Diagnostically challenging human papillomavirus-associated primary squamous cell carcinoma of the rectum with metastasis in both ovaries: a case report.

INTRODUCTION: Squamous cell carcinomas of the rectum are extremely rare and their pathogenesis is still under debate. Their proper diagnosis and treatment may thus be challenging. CASE PRESENTATION: A 52-year-old Caucasian woman was transferred to our department with a history of pelvic pain. Colonoscopy revealed a small tumorous lesion of the upper rectum and an endoscopic biopsy showed infiltration of the rectal mucosa by a squamous cell carcinoma. Afterward, tumorous lesions were found on imaging in both her ovaries. A laparoscopy with adnexectomy and anal mapping was performed and revealed tumor masses of squamous cell carcinoma in both ovaries. Based on the large size of the ovarian tumors and the concurrence of extensive, partly ciliated, macrocystic epithelium in one of the ovaries, a diagnosis of ovarian squamous cell carcinoma arising from a mature teratoma was rendered. However, human papillomavirus genotyping analyses were positive for human papillomavirus-16 in both the rectal tumor and ovarian tumors leading to a final diagnosis of a human papillomavirus-associated rectal squamous cell carcinoma metastatic to both ovaries. Neoadjuvant chemoradiation therapy of her rectum, total mesorectal excision, and hysterectomy were performed followed by adjuvant chemotherapy. CONCLUSION: Colorectal squamous cell carcinoma is a rare disease. In cases of colorectal squamous cell carcinoma, metastatic disease at any other location has to be excluded. Human papillomavirus genotyping is essential in this context. Discussion of the treatment strategies should be interdisciplinary and include chemoradiation therapy and radical surgery.

Methylation and silencing of the retinoic acid receptor-beta2 gene in breast cancer.

BACKGROUND: A growing body of evidence supports the hypotheses that the retinoic acid receptor beta2 (RAR-beta2) gene is a tumor suppressor gene and that the chemopreventive effects of retinoids are due to induction of RAR-beta2. RAR-beta2 expression is reduced in many malignant tumors, and we examined whether methylation of RAR-beta2 could be responsible for this silencing. METHODS: RAR-beta2 expression was studied by reverse transcription-polymerase chain reaction (RT-PCR) analysis in eight breast cancer cell lines that were either treated with the demethylating agent 5-aza-2'-deoxycytidine and subsequently with all-trans-retinoic acid (ATRA) or left untreated. Sodium bisulfite genomic sequencing was used to determine the locations of 5-methylcytosines in the RAR-beta2 genes of three of these cell lines. In 16 breast cancer biopsy specimens and non-neoplastic breast tissue, methylation-specific PCR was used to determine the methylation status of RAR-beta2, and, in 13 of the specimens, RT-PCR analysis was used to detect RAR-beta2 expression. RESULTS: Cell lines SK-BR-3, T-47D, ZR-75-1, and MCF7 exhibited expression of RAR-beta2 only after demethylation and treatment with ATRA. The first exon expressed in the RAR-beta2 transcript was methylated in cell lines ZR-75-1 and SK-BR-3. Six breast cancer specimens showed methylation in the same region of the gene. No expression of RAR-beta2 was found in any grade III lesion. An inverse association between methylation and gene expression was found in all grade II lesions. The RAR-beta2 gene from non-neoplastic breast tissue was unmethylated and expressed. CONCLUSIONS: Methylation of the RAR-beta2 gene may be an initial step in breast carcinogenesis; treatment of cancer patients with demethylating agents followed by retinoic acid may offer a new therapeutic modality.

Selective growth hormone/placental lactogen gene transcription and hormone production in pre- and postmenopausal human ovaries.

In addition to effects of pituitary-derived gonadotropins, human GH modulates and regulates intraovarian reproductive processes in a dose-dependent manner via the endocrine GHRH/GH/insulin-like-growth-factor I (IGF-I) axis. Based on increasing evidence that ovarian regulation involves a complex system of putative para/autocrine factors, we investigated the possibility of gene-selective intraovarian GH/placental lactogen (PL) hormone production, with emphasis on differences between pre- and postmenopause. Analysis of both premenopausal (n = 8) and postmenopausal (n = 10) ovarian-derived messenger ribonucleic acid by reverse transcription-PCR, which amplifies all major gene products of the five-member GH/PL gene cluster GH-N, GH-V, PL-A/B, and PL-L, revealed specific transcripts in all specimens. Their share in gene selective expression by analytical restriction enzyme digestion was determined. The expression pattern of GH/PL messenger ribonucleic acid shows PL-A/B > GH-N, which sets it apart from those of pituitary and placenta. Local production of the respective protein hormones was verified by two time-resolved immunofluorometric assays for human PL-A/B and GH-N; significant amounts of these hormones were detected in cytosolic extracts of premenopausal (n = 6; 555.5 +/- 171 ng PL-A/B and 0.8 +/- 0.6 ng GH-N/g tissue wet wt) and postmenopausal (n = 6; 5.2 +/- 2.7 ng PL-A/B and 0.9 +/- 0.6 ng GH-N/g tissue wet wt) ovaries. No difference was observed between pre- and postmenopausal ovarian GH-N contents, but PL values were 2-3 orders of magnitude lower in postmenopausal tissue (P < 0.001). Serum levels of healthy premenopausal (n = 21) and postmenopausal (n = 16) women were less than 0.02 ng PL/mL. In summary, ovarian-derived GH-N and PL-A/B synthesis correlates well with the established local cascade of GHRH, GHRH receptor, GH receptor, IGF-I, and IGF-I receptor as a putative para/autocrine regulator of ovarian reproductive function.

Prolactin gene expression and prolactin protein in premenopausal and postmenopausal human ovaries.

OBJECTIVE: To investigate intraovarian prolactin and prolactin-receptor gene expression and to assess local prolactin synthesis with emphasis on possible differences between premenopausal and postmenopausal status. DESIGN: The RNA extracted from human premenopausal and postmenopausal tissues was subjected to reverse transcription and polymerase chain reaction by using prolactin-specific intron- and exon-spanning primers. Prolactin-receptor expression was investigated accordingly. The amplified complementary DNA fragments were analyzed by gel electrophoresis and restriction enzyme mapping. Local prolactin hormone synthesis was verified by a time-resolved immunofluorometric assay based on our monoclonal antibodies. RESULT(S): Prolactin and prolactin-receptor gene expression was observed in all analyzed human ovaries (n = 18). Several other human tissue specimens, such as lung and kidney, served as negative control tissues. Significantly elevated concentrations of prolactin were detected in cytosolic extracts of premenopausal (n = 6; mean +/- SD; 20.6 +/- 3.3 ng/g tissue wet weight) versus postmenopausal (n = 6; 3.6 +/- 3.0 ng/g tissue wet weight) ovaries. CONCLUSION(S): The human ovary not only serves as a target for endocrine prolactin action but also as a site of local prolactin hormone production. In agreement with previous reports on extrapituitary sources of prolactin, we consider prolactin as a hormone as well as an autocrine or paracrine growth or regulatory factor. Significantly increased concentrations of prolactin in premenopausal ovarian tissue verifies its role in human reproduction.

Evaluation of RU-27987 as a ligand to determine the progesterone receptor.

RU-27987, a synthetic progestin, which was recently developed by Roussel Uclaf, Paris, was tested for its validity as a ligand to determine the progesterone receptor in breast cancer. The results were compared to those obtained with R-5020 and ORG-2058, two ligands that are already in use worldwide. The intra- and interassay variation of receptor determination was similar for all 3 ligands. Receptor levels were analyzed with each of the 3 progestins in control cytosols and in 26 mammary carcinoma samples. A good correlation between receptor levels was found although the values of ORG-2058 were somewhat lower, but not significantly. This resulted in a lower proportion of receptor positive samples for ORG-2058 (11/26) compared to R-5020 (13/26) and RU-27987 (14/26). The affinity to the progesterone and to the glucocorticoid receptor, as well as the precision of the Scatchard plot analysis were comparable for the 3 ligands tested. Intra- and interassay variation of receptor determination were also similar. We therefore conclude, that RU-27987 is a suitable ligand to determine progesterone receptor in mammary carcinoma.

Predictive value of uPA, PAI-1, HER-2 and VEGF in the serum of ovarian cancer patients.

BACKGROUND: Tissue levels of uPA, PAI-1, HER-2 and VEGF are known to have prognostic value in different malignant tumors. The prognostic potential of serum concentrations of these markers is less clear and was investigated. PATIENTS AND METHODS: The response to 2nd line chemotherapy was studied in 61 patients with recurrent ovarian cancer. Marker analyses were performed using specific and sensitive ELISA tests and the response to therapy was evaluated using multiple CA 125 determinations and including these values in a simple and comprehensive formula. RESULTS: Correlations were observed between VEGF and CA 125, HER-2 (inversely) as well as PAI-1, and between uPA and PAI-1. However, no marker showed a significant relation to the overall survival of patients, nor to treatment response. CONCLUSIONS: Serum levels of uPA, PAI-1, HER-2 and VEGF do not have enough predictive potential in recurrent ovarian cancer. Most likely additional sources contribute to the serum levels of the markers studied so that their levels are not only tumor specific.

Peritoneal mesothelial cells as a significant source of ascitic immunostimulatory protein 90K.

The tumor associated antigen 90K is known to possess cytokine-like modulatory properties on the cellular immune system, whereby accessory cells are the primary target of this molecule. In 67 ovarian cancer patients presenting with significant amounts of ascites, immunostimulatory protein 90K was detected in all ascitic fluid samples examined. Furthermore, 90K levels correlated to ascitic s-IL-2R content. To elucidate the source of protein 90K in ascitic fluid; its in vitro release was investigated in primary cultured normal human peritoneal mesothelial cells (HPMC). Peritoneal mesothelium was found to produce five-fold more 90K than ovarian cancer cells. Release of protein 90K was significantly increased by treatment with IFN-gamma in both mesothelial and ovarian cancer cells. In contrast neither IL-1 beta nor TNF-alpha treatment consistently influenced the secretion of 90K in either cell type.

Preliminary experience with steroidal ovarian suppression for prevention of severe ovarian hyperstimulation syndrome in IVF patients.

The purpose of the study was to evaluate the efficiency of administration of high dose progesterone in combination with oestradiol during the luteal phase for the prevention of ovarian hyperstimulation syndrome in a high-risk population of patients undergoing in vitro fertilization. An observational study was carried out involving 21 women (mean age 28.6 years) undergoing controlled ovarian stimulation for in vitro fertilization. The women were identified as at risk of ovarian hyperstimulation syndrome as they had suffered from the condition when hCG was used for luteal phase support in previous cycles. Steroidal suppression of the stimulated ovary on days 2, 6, 10 and 14 after embryo transfer was achieved by intramuscular injections of 500 mg hydroxyprogesterone caproate and 10 mg oestradiol valerate. The incidence of moderate and severe ovarian hyperstimulation syndrome under steroidal ovarian suppression, serum progesterone concentration and pregnancy rates were compared with those in cycles in which human chorionic gonadotrophin was used for luteal phase support. No cases of moderate or severe ovarian hyperstimulation syndrome occurred under steroidal ovarian suppression. Despite low progesterone concentrations (mean 10.7 nmol l(-1), range 2.6-24.5), indicating almost complete ovarian suppression, the pregnancy rate was not impaired. These preliminary results indicate that steroidal ovarian suppression during the luteal phase is a promising tool for reducing the incidence and severity of ovarian hyperstimulation syndrome in a high-risk population, without compromising the pregnancy rate.

[Spontaneous pregnancy after ligation of the uterine artery]. / Spontanschwangerschaft nach Ligatur der Arteria uterina.

In this case report, the functional anastomoses of the uterine arteries are demonstrated. In our opinion, the selective ligation of one or both uterine arteries is the method of choice for treating severe gynaecological or obstetrical bleeding complications. Successful haemostasis and preservation of the uterus can be achieved permitting future spontaneous pregnancies.

The surgical anatomy of rectocele and anterior rectal wall intussusception.

The aim of the study was to analyse the dynamic anatomical supports of the posterior vaginal wall from the perspective of rectocele and rectal intussusception repair. Two groups of patients were studied. Group 1 (n = 24) with genuine stress incontinence but no major vault prolapse had vagino/proctomyograms and transperineal ultrasound examinations. Group 2 with vaginal vault prolapse, clinical rectoceles and obstructive defecation symptoms (n = 19 had single-contrast defecating proctography before and after posterior-sling surgery. The posterior vaginal wall is suspended between perineal body, which underlies half its length, and uterosacral ligaments, which also support the anterior wall of rectum. Muscle forces stretch the vagina and rectum against the perineal body and uterosacral ligaments, creating shape and strength, like a suspension bridge. Postoperative proctogram studies indicated that anterior rectal wall intussusception has the same etiology as rectocele, deficient recto-vaginal ligamentous support. Repair to uterosacral ligaments and perineal body should be considered with large rectoceles, anterior rectal wall intussusception and obstructive defecation disorders.

[Multi-morbidity as a responsibility: 1,000 illnesses--one health. The physician's image 200]. / Multimorbidität als Aufgabe: 1000 Krankheiten--eine Gesundheit. Arztbild 2000.

The prototype physician 2000 A.D. will have to be able to recognise multimorbidity and its individual importance in a general medical and social sense. There will be a specifically challenge in the fields of individual prophylaxis, interdisciplinary communication, integration of all nursing and treating partners and the ethical judgement between individually useful and theoretically possible treatment options. Medical education and social systems will have to provide enough knowledge and skills as well as opportunities to allow this necessary development of our future physicians 2000 A.D.

Use of the greater omentum for treatment and prophylaxis of anastomotic and stump dehiscence in major airway surgery.

In 6 patients suffering from anastomotic dehiscence following bronchoplastic procedures of the central airways or from acute bronchial stump fistula following pneumonectomy, the therapeutic efficiency of omentopexy in the management of the fistula was investigated. In 5 other patients with an increased risk of anastomotic leakage after sleeve pneumonectomy or pneumonectomy with carinal resection the omentum was effectfully used to prevent such complication. 4 out of 5 evaluable patients had successful treatment of the anastomosis and stump fistula. Complications arising from the additional laparotomy were not observed.

Management of ingested foreign bodies within the appendix: a case report with review of the literature.

A case is reported of an elective appendectomy in a patient with known ingestion of a sharp foreign body. The metal drill bit was ingested unintentionally 3 months before presentation at our institution. Plain abdominal films demonstrated the foreign body in the right lower abdominal quadrant. Because the gold dental drill bit was sharp and thought to be lodged in the terminal ileum or cecum, an attempt was made to remove the object during colonoscopy. This attempt was unsuccessful because no drill bit could be detected in the colon or terminal ileum. A laparoscopic exploration was performed, and the foreign body was found to lie in the appendix, after bowel manipulation under fluoroscopic guidance and with direct laparoscopic visualization. A laparoscopic assisted appendectomy was performed. On pathologic examination the drill bit was embedded in the tip of the appendix with signs of intramucosal acute inflammation. Management and indication for surgery of foreign bodies in the appendix are discussed, and we review the related literature. This is the second reported case of a dental drill bit in the appendix causing appendicitis.

Hand-assisted laparoscopic splenectomy for isolated splenic metastasis from an ovarian carcinoma: a case report with review of the literature.

A 56-year-old woman was found to have a solitary metastasis to the spleen from ovarian cancer. A hand-assisted laparoscopic splenectomy was carried out. The operative technique and advantages of this technique are discussed. Laparoscopy with mini laparotomy allows for manual manipulation of the spleen with the ability to control bleeding, and facilitates mobilization and removal of the specimen. Postoperative recovery is rapid. Review of the literature indicates that secondary metastasis to the spleen is quite common.

Clinical significance of serum and ascitic p53 autoantibodies in epithelial ovarian carcinoma.

BACKGROUND: Accumulation of mutated p53 in malignant cells can lead to the generation of anti-p53 autoantibodies in the serum and other body fluids of cancer patients. This retrospective study was performed to evaluate the prognostic significance of preoperative serum and ascitic anti-p53 antibodies in advanced ovarian carcinoma. METHODS: In 113 ovarian carcinoma patients who presented with significant amounts of ascites, anti-p53 autoantibodies were determined by a highly specific enzyme-linked immunosorbent assay of blood and ascites. Disease free and overall survival of study patients was estimated by the product limit method of Kaplan and Meier. Differences in survival were examined according to criteria of Mantel and Breslow. A multiple regression analysis based on the Cox proportional hazards model was used to determine the independence of prognostic variables. RESULTS: Serum and ascitic anti-p53 antibodies were found in 28 (25%) and 21 (19%) of the study patients, respectively. In univariate analysis, detection of anti-p53 antibodies in ascites but not in serum was found to be a sign of unfavorable disease free survival (P<0.003) and overall survival (P < 0.01). Multivariate analysis revealed that anti-p53 positivity in ascites retained independent significance only in the prediction of adverse progression free survival (P<0.01). CONCLUSIONS: The generation of a humoral immune response against p53 protein in the close tumor environment, as demonstrated by the occurrence of p53 autoantibodies in the ascitic fluid of ovarian carcinoma patients, is associated with poor disease free survival.

[Epignathus: prenatal diagnosis by sonography and magnetic resonance imaging]. / Epignathus: Pränatale Diagnostik mittels Ultraschall und Magnetresonanztomographie.

Prenatal diagnosis of a teratoma of the oral cavity (epignathus) is presented using ultrasonography and magnetic resonance imaging as complementary techniques. Chromosome analysis from amniotic fluid revealed an inverted duplication of chromosome 1 that was confined to the tumour, whereas the constitutional karyotype was normal. The development of polyhydramnios, presumably reflecting impaired fetal swallowing, led to premature rupture of membranes and spontaneous delivery at 23 + 4 weeks of pregnancy. The premature neonate succumbed to acute respiratory distress secondary to airway obstruction by the tumour, and died immediately after birth.

Sodium-taurocholate-induced acute necrotizing pancreatitis does not affect jejunal oxygenation in pigs.

OBJECTIVE: To study the influence of experimentally induced acute necrotizing pancreatitis on jejunal oxygen transport, jejunal oxygen consumption, and mucosal PO2. DESIGN: Prospective, randomized trial. SETTING: Animal laboratory. SUBJECTS: Domestic pigs aged 7 to 8 wks. INTERVENTIONS: Two groups of pigs were anesthetized with midazolam and sufentanyl, mechanically ventilated, and hemodynamically monitored. In controls (n = 9) and in animals with acute necrotizing pancreatitis (n = 9), a segment of the jejunum was isolated and autoperfused in situ. Through an antimesenteric enterotomy, an area of jejunal mucosa was exposed for mucosal PO2 measurements. Acute necrotizing pancreatitis was induced by the injection of 10 mL of 10% sodium-taurocholate into the main pancreatic duct. Both groups received normal saline solution to keep pulmonary artery occlusion pressure constant. MEASUREMENTS: Mucosal PO2 was assessed with a modified Clark-type multiwire surface electrode. After two baseline measurements, systemic and regional oxygen transport variables and mucosal PO2 were determined at designated intervals (20, 40, 60, 100, 120, 160, 200, 240, 280 mins). MAIN RESULTS: Systemic hemodynamics and oxygen transport were maintained in both groups. In contrast to controls, all animals with pancreatitis showed gross macroscopic and histologic evidence of severe acute necrotizing pancreatitis at autopsy. There were no significant differences between groups in jejunal blood flow, oxygen transport, oxygen consumption, oxygen extraction ratio, or mucosal PO2. CONCLUSIONS: Our results demonstrate that, under conditions of sustained systemic hemodynamics, jejunal oxygen transport and mucosal oxygenation are well maintained during the early course of sodium-taurocholate-induced acute necrotizing pancreatitis.

IL-6 secretion by human peritoneal mesothelial and ovarian cancer cells.

Malignant ascites of epithelial ovarian cancer patients contains high levels of interleukin 6 (IL-6). The present study was conducted to compare the secretion of IL-6 by seven different human ovarian cancer cell lines (OVCA) and cultured human peritoneal mesothelial cells (HPMC) and to examine the regulation of its production by other cytokines. IL-6 was detected in supernatant medium of all mesothelial cell cultures (8/8) and 6/7 ovarian cancer cell lines. Levels of IL-6 secreted by HPMC (median 27,100 pg/1 x 10(5) cells; range 3870-168,200) were 590-fold higher (P < 0.01) than those secreted by OVCA (median 46 pg/1 x 10(5) cells; range 0-16,450). Treatment with TNF-alpha or IL-1 beta (both 10 ng/ml) for both types of cells and both cytokines resulted in a significant (P < 0.05) elevation of IL-6 production. In OVCA IL-6 secretion was increased 7- and 39-fold and in HPMC 6- and 8-fold, respectively. Under TNF-alpha treatment IL-6-levels secreted by HPMC were 149-fold higher (P < 0.01) than those generated by OVCA. Similarly, IL-1 beta-induced IL-6 levels were 102-fold higher in HPMC (median 288,800 pg/1 x 10(5) cells; range 93,125-552,800) than in OVCA. IFN-gamma (10 ng/ml) increased IL-6 generation in OVCA (6-fold) but not HPMC. The proliferation of both cell types however, was significantly (P < 0.05) inhibited by IFN-gamma. Our results suggest that peritoneal mesothelial cells may be a prominent source of IL-6 in ovarian cancer-related ascites.

Limb sparing surgery for vulvar groin recurrence: a case report and review of the literature.

Hemipelvectomy was successfully avoided in a patient with extensive necrotic groin recurrence of vulvar cancer after prior radiation therapy. Tumor-free resection margins were achieved by wide excision of the recurrence including resection of the pubic bone and adjacent muscles. After resection of the femoral artery, blood supply to the leg was restored by an extra-anatomic axillopopliteal bypass. A myocutaneous flap from the contralateral rectus abdominis was used for primary wound closure. Limb salvage was achieved and the patient experienced pain relief, excellent cosmesis, and independent gait. Aspects of treatment options, even though primarily palliative, in groin recurrence of vulvar carcinoma are discussed.

Peritoneum and tissues of the female reproductive tract as physiological sources of CA-125.

The origin of physiological CA-125 serum levels, which in normally menstruating women were shown to depend on their actual menstrual cycle phase, has not yet been completely elucidated. It is furthermore conceivable that physiological CA-125 sources may contribute to serum elevations in the various pathologies associated with increased circulating CA-125. The present review deals with menstrual cycle-dependent expression of CA-125 in normal tissues of the female reproductive tract in relation to the actual circulating CA-125 levels together with in vivo data concerning the inductive effect of medroxyprogesterone acetate on circulating CA-125 studied in 24 postmenopausal women. Furthermore, in vitro results on constitutive, steroid hormone- and cytokine-modulated CA-125 shedding from human peritoneal mesothelial and ovarian surface epithelial cells are summarized.