The management of retrorectal tumors - a single-center analysis of 21 cases and overview of the literature.

AIM: Retrorectal tumors are rare and heterogeneous. They are often asymptomatic or present with nonspecific symptoms, making management challenging. This study examines the diagnosis and treatment of retrorectal tumors. METHODS: Between 2002 and 2022, 21 patients with retrorectal tumors were treated in our department. We analyzed patient characteristics, diagnosis and treatment modalities retrospectively. Additionally, a literature review (2002-2023, "retrorectal tumors" and "presacral tumors", 20 or more cases included) was performed. RESULTS: Of the 21 patients (median age 54 years, 62% female), 17 patients (81%) suffered from benign lesions and 4 (19%) from malignant lesions. Symptoms were mostly nonspecific, with pain being the most common (11/21 (52%)). Diagnosis was incidental in eight cases. Magnetic resonance imaging was performed in 20 (95%) and biopsy was obtained in 10 (48%). Twenty patients underwent surgery, mostly via a posterior approach (14/20 (70%)). At a mean follow-up of 42 months (median 10 months, range 1-166 months), the local recurrence rate was 19%. There was no mortality. Our Pubmed search identified 39 publications. CONCLUSION: Our data confirms the significant heterogeneity of retrorectal tumors, which poses a challenge to management, especially considering the often nonspecific symptoms. Regarding diagnosis and treatment, our data highlights the importance of MRI and surgical resection. In particular a malignancy rate of almost 20% warrants a surgical resection in case of the findings of a retrorectal tumour. A local recurrence rate of 19% supports the need for follow up.

Oncological outcome after hyperthermic isolated limb perfusion for primarily unresectable versus locally recurrent soft tissue sarcoma of extremities.

INTRODUCTION: The management of locally advanced extremity soft tissue sarcomas, particularly in terms of a limb salvage strategy, represents a challenge, especially in recurrent tumors. In the context of a patient-tailored multimodal therapy, hyperthermic isolated limb perfusion (ILP) is a promising limb-saving treatment option. We report the outcome of patients with primarily irresectable and locally recurrent soft tissue sarcoma (STS) treated by ILP. PATIENTS AND METHODS: Data about patient demographics, clinical und histopathological characteristics, tumor response, morbidity and oncological outcome of all patients with STS, who underwent an ILP at our institution in a 10-year period, were retrospectively detected and analyzed. RESULTS: The cohort comprised 30 patients. Two patients were treated with ILP for palliative tumor control, 13 patients because of a local recurrent soft tissue sarcoma (rSTS) and 15 patients because of primarily unresectable soft tissue sarcoma (puSTS). 25 of the 28 patients with curative intention received surgery after ILP (11 pts with rSTS and 14 pts with puSTS). Histopathologically we observed complete response in 6 patients (24%) and partial responses in 19 patients (76%) with a significant better remission in patients with puSTS (p = 0,043). Limb salvage rate was 75%. Mean follow-up was 69 months [range 13-142 months]. Seven (7/11; 64%) patients with rSTS and one (1/14; 7%) patient with puSTS developed local recurrence after ILP and surgery, whereas eight (8/13; 62%) rSTS patients and seven (7/15; 47%) puSTS patients developed distant metastasis. During follow-up, eight patients (28.5%) died of disease (5/13; 38%) rSTS and 3/15 (20%) puSTS. ILP in the group of previously irradiated sarcoma patients (n = 13) resulted in a limb salvage rate of 69% and was not associated in an increased risk for adverse events. DISCUSSION: ILP for advanced extremity STS is a treatment option for both puSTS and rSTS resulting in good local control and should be considered in multimodal management. ILP is also a good option for patients after radiation history.

Ventral rectopexy with biological mesh for recurrent disorders of the posterior pelvic organ compartment.

PURPOSE: Recurrent prolapse of the posterior pelvic organ compartment presents a management challenge, with the best surgical procedure remaining unclear. We present functional outcome and patient satisfaction after laparoscopic and robotic ventral mesh rectopexy (VMR) with biological mesh in patients with recurrence. METHODS: We analyzed data from 30 patients with recurrent posterior pelvic organ prolapse who underwent VMR with biological mesh from August 2012 to January 2018. Data included patient demographics and intra- and postoperative findings; functional outcome as assessed by Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), and Cleveland Clinic Incontinence Score (CCIS); and patient satisfaction. RESULTS: CCCS, CCIS, and ODS were significantly improved at 6-12 months postoperatively and at last follow-up. Patient satisfaction (visual analog scale [VAS] 6.7 [0 to 10]), subjective symptoms (+ 3.4 [scale - 5 to + 5]), and quality of life improvement (+ 3.0 [scale from - 5 to + 5]) were high at last follow-up. The rates of morbidity and major complications were 13% and 3%, respectively. There were no mesh-related complications or deaths. Difference in type of previous surgery (abdominal or transanal/perineal) had no significant effect on results. CONCLUSIONS: VMR with biological mesh is a safe and effective option for patients with recurrent posterior pelvic organ prolapse. It reduces functional symptoms, has a low complication rate, and promotes patient satisfaction.

Permacol™ collagen paste for cryptoglandular and Crohn's anal fistula.

BACKGROUND: Permacol™ collagen paste, an acellular crosslinked porcine dermal collagen matrix suspension, is a new treatment option for anal fistula. Data remain limited, however, and as yet only the results of one case of Crohn's fistula treated with Permacol™ paste has been reported. The aim of this study was to assess the use of Permacol™ collagen paste in patients with cryptoglandular and Crohn's perianal fistulae. METHODS: A prospective study was conducted on patients with anal fistula, treated with Permacol™ paste. Patients were followed at 1 week, 6 and 12 months, and on demand thereafter. The main focus was on fistula healing and postoperative continence. The former was defined as the absence of signs of recurrence on clinical examination, proctoscopy and rigid rectoscopy. Fecal incontinence was assessed before surgery and at each follow-up. RESULTS: Thirty patients (19 women, 11 men; mean age 46 years), 12 (40%) of whom had Crohn's disease were included. The average number of previous fistula operations was 6. All patients had ≥ 6 months of follow-up, and 24 patients (80%) had ≥ 12 months of follow-up. The healing rate in all patients was 57% (17 of 30 patients) at 6 months and 63% (15 of 24 patients) at 12 months. One patient reported a worsening of fecal incontinence at 12 months; 2 patients had adverse events (perianal pain: n = 1, fluid accumulation n = 1) requiring fistula drainage. Patient characteristics, healing, incontinence, and adverse events did not differ significantly between patients with and without Crohn's disease. CONCLUSIONS: Our data indicate that Permacol™ paste is a safe and moderately effective treatment for cryptoglandular and Crohn's fistulae.

A second KRT71 allele in curly coated dogs.

Major characteristics of coat variation in dogs can be explained by variants in only a few genes. Until now, only one missense variant in the KRT71 gene, p.Arg151Trp, has been reported to cause curly hair in dogs. However, this variant does not explain the curly coat in all breeds as the mutant 151 Trp allele, for example, is absent in Curly Coated Retrievers. We sequenced the genome of a Curly Coated Retriever at 22× coverage and searched for variants in the KRT71 gene. Only one protein-changing variant was present in a homozygous state in the Curly Coated Retriever and absent or present in a heterozygous state in 221 control dogs from different dog breeds. This variant, NM_001197029.1:c.1266_1273delinsACA, was an indel variant in exon 7 that caused a frameshift and an altered and probably extended C-terminus of the KRT71 protein NP_001183958.1:p.(Ser422ArgfsTer?). Using Sanger sequencing, we found that the variant was fixed in a cohort of 125 Curly Coated Retrievers and segregating in five of 14 additionally tested breeds with a curly or wavy coat. KRT71 variants cause curly hair in humans, mice, rats, cats and dogs. Specific KRT71 variants were further shown to cause alopecia. Based on this knowledge from other species and the predicted molecular consequence of the newly identified canine KRT71 variant, it is a compelling candidate causing a second curly hair allele in dogs. It might cause a slightly different coat phenotype than the previously published p.Arg151Trp variant and could potentially be associated with follicular dysplasia in dogs.

[Palliative therapy concepts for pancreatic carcinoma]. / Palliative Konzepte beim Pankreaskarzinom.

The majority of patients with ductal pancreatic adenocarcinoma are already in a locally advanced or metastatic stage at the time of diagnosis and require palliative therapy. Interventional and operative measures are available for the restoration of biliary outflow in bile duct obstruction and the continuity of the upper intestinal lumen in duodenal or gastric outlet obstruction. In the presence of tumor-related pain, pain therapy according to the World Health Organization (WHO) scheme or a truncus coeliacus blockade, in cachexia a nutritional therapy and in thromboembolic events an anticoagulant therapy are used. An individualized palliative chemotherapy regimen should be selected for each patient, taking into account the patient's general condition and the side effects profile of the chemotherapeutic agents. Radiochemotherapy and local ablative therapies should currently only be used within the framework of studies. A palliative resection is not recommended according to current knowledge.

Effectiveness of sacral nerve stimulation in fecal incontinence after multimodal oncologic treatment for pelvic malignancies: a multicenter study with 2-year follow-up.

BACKGROUND: To assess whether sacral nerve stimulation (SNS) is an effective treatment for severe fecal incontinence (FI) after radiotherapy (RT)/chemoRT (CRT) in combination with pelvic surgery. METHODS: A multicenter study was conducted on patients with FI that developed after multimodal therapy for pelvic tumors and was refractory to non-operative management, who were treated with SNS between November 2009 and November 2012. Data were prospectively collected and retrospectively analyzed. Cleveland Clinic FI score (CCFIS), FI episodes per week, FI Quality of Life (FIQoL), anorectal manometry and pudendal nerve terminal motor latency were evaluated before and after SNS. RESULTS: Eleven patients (seven females, mean age 67.3 ± 4.8 years) were evaluated in the study period. Multimodal treatments included surgery and CRT (four rectal, two cervical and one prostate cancers), surgery and RT (one cervical and two endometrial cancers) and CRT (one anal cancer). The mean radiation dose was 5.3 Gy, and mean interval between the end of RT and onset of FI was 43.7 ± 23 months. Before SNS, the mean CCFIS and the mean number of FI episodes per week were 15.7 ± 2.8 and 12.3 ± 4.2, respectively. At 12-month follow-up, mean CCFIS improved to 3.6 ± 1.8 (p = 0.003) and the mean number of FI episodes decreased to 2.0 ± 1.9 per week (p = 0.003). These results persisted at 24-month follow-up. Significant improvement was also observed for each of the four domains of FIQoL at 12- and 24-month follow-up. Anorectal manometry values did not change significantly at follow-up. CONCLUSIONS: SNS is feasible and may be an effective therapeutic option for FI after multimodal treatment of pelvic malignancies.

Prevalence of upper extremity pain in a population of people with paraplegia.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To determine the prevalence, patterns, and predictors of musculoskeletal pain in the upper extremity joints among wheelchair-dependent individuals with post-traumatic paraplegia. Secondarily, to document most common reported causes of upper extremity pain. SETTING: Centre for Orthopaedics, Trauma Surgery and Spinal Cord Injury, Germany. METHODS: The study was done by means of a structured questionnaire, which was mailed to the individuals who had been treated between 1990 and 2007 for newly sustained or pre-existing, accident-related paraplegia (n = 670). The questionnaire was designed mainly to obtain the information regarding shoulder, elbow, and wrist pain. Additional data included participant demographics, mechanism, level and completeness of injury as well as wheelchair dependence and time since injury. The Frankel classification system was used to define the completeness of injury. RESULTS: Four hundred and fifty-one (67%) questionnaires were included. Pain was reported by approximately 81% of the participants. Of this sample, 61% had shoulder pain, 33% had elbow pain, and 43% had wrist pain, 19% had shoulder, elbow, and wrist pain, 27% had shoulder and elbow pain, 34% had shoulder and wrist pain, 21% had elbow and wrist pain. The main diagnoses were rotator cuff tears for individuals with shoulder pain, epicondylitis for those with elbow pain, and carpal tunnel syndrome for those with wrist pain. The development of shoulder/elbow and wrist pain correlated with age and time since injury. CONCLUSIONS: Age and the length of time since injury correlated with a higher rate of shoulder, elbow, and wrist pain. The completeness of injury, neurological level, and gender were correlated with shoulder, elbow, and wrist pain, respectively.

[Branch duct intraductal papillary mucinous neoplasm - contra resection]. / Intraduktale papillär-muzinöse Neoplasie des Seitengangs­ Kontra Resektion.

Due to improvements in imaging modalities the diagnosis of branch duct intraductal papillary mucinous neoplasms (BD-IPMN) has been significantly increased in recent years. A BD-IPMN is frequently diagnosed as an incidental finding in asymptomatic patients. The optimal management of BD-IPMN is the subject of controversial discussions. Numerous studies have shown that an individualized therapeutic strategy with a follow-up observation of most BD-IPMNs is feasible and safe, considering age, comorbidities and patient preference. An accurate evaluation of BD-IPMN with a detailed anamnesis, high-resolution imaging techniques and endoscopic ultrasound is necessary. Symptomatic patients as well as patients with so-called high-risk stigmata should undergo resection. Asymptomatic patients with so-called worrisome features can either undergo surveillance or surgical resection, taking age and comorbidities into account. For BD-IPMN patients without high-risk stigmata and worrisome features and showing no symptoms, surveillance of the pancreatic lesion is the preferred approach. The high prevalence of BD-IPMN, limitations in differential diagnostics, an overestimation of the risk of malignancy due to an overrepresentation of symptomatic and suspected BD-IPMN in resected cohorts, an overestimated role of BD-IPMN as precursor lesions for pancreatic carcinoma and evidence of the safety of follow-up surveillance, underline the enormous importance of surveillance. Based on this and considering the background of a notable mortality and morbidity of pancreatic surgery, aggressive management with prophylactic surgical resection is not justified for all BD-IPMN, in particular for low-risk lesions.

Benign atrophic papulosis (Köhlmeier-Degos disease): the wedge-shaped dermal necrosis can resolve with time.

BACKGROUND: Atrophic papulosis is a rare thrombo-occlusive disease, characterized by the appearance of multiple atrophic porcelain-white skin papules, with a surrounding erythematous rim, which are histologically consisting of wedge-shaped necrosis of the dermis. OBJECTIVE: It consists of two variants: (i) the benign atrophic papulosis (BAP) only involving the skin and (ii) the malignant atrophic papulosis (MAP) also involving several internal organs with a cumulative five-year survival rate of approx. 55%. While the probability of only having a BAP at onset is approximately 70%, increasing to 97% after 7 years of monosymptomatic cutaneous course, no close long-term follow-up of the development of the skin lesions has been reported. METHODS: We present a precise visual documentation of the evolution of the disseminated skin lesions in a female patient with BAP spanning over two decades. RESULTS: A considerable improvement and/or clinical resolution of the majority of the lesions disputing the scarring character of the atrophic porcelain-white skin papules has been detected. CONCLUSION: BAP not only exhibits an excellent prognosis, but resolution of lesions can also occur after a considerable period of time.

[Robot-assisted liver resection]. / Roboterassistierte Leberresektion.

Robotic liver resection can overcome some of the limitations of laparoscopic liver surgery; therefore, it is a promising tool to increase the proportion of minimally invasive liver resections. The present article gives an overview of the current literature. Furthermore, the results of a nationwide survey on robotic liver surgery among hospitals in Germany with a DaVinci system used in general visceral surgery and the perioperative results of two German robotic centers are presented.

[Two annular, atrophic plaques on the abdomen of a 35-year-old man]. / Zwei anuläre, atrophische Plaques am Abdomen bei einem 35-jährigen Patienten.

A 35-year-old man presented with two annular, reddish-brown, atrophic skin lesions in the navel and on the right lower abdomen. The lesions had persisted for more than 4 years and had remained unchanged and asymptomatic. Histology revealed annular atrophic lichen planus with a lichenoid lymphocytic infiltration and cystoid bodies. The patient was treated with local corticosteroids without improvement.

Effects of neratinib and combination with irradiation and chemotherapy in head and neck cancer cells.

OBJECTIVE: Prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. Novel therapeutic approaches are of great interest to improve the effects of radiochemotherapy. We evaluated the effects of tyrosine kinase inhibitor neratinib on HNSCC cell lines CAL27, SCC25 and FaDu as a single agent and in combination with irradiation and chemotherapy. METHODS: Effects of neratinib were evaluated in HNSCC cell lines CAL27, SCC25 and FaDu. Effect on cell viability of neratinib and combination with cisplatin and irradiation was measured using CCK-8 assays and clonogenic assays. Western blot analysis was performed to distinguish the effect on epithelial growth factor receptor and HER2 expression. Apoptosis was evaluated by flow cytometry analysis. RESULTS: Growth inhibition was achieved in all cell lines, whereas combination of cisplatin and neratinib showed greater inhibition than each agent alone. Apoptosis was induced in all cell lines. Combination of neratinib with irradiation or cisplatin showed significantly increased apoptosis. In clonogenic assays, significant growth inhibition was observed in all investigated cell lines. CONCLUSION: Neratinib, as a single agent or in combination with chemo-irradiation, may be a promising treatment option for patients with head and neck cancer.

[Robotic-Assisted Liver Surgery]. / Roboterassistierte Leberchirurgie.

BACKGROUND: The advantages of minimally invasive liver resections for selected patients are evident. Robots provide new innovations that will influence minimally invasive liver surgery in the future. This article presents our initial experience with this technology in our patient population. Material und Methods: In 14 patients with benign or malignant liver tumours, robotic-assisted liver surgery was performed. Selection criteria were compensated liver function and resection of ≤ 3 liver segments. Chronic liver disease or previous abdominal surgery were no exclusion criteria. RESULTS: Malignant liver tumours were removed in 10 patients (71%) and benign symptomatic liver tumors in 3 patients (21%), respectively, with histopathologically negative margins (R0). One patient suffering from HCC underwent intraoperative ablation. In one case (7%) conversion was necessary. Mean operation time was 296 min (120-458 min); mean estimated blood loss was 319 ± 298 ml. The mean hospital stay of the patients was 8 days (3-17 days). Three patients (21%) suffered from postoperative complications, which were manageable by conservative treatment (Clavien-Dindo I) in 2 cases (14%). One patient (7%) needed endoscopic treatment for postoperative bile leak (Clavien-Dindo III a). No patient died intra- or perioperatively. CONCLUSION: Robotic-assisted liver surgery is a safe procedure, which provides patients with all benefits of minimally invasive surgery. This highly advanced technology requires surgeons to strive for an increasing level of specialisation, in addition to being well-trained in liver surgery. Hence, a clear definition of the procedures and standardised teaching programs are necessary.

The effect of resveratrol in combination with irradiation and chemotherapy: study using Merkel cell carcinoma cell lines.

BACKGROUND AND PURPOSE: Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines. MATERIALS AND METHODS: The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array. RESULTS: Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines. CONCLUSION: Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested.

[Dexamethason implant in the treatment of macular edema in retinal vein occlusion and intraocular inflammatory disease]. / Dexamethasonimplantat zur Behandlung des Makulaödems bei retinalen venösen Gefäßverschlüssen und entzündlichen Augenerkrankungen.

BACKGROUND: The efficacy of a single dose of Ozurdex® was evaluated over a 6-month period in eyes with macular edema due to retinal vein occlusion and intraocular inflammatory disease. HISTORY AND SIGNS: 20 eyes of 20 consecutive patients with macular edema received a single injection of Ozurdex® (intravitreal dexamethasone implant 0.7 mg). Patients with branch retinal vein occlusion (n = 11), central retinal vein occlusion (n = 6), non-infectious posterior uveitis (n = 1) and Irvine-Gass Syndrome (n = 2) were included. In 10 patients Ozurdex® was used as the first treatment, 10 patients had undergone previous treatments for macular edema. The mean duration from the symptoms to the initiation of the treatment was 14.2 (1-60) months. The follow-up measurements were performed 1, 3 and 6 months after treatment. The main interest of the study was the visual and structural development over the duration of 6 months after a single dose of Ozurdex® with outcome measures including changes in best-corrected visual acuity and central retinal thickness. THERAPY AND OUTCOME: At baseline, the mean best-corrected visual acuity of all patients was 50 (± 16) ETDRS letters and the mean central retinal thickness was 632 (± 168.3) microns. Mean follow-up time was 3.4 (± 1.5) months and 7 patients dropped out during the follow-up period (4 patients after 3 months, additional 3 patients after 6 months). One month after treatment, 14 out of 20 patients (70%) showed a complete regression of macular edema, and in 6 cases (30%) it was partially recurrent. The mean best-corrected visual acuity improved to 56 (± 20.8) ETDRS. Central retinal thickness showed a mean decrease to 278 (± 84.9) microns. 6 months after treatment, recurrence was observed in 9 cases out of the remaining 13 patients (69.2%). In 3 cases, macular edema persisted (23.1%) and in one case (7.7%) the macula remained dry. The mean best-corrected visual acuity was 55 (± 13.9) ETDRS letters. The mean central retinal thickness decreased to 603 (± 174.6) microns. CONCLUSIONS: Ozurdex® showed a good effect in the treatment of macular edema one month after its application, namely a temporary decrease in central retinal thickness and a corresponding increase in best-corrected visual acuity. 6 months after treatment, the recurrence rate was high, and only one person with a branch retinal vein occlusion remained relapse-free over the entire follow-up. Based on our data, the patients should be checked at the latest after 3 months and then monthly in order to detect relapse in time and to initiate another treatment if needed.

[Heavy tamponade in complicated inferior retinal detachment]. / Schwere Tamponade bei komplizierten inferioren Netzhautablösungen.

BACKGROUND: Retinal detachment with inferior proliferative vitreoretinopathy is a difficult to treat problem. The aim of our study was to assess the safety and efficacy of Densiron in the clinical management of complicated retinal detachment. HISTORY AND SIGNS: 6 eyes of 6 consecutive patients presenting with a retinal detachment with inferior proliferative vitreoretinopathy grade 3 were treated with pars plana vitrectomy and injection of Densiron. The mean age of the patients was 61 years. 3 patients had a previous unsuccessful vitreoretinal surgery and 3 patients had Densiron as a first procedure. The extent of detachment was at least 2 or more quadrants with macular involvement in 3 cases. Preoperatively the mean visual acuity was 29.2 letters with ETDRS. THERAPY AND OUTCOME: Densiron was removed after an average of 58 days. 5 patients achieved retinal re-attachment without further tamponade, and 1 patient after additional injection of conventional silicon oil. 4 - 6 weeks after removal of Densiron the mean visual acuity was 50.2 letters with ETDRS. The most common complication was an elevated intraocular pressure during endotamponade, which resolved following removal of the agent. CONCLUSIONS: Densiron improves inferior tamponade, and in clinical practice may be considered to increase the anatomic success rate in selected cases of complicated retinal detachment with inferior proliferative vitreoretinopathy.

RCAS-1 serum and tumor levels in head and neck squamous cell carcinoma.

BACKGROUND/AIMS: RCAS-1 is a transmembrane protein that is involved in the evasion of host immune surveillance by tumor cells. It has been found to be a valuable prognostic and diagnostic marker in a number of different malignancies. The objective of the study was to analyze the potency of RCAS-1 as a biomarker in the serum of patients with head and neck squamous cell carcinoma (HNSCC). METHODS: ELISA was performed with prospectively collected serum samples from 60 patients with HNSCC (taken at the time of diagnosis, after 3 and 12 months) and from 31 healthy controls. To correlate serum levels with RCAS-1 expression in the tumor, immunohistochemical staining of RCAS-1 was done using a tissue microarray. RESULTS: Surprisingly, median sRCAS-1 levels were basically identical between tumor patients and controls. Interestingly, patients with low RCAS-1 values at the time of diagnosis had better disease-free survival. 62% of tumor samples expressed RCAS-1 but we could not demonstrate a correlation between protein expression and serum levels. CONCLUSION: This study was the first to correlate RCAS-1 levels in the serum and in the tumor of the same patients. RCAS-1 seems to have prognostic properties although larger studies will be necessary to fully evaluate its role in HNSCC.

A T-cell-specific CD154 transcriptional enhancer located just upstream of the promoter.

CD154 (CD40-ligand) is a critical immune regulator. CD154 expression is tightly regulated and largely restricted to activated CD4 T cells. Using DNase I hypersensitivity site (HSS) mapping, we identified two novel HSS mapping to the human CD154 promoter element and just upstream. Both HSS were activation independent and CD4 T-cell specific. Approximately 350 bp of DNA sequence flanking the upstream HSS site was highly conserved between mouse and man, and was rich in binding sites for GATA and NFAT proteins. Gel shift and chromatin immunoprecipitation assays demonstrated both NFAT1 and the Th2 factor, GATA-3, bound this enhancer element in vitro and in vivo, respectively. A PstI/XbaI 345 bp fragment of this region acted as a transcriptional enhancer of the CD154 promoter in primary human CD4 T cells. Overexpression of repressor of GATA and a dominant negative GATA-3 protein independently inhibited transcription, whereas overexpression of wild-type GATA-3 enhanced transcriptional activity, by this element in primary CD4 T cells. Moreover, more interleukin-4-producing CD4 T cells expressed CD154 following activation than interferon-gamma-producing CD4 T cells. Thus, we identified a novel T-cell-specific, GATA-3 responsive, CD154 transcriptional enhancer, which may contribute to increased propensity of Th2 cells to express CD154.