Laparoscopic and open surgery in rectal cancer patients in Germany: short and long-term results of a large 10-year population-based cohort

Rectal cancer is frequent in Germany and worldwide. Several studies have assessed laparoscopic surgery as a treatment option and most have shown favorable results. However, long-term oncologic safety remains a controversial issue. The current dataset derives from 30 clinical cancer registries in Germany and includes 16,378 patients diagnosed with rectal cancer between 2007 and 2016. Outcomes were 90-day mortality, overall survival (OS), local recurrence-free survival (RFS) and relative survival of patients treated with either open or laparoscopic surgery. Multivariable logistic regression was used to evaluate factors that affected the probability of a patient undergoing laparoscopic surgery as well as to evaluate short-term mortality. OS and RFS were analyzed by Kaplan–Meier plots and multivariable Cox regression conducted separately for UICC stages I–III, tumor location, and sex as well as by propensity score matching followed by univariable and multivariable survival analysis. Of 16,378 patients, 4540 (27.7%) underwent laparoscopic surgery, a trend which increased during the observation period. Patients undergoing laparoscopy attained better results for 90-day mortality (odds ratio, OR 0.658, 95% confidence interval, CI 0.526–0.822). The 5-year OS rate in the laparoscopic group was 82.6%, vs. 76.6% in the open surgery group, with a hazard ratio (HR) of 0.819 in multivariable Cox regression (95% CI 0.747–0.899, p < 0.001). The laparoscopic group showed a better 5-year RFS, with 81.8 vs. 74.3% and HR 0.770 (95% CI 0.705–0.842, p < 0.001). The 5-year relative survival rates were also in favor of laparoscopy, with 93.1 vs. 88.4% (p = 0.012). Laparoscopic surgery for rectal cancer can be performed safely and, according to this study, is associated with an oncological outcome superior to that of the open procedure. Therefore, in the absence of individual contraindications, it should be considered as a standard approach.     

The impact of interleukin serum levels on the prognosis of patients undergoing venoarterial extracorporeal membrane oxygenation

Extracorporeal life support is increasingly used in the treatment of patients presenting with cardiogenic shock or in need of cardiopulmonary resuscitation. Identifying therapeutic targets and factors associated with the prognosis are highly desirable. The present study analyzed the impact of interleukin 6 and 8 on the outcome of patients undergoing venoarterial extracorporeal membrane oxygenation (VA ECMO). Interleukin 6 and 8 serum levels of 329 patients were analyzed prior to, on days 1 and 5 of VA ECMO therapy. Interleukin 6 and 8 serum levels of surviving and nonsurviving patients were compared. At time points with significant differences, receiver operating characteristics and cutoff levels were analyzed to determine the prognostic value of interleukin serum levels. Survival analysis was performed to compare patients above and below cutoff levels. Interleukin 6 serum levels were significantly elevated in nonsurviving patients prior to VA ECMO initiation. Interleukin 6 and 8 serum levels in nonsurviving patients were significantly elevated on day 1 of VA ECMO. Receiver operating characteristics analysis revealed significant prognostic impact of interleukin 6 and 8 on day 1 of VA ECMO (AUC 0.70 and 0.72). Survival analysis comparing patients above and below the cutoff showed a 1-year survival of 32.6% for IL6 and 20.8% for IL8 above, as well as 66.9% for IL6 and 61.9% for IL8 below the cutoff (P < .05). Interleukin 6 and 8 serum levels demonstrated prognostic value early in VA ECMO therapy. The technical applicability of interleukin reduction raises interest in interleukins 6 and 8 as therapeutic targets.     

Comparison of fluconazole with oral polyenes in the prevention of fungal infections in neutropenic patients

The goal of this prospective randomized single-center study was the comparison of safety and efficacy of high-dose oral/intravenous fluconazole (400 mg daily) (group A) with oral nystatin plus miconazole inhalations (group B) in the prevention of fungal infections on a hemato-oncological isolation Ward. Of 157 patients admitted to the isolation ward during the study period only 90 (57%) were eligible for randomization; 22 (14%) had a fungal infection at admission. Of the 90 randomized patients, 89 were evaluable, 43 in group A and 46 in group B. The age, sex, diagnosis, planned therapy and risk factors for fungal infections at admission as well as the duration of neutropenia were in the same proportions in both groups. Oral thrush and mucocutaneous candidiasis were prevented in all patients of both groups, and 29 patients (32%: 17 in group A, 12 in group B) were discharged after successful prophylaxis (NS). Empiric amphotericin B was given according to predetermined criteria to 45 patients (51%: 23 group A, 22 group B; NS). Fluconazole significantly delayed the time before the start of intravenous amphotericin B. It was begun after a median of 10 days (0–45 days, range) of neutropenia below 0.5x10⁹ granulocytes/l in group A and 7.5 days (0–26, range) in group B (P<0.05). The duration of successful prophylaxis was significantly longer in group A (26 days median) than in group B (21 days, median) (P<0.05). Systemic fungal infection was documented in 3 patients (1 group A, 2 group B; NS). Colonisation with Candida persisted for more than 14 days or occurred de novo after admission in 1 patient in group A and in 7 patients in group B (NS). Oral nystatin had to be discontinued because of oral intolerance in 3 patients and fluconazol had to be stopped because of increased liver values in one patient. Compliance was worse (P<0.01) in group B; 82% of the planned dose was given in group B compared to 99% in group A. Both regimens successfully prevented oral fungal complications. Fluconazole was better tolerated and delayed the need for empiric amphotericin B. Neither approach cancelled the need for the empiric use of amphotericin B nor prevented fungal infections or colonization. Systemic fungal infections occur probably independently of oral or mucocutaneous candidiasis.     

The visual word form area and the frequency with which words are encountered: evidence from a parametric fMRI study

Cohen and Dehaene et al. proposed that the Visual Word Form Area (VWFA) in the left midfusiform gyrus, contrary to its name, is limited to the extraction of an abstract letter string and not involved in proper visual word recognition. We examined this prelexical function of the VWFA by a parametric block design with five levels of written word frequency. The lowest level was represented by pseudowords and the highest level by words of very high frequency. Contrary to the assumed prelexical function of the VWFA, increasing frequency was associated with decreasing brain activation in a large posterior cluster of the left hemisphere including middle and posterior fusiform regions. The same negative relation between frequency and activation was found in several left frontal clusters. The relation of increasing frequency and decreasing activation in occipitotemporal regions corresponds to a similar relation in the same brain regions found by studies which experimentally manipulated object or face familiarity. This convergence suggests that fusiform regions are specialized for extracting and storing abstract patterns when processing visual objects and these patterns serve as recognition units in subsequent encounters with the same objects.     

Multiple endocrine neoplasia 1--current recommendations for diagnosis and treatment

BACKGROUND: The principally affected glands in the MEN 1 syndrome (parathyroids, pancreas, pituitary and adrenal glands) are often diffusely or multi-centrically involved, making different therapeutic approaches necessary. METHODS: In a retrospective analysis of 10 patients with genetically proven (n = 7) or clinically suspected (n = 3) MEN 1 syndrome, recommendations for diagnosis, timing of interventions and surgical procedures are reviewed. RESULTS: All patients had primary hyperparathyroidism (PHPT). An extended bilateral exploration localized 4 or more enlarged glands in 6 patients and subtotal parathyroidectomy (SPTX) was performed. In 4 patients, only one (n = 2) or two (n = 2) enlarged glands were removed. Two patients were reoperated for persistent PHPT and one patient developed recurrent PHPT. In 3 out of 6 patients, neuroendocrine pancreatic tumors were the first manifestation. 2 patients had solitary, one patient multiple benign and one patient multiple malignant insulinomas. Tumors were removed by enucleation, distal pancreatic resection or a combination of both. Out of the 2 patients with gastrinomas, one underwent partial pancreatoduodenectomy and the other has refused operation up to now. During follow-up, no persistence or recurrence of hormone excess was diagnosed. Three patients had non-functioning bilateral lesions of the adrenal glands, and one of these additionally had a small, clinically insignificant pheochromocytoma. Adrenalectomy was performed during pancreatic surgery in 2 patients, and endoscopically in one patient. Pituitary tumors were treated in 3 patients. CONCLUSION: A high index of clinical suspicion, biochemical screening and menin gene testing, according to current guidelines, is mandatory for early diagnosis of MEN 1. In PHPT with multiglandular involvement and neuroendocrine pancreatic tumors, meticulous surgery can achieve a long-term cure in the majority of patients, with low morbidity.     

Development of leukemia in donor cells after allogeneic stem cell transplantation--a survey of the European Group for Blood and Marrow Transplantation (EBMT)

Leukemia in donor cells (donor cell leukemia; DCL) has been reported as a rare but severe complication of allogeneic stem cell transplantation (SCT). However, the incidence, potential pathogenetic factors, therapeutic options and outcome of patients suffering from DCL and the leukemia risk of their donors are not well defined. A questionnaire survey was carried out within European Blood and Marrow Transplantation Group (EBMT) centers. Ninety-one EBMT centers participated in this survey, covering 10489 allogeneic SCT between 12/1982 and 09/2003. Fourteen cases of DCL, most with a myeloid phenotype (7 cases of acute myeloid leukemia, 3 each of acute lymphocytic leukemia and 1 case of chronic myeloid leukemia) were identified. Demonstration of donor cell origin included molecular analysis of chimerism in most cases. DCL type and cytogenetic alterations were independent from the original disease. The median time between transplantation and diagnosis of DCL was 17 months (4-164). No type of conditioning, donor, graft manipulation, graft-versus-host disease prophylaxis or subsequent complications were identified as risk factors for DCL. Chemotherapy induced remissions in DCL and 2 of 5 patients remain alive in remission after a second transplant. None of the stem cell donors developed hematologic malignancies (median follow-up period of 9 years; range 6-30 years). DCL is an extremely rare complication of allogeneic SCT in which treatment attempts with chemotherapy and a second SCT are justified. Donors are not at an increased risk of developing hematologic malignancies.     

Cell Migration Inhibition in Human Lymphomas Using Lymph Node and Cell Line Antigens

In an attempt to demonstrate in vitroreactions against autologous and allogenic lymph node (LN) extracts inlymphoma patients, 15 cases werestudied using as controls two normalLN extracts and leukocytes from 17blood donors. The techniques appliedwere migration inhibition tests carriedout directly on peripheral leukocytesand indirectly using lymphocyte culture supernatants on guinea pig peritoneal macrophages. The antigens(Ag) used were partially purified salineextracts of neoplastic LN, culturedneoplastic cells of lymphosarcoma(LS) origin, and normal LN. It wasobserved that autologous LN extractselicited migration inhibition in the fourcases of LS studied and in four out ofsix cases of Hodgkin’s disease (HD),while normal LN extracts gave negative results in these patients. Positivereactions were observed in four out ofsix LS cases using allogenic LS extracts, either from LN or from cell lines.No cross-reactions could be demonstrated in HD. All Ag gave negativeresults with leukocytes from normalblood donors. The positive autologousreaction suggests the presence of atumor Ag in neoplastic LN, while theimmunologic cross-reaction betweensome of the LS patients would pointto a common Ag, persisting in at leastone of the LS cell lines and perhapsrelated to a virus.

Submitted on July 15, 1971 Accepted on September 12, 1971     

The Wuerzburg Hybridoma Library against Drosophila Brain

Abstract: This review describes the present state of a project to identify and characterize novel nervous system proteins by using monoclonal antibodies (mAbs) against the Drosophila brain. Some 1,000 hybridoma clones were generated by injection of homogenized Drosophila brains or heads into mice and fusion of their spleen cells with myeloma cells. Testing the mAbs secreted by these clones identified a library of about 200 mAbs, which selectively stain specific structures of the Drosophila brain. Using the approach “from antibody to gene”, several genes coding for novel proteins of the presynaptic terminal were cloned and characterized. These include the “cysteine string protein” gene (Csp, mAb ab49), the “synapse-associated protein of 47 kDa” gene (Sap47, mAbs nc46 and nb200), and the “Bruchpilot” gene (brp, mAb nc82). By a “candidate” approach, mAb nb33 was shown to recognize the pigment dispersing factor precursor protein. mAbs 3C11 and pok13 were raised against bacterially expressed Drosophila synapsin and calbindin-32, respectively, after the corresponding cDNAs had been isolated from an expression library by using antisera against mammalian proteins. Recently, it was shown that mAb aa2 binds the Drosophila homolog of “epidermal growth factor receptor pathway substrate clone 15” (Eps15). Identification of the targets of mAbs na21, ab52, and nb181 is presently attempted. Here, we review the available information on the function of these proteins and present staining patterns in the Drosophila brain for classes of mAbs that either bind differentially in the eye, in neuropil, in the cell-body layer, or in small subsets of neurons. The prospects of identifying the corresponding antigens by various approaches, including protein purification and mass spectrometry, are discussed.     

Women's quality of life and sexual function after transvaginal anterior repair with mesh insertion

Objective

Current evidence about the impact of pelvic floor surgery on sexual function is conflicting. Only a few studies have reported with validated questionnaires on sexual function after transvaginal mesh repair, with a discrepancy in reported outcomes. The aim of this study was to prospectively explore the impact of anterior repair (AR) with mesh insertion on sexual function, quality of life and dyspareunia.

Study design

69 women with symptomatic stage II or greater prolapse exclusively of the anterior compartment participated in a prospective study on safety and efficacy of two mesh implantation techniques for anterior vaginal wall prolapse repair between September 2007 and May 2009. They were invited to complete the validated condition-specific short form of the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and quality of life (QoL) questionnaires (Pelvic Organ Prolapse (POP) Distress Inventory (POPDI), Urinary Distress Inventory (UDI), POP Impact Questionnaire (POPIQ), and Urinary Impact Questionnaire (UIQ)) pre-operatively and 6 months post-operatively. All data were processed and analyzed in Statistical Computing Environment R, version 2.9.1.

Results

A significant decrease of Qol scores and a significant increase of PISQ-12 scores occurred after surgery. All sexually active women resumed sexual activity postoperatively. The majority of non-sexually active women remained sexually inactive. Postoperatively the frequency of pain during intercourse increased in 31% of cases and decreased or stayed unchanged in 69% of cases. The incidence of de novo dyspareunia after mesh repair was 4% while the incidence of dyspareunia slightly increased from 25% to 29% postoperatively.

Conclusions

The results of this study suggest no deterioration in sexual function, a significant improvement in quality of life and a low incidence of de novo dyspareunia six months after AR with mesh insertion. Despite these findings, the majority of non-sexually active women remain sexually inactive postoperatively. These conclusions should be confirmed in a longer follow-up.