Consequence of restaging after neoadjuvant treatment for locally advanced rectal cancer.

BACKGROUND: Locally advanced rectal cancer is customarily treated with neoadjuvant chemoradiotherapy (CRT) followed by a total mesorectal excision. During the course of CRT, previously non-detectable distant metastases can appear. Therefore, a restaging CT scan of the chest and abdomen was performed prior to surgery. The aim of this study was to determine the frequency of a change in treatment strategy after this restaging CT scan. METHODS: Patients treated with neoadjuvant CRT for locally advanced rectal cancer between January 2003 and July 2013 were included retrospectively. To determine the value of the restaging CT scan, the surgical treatment as planned before CRT was compared with the treatment ultimately received. RESULTS: A total of 153 patients (91 male) were eligible, and median age was 62 (32-82) years. The restaging CT scan revealed the presence of distant metastases in 19 patients (12.4, 95 % confidence interval [CI] 7.0-17.8). In 17 patients (11.1, 95 % CI 6.1-16.1), a change in treatment strategy occurred due to the detection of metastases with a restaging CT scan. CONCLUSION: A restaging CT scan after completion of neoadjuvant CRT may detect newly developed metastases and consequently alter the initial treatment strategy. This study demonstrated the added value of the restaging CT scan prior to surgery.

Immunohistochemical detection of very recent myocardial infarctions in humans with antibodies against heart-type fatty acid-binding protein.

Depletion of human heart-type fatty acid-binding protein (H-FABP) from cardiomyocytes in infarcted areas with varying postinfarction intervals was studied in 25 autopsy cases. In 23 autopsy cases myocardial infarction was the clinical diagnosis; 2 cases were noncardiac deaths and served as controls. Formaldehyde-fixed and paraffin-embedded myocardial tissue sections were stained immunohistochemically with antibodies to human H-FABP. H-FABP immunohistochemical findings were compared with those from conventional nitroblue tetrazolium (NBT) macroenzyme staining and conventional histochemical hematoxylin-eosin staining of sections of the same infarctions. In all cases of infarction confirmed by NBT staining, decreased or absent H-FABP immunostaining was observed. In 12 cases of clinically diagnosed infarction, H-FABP depletion could be demonstrated in areas that showed normal NBT staining. These findings strongly suggest that immunohistochemical staining with antibodies to H-FABP can confirm the clinical diagnosis or suspicion of early myocardial infarction. In both control cases no depletion of H-FABP was observed in cardiomyocytes in different myocardial tissue sections, and macroenzyme staining with NBT was normal. We conclude that H-FABP immunostaining may detect very recent ischemia/ infarction in human myocardium and can be applied in routine autopsy pathology.

Changes in canine latissimus dorsi muscle during 24 wk of continuous electrical stimulation.

To study functional, structural, and biochemical adaptations to electrical stimulation of striated muscle in a large animal, the canine latissimus dorsi (LD) muscle was conditioned continuously for 24 wk with an increasing number of pulse bursts (burst duration 250 ms, burst frequency 30 Hz). Force measurements in vivo after 12 wk showed a significant decrease in the ripple, the ratio of interstimulus to peak force amplitude, from 0.94 +/- 0.03 to 0.13 +/- 0.08 (SE; n = 8, P less than 0.05), indicating reduction in contractile speed. Also the steep part of the force-frequency relation shifted to lower frequencies. A significant change in fiber-type composition was seen with both enzyme- and immunohistochemistry, manifested by an increase of type I fibers from 29.5 +/- 2.9 to 83 +/- 8% (SE; n = 8, P less than 0.05). During this period a transient rise in the number of type IIc/Ic fibers (from 3 to 10%) was seen. In the stimulated muscle, capillary-to-fiber ratio increased from 1.9 +/- 0.4 to 2.7 +/- 0.1 (P less than 0.05). A significant increase in mitochondrial volume was also seen, especially in the peripheral part of the fiber. Both creatine kinase and lactate dehydrogenase revealed a significant decline in activity within 12 wk. At the same time a shift in lactate dehydrogenase-isozyme pattern was observed toward the cardiac composition. No additional changes occurred after 12 wk of stimulation, indicating that conversion of the canine LD muscle was complete within this period.

Histopathologic validation of intracoronary ultrasound imaging.

The purpose of this study was to validate intracoronary ultrasound imaging by correlation with histologic examination. In this in-vitro study of pressure-perfused human coronary arteries, 104 matching intracoronary ultrasound imaging images and histologic cross-sections from 12 hearts were compared to determine the diagnostic accuracy of 30 MHz commercially available intracoronary ultrasound imaging. For lipid deposits, sensitivity was 46% and specificity 97%. The smallest lipid deposit that was visualized measured 0.25 mm in axial diameter on histologic study. For calcific deposits, sensitivity was 77% and specificity 100%. The smallest calcific deposit that was visualized measured 0.25 mm in axial diameter on histologic examination. Atherosclerotic intimal thickening could not be distinguished qualitatively or quantitatively from nonatherosclerotic intimal thickening unless there were localized deposits of lipids or calcium. Intracoronary ultrasound imaging is accurate in detecting lipid and calcium deposits. Intimal thickening in intracoronary ultrasound imaging images does not prove the presence of atherosclerosis.

Evaluation of gracilis muscle transposition for fecal incontinence with magnetic resonance imaging.

Ten consecutive patients with incapacitating fecal incontinence were treated with 'anal dynamic graciloplasty' (transposition of the gracilis muscle around the anal canal and implantation of intramuscular electrodes connected with an implanted pulse generator, 6 weeks later) to achieve continence. We measured the gracilis muscle diameter immediately after transposition and before implantation of the stimulation device. It was found that gracilis diameter decreased from 12 (5 days after transposition) to 8 mm, 6 weeks later (mean decrease: 4 mm (95% confidence interval 3.6), n = 10, P < 0.05). In addition, morphology demonstrated a decrease of both Type I and Type II muscle fiber diameter and an increase in endomysial collagen. Despite this decrease in muscle (and muscle fiber) diameter, electrical stimulation of the transposed gracilis muscle increased the pressure into the anal canal from 37 to 55 mmHg (mean increase: 17 mmHg (95% confidence interval 6.29), P < 0.05). Fecal continence was achieved in seven (70%) of these patients. Further analysis revealed no correlations between reduction of the gracilis muscle diameter before implantation of the stimulation device and clinical outcome in terms of achieved continence and/or anal canal pressures. MRI is an excellent method to demonstrate the shape of gracilis muscle after transposition. However, the size of transposed gracilis muscle is not associated with the functional outcome.

[Anal dynamic plastic surgery of the gracilis muscle; a new surgical technique for the treatment of fecal incontinence]. / Anale dynamische M. gracilis-plastiek; een nieuwe chirurgische techniek voor de behandeling van fecale incontinentie.

OBJECTIVE: To study the clinical outcome of anal dynamic graciloplasty (gracilis muscle transposition and implantation of electric stimulation device) in a consecutive series of 12 patients. DESIGN: Prospective study. SETTING: Maastricht University Hospital. PATIENTS AND METHODS: Twelve patients with incapacitating faecal incontinence were treated using anal dynamic graciloplasty because they were not amenable to other medical management. The data were analysed with emphasis on the clinical outcome, anal manometry, and gracilis muscle composition before and after electric stimulation. Results were considered significant if p < or = 0.05, using the paired Student's t-test. RESULTS: Eight patients achieved complete faecal continence, one patient still has a previously constructed colostomy and in three patients no faecal incontinence could be achieved, due to infections. Median follow-up is now over 18 months (range 16 weeks-5 years). Anal manometry demonstrated an anal pressure increased from 39 mmHg (without stimulation) to 66 mmHg with electric stimulation (mean increase 27 mmHg (CI: 19-35; n = 12, p < 0.01). Gracilis muscle composition showed an increase of type I relatively fatigue-resistant fibres, capable of prolonged contractions, from 45% before stimulation to 64% afterwards (mean increase 19% (CI: 14-21; n = 8, p < 0.01). CONCLUSION: Dynamic graciloplasty is capable of replacing the function of damaged or absent anal sphincters. The construction of a colostomy in patients with incapacitating faecal incontinence can be avoided.

Recurrent adult nephroblastoma. Long-term remission after surgery plus adjuvant high-dose chemotherapy, radiation therapy, and allogeneic bone marrow transplantation.

The authors report a case of Stage IV, unfavorable histologic type adult nephroblastoma. The patient was treated with multimodal therapy: combination chemotherapy consisting of cyclophosphamide, doxorubicin, cisplatin, and etoposide succeeded by nephrectomy and radiation therapy. After a disease-free period of 27 months, a pararectal relapse was treated by surgery, high-dose chemotherapy, and allogeneic bone marrow transplantation (BMT). The patient is alive and disease-free 3.5 years after BMT.

Endobronchial non-Hodgkin lymphoma: report of two cases.

Two cases of endobronchial localised non-Hodgkin lymphoma are presented. Pathogenesis, clinical history, diagnosis and treatment of this unusual localisation of non-Hodgkin lymphoma are reviewed.

The spectrum of death after myocardial infarction: a necropsy study.

To determine the relative frequency of the causes of death in the acute (less than 24 hours), early (24 hours to 3 weeks), and chronic (greater than 3 weeks) phases of myocardial infarction, data from all autopsies performed at a university hospital during a 56-month period were reviewed. Autopsies were performed in 56% of in-hospital deaths and 27% of patients dead on arrival in the emergency room (out-of-hospital deaths). In 271 cases of suspected cardiac death, a myocardial infarction of any age was identified. Death had occurred in the acute phase of a first infarction in 19 patients and was most frequently due to pump failure (37%) followed by cardiac rupture (26%) and arrhythmias (21%). Death had occurred 24 hours to 3 weeks after a first infarction in 80 patients and was most frequently due to pump failure (44%), rupture (27%), and arrhythmias (16%). Recurrent acute infarction was found in 32% of patients whose deaths were due to arrhythmias or pump failure and in 19% of those whose deaths were due to rupture. Death had occurred greater than 3 weeks after a first infarction in 172 patients. In 132 (77%) of these patients death was due to a complication of a new acute or recent infarction. Myocardial rupture was a less frequent cause of death in patients with recurrent infarction (8%) than in those dying in the acute or early phase after their first infarction (27%, p = 0.0009). A primary arrhythmia in the absence of recurrent infarction or ischemia accounted for only 14% of out-of-hospital deaths late after an infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Basement membrane deposition in benign and malignant naevo-melanocytic lesions: an immunohistochemical study with antibodies to type IV collagen and laminin.

Patterns of basement membrane deposition were investigated in benign and malignant naevo-melanocytic lesions using antibodies to type IV collagen and laminin. Paraffin sections required pretreatment with 6 M guanidine-HCl in addition to pepsin pretreatment. Basement membrane deposition was found around clusters as well as individual naevo-melanocytic cells in contact with dermal stroma. However, between keratinocytes and intra-epidermally located naevo-melanocytic cells, basement membrane immunostaining could not be detected. Tumour cell-stromal interaction is apparently a prerequisite for basement membrane deposition in naevo-melanocytic lesions. Basement membrane discontinuities, in the absence of inflammatory infiltrate, appeared, in doubtful cases, to be evidence in favour of malignant melanoma. The general pattern of basement membrane deposition in benign and malignant lesions was found to be similar and therefore of no help in differential diagnosis. Identification of hyaline bodies, which show immunoreactivity with antibodies to basement membrane components, may be helpful in distinguishing between Spitz naevi and malignant melanomas. Detection of vascular invasion, a prognostic indicator in malignant melanoma, is facilitated by basement membrane immunostaining.

Muscle fiber typing in routinely processed skeletal muscle with monoclonal antibodies.

Muscle fiber typing is conventionally performed using mATPase enzyme histochemistry on cryostat sections. After pre-incubation of sections at pH 4.3, 4.6 and 10.3, based on the pattern of enzyme reactivity, the fibers can be classified in types I, II (subtypes A, AB and B) and the intermediate C (I and II) fibers. We have attempted to perform fiber typing of human psoas muscle by immunohistochemistry, using monoclonal antibodies R11D10 (specific for cardiac and type I skeletal myosin) and MY-32 (specific for fast muscle fibers) on cryostat as well as on paraffin sections. Staining of consecutive cryostat sections showed that type I fibers are R11D10 reactive whereas type II fibers are MY-32 reactive. Subtyping of type II fibers could not be performed by immunohistochemistry. Quantitative analysis of type I and II fibers showed that enzyme histochemical and immunohistochemical analysis are in close agreement.

Renal cell carcinoma in a multilocular renal cyst: a case report of a 27-year-old female and review of the literature.

A case of renal cell carcinoma in a multilocular renal cyst is reported. Excretory urography showed a mass, and ultrasound revealed multiple renal cysts in the middle part of the left kidney. This finding could also be visualized by computer tomography, a solid structure could not be detected. During operation a 6-cm multiloculated cyst was enucleated from the left kidney. A frozen section of the cystic lesion did not indicate a malignancy; however, further histopathological examination revealed a renal cell carcinoma, especially in the septal parts of the tumor.

Prognostic significance of basement membrane deposition in operable squamous cell carcinomas of the lung.

Tumor histology, stage of disease, and performance status are the most important prognostic factors in squamous cell lung cancer (SqCLC). A potentially important descriptor is the pattern of tumor growth as reflected in the dissolution of preexisting or deposition of newly formed basement membrane (BM) around tumor cell nests. The possible correlation between the pattern of BM deposition and patient survival was investigated. Immunohistochemistry testing, using polyclonal antibodies to human type IV collagen, was done on tumor samples of 68 patients with operable Stages I or II SqCLC, and BM staining was scored semiquantitatively. More than 75% immunoreactivity was scored as extensive BM and less than 75% as moderate or limited BM. In six patients, no immunoreactivity could be detected. In 27 of 62 patients, extensive and, in 35 of 62 patients, moderate-limited BM deposition was found. This deposition had a significant effect on survival (P = 0.02). Cox regression analysis, including BM deposition and tumor stage, indicated that BM deposition might also have value as an additional independent prognostic indicator for survival (P = 0.02). Deposition of an appreciable amount of BM in the center of the SqCLC was a prognostically favorable sign, independent of tumor stage.

Structural alterations in heart valves during left ventricular pressure overload in the rat.

BACKGROUND: Heart valves are an important denominator of the function of the heart but detailed studies of structural alterations of heart valves after hemodynamic changes are lacking. EXPERIMENTAL DESIGN: Structural alterations of heart valves, including DNA synthesis, collagen mRNA, and protein concentration were measured in heart valves of Wistar Kyoto (WKY) rats with acute left ventricular pressure overload, created by intrarenal aortic ligation (AL, N = 18) as well as in heart valves of age-matched spontaneously hypertensive rats, a model of chronic hypertension (N = 18). SHAM aortic ligation and normal WKYs (N = 17 and N = 17) served as controls. All animals received 5'bromo-2' deoxyuridine, during the last 7 days of the experiment, in a dose of 2.4 mg/kg.day. RESULTS: The cumulative labeling fraction (LF) in the mitral valve of AL animals was 47.8 +/- 5.2% as compared with 9.4 +/- 2.6% in SHAM animals (mean +/- SEM, p < 0.01). The LF in the aortic valve of AL animals was 33.3 +/- 2.9% as compared with 7.7 +/- 0.7% in SHAM animals (p < 0.01). The LF in the tricuspid valve was also significantly increased: 11.3 +/- 1.4% in AL versus 5.8 +/- 0.7% in SHAM (p < 0.01). Labeling fractions of heart valves in SHR were not increased as compared with normal WKY. The total collagen concentration in the three heart valves, measured by the hydroxyproline assay, did not change. The mRNA amounts of both collagen type I and III, detected by in situ hybridization, were increased in the heart valves of AL and spontaneously hypertensive animals as compared with the two control groups (SHAM and WKY). In all 3 heart valves, interstitial cells were vimentin-positive, but desmin-negative. A fraction of interstitial cells showed alpha-smooth muscle actin positivity. This immunophenotype did not change during pressure overload. CONCLUSIONS: Heart valves have the capacity to adapt to acute pressure overload, by means of DNA synthesis and increased collagen turnover. The increase in LF in the normotensive tricuspid valve suggests a role for an additional circulating factor. A constant fraction of the interstitial heart valve cells consists of myofibroblasts.

The alpha-smooth muscle actin-positive cells in healing human myocardial scars.

Interstitial cells in the scars of human myocardial infarctions of different postinfarction times (6 hours to 17 years old) were characterized by antibodies to alpha-smooth muscle actin (ASMA), vimentin, and desmin. Basal lamina deposition was studied with antibodies to the basal lamina protein type IV collagen. Nonvascular spindle-shaped cells expressing ASMA were present within 4 to 6 days after infarction. These cells co-expressed vimentin but no desmin and showed discontinuous basal lamina deposition. In electron microscopy these cells showed features characteristic of myofibroblasts. The spindle-shaped cells persisted for a long period of time and could even be identified 17 years postinfarction. In transmural infarctions they were orientated parallel to the endocardium and epicardium. In nontransmural patchy infarctions they showed an orientation adjacent to the cardiomyocytes and appeared to be less dense than in the transmural infarctions. In conclusion, myofibroblasts expressing ASMA persist within human myocardial scars and show a preferential alignment that may be the result of the continuous mechanical stress caused by the ongoing contraction and relaxation of the surrounding viable myocardium.

Monoclonal antibodies to native basement membranes reveal heterogeneous immunoreactivity patterns.

In this paper we describe the development of basement membrane (BM) reactive monoclonal antibodies (MA), by immunization of mice with intact denuded BM. The MA raised against denuded amniotic BM (clones 1052, 1053 and 1065) showed heterogeneous staining patterns. MA 1052 and 1053 reacted with epithelial BM of the epidermis and epidermal adnexa and furthermore with the epithelial alveolar BM in the lung and the superficial part of the epithelial BM in the gastrointestinal tract. MA 1065 showed immunoreactivity with the epithelial BM of epidermis and epidermal adnexa and the epithelial BM of trachea and oesophagus, and furthermore pericellular staining of the basal keratinocytes and basal corneal epithelial cells. MA 1087, raised against human glomerular BM, showed immunoreactivity with all BM, except the central epithelial BM in the cornea. The precise localization of the target epitopes in the BM was investigated on chemically cleaved human skin. Reactivity for the MA occurred predominantly in the BM lamina adherent to the dermis, suggesting that the target epitopes reside in the lamina densa and/or lamina fibroreticularis. We furthermore examined the nature of the epitopes by preincubation of tissue sections with various enzymes prior to immunohistochemistry. The reactivity of the target epitopes was not affected by bacterial collagenase, but after various protease treatments the reactivity disappeared, suggesting that the epitopes are not localized on the triple helical part of collagenous proteins.