Oncological outcome after MRI-based selection for neoadjuvant chemoradiotherapy in the OCUM Rectal Cancer Trial.

BACKGROUND: It is not clear whether all patients with rectal cancer need chemoradiotherapy. A restrictive use of neoadjuvant chemoradiotherapy (nCRT) based on MRI findings for rectal cancer was investigated in this study. METHODS: This prospective multicentre observational study included patients with stage cT2-4 rectal cancer, with any cN and cM0 status. Carcinomas in the middle and lower third that were 1 mm or less from the mesorectal fascia, all cT4 tumours, and all cT3 tumours of the lower third were classified as high risk, and these patients received nCRT followed by total mesorectal excision (TME). All other carcinomas with a minimum distance of more than 1 mm from the mesorectal fascia and those in the upper third were classified as low risk; these patients underwent TME alone (no nCRT). Patients were followed for at least 3 years. Outcomes were the rates of local recurrence, distant metastasis and survival. RESULTS: Among 545 patients included, 428 were treated according to the study protocol: 254 (59·3 per cent) had TME alone and 174 (40·7 per cent) received nCRT and TME. Median follow-up was 60 months. The 3- and 5-year local recurrence rates were 1·3 and 2·7 per cent respectively, with no differences between the two treatment protocols. Patients with disease requiring nCRT had higher 3- and 5-year rates of distant metastasis (17·3 and 24·9 per cent respectively versus 8·9 and 14·4 per cent in patients who had TME alone; P = 0·005) and worse disease-free survival compared with that in patients who did not need nCRT (3- and 5-year rates 76·7 and 66·7 per cent, versus 84·9 and 76·0 per cent in the TME-alone group; P = 0·016). CONCLUSION: Restriction of nCRT to high-risk patients achieved good results.

Damage control surgery in perforated diverticulitis: ongoing peritonitis at second surgery predicts a worse outcome.

PURPOSE: Damage control strategy (DCS) is a two-staged procedure for the treatment of perforated diverticular disease complicated by generalized peritonitis. The aim of this retrospective multicenter cohort study was to evaluate the prognostic impact of an ongoing peritonitis at the time of second surgery. METHODS: Consecutive patients who underwent DCS for perforated diverticular disease of the sigmoid colon with generalized peritonitis at four surgical centers were included. Damage control strategy is a two-stage emergency procedure: limited resection of the diseased colonic segment, closure of oral and aboral colon, and application of a negative pressure assisted abdominal closure system at the initial surgery followed by second laparotomy 48 h later. Therein, decision for definite reconstruction (anastomosis or Hartmann's procedure (HP)) is made. An ongoing peritonitis at second surgery was defined as presence of visible fibrinous, purulent, or fecal peritoneal fluid. Microbiologic findings from peritoneal smear at first surgery were collected and analyzed. RESULTS: Between 5/2011 and 7/2017, 74 patients underwent a DCS for perforated diverticular disease complicated by generalized peritonitis (female: 40, male: 34). At second surgery, 55% presented with ongoing peritonitis (OP). Patients with OP had higher rate of organ failure (32 vs. 9%, p = 0.024), higher Mannheim Peritonitis Index (25.2 vs. 18.9; p = 0.001), and increased operation time (105 vs. 84 min., p = 0.008) at first surgery. An anastomosis was constructed in all patients with no OP (nOP) at second surgery as opposed to 71% in the OP group (p < 0.001). Complication rate (44 vs. 24%, p = 0.092), mortality (12 vs. 0%, p = 0.061), overall number of surgeries (3.4 vs. 2.4, p = 0.017), enterostomy rate (76 vs. 36%, p = 0.001), and length of hospital stay (25 vs. 18.8 days, p = 0.03) were all increased in OP group. OP at second surgery occurred significantly more often in patients with Enterococcus infection (81 vs. 44%, p = 0.005) and with fungal infection (100 vs. 49%, p = 0.007). In a multivariate analysis, Enterococcus infection was associated with increased morbidity (67 vs. 21%, p < 0.001), enterostomy rate (81 vs. 48%, p = 0.017), and anastomotic leakage (29 vs. 6%, p = 0.042), whereas fungal peritonitis was associated with an increased mortality (43 vs. 4%, p = 0.014). CONCLUSION: Ongoing peritonitis after DCS is a predictor of a worse outcome in patients with perforated diverticulitis. Enterococcal and fungal infections have a negative impact on occurrence of OP and overall outcome.

COMPRES: a prospective postmarketing evaluation of the compression anastomosis ring CAR 27(™) /ColonRing(™).

AIM: Preclinical studies have suggested that nitinol-based compression anastomosis might be a viable solution to anastomotic leak following low anterior resection. A prospective multicentre open label study was therefore designed to evaluate the performance of the ColonRing(™) in (low) colorectal anastomosis. METHOD: The primary outcome measure was anastomotic leakage. Patients were recruited at 13 different colorectal surgical units in Europe, the United States and Israel. Institutional review board approval was obtained. RESULTS: Between 21 March 2010 and 3 August 2011, 266 patients completed the study protocol. The overall anastomotic leakage rate was 5.3% for all anastomoses, including a rate of 3.1% for low anastomoses. Septic anastomotic complications occurred in 8.3% of all anastomoses and 8.2% of low anastomoses. CONCLUSION: Nitinol compression anastomosis is safe, effective and easy to use and may offer an advantage for low colorectal anastomosis. A prospective randomized trial comparing ColonRing(™) with conventional stapling is needed.

[Quality indicators of diagnosis and therapy in MRI-based neoadjuvant radiochemotherapy for rectal cancer - interim analysis of a Prospective Multicentre Observational Study (OCUM)]. / Qualitätsindikaktoren der Diagnose und Therapie bei MRT-basierter neoadjuvanter Radiochemotherapie des Rektumkarzinoms - Interimsanalyse einer prospektiven, multizentrischen Beobachtungsstudie (OCUM).

BACKGROUND: The interim analysis of a prospective multicentre observational study of selective neoadjuvant chemoradiotherapy (OCUM) in patients with rectal cancer should evaluate the quality of diagnosis and therapy as a prerequisite for continuation of the study. PATIENTS AND METHODS: 230 patients with the clinical stage cT2 - 4, each cN, M0 with radical tumour resection were enrolled until now. The values of 13 quality indicators were compared with the target values formulated by the workflow of the Working Group rectal cancer II and the German Cancer Society and were also compared with the results of the certified bowel centres of Germany 2010. RESULTS: The target values were fulfilled to a high degree regardless of caseload. 83 % of parameters have been fully achieved and 14 % nearly achieved. In primary surgery the proportion of patients with 12 or more histologically examined lymph nodes was 99.2 %, after neoadjuvant chemoradiotherapy 90 %. A R0 resection was performed in 98.3 % and a resection of TME in muscularis propria plane only in 2.2 %. The rate of positive circumferential resection margins (pCRM + ) was 5.7 % only. CONCLUSIONS: The high quality of rectal surgery justifies the concept and the continuation of the study.

[Abdominal vacuum therapy for the open abdomen - a retrospective analysis of 82 consecutive patients]. / Intraabdominelle Vakuumtherapie des offenen Abdomens - Eine retrospektive Analyse von 82 konsekutiven Patienten.

BACKGROUND: The therapy for open abdomen remains challenging. Abdominal vacuum therapy seems to simplify the treatment and to enable a direct fascial closure in a high percentage of the patients. PATIENTS AND METHODS: A retrospective analysis of 82 consecutive patients who underwent abdominal vacuum therapy between January 2005 and December 2007 was undertaken. Indications, -duration of treatment, complications as well as rate and type of abdominal wall closure were evaluated. RESULTS: The 82 consecutive patients consisted of 46 % female and 54 % male patients with a median age of 65.5 years. The most frequent diagnoses were colorectal carcinoma (24 %, n = 28, colon n = 18 and rectum n = 10), inflammatory bowel dis-ease (13 %), perforated peptic ulcer (9 %), necrotising pancreatitis (7 %), peritoneal carcinosis (5 %), ileus (5 %) and mesenteric ischaemia (4 %). The predominant indication for vacuum therapy was peritonitis (88 %). Vacuum therapy treatment was applied for a median of 6 days (range: 1-73 days). 18 patients (22 %) received intraabdominal foam dressings without the fenestrated polyurethane layer. In 70 % of all cases the abdominal vacuum therapy was performed without complications. 16 patients (19.5 %) developed intestinal fistulas. However, fistulas were not observed among the patients who were treated with foam dressings without a polyurethane layer. Abdominal bleeding was observed in 8 patients (10 %) and a persistent abdominal compartment syndrome was seen in one patient. Nine patients (11 %) died during hospitalisation. After completion of the intraabdominal vacuum therapy, -direct fascial closure was feasible in 35 patients (43 %). In 47 patients (57 %) an absorbable synthetic mesh was required for fascial closure. Symptomatic incisional hernias -occurred in 22 % of the patients. CONCLUSION: Abdominal vacuum therapy simplifies the treatment of patients with abdominal catastrophes such as peritonitis or necrotising pancreatitis. The cost-effective intraperitoneal use of a foam dressing without a fenestrated polyurethane layer was possible without an increased rate of fistulas. This retrospective analysis demonstrates that abdominal vacuum therapy can be performed without complications in the majority of patients. Furthermore, direct fascial closure is possible in almost half of the patients.

Inhibition of protein synthesis: a mechanism for the production of impaired iron absorption.

Treatment of rats with cycloheximide results in a defect in intestinal iron transport. A similar defect occurs after the parenteral administration of iron. Under both conditions there is impaired uptake of iron into the mucosal cells as well as defective transfer from the intestinal mucosa. It is suggested that the interference in iron transport may be due to a deficiency of an unidenti-fild carrier Substance.

Metal-mediated linear self-assembly of porphyrins.

Porphyrin derivatives are highly relevant to biological processes such as light harvesting and charge separation. Their aromatic electronic structure and their accessible HOMO-LUMO gap render porphyrins highly attractive for the development of opto- and electro-active materials. Due to the often difficult covalent synthesis of multiporphyrins, self-assembly using metal complexation as the driving force can lead to well defined objects exhibiting a controlled morphology, which will be required to analyse and understand the electronic properties of porphyrin wires. This article presents two assembly approaches, namely by peripheral coordination or by binding to a metal ion in the porphyrin core, that are efficient and well designed for future developments requiring interactions with a surface.

[Anopexy according to Longo for hemorrhoids]. / Anopexie nach Longo bei Hämorrhoiden.

The treatment for hemorrhoids ranges from conservative management to surgical procedures. The procedures are tailored to the individual grading of hemorrhoids and the individual complaints. The standard Goligher classification of the hemorrhoids is the basis for further treatment and no differentiation is made between segmental hemorrhoids and circular hemorrhoids. In the case of advanced circular hemorrhoid disease the surgical procedure with a stapler, so-called stapler anopexy, is the procedure of choice.

Use of Preoperative Magnetic Resonance Imaging to Select Patients with Rectal Cancer for Neoadjuvant Chemoradiation--Interim Analysis of the German OCUM Trial (NCT01325649).

INTRODUCTION: Introduction of total mesorectal excision (TME) surgery for rectal cancer decreased local recurrence dramatically. Additional neoadjuvant chemoradiation (nCR) is frequently given in UICC II and III tumors based on TNM staging which is of limited accuracy. We aimed to evaluate determination of circumferential margin by magnetic resonance imaging (mrCRM) as an alternative criterium for nCR. METHODS: Multicenter prospective cohort study which enrolled 642 patients in 13 centers with non-metastasized rectal adenocarcinoma. Patients with T4 tumors or patients with a mrCRM of 1 mm or less were treated by neoadjuvant chemoradiation. All others proceeded directly to surgery when inclusion criteria and no exclusion criteria were met. Quality of TME and accuracy of mrCRM determination were assessed during pathology workup. RESULTS: TME was complete in 381 of 389 patients after surgery without nCR (97.9%) and in 245 of 253 patients (96.8%) after nCR. Negative pathology circumferential margins (pCRM) were seen in 97.4% without nCR and in 89% of patients after nCR. Negative pCRM was predicted by negative mrCRM in 98.3% of rectal cancers. NCR was given to 253 of 642 patients (39.5%). Lymph node count was 23 (range 7-79; median/range) for surgery without nCR and 19 (range 2-56) for surgery after nCR. CONCLUSIONS: Surgical quality determined by pathology workup of specimen was very good in this study. Magnetic resonance imaging guided indication for nCR allows to achieve superb results concerning surrogate parameters for good oncological outcome. Thus, use of neoadjuvant chemoradiation with its potential detrimental side effects may be substantially reduced in selected patients.

[Lymph node dissection after primary surgery and neoadjuvant radiochemotherapy of rectal cancer. Interim analysis of a multicenter prospective observational study (OCUM)]. / Lymphknotendissektion nach primärer Chirurgie und neoadjuvanter Radiochemotherapie des Rektumkarzinoms. Interimsanalyse einer multizentrischen prospektiven Beobachtungsstudie (OCUM).

INTRODUCTION: The OCUM trial (NCT01325649) aims to clarify whether low rates of local recurrence are also achieved when the indications for neoadjuvant radiochemotherapy are not based on the clinical TNM staging but on preoperative magnetic resonance imaging with measurement of the tumor distance to the circumferential resection margin. In this interim analysis the lymph node status in OCUM patients was investigated as a surrogate parameter for quality of surgery and histopathological work-up. MATERIAL AND METHODS: Until now a total of 560 patients have been included in this study. Total mesorectal excision (TME) without pretreatment was undertaken in 338 patients (60.4 %) and neoadjuvant radiochemotherapy was administered in 222 (39.6 %) patients. The histological work-up was performed according to the guidelines of the German Association of Pathologists. Data are given as median values and ranges in brackets. RESULTS: The lymph node yield was 24 (7-79) in 338 patients undergoing primary TME surgery without pretreatment, while 20 (3-56) lymph nodes were identified in patients after neoadjuvant radiochemotherapy (p = 0.001). A minimum of 12 lymph nodes were analyzed in 335 out of 338 patients (99.1 %) and in 209 out of 222 patients (94.1 %) following neoadjuvant radiochemotherapy (p = 0.001). Lymph node metastasis was identified (p = 0.362) in 116 out of 338 patients without pretreatment (34.3 %) and in 71 out of 222 patients after neoadjuvant radiochemotherapy (32.0 %). Patient age did not influence the number of identified lymph nodes or rate of lymph node metastasis. CONCLUSION: In this trial the number of identified lymph nodes suggests that the quality of surgery and histopathological work-up were adequate compared to the standards defined by national guidelines. Neoadjuvant radiochemotherapy led to a reduced lymph node yield compared to surgery without pretreatment; however, this did not influence the rate of lymph node metastasis.

[Spincter preservation after selective chemoradiotherapy of rectal cancer. Interim results of the OCUM study]. / Spinktererhalt nach selektiver Radiochemotherapie des Rektumkarzinoms. Zwischenergebnisse der OCUM-Studie.

BACKGROUND: In a prospective multicenter observational study (OCUM) neoadjuvant chemoradiotherapy (nRCT) was selectively administered depending on the risk of local recurrence and based on the distance between tumor and mesorectal fascia in pretherapeutic high-resolution magnetic resonance imaging (MRI). OBJECTIVE: Frequency and quality of abdominoperineal excision (APE) and sphincter preserving operations. PATIENTS AND METHODS: Of 642 patients treated in 13 hospitals 389 received surgery alone and 253 nRCT followed by surgery. By univariate and multivariate analysis risk factors for APE were determined. Quality parameters were the quality grade of mesorectal excision, the pathohistological involvement of the circumferential resection margin and intraoperative local dissemination of tumor cells. RESULTS AND DISCUSSION: In 12.8 % of the patients APE was performed. Independent risk factors for APE were tumor location in the lower third of the rectum and the individual hospitals, where APE varied between 0 and 32 %. This variation was chiefly caused by the different case mix. Hospitals with a high APE rate (> 30 %) treated significantly more patients with very low lying carcinomas (< 3 cm above the anal verge) and more advanced tumors. The median height of the tumor in cases of APE was nearly equal in all participating hospitals. Independent on the number of cases the quality of rectal surgery was high. Within the patient groups of primary surgery and nRCT the oncological quality parameter did not significantly differ between sphincter preservation and APE. As far as sphincter preservation is concerned the results justify a selective application of nRCT in patients with rectal carcinoma. The long-term results still have to be awaited.

Oligodendroglioma with a twenty-two year history. Clinicopathological case report.

Clinico-pathologic report of a patient with an oligodendroglioma who ran a 22-year course characterized by focal epileptic seizures of the Jaksonian type. The EEG remained normal for many years. Since the tumor had not been influenced by therapeutic measures, the histologic picture permitted considering some basic problems of origin, growth, and differentiation of oligodendrogliomas.

Intracranial giant cell arteritis.

A case of giant cell arteritis of intracranial vessels diagnosed by autopsy is described. Giant cell arteritis of the proximal basal brain arteries was exceptionally marked in a man of 60 years. The clinical course, laboratory findings and the pathological alterations of the brain and intracranial blood vessels are described. The case is discussed on the basis of the literature on giant cell arteritis with cerebral symptoms as well as on granulomatous giant cells arteritis of the brain. A separation of these two entities does not seem justified.

A modular approach to porphyrin oligomers using metal ions as connectors.

Porphyrins bearing two external coordination sites allowed the stepwise preparation of polymetallic oligomers connected by metal centers.

Kinetic studies on glial, Schwann and capsular cells labelled with [3H] thymidine in cerebrospinal tissue of young mice.

Neuroglia, capsular and Schwann cell renewal and turnover in the cerebellum, the spinal cord and spinal ganglia have been evaluated in 2-months-old mice. The animals received intraperitoneal injections of [3H] thymidine at 8 hr intervals starting on the 28th day of postnatal life for a period of 30 days and were killed 1 hr after the last injection. Substantial numbers of labelled neuroglial cells but no labelled neurons were observed. Oligodendrocytes of the cerebellum and the spinal cord showed higher labelling indices (19.8% and 18.0%, respectively) than astrocytes (10.0%) and Bergmann's supporting cells (7.2%). The labelling indices of capsular cells in the spinal ganglia and Schwann cells in the spinal roots were 35.8% and 25.8%, respectively. The experiments failed to provide evidence for matrix cell layers in the cerebellum, the spinal cord and spinal ganglia. It may be concluded therefore that glial and Schwann cells in these parts of the nervous system proliferate in situ.

Effects of colchicine on myelination of rabbit optic nerve: a biochemical study.

The effects of intravitreous injections of colchicine on the myelination of the optic nerve were studied in rabbits at different times during development using biochemical and morphological techniques. Myelin basic protein concentrations and 2',3-cyclic nucleotide 3'-phosphodiesterase activities were affected in a similar way by colchicine treatment and reflected the degree of myelination of the tissue. During early development, colchicine produced axonal degeneration and secondary demyelination (Wallerian degeneration). Later, axonal and myelin abnormalities were more variable. Some demyelination was observed amd myelin formation also may have been inhibited. Thus, the effect of colchicine was proportional to the degree of optic nerve and retinal maturation (the youngest being the most sensitive) and, to a lesser extent, to the dosage, Under conditions used for this study, no remyelination was observed. In adult animals, no lesions could be detected histologically one to four months after injection of colchicine, Thus, intravitreous administration of colchicine is a useful chemical technique for producing Wallerian degeneration in optic nerves of young developing rabbits.

Inductive properties of recombinant human BMP-2 produced in a bacterial expression system.

Recombinant human BMP-2, produced in E. coli, refolded and concentrated to a purity of more than 98%, has been demonstrated to be biologically active. In vitro, amounts of 0.4 microg BMP-2 or more induced new cartilage formation in 27 out of 47 samples of a neonatal muscle tissue assay, with chondroneogenesis occurring 14 days after a four-hour contact between BMP-2 and the muscle tissue. In vivo, BMP-2 was implanted in the thigh muscle of ICR mice for a period of three weeks. Amounts of 4 microg BMP-2 and more showed heterotopic bone formation in 15 out of 17 samples. When BMP-2 was combined with a collagen carrier, amounts of 0.4 microg protein or more induced heterotopic bone formation in 30 out of 33 samples four weeks after the implantation in the abdominal wall of Sprague-Dawley rats. The results show that the E. coli-derived BMP-2 was active in different assay systems in concentrations equal to those required with mammalian cell-expressed BMP-2. It could also be demonstrated that a single morphogen (BMP-2) is enough to initiate the differentiation process associated with bone induction. The presented bacterial expression system also offers the opportunity to produce large quantities of recombinant BMP-2 for clinical applications.

Psychological aspects of lay caregiving.

Caregiving is an extremely demanding task that frequently takes a toll on lay caregivers. Furthermore, the psychological aspects of caregiving are frequently overlooked. To study this issue, a nurse surveyor conducted an informal nonscientific survey of 68 lay caregivers over a 14-month period. An interview process was used to obtain information. Those who were surveyed identified depression, powerlessness, role strain, guilt, and grief as the psychological aspects most frequently related to the caregiving experience. This information can be used to initiate nursing care plans, assessments, and interventions. It is vital for the healthcare community to recognize the needs of lay caregivers. Training programs must be implemented and other support and resources should be available so that the needs and issues of lay caregivers can be dealt with effectively.

[Traumatic anterior dislocation of the sportsman's hip]. / Traumatische anteriore Erstluxation der Hüfte beim Sportler.

We report on a 46-year-old male patient without any prior deformities who got a luxation of the right hip when he played soccer. After the immediate reposition during general anaesthesia the patient is symptom-free up to now. Luxations after hip replacement are indeed well-known and common, but this traumatic luxation in an adult patient is an unusual sports injury.