Endovascular stenting in the management of malignant superior vena cava obstruction: comparing safety, effectiveness, and outcomes between primary stenting and salvage stenting.

OBJECTIVE: To compare the safety, effectiveness, and outcomes of primary stenting and salvage stenting for malignant superior vena cava obstruction. DESIGN: Case series with internal comparison. SETTING: Regional hospital, Hong Kong. PATIENTS: A total of 56 patients with malignant superior vena cava obstruction underwent 59 stentings from 1 May 1999 to 31 January 2014. Patients' characteristics, procedural details, and outcomes were retrospectively reviewed. Of the 56 patients, 33 had primary stenting before conventional therapy and 23 had salvage stenting after failure of conventional therapy. Statistical analyses were made by Fisher's exact test and Mann-Whitney U test. RESULTS: Primary lung carcinoma was the most common cause of malignant superior vena cava obstruction (primary stenting, 22 patients; salvage stenting, 16 patients; P=0.768), followed by metastatic lymphadenopathy. Most patients had superior vena cava obstruction only (primary stenting, 16 patients; salvage stenting, 15 patients; P=0.633), followed by additional right brachiocephalic vein involvement. Wallstents (Boston Scientific, Natick [MA], US) were used in all patients. Technical success was achieved in all but two patients, one in each group (P=1.000). Only one stent placement was required in most patients (primary stenting, 28 patients; salvage stenting, 20 patients; P=0.726). Procedure time was comparable in both groups (mean time: primary stenting, 89 minutes; salvage stenting, 84 minutes; P=0.526). Symptomatic relief was achieved in most patients (primary stenting, 32 patients; salvage stenting, 23 patients; P=0.639). In-stent restenosis and bleeding were the commonest complications (primary stenting, 6 and 1 patients, respectively; salvage stenting, 2 and 2 patients, respectively). Nine patients required further treatment for symptom recurrence (primary stenting, 6 patients; salvage stenting, 3 patients; P=0.725). CONCLUSION: Endovascular stenting is safe and effective for relieving malignant superior vena cava obstruction. No statistically significant differences in number of stents, success rates, procedure times, symptom relief rates, complication rates, and re-procedure rates were found between primary stenting and salvage stenting.

Scrotal wall metastasis as the first manifestation of primary gastric adenocarcinoma.

Metastases to the scrotal wall are very rare, and being the initial manifestation of occult primary tumours is even rarer. We report on a patient presenting with painless scrotal swelling, attributed to a solid extra-testicular mass found on ultrasonography. Subsequent investigations and surgical exploration revealed it to be a scrotal wall metastasis from an occult gastric primary. To our knowledge, this is the first report of a scrotal wall metastasis from gastric adenocarcinoma. The ensuing discussion and literature review highlight the diagnostic challenges posed by an extra-testicular scrotal metastasis from an occult primary tumour.

Coincident increases in oxytocin receptor expression and EMG responsiveness to oxytocin in the ovine cervix at oestrus.

This study has localised oxytocin receptor (OTR) mRNA expression within the cervix of non-pregnant ewes and related this to changes in the sensitivity of the cervical musculature to administered oxytocin (OT) during the oestrous cycle by recording electromyographic (EMG) activity. Cervices were collected from 34 ewes at specified time points throughout the cycle. OTR mRNA expression was localised by in situ hybridisation and results were expressed as optical density measurements from autoradiographs in each of four different cervical regions. EMG recordings were made for up to 8 h per day from four non-pregnant ewes undergoing seasonal oestrous cycles between Days -3 and +3 relative to oestrus (Day 0). The highest concentrations of OTR mRNA were detectable within the luminal epithelium (LE) of the cervix, with values increasing from Day 15 of the cycle, peaking during the follicular phase (P<0.001, compared to the mid-luteal phase) and returning to basal by Day 2. There was a small but significant increase in OTR mRNA hybridisation (above basal/luteal phase values) within the stromal cells (STR) adjacent to the lumen (P<0.05) during the same time period, but no differences from basal values were detectable in the dense collagenous annular ring or in tissue superficial to this. Analysis of pooled EMG activity recorded daily from the cervix indicated that endogenous contractile activity was higher on Day 0 than on the Days +1 (P<0.05), -2, +2 and +3 (P<0.001). The response to bolus intravenous (i.v.) injections of 25 mU OT (25 mU) varied with day of the cycle. This dose produced a measurable and significant response on Days 0 (P<0.001) and +1 (P<0.001), but not on any of the other days, indicating that the sensitivity of the cervical musculature to OT peaked on these days. These data show that the cervix is highly responsive to OT at oestrus. This coincides with an increase in OTR mRNA expression in the luminal epithelial cells, suggesting the likely production of an intermediary messenger between the epithelial and smooth muscle cells.

The effects of lipopolysaccharide and interleukins-1alpha, -2 and -6 on oxytocin receptor expression and prostaglandin production in bovine endometrium.

Up-regulation of endometrial oxytocin receptor (OTR) expression followed by an increase in pulsatile endometrial prostaglandin (PG) F(2alpha) secretion causes luteolysis in cattle. Inhibition of luteolysis is essential for the maternal recognition of pregnancy but also occurs in association with endometritis. The factors regulating OTR expression at this time are unclear. The OTR gene promoter region contains binding elements for acute phase proteins but their function has not been established. This study investigated the effects of various cytokines on OTR expression and on PGF(2alpha) and PGE(2) production in explant cultures of bovine endometrium. Endometrium was collected in the late luteal phase (mean day of cycle 15.4+/-0.50) or early luteolysis (mean day of cycle 16.4+/-0.24) as determined by the initial concentration of endometrial OTR. Explants were treated for 48 h with: (i) lipopolysaccharide (LPS) and/or dexamethasone (DEX), (ii) ovine interferon-tau (oIFN-tau), or (iii) human recombinant interleukin (IL)-1alpha, -2 or -6. OTR mRNA was then measured in the explants by in situ hybridisation and the medium was collected for measurement of PGF(2alpha) and PGE(2) by RIA. LPS treatment stimulated production of PGF(2alpha), whereas DEX either alone or in combination with LPS was inhibitory to both PGF(2alpha) and PGE(2). Neither of these treatments altered OTR mRNA expression. oIFN-tau reduced OTR mRNA expression but stimulated production of both PGF(2alpha) and PGE(2). In endometrial samples collected in the late luteal phase, IL-1alpha, -2 and -6 all inhibited OTR mRNA expression, but IL-1alpha and -2 both stimulated PGF(2alpha) production. In contrast, when endometrium was collected in early luteolysis, none of the interleukins altered OTR expression or caused a significant stimulation of PGF(2alpha) production but IL-2 increased PGE(2). Neither IL-1alpha nor -2 altered OTR promoter activity in Chinese hamster ovary cells transfected with a bovine OTR promoter/chloramphenicol acetyl transferase reporter gene construct. In conclusion, the action of interleukins on both OTR mRNA expression and endometrial prostaglandin production alters around luteolysis. Pro-inflammatory interleukins suppress OTR expression in the late luteal phase, while LPS stimulates PGF(2alpha) without altering OTR mRNA expression. IL-I and -2 and LPS are therefore unlikely to initiate luteolysis but may cause raised production of PGF(2alpha) during uterine infection.

Uterine lymphocyte distribution and interleukin expression during early pregnancy in cows.

Both the production of cytokines and the distribution of immune cells within the uterus change during early pregnancy. Evidence obtained mainly from mice indicates that these changes are important for implantation and in preventing a maternal immune response to the conceptus. The ruminant embryo also produces interferon tau at this time, the signal for the maternal recognition of pregnancy. The relationship between these events in cows was studied using uteri from three groups of animals on day 16 after observed oestrus: (i) cyclic controls, (ii) pregnant and (iii) inseminated but with no embryo present. Embryo size and the antiviral activity in uterine flushings (indicative of the interferon tau concentration) were measured. Sections of intact uterus were frozen for the localization and quantitation of CD4(+) (T lymphocytes), CD14(+) (macrophages) and CD21(+) (B lymphocytes) uterine cells by immunohistochemistry. The expression of interleukin (IL)-1alpha, IL-2, IL-6 and IL-10 mRNAs in uterine extracts was measured by RT-PCR. Neither embryo size, interferon tau concentration nor pregnancy status influenced the distribution of CD4(+), CD14(+) or CD21(+) cells in the day 16 uterus. Endometrial IL-1alpha mRNA was detected in most cows across the groups, whereas IL-2 mRNA was only present in the non-pregnant uterus. IL-6 and IL-10 mRNAs were not detectable in any uteri. In conclusion, IL-2 mRNA expression is detectable in the non-pregnant but not the pregnant uterus on day 16 and interferon t is unlikely to play a role in the redistribution of immune cells in the uterus during early bovine pregnancy.

Oestradiol regulation of oxytocin receptor expression in cyclic bovine endometrium.

Oestradiol treatment can increase uterine oxytocin receptor expression in vivo. The actions of oestrogen are usually mediated via its receptor, but it also has direct non-genomic effects in some cells. This study investigated the effect of oestradiol and the role of the oestradiol receptor in regulating endometrial oxytocin receptor expression in the bovine uterus. Explant cultures (in triplicate) from late luteal phase non-pregnant endometrium received the following treatments: control (serum-free medium), oestradiol (0. 1 and 0.01 micromol l(-1)), oestradiol (0.1 micromol l(-1)) with the oestradiol receptor antagonist ICI 182780 (0.5 micromol l(-1)), and ICI 182780 (0.5 micromol l(-1)) alone. Explants were collected 12, 24 and 48 h after the start of culture. Oxytocin receptor mRNA expression in the explants was measured by in situ hybridization and oxytocin protein concentrations were measured by autoradiography with the iodinated oxytocin receptor antagonist d(CH(2))(5) [Tyr (Me)(2) Thr(4) Tyr NH(2)(9)]-vasotocin ((125)I-labelled oxytocin receptor antagonist). Oxytocin receptor mRNA and protein expression were initially low but spontaneous upregulation occurred in the luminal epithelium between 24 and 48 h (P < 0.01). Oestradiol increased oxytocin receptor mRNA upregulation in the first 24 h (P < 0.05) but the effect on 125 I-labelled oxytocin receptor antagonist binding was not significant. ICI 182780 inhibited the oestrogenic effect but had no significant effect on oxytocin receptor mRNA expression when given alone. In conclusion, the results showed that oestradiol exerts its effect via the oestradiol receptor. Oestradiol facilitates oxytocin receptor gene transcription by increasing it more rapidly, but spontaneous upregulation of endometrial oxytocin receptor still occurs in the absence of oestradiol.

Regulatory effect of steroid hormones and fetal tissues on expression of oxytocin receptor in the endometrium of late pregnant ewes.

Oxytocin receptors play an important role in the establishment of pregnancy and parturition in ruminants. Previous studies in cyclic and early pregnant ewes have indicated that receptor concentrations are regulated by steroid hormones and fetal secretory products. This study investigated the effect of oestradiol and progesterone, or co-culture with placenta or corpus luteum on oxytocin receptor expression. Endometrial explants from late pregnant ewes were cultured for up to 96 h in various treatment combinations. After culture, tissues were subjected to in situ hybridization and autoradiography with 125I-labelled oxytocin receptor antagonist to localize and measure the expression of oxytocin receptor mRNA and protein. Results were quantified as absorbance units from autoradiographs. Oxytocin receptors were confined to the endometrial luminal epithelium and both mRNA and 125I-labelled oxytocin receptor antagonist binding were upregulated spontaneously in basic serum-free medium. Upregulation occurred earlier in the presence of oestradiol (0.1 mumol l-1) but the final receptor concentration was similar to that found in the basic medium. Continuous progesterone treatment (1 mumol l-1) and co-culture with corpus luteum both delayed the increase in oxytocin receptor mRNA, but a short initial (4 h) period in progesterone-free basic medium resulted in loss of the inhibitory effect. Co-culture with placental tissues had no effect. In conclusion, oxytocin receptor expression in the luminal epithelium increased immediately on removal from the maternal environment. This occurred regardless of treatment and did not require the presence of steroid hormones, but could be accelerated or delayed by oestradiol and progesterone, respectively. There may be an additional inhibitory factor present in the corpus luteum.

Oxytocin receptor expression in human term and preterm gestational tissues prior to and following the onset of labour.

Oxytocin receptor (OTR) mRNA expression has previously been demonstrated in human myometrium, decidua, chorion and amnion but the effect of gestational age and the onset of labour has not been determined in these individual tissues. Spatial OTR mRNA expression was examined by in situ hybridization and ligand binding was confirmed using autoradiography with the iodinated oxytocin antagonist d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29]-vasotocin (125I-OTA). Tissue was collected at term (>37 weeks of gestation) or preterm (24-36 weeks of gestation) caesarean section and classified as labour (contractions every 5 min associated with cervical dilatation) or non-labour. OTR mRNA expression was measured as optical density units from autoradiographs. There was a highly significant (P<0.001) effect of tissue type on expression of OTR mRNA with expression greatest in myometrium, low in decidua and chorion and not detected in placenta. Similar results were obtained with the 125I-OTA-binding studies, indicating that the message was translated. Amnion had an apparently high level of both hybridization and 125I-OTA binding in some samples, but a lack of specificity prevented quantification of the signal in this tissue type. Term myometrium (labour and non-labour) had significantly higher (P<0.01) OTR mRNA expression than preterm myometrium, but there was no further increase in mRNA concentration associated with labour onset. In contrast, 125I-OTA binding in myometrium was already high at 33 weeks and did not increase further either later in pregnancy or with labour. In decidua there was no effect of gestational age or labour onset on OTR mRNA expression or 125I-OTA binding. In summary, OTR mRNA expression in the myometrium increased in late pregnancy whereas decidual expression was much lower and did not rise at term.

Effect of labor induction on the expression of oxytocin receptor, cytochrome P450 aromatase, and estradiol receptor in the reproductive tract of the late-pregnant ewe.

UNLABELLED: In this study, we investigated the timing of changes in aromatase, estradiol receptor, and oxytocin receptor expression in ovine uterine and placental tissues before parturition. Labor was induced by betamethasone injection into the fetus on Days 130-132 of pregnancy. Tissue samples were collected at injection and then every 14 h until labor (56 h) from four ewes at each time point. Samples were analyzed for aromatase, estradiol receptor, and oxytocin receptor expression by in situ hybridization; for oxytocin binding to its receptor using a specific antagonist; and for estradiol receptor quantitation by immunocytochemistry. Aromatase mRNA expression increased by 14 h postinjection (p < 0.02) in the fetal villi and remained high until labor. Expression of estradiol and oxytocin receptor mRNAs was unchanged in myometrium but increased in the endometrial luminal epithelium by 28 h (p < 0.05) and remained high until labor. Estradiol receptor protein concentration increased modestly at labor while oxytocin receptor binding in the luminal epithelium changed in parallel to the mRNA concentration. IN CONCLUSION: 1) induction of aromatase may facilitate the expression of endometrial estradiol and oxytocin receptors in the placentome, 2) changes in endometrial rather than myometrial oxytocin receptor may be important in inducing parturition, and 3) the transcription of estradiol receptor and oxytocin receptor in the uterine epithelium are positively correlated during parturition.

Regulation of oxytocin receptor in the placentome capsule throughout pregnancy in the ewe: the possible role of oestradiol receptor, progesterone receptor and aromatase.

UNLABELLED: The hormonal regulation of uterine oxytocin receptors (OTR) during the establishment of pregnancy and at parturition has been studied extensively, but little information is available during mid-pregnancy. This study investigated the localisation of OTR mRNA in the ovine placentome throughout gestation and related this to expression patterns for the putative regulatory agents aromatase, oestradiol receptor, progesterone receptor and oxytocin. Placentomes were collected at regular intervals throughout pregnancy for in situ hybridisation analysis and immunocytochemistry (oestradiol receptor only). Results were quantified by optical density measurements of autoradiographs. Progesterone receptor mRNA was localised to the caruncular tissues on day 30 but became undetectable by day 34. Aromatase mRNA appeared in the fetal villi at days 34-40, with concentrations peaking at days 52-55 and again at days 132-137. Oestradiol receptor mRNA was localised to the caruncular tissues from days 13 to 30 and found in the maternal villi and placentome capsule from days 45 to 70. Oestradiol receptor protein was barely detectable in either tissue. OTR mRNA was localised to the placentome capsule at days 34-40, remaining high at day 45 and declining to basal levels by days 132-137. Oxytocin mRNA was not detected in the placentome. IN CONCLUSION: (1) progesterone acting via its receptor may suppress the expression of aromatase and OTR in early pregnancy; (2) the up-regulation of OTR expression in the capsule may not involve the oestradiol receptor; (3) there is a differential regulation between different regions of the uterus as the increase in the placentome capsule occurs at a time when concentrations in the rest of the endometrium and myometrium remain low; (4) oestradiol receptor expression in the placentome may be regulated at the translational level; and (5) there is no local production of oxytocin in the sheep placenta. The role of ORTs in the capsule during mid-pregnancy remains to be determined.

Oxytocin receptor development in ovine uterus and cervix throughout pregnancy and at parturition as determined by in situ hybridization analysis.

The development of uterine oxytocin receptors is an important regulatory step in the initiation of labour. Paracrine production of oxytocin by uterine and placental tissues may also be involved in some species. Placentome, intercotyledonary endometrium, myometrium and fetal membranes were collected from 3-5 ewes each, at regular intervals throughout pregnancy and from eight ewes during labour. Localization of mRNA encoding oxytocin and its receptor was by in situ hybridization; oxytocin peptide concentrations were measured by radioimmunoassay and oxytocin receptor concentrations were measured by autoradiography and radioreceptor assay. In the intercotyledonary endometrium, mRNA encoding the oxytocin receptor was located in the luminal epithelium only. Both the epithelial and myometrial receptors were detected at low concentrations from the fourth week of gestation onwards, with a major increase associated with the onset of labour. In the placentomes, oxytocin receptors were localized to a stromal capsule surrounding the placental villi. Expression in this region was maximal in mid-gestation, declining in the second half of pregnancy and remaining low during labour. Cervical oxytocin receptors were detected at low concentrations in the epithelium and the muscular/connective tissue layers from day 22 of pregnancy onwards. There was no evidence for the local uterine production of oxytocin in the ewe; mRNA encoding oxytocin was undetectable and oxytocin concentrations were always < 23 pg g-1 wet mass of tissue. These results suggest that regulation of the timing of oxytocin receptor development varies between the different tissue types, despite a similar steroidal background. The receptors in the luminal epithelium are probably associated with the ability of exogenous oxytocin to induce the release of PGF2 alpha throughout most of pregnancy. The increase in receptors in both the intercotyledonary endometrium and myometrium at term suggest an involvement in labour, whereas their role in caruncular stroma in mid-pregnancy is unknown.

HLA-DRB, -DQA, and -DQB polymorphism in celiac disease and enteropathy-associated T-cell lymphoma. Common features and additional risk factors for malignancy.

CD is a gluten-sensitive enteropathy, strongly associated with expression of the DQA1*0501, DQB1*0201 genotype. CD patients have an increased risk of malignancy, particularly EATCL. However, it is controversial as to whether adults with EATCL represent a subgroup of patients with CD or should be regarded as a distinct entity. To investigate the genetic relationship between CD and EATCL, HLA class II DRB1, DQA1, and DQB1 typing of peripheral blood, frozen or paraffin-embedded biopsy tissue obtained from Caucasian patients with CD (n = 91) or EATCL (n = 47) was performed by PCR-SSOP typing. Genotype frequencies were compared with those observed in 151 unrelated control individuals. A total of 83 (91%) of 91 CD patients were of DQA1*0501, DQB1*0201 genotype (pc < 10(-6), RR = 522.2), compared with 40 (93%) of 43 EATCL patients (pc < 10(-6), RR = 44.2) with amplifiable DNA versus 35 (23%) of 151 controls. DRB1*03 frequencies were also elevated in both patient groups (79 of 91 in CD [87%; pc < 10(-6), RR = 24.5] and 38 of 40 in EATCL [95%; pc < 10(-6), RR = 70.7]) compared with controls (32 of 151, 21%). These results confirm previous studies of HLA associations in CD and also suggest that EATCL arises in individuals with the DQA1*0501, DQB1*0201 CD-predisposing genotype. However, the frequency of DRB1*03,04 heterozygotes was significantly increased in the EATCL group (16 of 40, 40%) compared with both control individuals (3 of 151, 2%; pc < 10(-6), RR = 32.9) and uncomplicated CD patients (6 of 91, 7%; pc = 0.04, RR = 9.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of specimen contamination in routine histopathology by HLA class II typing using the polymerase chain reaction and sequence specific oligonucleotide probing.

This study evaluates the use of human leukocyte antigen (HLA) class II PCR-SSO typing for the investigation of suspected specimen contamination in four routine surgical histopathology cases. Two cases were of patients undergoing transurethral resection of the prostate gland. The third case was a patient undergoing excision of a subcutaneous small cell carcinoma. The fourth case was a patient undergoing reversal of a Hartman's procedure for adenocarcinoma of the colon. Tissue was extracted from routinely processed formalin-fixed, paraffin-embedded material and HLA class II typed, using a non-radioactive polymerase chain reaction-sequence specific oligonucleotide probe technique (PCR-SSO), using probes specific for the DRB, DQA, and DQB loci. The accuracy of PCR-SSO typing of DNA extracted from paraffin biopsy material was confirmed by concordant results for DRB, DQA, and DQB typing in five separate control individuals from whom frozen and paraffin lymph node biopsies were available. PCR-SSO typing was also successful in the four study cases and revealed that contamination had occurred in two cases, eliminating this possibility in the remaining cases. This study demonstrates that DNA can be reliably amplified and accurately typed from routinely processed material, and reveals a useful new application for PCR-SSO tissue typing.

Influence of a new impoundment on pesticide concentrations in warmwater fish, Saylorville Reservoir, Des Moines River, Iowa, 1977-78.

Samples of seven species of warmwater fish were collected above, within, and below newly impounded Saylorville Reservoir, Des Moines River, Iowa, from October 1977 to October 1978. Whole-body analyses by gas chromatography were significantly higher in river carpsucker (Carpiodes cyanazine and for the organochlorine insecticides dieldrin, p,p'-DDE, p,p'-TDE, p,p'-DDT, and heptachlor epoxide. Only the organochlorine insecticides were detected in fish tissue. Concentrations of dieldrin and heptachlor epoxide were significantly higher in river carpsucker (Carpiodes carpio) from the reservoir than in those from the river. Other species of fish showed no differences in pesticide concentration related to locality of collection.