Hans Jörg Altermatt

Malignant cells are collected on circular staplers.

Anastomotic recurrence after resection of colorectal carcinoma has been attributed to insufficient clearance, migration of tumor cells into lymphatics, or implantation of exfoliated malignant cells during anastomosis. We studied 10 patients submitting to low anterior resection for cancer 6 to 16 cm (mean, 12.6 cm) from the anal verge. The anastomosis was performed with a circular stapler introduced transanally into the rectum using the established technique. No lavage of the rectal stump with a cytotoxic agent was conducted before the anastomosis was performed. Having completed the anastomosis, the stapler and the doughnuts were washed with saline, which was collected for cytologic examination. The doughnuts were then examined histologically; all were tumor free. In 9 of the 10 cases, malignant cells were identified in the centrifuged saline. It may be that malignant cells collected by the stapler are implanted during anastomosis and cause subsequent anastomotic recurrence.

Significant correlation of hypoxia-inducible factor-1α with treatment outcome in cervical cancer treated with radical radiotherapy

PURPOSE In the early stages of cervical cancer treated with surgery alone, hypoxia-inducible factor-1alpha (hif-1alpha) expression is prognostic for overall survival. Because hypoxia plays an important role in radiation resistance, we investigated hif-1alpha expression in cervical cancer treated with local radical radiotherapy (RT). METHODS AND MATERIALS Between 1990 and 1998, 91 patients with squamous cell or adenocarcinoma of the uterine cervix were treated with external beam RT with and without brachytherapy. Biopsies from 78 patients were available for immunohistochemistry. The impact of the immunoreactivity of hif-1alpha in regard to survival end points was determined by univariate and multivariate analyses. Correlations with clinicopathologic characteristics were determined by cross-tabulations. RESULTS Hif-1alpha was expressed in 73 (94%) of 78 patients. It was closely linked to the pretreatment hemoglobin level (p = 0.04, r = -0.22, Spearman correlation test). The Kaplan-Meier curves showed a significantly shorter local progression-free survival (p = 0.04, log-rank) and overall survival (p = 0.01, log-rank) and a trend for shorter disease-free survival (p = 0.15) for patients with increased hif-1alpha expression. The multivariate analyses revealed hif-1alpha expression to be an independent factor for overall survival (p = 0.02). CONCLUSION Hif-1alpha is expressed in the vast majority of patients with advanced cervical cancer and had a prognostic significance. A weak but significant correlation was noted with pretreatment hemoglobin level.

Expression of p16INK4a/p16alpha and p19ARF/p16beta is frequently altered in non-small cell lung cancer and correlates with p53 overexpression.

The CDKN2 locus expresses two different mRNA transcripts, designated α and β. The protein product of the α transcript is the cell cycle inhibitor and tumour suppressor p16INK4a. The β transcript is translated in an alternate reading frame (ARF) and in humans encodes a 15 kDa protein (p19ARF). Immunohistochemical and Western analysis of p16INK4a has shown that the protein is downregulated in a significant number of tumours, but less is known on the expression of the p19ARF. We have examined the expression of p16INK4a and p19ARF in resectable non-small cell lung cancer (NSCLC) by immunostaining (n=49) and multiplex RT–PCR (n=28). In order to investigate the mechanism responsible for p16INK4a downregulation, exon 1α methylation was analysed in a PCR-based assay. Of 49 tumours examined by immunostaining, 24 and 20 tumours expressed p16INK4a and p19ARF at nil to low levels, respectively. p19ARF was localized primarily to the nuclei of tumour cells, but was also seen to varying degrees in nuclei of lymphocytes, chondrocytes, fibroblasts, and epithelial cells. No tumour with normal p16INK4a had decreased p19ARF expression. Among 16 tumours with nil to low p16INK4a expression, 11 tumours exhibited full methylation of at least one site within exon 1α and these tumours showed normal p19ARF expression. In contrast, no methylation of exon 1α was observed in five tumours which also lacked p19ARF. In normal lung, p16INK4a and p19ARF were not expressed at detectable levels, the multiplex RT–PCR results were balanced, and sites within exon 1α were strongly methylated. In tumours, imbalanced multiplex RT–PCR data (p16INK4a<p19ARF) predicted methylation of exon 1α (P=0.0006) as well as downregulation of p16INK4a. p19ARF downregulation was inversely correlated with p53 overexpression (P=0.025), whilst negative immunostaining for p16INK4a was inversely correlated with pRb downregulation (P=0.003) and directly correlated with p53 overexpression as assessed by immunostaining (P=0.015). Our results show that: (1) p16INK4a and p19ARF expression are altered in almost half of resectable NSCLC; (2) methylation within exon 1α is a frequent, but not the only mechanism of p16INK4a downregulation; and that (3) the inverse association of p19ARF and p53 alteration is consistent with a linked pathway.

Intraoperative photodynamic therapy with m‐tetrahydroxyphenylchlorin for chest malignancies

Since there is no satisfactory treatment modality for diffuse malignant mesothelioma of the chest, we assessed surgical tumor resection followed by intraoperative photodynamic therapy with mTHPC in a phase I study.

Hypoxia-inducible factor 1 alpha in high-risk breast cancer: an independent prognostic parameter?

BackgroundHypoxia-inducible factor 1 alpha (hif-1α) furnishes tumor cells with the means of adapting to stress parameters like tumor hypoxia and promotes critical steps in tumor progression and aggressiveness. We investigated the role of hif-1α expression in patients with node-positive breast cancer.MethodsTumor samples from 77 patients were available for immunohistochemistry. The impact of hif-1α immunoreactivity on survival endpoints was determined by univariate and multivariate analyses, and correlations to clinicopathological characteristics were determined by cross-tabulations.Resultshif-1α was expressed in 56% (n = 43/77) of the patients. Its expression correlated with progesterone receptor negativity (P = 0.002). The Kaplan–Meier curves revealed significantly shorter distant metastasis-free survival (DMFS) (P = 0.04, log-rank) and disease-free survival (DFS) (P = 0.04, log-rank) in patients with increased hif-1α expression. The difference in overall survival (OS) did not attain statistical significance (5-year OS, 66% without hif-1α expression and 55% with hif-1α expression; P = 0.21). The multivariate analysis failed to reveal an independent prognostic value for hif-1α expression in the whole patient group. The only significant parameter for all endpoints was the T stage (T3/T4 versus T1/T2: DMFS, relative risk = 3.16, P = 0.01; DFS, relative risk = 2.57, P = 0.03; OS, relative risk = 3.03, P = 0.03). Restricting the univariate and multivariate analyses to T1/T2 tumors, hif-1α expression was a significant parameter for DFS and DMFS.Conclusionshif-1α is expressed in the majority of patients with node-positive breast cancer. It can serve as a prognostic marker for an unfavorable outcome in those with T1/T2 tumors and positive axillary lymph nodes.

Bone-ablation mechanism using CO2 lasers of different pulse duration and wavelength

Bone ablation using different pulse parameters and four emission lines of 9.3, 9.6, 10.3, and 10.6 μm of the CO2 laser exhibits effects which are caused by the thermal properties and the absorption spectrum of bone material. The ablation mechanism was investigated with light- and electron-microscopy at short laser-pulse durations of 0.9 and 1.8 μs and a long pulse of 250 μs. It is shown that different processes are responsible for the ablation mechanism either using the short or the long pulse durations. In the case of short pulse durations it is shown that, although the mineral components are the main absorber for CO2 radiation, water is the driving force for the ablation process. The destruction of material is based on explosive evaporation of water with an ablation energy of 1.3 kJ/cm3. Histological examination revealed a minimal zone of 10–15 μm of thermally altered material at the bottom of the laser drilled hole. Within the investigated spectral range we found that the ablation threshold at 9.3 and 9.6 μm is lower than at 10.3 and 10.6 μm. In comparison the ablation with a long pulse duration is determined by two processes. On the one side, the heat lost by heat conduction leads to carbonization of a surface layer, and the absorption of the CO2 radiation in this carbonized layer is the driving force of the ablation process. On the other side, it is shown that up to 60% of the pulse energy is absorbed in the ablation plume. Therefore, a long pulse duration results in an eight-times higher specific ablation energy of 10 kJ/cm3.

Laser–Tissue Interaction During Transmyocardial Laser Revascularization

BACKGROUND The clinical procedure known as transmyocardial revascularization has recently seen its renaissance. Despite the promising preliminary clinical results, the associated mechanisms are subject to much discussion. This study is an attempt to unravel the basics of the interaction between 800-W CO2 laser radiation and biological tissue. METHODS Time-resolved flash photography was used to visualize the laser-induced channel formation in water and in vitro porcine myocardium. In addition, laser-induced pressures were measured. Light microscopy and birefringence microscopy were used to assess the histologic characteristics of laser-induced thermal damage. RESULTS The channel depth increased logarithmically with time (ie, with pulse duration) in water and porcine myocardium. Pressure measurements showed the occurrence of numerous small transients during the laser pulse, which corresponded with channel formation, as well as local and partial channel collapse during the laser pulse. Twenty millimeters of myocardium was perforated in 25 ms. Increasing the pulse duration had a small effect on the maximum transversable thickness, but histologic analysis showed that thermal damage around the crater increased with increasing pulse duration. CONCLUSIONS Several basic aspects of the interaction of high-power CO2 laser radiation with myocardial tissue and tissue phantoms were studied in vitro. Although the goal of this study was not to unravel the mechanisms responsible for the beneficial effects of transmyocardial revascularization, it provided important information on the process of channel formation and collapse and tissue damage.

Value of One-View Breast Tomosynthesis Versus Two-View Mammography in Diagnostic Workup of Women With Clinical Signs and Symptoms and in Women Recalled From Screening

OBJECTIVE The purpose of this study is to compare the diagnostic value of one-view digital breast tomosynthesis versus two-view full-field digital mammography (FFDM) alone, and versus a combined reading of both modalities. MATERIALS AND METHODS The datasets of one-view digital breast tomosynthesis and two-view FFDM of abnormal mammograms in 144 consecutive women admitted for diagnostic workup with clinical signs and symptoms (n = 78) or recalled from screening (n = 66) were read alone and in a combined setting. The malignant or benign nature of the lesions was established by histologic analysis of biopsied lesions or by 12-16-month follow-up. RESULTS Eighty-six of the 144 patients were found to have breast cancer. The BI-RADS categories for one-view digital breast tomosynthesis were significantly better than those for two-view FFDM (p < 0.001) and were equal to those of the combined reading in both women admitted for diagnostic workup and women recalled from screening. The sensitivity and negative predictive values of digital breast tomosynthesis were superior to those of FFDM in fatty and dense breasts overall and in women admitted for diagnostic workup and in women recalled from screening. Only 11% of digital breast tomosynthesis examinations required additional imaging, compared with 23% of FFDMs. CONCLUSION In patients with abnormal mammograms, one-view digital breast tomosynthesis had better sensitivity and negative predictive value than did FFDM in patients with fatty and dense breasts. They also suggest that digital breast tomosynthesis would likely increase the predictive values if incorporated in routine screening.

Temperature and pressure effects during erbium laser stapedotomy

Laser‐assisted stapedotomy has become a well‐established alternative to the mechanical drilling method. The goal of this study is to quantify the mechanical and thermal tissue effects and to determine optimum erbium laser parameters for safe clinical treatment.

Histology of Periapical Lesions Obtained During Apical Surgery

The aim of this was to evaluate the histology of periapical lesions in teeth treated with periapical surgery. After root-end resection, the root tip was removed together with the periapical pathological tissue. Histologic sectioning was performed on calcified specimens embedded in methylmethacrylate (MMA) and on demineralized specimens embedded in LR White (Fluka, Buchs, Switzerland). The samples were evaluated with light and transmission electron microscopy (TEM). The histologic findings were classified into periapical abscesses, granulomas, or cystic lesions (true or pocket cysts). The final material comprised 70% granulomas, 23% cysts and 5% abscesses, 1% scar tissues, and 1% keratocysts. Six of 125 samples could not be used. The cystic lesions could not be subdivided into pocket or true cysts. All cysts had an epithelium-lined cavity, two of them with cilia-lined epithelium. These results show the high incidence of periapical granulomas among periapical lesions obtained during apical surgery. Periapical abscesses were a rare occasion. The histologic findings from samples obtained during apical surgery may differ from findings obtained by teeth extractions. A determination between pocket and true apical cysts is hardly possible when collecting samples by apical surgery.