes of the two regression lines were also not statistically different. CONCLUSION: For practical purposes, the hCG-time relationship in early pregnancy can be treated as log-linear, but short sampling intervals should be used if doubling times are to be calculated from paired samples.

Multiple gestation is associated with the use of high sperm numbers in the intrauterine insemination specimen in women undergoing gonadotropin stimulation.

Over a 27-month period, the authors observed 70 pregnancies in 66 women following intrauterine insemination (IUI) in conjunction with human menopausal gonadotropins/human chorionic gonadotropin (hMG/hCG) stimulation. Excluding ectopic pregnancies (n = 3) and spontaneous miscarriages (n = 15) during the first 10 weeks of gestation, 14 of the 52 pregnancies (27%) included multiple fetuses: nine twins, four triplets, and one quadruplet. Analysis of patient characteristics and clinical management, as well as semen characteristics of the conception cycle, revealed a significant correlation between gestation type (multiple versus singleton) and the total number of motile sperm in the IUI inseminate (P less than 0.01, Fisher's exact test). General linear models procedures did not identify additional significant relationships between various combinations of parameters examined and the gestation type. The authors conclude that IUI with high numbers of motile sperm constitutes a risk factor in the genesis of multiple gestation. The risk of multiple gestation rises significantly when the inseminate contains more than 20 million motile sperm.

The discriminatory human chorionic gonadotropin zone for endovaginal sonography: a prospective, randomized study.

OBJECTIVE: To determine the probability of detecting the gestational sac of a normal intrauterine pregnancy by vaginal ultrasound at different gestational ages and serum hCG concentrations. DESIGN: Prospective, randomized study. SETTING: Pregnant human volunteers in a university-based clinical research environment. PATIENTS: Women with viable pregnancies who conceived spontaneously or after ovulation induction. INTERVENTIONS: Vaginal ultrasound and serum hCG determinations were performed between 20 and 30 days after conception. The timing of the tests was determined randomly. MAIN OUTCOME MEASURE: Detection of gestational sac. RESULTS: The probability of detecting a gestational sac increased significantly with both gestational age and serum hCG concentration, but the regression on gestational age fitted the data much better than the regression on loge (hCG). The probability of detecting a sac was similar in multiple and singleton pregnancies of the same gestational age but, for a given hCG concentration, the probability of detecting a sac was lower for multiple than for singleton pregnancies because multiple gestations were associated with higher serum hCG concentrations than singleton pregnancies of the same gestational age. CONCLUSION: If it is known, gestational age rather than the serum hCG concentration should be used to determine whether the gestational sac of an intrauterine pregnancy should be detectable by vaginal ultrasound. Failure to image a gestational sac > or = 24 days after conception is presumptive evidence of an ectopic pregnancy. Reliance on serum hCG rather than gestational age may lead to an erroneous diagnosis of ectopic pregnancy in women with multiple pregnancies.

The difference in miscarriage rates between menotropin-induced and natural cycle pregnancies is not surveillance related.

OBJECTIVE: To assess the reportedly higher miscarriage rate during menotropin-induced cycle pregnancies as compared with natural cycle. DESIGN: Prospective cohort groups were selected, and pregnancies were identified 16 to 18 days after insemination and followed through to outcome. PATIENTS: Three hundred twelve patients were studied: 251 women receiving human menopausal gonadotropin and 61 requiring donor insemination without medication. RESULTS: A significant difference between the spontaneous abortion rate of gonadotropin-treated women (28.5%) and women conceiving during natural cycles (11.7%) was demonstrated. CONCLUSION: The opinion that higher miscarriage rates in menotropin-treated women are related to a surveillance bias compared with natural cycle conceptions should be reconsidered.

Active ovulation management increases the monthly probability of pregnancy occurrence in ovulatory women who receive intrauterine insemination.

The authors examined the hypothesis that active ovulation management would increase the monthly probability of pregnancy occurrence (MPO) in ovulatory women who require intrauterine insemination (IUI). All patients were initially treated during spontaneous ovulatory cycles with IUI performed after the detection of an endogenous lutenizing hormone (LH) surge (phase 1). For phase 2, those patients who had not conceived were offered treatment with fertility medication and IUIs were scheduled accordingly. Four of 76 (5.3%) patients conceived during 180 treatment cycles in phase 1; 9 of 44 (20.5%) patients conceived during 105 treatment cycles in phase 2. The average MPO was 0.022 in phase 1, and 0.085 in phase 2: the difference is significant (P less than 0.02). The authors conclude that fertility medication improves MPO in ovulatory women who undergo IUI for certain infertility situations.