Aromatase inhibitors as a therapeutic strategy for male prolactinoma resistant to dopamine agonists: a retrospective cohort study and literature review.

PURPOSE: To assess the effect of letrozole, an aromatase inhibitor (AI), in patients with resistant prolactinoma that presented an increase in serum prolactin (PRL) levels during testosterone replacement therapy (TRT). METHODS: A retrospective cohort study in a single tertiary care center. From March 2012 to July 2023, 53 male patients over 18 years with prolactinoma were followed in our Neuroendocrine Unit. Of those, 90.6% presented macroadenomas, 41% of them were resistant to cabergoline and 25% presented persistent hypogonadism to whom TRT was indicated. Among them, five presented a significant increase in PRL levels and AI was initiated. All five patients had resistant prolactinomas. One of them was excluded due to tumor aggressiveness and concomitant use of temozolomide during AI therapy. RESULTS: Four patients were included in the analysis, with a mean age of 28.5 (± 7.5) years, median prolactin of 1060 (600 to 6700) ng/mL and median of the largest tumor diameter of 3.6 (1.5 to 5) cm at the time of prolactinoma diagnosis. On TRT, all presented an increase in serum PRL levels (231 to 396%), with a subsequent decrease (61 to 93%) after adding AI. During AI treatment for a median time of 60.5 (21 to 120) months, tumor shrinkage was observed in two cases (-8 and -3 mm in the maximum diameter) and tumor stability in the other two. No major side effects occurred and AI was well tolerated. CONCLUSION: AI might be an option for men with resistant prolactinoma who have an increase in PRL levels on TRT. Nevertheless, prospective randomized clinical trials are needed to ensure efficacy and security for this approach.

Preoperative factors correlated with post-bariatric surgery weight loss.

Whether preoperative parameters can predict weight loss following bariatric surgery is a matter of debate. We conducted a longitudinal and prospective pilot study on 35 patients that underwent bariatric surgery, with a 12-month follow-up. In the preoperative period, a high HOMA-beta index, lower fasting blood glucose, and lower HbA1c were correlated with a lower BMI at 12 months. Traditional preoperative factors, such as weight and BMI, were correlated with the postoperative BMI values. The presence of well-controlled diabetes may influence weight loss after surgery.

Phylodynamics for cell biologists.

Multicellular organisms are composed of cells connected by ancestry and descent from progenitor cells. The dynamics of cell birth, death, and inheritance within an organism give rise to the fundamental processes of development, differentiation, and cancer. Technical advances in molecular biology now allow us to study cellular composition, ancestry, and evolution at the resolution of individual cells within an organism or tissue. Here, we take a phylogenetic and phylodynamic approach to single-cell biology. We explain how "tree thinking" is important to the interpretation of the growing body of cell-level data and how ecological null models can benefit statistical hypothesis testing. Experimental progress in cell biology should be accompanied by theoretical developments if we are to exploit fully the dynamical information in single-cell data.

[Stabilization of the pelvic ring with photodynamic bone stabilization (IlluminOss™)]. / Stabilisierung einer Beckeninsuffizienzfraktur mit einem photosensiblen Kunststoff (IlluminOss™).

We describe the case of an 88-year-old woman who presented with painful symptoms of the pelvis after low-energy trauma. Conservative treatment with pain therapy and pain-adapted mobilization was unsuccessful. Diagnostics showed a fragility fracture of the pelvic ring; therefore, we performed photodynamic bone stabilization (IlluminOss™) of the pubic bone and percutaneous cement-augmented fixation of the iliosacral joint assisted by computed tomography (CT) fluoroscopy. Imaging showed a stable healed fracture 4 months after surgery.

Suture-free and mesh reinforced small intestinal anstomoses: a feasibility study in rabbits.

INTRODUCTION: Anastomotic leakage still remains a major complication in general surgery. Beside general risk factors, the ideal method of anastomotic technique has not been found until now. The aim of the present study was to analyze wound healing in suture-free small intestine anastomoses using fibrin glue with and without mesh-reinforcement. METHODS: Laparotomy and four different types of small bowel anastomoses were performed in 32 chinchilla rabbits. Standard hand-sewn anastomoses (CG), suture-free glued anastomoses (FG) with and without mesh reinforcement using two different types of meshes [Vicryl-mesh (VM) and Surgisis (SM)]. Animals were sacrificed after 5 and 21 days. Bursting pressure, collagen type I/III ratio, and matrix-metalloproteinase 2, 9, and 13 were analyzed. RESULTS: None of the animals died due to an anastomotic leakage. All animals in the long term group with Surgisis mesh died due to a mechanical bowel obstruction based on a distinctive stenosis of the anastomosis. The bursting pressures did significantly differed in animals with fibrin glue alone compared to animals with Vicryl-mesh reinforcement (p < 0.05). Histological examination revealed statistically significant differences (p < 0.05) in the values for MMP-2 (VM < SM), MMP-9 (VM < CG), and MMP-13 (CG < SM, VM < FG, and VM < SM). However, collagen type I/III ratios were not significantly different between groups. CONCLUSIONS: Our results suggest that a mesh reinforced glued anastomosis is technically feasible. Furthermore, mesh-reinforcement using VM increased the integrity and simplified the technique of suture-free anastomoses.

[Realistic surgical training. The Aachen model]. / Praxisnahe Weiterbildung: Das Aachener Modell.

The Aachen model is a practical mode in teaching and advanced training, which is closely geared to the areas of academic acquisition and training. During medical education optional student courses with constitutive curricula offer practical points of contact to the surgical department at all times. Besides improvement of manual training the aims are enhancing interests and acquisition of talents. This guided structure will be intensified with progression into advanced education. Next to the formal guidelines of the curriculum, education logbook and progression conversations, quality, transparency and reliability are particularly emphasized. An evaluation of both the reforms and the surgical trainers is still to be made. In addition procurement of an affirmative occupational image is essential.

Intraepithelial CD8-positive T lymphocytes predict survival for patients with serous stage III ovarian carcinomas: relevance of clonal selection of T lymphocytes.

BACKGROUND: The aim of this study was to investigate the prognostic effect of tumour-infiltrating lymphocytes (TILs) in serous stage III ovarian carcinoma to determine TIL clonality and to correlate this to Her2/neu expression. METHODS: Formalin-fixed and paraffin-embedded ovarian carcinomas were examined for CD20-, CD3-, CD4- and CD8-positive lymphocytes (n=100), and for Her2/neu-positive tumour cells (n=55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor gamma (TCRgamma) gene rearrangements (n=93/100). Statistical analyses included experimental and clinico-pathological variables, as well as disease-free (DFS) and overall (OS) survival. RESULTS: CD20-positive B lymphocytes were present in 57.7% (stromal)/33.0% (intraepithelial) and CD3-positive T lymphocytes in 99.0% (stromal)/90.2% (intraepithelial) of ovarian carcinomas. Intraepithelial CD3-positive T lymphocytes were correlated with improved DFS in optimally debulked patients (P=0.0402). Intraepithelial CD8-positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P=0.0201) and in those undergoing paclitaxel/carboplatin therapy (P=0.0092). Finally, rarified and clonal TCRgamma gene rearrangements were detected in 37 out of 93 (39.8%) and 15 out of 93 (16.1%) cases, respectively. This was marginally associated with improved DFS (P=0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8-positive lymphocytes (P=0.0264), this was non-directional (R=-0.257; P=0.0626). CONCLUSION: Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes.

[Risk factors for anastomotic leakage after colorectal surgery]. / Risikofaktoren für das Auftreten postoperativer Anastomoseninsuffizienzen nach kolorektalen Resektionen.

BACKGROUND: Despite improved surgical techniques, anastomotic leakage is still a serious complication in colorectal surgery, resulting in increased morbidity and mortality. This study was initiated to investigate those clinical risk factors which may influence the onset of anastomotic wound-healing complications. METHODS: The postoperative courses were assessed in 400 consecutive patients who underwent colonic or rectal resection. Possible clinical risk factors were investigated by unvariate and multivariate analysis. RESULTS: 23 patients developed an anastomotic leakage (5.8 %). 10 patients could be treated conservatively, 13 had a second operation. In the multivariate analysis significant risk factors were perioperative radiotherapy (OR = 3.76 [95 % CI 1.03-13.7]), blood transfusion (OR = 2.98 [95 % CI 1.18-7.54]), alcohol consumption (OR = 2.94 [95 % CI 1.06-8.17]), and steroid medication (OR = 3.91 [95 % CI 1.17-13.07]). CONCLUSION: The clinically most important risk factors for leakage were radiotherapy and blood transfusion. Further analyses with a focus on the extracellular matrix, including other clinical factors may be valuable in identifying targets for improvement.

[Acute appendicitis. Modern diagnostics--surgical ultrasound]. / Akute Appendizitis. Moderne Diagnostik--der chirurgische Ultraschall.

Acute appendicitis is one of the most common acute surgical conditions of the abdomen. Nevertheless, the indications for appendectomy are associated with a high preoperative rate of false diagnoses. Although the rate of unnecessary appendectomies is comparatively high (20-30%) it is considered acceptable because the rate of perforated appendices is 7-30%. With good availability and lack of radiation exposure, ultrasound is the slice imaging modality of first choice. The sensitivity of ultrasonic detection of appendicitis lies between 55 and 98% and the specificity between 78 and 100%. Computed tomography (CT) has a significantly higher sensitivity for detecting acute appendicitis compared to ultrasound both in infancy and adulthood but the specificity shows no significant differences. CT is, therefore, the imaging modality of choice in cases of relevant differential diagnosis that cannot be visualized adequately or inconclusively by sonography especially in obese and critically ill patients. Comparison of ultrasound and magnet resonance imaging (MRI) revealed a significant advantage for MRI regarding accuracy, sensitivity and negative predictive value. In contrast, specificity and positive predictive value showed no significant differences. Currently MRI is only an alternative imaging modality to ultrasound in cases of undetermined and inconclusive ultrasonic findings especially in childhood and pregnancy. The value of ultrasound in the diagnosis of acute appendicitis is increasing and, particularly in the hands of experienced investigators, is an important imaging modality which delivers important and decision-making findings. Nevertheless, the final decision for appendectomy depends on the findings of the physical examination.

[Surgery for rectal cancer]. / Chirurgie des Rektumkarzinoms.

During the last decade surgical treatment of rectal cancer has seen various improvements. Partial or total mesorectal excision (TME) became standard procedure. The surgical quality of the TME has a high effect on prognosis. Besides metastases, the circumferential resection margin receives the most attention. As recent studies established a distal resection margin of 1 cm, the rate of continence-preserving resections has grown, especially after neoadjuvant radiochemotherapy. In the hands of an expert, laparoscopic rectal resection is a technically safe procedure. Its oncological efficacy cannot yet be decided. Modern therapy for rectal cancer comprises multilateral considerations and therefore needs a multimodal orientation.

The lateral incisional hernia: anatomical considerations for a standardized retromuscular sublay repair.

BACKGROUND: The management of incisional hernias outside the midline remains a challenging procedure. Evidence-based data and even any kind of guidelines for dealing with this problem are still lacking. The aim of the study was to elucidate this field of hernia surgery and give some guidelines for retromuscular sublay mesh repair outside the midline. MATERIALS AND METHODS: Fresh-frozen corpses were used to perform anatomical studies. During all the investigations the main target was to find the layer which can maintain the maximum overlap of healthy tissue with the implanted mesh material. Afterwards the findings were evaluated during clinical situations, using photo-documentation and drawings. RESULTS: The layer between the external oblique muscle and the internal oblique muscle is the ideal place to position the mesh with adequate overlap. Even for subcostal hernias, this layer offers adequate mesh overlap behind the ribs. For lumbar hernias the same plane of dissection is usually useful. Only if the defect is situated close to the bone might preperitoneal dissection and mesh placement be necessary. CONCLUSION: The repair of lateral hernias must follow the same principles as median sublay repair. With sufficient knowledge of the anatomical layers of the abdominal wall, adequate mesh overlap can be achieved for any kind of lateral hernia. Therefore the retromuscular sublay repair can be regarded as the standard procedure for all types of hernia outside the midline.

Influence of mesh materials on the integrity of the vas deferens following Lichtenstein hernioplasty: an experimental model.

BACKGROUND: The utilization of mesh reinforcement of the inguinal area with polypropylene mesh has increased drastically over the last decade. Infertility due to obstructive azoospermia is a rare but serious complication following inguinal hernia repair, especially in young patients. The aim of this study was to evaluate the effect of different mesh structures on integrity of the vas deferens. MATERIALS AND METHODS: Twenty male Chinchilla rabbits were used. The spermatic cord was dissected free and a Lichtenstein repair was performed with a low-weight polypropylene mesh (UltraPro) and a heavy-weight polypropylene mesh (Prolene) on the contralateral side. A vasography was performed after six months in order to investigate obstructions of the vas deferens. Light microscopy of the mesh host tissue interface was also performed and the foreign body reaction analyzed. Spermatogenesis was evaluated using the Johnsen score. RESULTS: Vasography revealed relevant obstructions (>75% of lumen diameter) located at the mesh margins (50% of Prolene and 22.2% of UltraPro mesh samples). Microscopic investigation of the mesh-host tissue interface showed typical formation of foreign body granulomas. The diameters of the foreign body granulomas were significantly reduced in the UltraPro mesh group (41.7 +/- 5.5 microm) compared to the Prolene mesh group (48.7 +/- 7.7 microm). Upon investigating the percentages of apoptotic (TUNEL) and proliferating (Ki67) cells, no significant differences were found. Following Prolene mesh implantation, a mean Johnsen score of 9.1 +/- 1.2 was estimated, which was not significantly different from the UltraPro mesh samples (8.9 +/- 1.4, P > 0.05). CONCLUSIONS: If a mesh material is needed for inguinal hernia repair in young patients, the use of modern low-weight large porous and elastic samples appears to have a beneficial effect on integrity of the vas deferens.

Molecular mechanism underlying the association of Coronin-7 with Golgi membranes.

Coronin-7 (Crn7) is a ubiquitous mammalian WD40-repeat protein that localizes to the Golgi complex, interacts with AP-1 adaptor complex via binding of a tyrosine-288-based sorting signal to the mu1-subunit of AP-1, and participates in the maintenance of the Golgi structure and function. Here, we define the requirements for the recruitment of Crn7 from the cytosol to the Golgi. We establish that Src activity is indispensable for the interaction of Crn7 with Golgi membranes. Crn7 binds Src in vivo and can be phosphorylated by recombinant Src in vitro. We demonstrate that tyrosine-758 is the major Src phosphorylation site. Further, to be targeted to membranes Crn7 requires the presence of cargo in the Golgi complex. Finally, downregulation of the mu1-subunit of AP-1 leads to the dispersal of Crn7 from the Golgi membranes. We propose a mechanism whereby sequential events of protein interaction and posttranslational modification result in the membrane targeting of Crn7.

The MSKCC nomogram for prediction the likelihood of non-sentinel node involvement in a German breast cancer population.

OBJECTIVE: To assess whether the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram for prediction of NSLN metastasis is useful in a German breast cancer population and whether the characteristics of the breast tumor and the sentinel lymph node (SLN) are able to predict the likelihood of non-sentinel lymph node (NSLN) metastasis. METHODS: A total of 545 patients with primary breast cancer and SLN examination were evaluated. The MSKCC nomogram was applied to 98 patients with a positive SLN who subsequently had completion axillary lymph node dissection (ALND). Predictive accuracy was assessed by calculating the area under the receiver-operator characteristic (ROC) curve. The collective was evaluated by correlating the prevalence of NSLN and SLN metastasis to pathological features. RESULTS: The MSKCC nomogram achieved a ROC of 0.58 indicating a bad accuracy of the nomogram. Tumor size, histology, lymphovascular infiltration, multifocality, Her-2-neu positivity, and nuclear grade correlated with the probability of SLN metastasis. Histology and primary tumor localization correlated significantly with the probability of NSLN metastasis. CONCLUSIONS: The MSKCC nomogram did not provide a reliable predictive model in our study population. However, the likelihood of SLN metastasis correlated with the presumed risk factors and no obvious differences between the MSKCC population and our population could be seen. In order to achieve interinstitutional reproducibility, standardization of surgical procedure and of the pathological assessment of the SLN is desirable.

Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy.

Coronin-3 (coronin-1C), a homotrimeric F-actin binding protein, has been shown to be important for cell migration and brain morphogenesis. Here, we present for the first time a detailed analysis of the expression pattern of coronin-3 in human brain tumours and demonstrate that coronin-3 expression correlates with malignant phenotype in diffuse gliomas. In general, the expression of coronin-3 varies in different brain tumour entities. However, in diffuse gliomas, the number of coronin-3 expressing tumour cells correlates with the degree of malignancy. High-grade gliomas, such as anaplastic astrocytomas, anaplastic oligodendrogliomas, anaplastic oligoastrocytomas and glioblastomas, show high numbers of tumour cells positive for coronin-3, while diffuse low-grade gliomas, such as diffuse astrocytomas, oligodendrogliomas and oligoastrocytomas, exhibit low numbers of coronin-3-positive tumour cells. In order to explore and verify a contribution of coronin-3 to the malignant phenotype of diffuse gliomas, we employed an efficient shRNA-mediated coronin-3 knockdown in U373 and A172 human glioblastoma cells. Coronin-3 knockdown glioblastoma cells exhibited reduced levels of cell proliferation, cell motility and invasion into extracellular matrix compared to control cells. Together, our findings demonstrate evidence for a contribution of coronin-3 expression in the malignant progression of diffuse gliomas.

Different matrix micro-environments in colon cancer and diverticular disease.

BACKGROUND AND AIMS: The extracellular matrix and the interactive signalling between its components are thought to play a pivotal role for tumour development and metastasis formation. An altered matrix composition as potential underlying pathology for the development of colorectal cancer was hypothesized. METHODS: In a retrospective study of patients with colon cancer, the extracellular matrix in tumour-free bowel specimen was investigated in comparison with non-infected bowel specimen from patients operated on for colonic diverticulosis. The following matrix parameters with known associations to tumour formation, cell proliferation, invasion and metastasis were analysed by immunohistochemistry and quantified by a scoring system: VEGF, TGF-beta, ESDN, CD117, c-erb-2, cyclin D1, p53, p27, COX-2, YB-1, collagen I/III, MMP-13, PAI and uPAR. Expression profiles and correlations were calculated. RESULTS: The comparison of the two groups revealed a significantly decreased immunostaining for CD117 and TGF-beta in the cancer group (8.5+/-2.6 vs 10.3+/-2,1 and 4.9+/-1.5 vs 8.1+/-3, respectively), whereas PAI scores were significantly higher than in patients with diverticular disease (8.1+/-1.6 vs 6.2+/-0.9). Overall correlation patterns of matrix parameters indicated pronounced differences between tumour-free tissue in cancer patients compared with patients with diverticular disease. CONCLUSIONS: Our results indicate distinct differences in the colonic tissue architecture between cancer patients and patients with diverticulitis that support the notion of an altered matrix composition predisposing to the development of colon cancer.

The rare epidemiologic coincidence of diverticular disease and advanced colonic neoplasia.

BACKGROUND AND AIMS: In Western industrialised countries the prevalence of neoplastic colonic lesions and diverticular disease markedly increases with age. In contrast, the coincident occurrence of both diseases seems to fall below their individual epidemiologic estimates. Because directly comparing data are rare, this retrospective study evaluates the coincidence of neoplastic lesions and diverticular disease. PATIENT AND METHODS: A total of 1,838 patients from 1986 to 2000 were admitted to the study. For 1,326 patients-56% male (n=741), 44% female (n=585), mean age 64 (+/-11.83 SD)-with a resection due to colonic cancer, the documented findings of colonoscopy, colonic contrast enema, and/or histopathology were analysed with regard to the prevalence of colonic diverticulosis. In 512 patients--51% male (n=263), 49% female (n=249), mean age 60 (+/-12.59 SD)--with a colonic resection due to diverticulitis, the synchronous or metachronous occurrence of neoplastic colonic lesions was recorded using the database of the Tumour Centre, Aachen. To compare the observed results with published epidemiology, statistical analysis included age-referred binomial tests and an age-stratified analysis (Cochran-Mantel-Haenszel test). Odds ratios (OR) were also calculated. P<0.05 was considered to indicate locally statistical significance. RESULTS: In the cancer group, we found a statistically significant reduced rate of diverticula in nearly all age categories and the age-stratified analyses (corresponding OR 0.30-0.51). Consistently, the diverticulitis group revealed a statistically significant decreased rate of advanced colonic neoplastic lesion in nearly all age categories and all age-stratified analyses (corresponding OR 0.13-0.43). CONCLUSION: Our results indicate that patients with colonic neoplastic lesions or diverticular disease probably form heterogeneous groups. Because current results from molecular biology emphasize the impact of the extracellular matrix on the genesis of diverticulosis and colonic cancer, the observed heterogeneity could be an expression of a distinct composition of the local milieu.

Influence of pneumoperitoneum on small bowel anastomoses: a histological analysis in the rat model.

Laparoscopic techniques are increasingly applied for the treatment of diverse gastrointestinal diseases. With regard to reports of a pronounced decrease of intra-abdominal blood flow with increasing intra-abdominal pressure, the present study investigates the impact of pressure and gas type on ischemia in small bowel anastomoses in the rat model. Laparotomy and ileoileal anastomosis were performed in 39 male Sprague-Dawley rats. A CO2 or helium pneumoperitoneum of 3 mm Hg or of 6 mm Hg was maintained before and after anastomoses. Rats in the control group received no pneumoperitoneum. Animals were sacrificed after 5 d, and the anastomotic region was explanted for subsequent histopathological examinations. In hematoxylin and eosin (HE)-stained sections, the Chiu score, villi configuration, and number of goblet cells were analyzed. Proliferation (Ki67) and expression of a matrix metalloproteinase (MMP-8) were examined by immunohistochemistry. Mucosal damage according to the scoring system by Chiu, the number of goblet cells, the villus length, the proliferation (Ki67), and the submucosal expression of MMP-8 was similar in all groups. Our results suggest that within a certain range of pressures and time, laparoscopic assisted surgery using CO2 pneumoperitoneum can be performed safely. Helium gas offers no advantages over CO2.