Hyperbaric Oxygen Therapy and Tissue Regeneration: A Literature Survey.

By addressing the mechanisms involved in transcription, signaling, stress reaction, apoptosis and cell-death, cellular structure and cell-to-cell contacts, adhesion, migration as well as inflammation; HBO upregulates processes involved in repair while mechanisms perpetuating tissue damage are downregulated. Many experimental and clinical studies, respectively, cover wound healing, regeneration of neural tissue, of bone and cartilage, muscle, and cardiac tissue as well as intestinal barrier function. Following acute injury or in chronic healing problems HBO modulates proteins or molecules involved in inflammation, apoptosis, cell growth, neuro- and angiogenesis, scaffolding, perfusion, vascularization, and stem-cell mobilization, initiating repair by a variety of mechanisms, some of them based on the modulation of micro-RNAs. HBO affects the oxidative stress response via nuclear factor erythroid 2-related factor 2 (Nrf2) or c-Jun N-terminal peptide and downregulates inflammation by the modulation of high-mobility group protein B1 (HMGB-1), toll-like receptor 4 and 2 (TLR-4, TLR-2), nuclear factor kappa-B (NFκB), hypoxia-inducible factor (HIF-1α) and nitric oxide (NO•). HBO enhances stem-cell homeostasis via Wnt glycoproteins and mammalian target of rapamycin (mTOR) and improves cell repair, growth, and differentiation via the two latter but also by modulation of extracellular-signal regulated kinases (ERK) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway. The HBO-induced downregulation of matrix metalloproteinases-2 and 9 (MMP-2/-9), rho-associated protein kinase (ROCK) and integrins improve healing by tissue remodeling. Interestingly, the action of HBO on single effector proteins or molecules may involve both up- or downregulation, respectively, depending on their initial level. This probably mirrors a generally stabilizing potential of HBO that tends to restore the physiological balance rather than enhancing or counteracting single mechanisms.

Preoperative Glasgow Prognostic Score as additional independent prognostic parameter for patients with esophageal cancer after curative esophagectomy.

BACKGROUND: Inflammation accelerates tumor growth followed by reduced survival in patients with cancer. The aim of this study was to evaluate the prognostic relevance of preoperatively increased levels of C-reactive protein (CRP) and the corresponding Glasgow Prognostic Score (GPS) on patients with esophageal carcinoma undergoing curative esophagectomy. METHODS: The data of 174 operated esophageal cancer patients were evaluated retrospectively. Patient's demographic and clinico-pathological data, tumor specific data, preoperative plasma levels of CRP and albumin, the corresponding GPS, overall survival (OS) and progression free survival (PFS) were assessed. RESULTS: 103 (59.2%) had adenocarcinoma and 71 (40.8%) had squamous cell carcinoma. 71 patients (43%) had elevated CRP concentrations. 118 patients (71%) had GPS 0, 41 (25%) GPS 1 and 8 (4%) GPS 2. Mean GPS was 0.3 (0-2). 5-year OS was higher in patients with normal CRP than in those with increased CRP (68% vs. 39%; p = 0.007). 5-year OS in patients with GPS 0 and GPS 1 and 2 were 65% and 31% (p = 0.001). 5-year OS for the whole cohort was 56% (1 year: 83%, 3 years: 64%). Recurrence rate was 16.1% closely associated with GPS (p = 0.002). Median follow-up was 23 months (0-118 months). In multivariate analysis GPS, lymph node involvement, T stage and tumor histology were the independent prognostic parameters (p = 0.004, <0.001, 0.035, 0.010). CONCLUSIONS: Preoperatively increased GPS is significantly associated with reduced postoperative survival and tumor recurrence. The GPS as an independent prognosticator should be interpreted together with the TNM stage when the further postoperative treatment has to be scheduled.

Resection in stage I/II non-small cell lung cancer.

In spite of the developments in chemo- and radiotherapy, surgery remains the mainstay of curative treatment of early stage non-small cell lung cancer (NSCLC). In stage Ia/Ib (T1, T2, N0), NSCLC lobectomy offers the best chance for cure, yielding survival rates of between 58 and 76%. Since the extent of mediastinal lymph node dissection does not seem to play a major prognostic role in stage Ia, video-thoracoscopic lobectomy yields equally good results as the open approach. Due to the necessity for a small thoracotomy when harvesting the specimen and the time-consuming lymph-node dissection minimally invasive lobar resections have failed to become routinely used. Minor resections, though sometimes necessary from the functional point of view, have a lower curative potential. They yield the best results if applied in tumors measuring less than 2 cm. Stage II, characterized by involvement of the N1-position and/or a more central tumor growth, has a 5-year survival of 45-52% and requires treatment by lobectomy or pneumonectomy. Sleeve resection may obviate the need for pneumonectomy in central upper-lobe tumors. In interlobar N1, however, pneumonectomy is indicated from the oncological point of view, since even meticulous lymph-node dissection is unable to achieve tumor control in this situation.

Hyperbaric oxygenation in the treatment of life-threatening isobutyl nitrite-induced methemoglobinemia--a case report.

Methemoglobinemia usually results from exposure to oxidizing substances such as nitrates or nitrites. Iron within hemoglobin is oxidized from the ferrous (Fe2+) state to the ferric (Fe3+) state, resulting in the inability to transport oxygen and carbon dioxide. Clinically, this condition causes functional cyanosis. As methemoglobin levels increase, patients show evidence of cellular hypoxia in all tissues. Death usually occurs when methemoglobin fractions approach 70% of total hemoglobin. We describe the case of a 35-year-old female patient with severe life-threatening isobutyl nitrite-induced methemoglobinemia of 75% of total hemoglobin. Toluidine-blue was administered as first-line antidotal therapy immediately, followed by hyperbaric oxygenation. The patient recovered uneventfully and could be discharged 3 days later.

Severe carbon monoxide poisoning treated by hyperbaric oxygen therapy--a case report.

Carbon monoxide (CO) poisoning is an important cause of mortality and late neurological sequelae such as memory loss, personality changes, psychosis, dementia, and so on. The benefits of hyperbaric oxygen (HBO) therapy are still discussed, but the majority of trials recommend it in severe cases with coma and/or hemodynamic instability, irrespective of carboxyhemoglobin (COHb) level, to prevent permanent neurological deficits. We present a 35-yr-old woman who underwent accidental CO poisoning. Although breathing 100% oxygen by mask during transfer to the hospital, she was in deep coma, hypotensive, cyanotic, and hypoxic (arterial pO(2) 7,41 kPa, HbO(2) 87.8%), with serum COHb 26.7% on hospital admission. Orotracheal intubation, mechanical ventilation, iv fluids, dobutamin, and norepinephrine were administered. COHb level decreased to 17.2% within 1 h. To prevent severe neurological sequelae, the patient was transferred as soon as possible to an HBO center 60 km distant to perform HBO therapy twice at 3.0 and once at 2.2 atm within 24 h. After the second HBO session, the patient regained consciousness, and respiratory failure and shock resolved. She was transferred to our hospital and discharged few weeks later with discrete paresis of peripheral nerves, discrete ischemic brain lesions on computed tomography (CT) scan, and moderately abnormal electroencephalogram (EEG) without cognitive disturbances. She was able to resume her daily activities. We conclude that in severe CO poisoning, normobaric oxygen therapy and resuscitation by fluids, inotropic agents, and catecholamines is essential for survival, but additional HBO therapy seems to prevent major neurological sequelae.

Hyperbaric oxygen--an effective tool to treat radiation morbidity in prostate cancer.

PURPOSE: We report the results of hyperbaric oxygen therapy (HBO) used in the treatment of radiation cystitis and proctitis following irradiation of prostate cancer. MATERIALS AND METHODS: Between June 1995 and March 2000, 18 men (median age 71 years) with radiation proctitis (n=7), cystitis (n=8), and combined proctitis/cystitis (n=3) underwent HBO therapy in a multiplace chamber for a median of 26 sessions (range 2-60). The treatment schedule (2.2-2.4 atmospheres absolute, 60 min bottom time, once-a-day, 7 days a week) was set at a lower limit of 20 sessions; the upper limit was left open to symptom-related adjustment. Prior to HBO treatment, RTOG/EORTC late genitourinal (GU) morbidity was Grade 2 (n=3), Grade 3 (n=6) or Grade 4 (n=2); modified RTOG/EORTC late gastrointestinal (GI) morbidity was either Grade 2 (n=4) or Grade 3 (n=6). RESULTS: Sixteen patients underwent an adequate number of sessions. RTOG/EORTC late GU as well as modified GI morbidity scores showed a significant improvement after HBO (GI, P=0.004; GU, P=0.004; exact Wilcoxon signed rank test); bleeding ceased in five out of five patients with proctitis and in six out of eight patients with cystitis; one of those two patients, in whom an ineffective treatment outcome was obtained, went on to have a cystectomy. CONCLUSIONS: HBO treatment seems to be an effective tool to treat those patients with late GI and GU morbidity when conventional treatment has led to unsatisfactory results. Particularly in patients with radiation cystitis, HBO should not be delayed too long, as in the case of extensive bladder shrinkage improvement is hard to achieve.

Radiotherapy for invasive thymoma and thymic carcinoma. Clinicopathological review.

PURPOSE: This study reports clinicopathological features and outcome of thymic tumors. Twenty-seven patients with invasive thymoma and 6 patients with thymic carcinoma who had received radiotherapy either primary or postoperatively were analyzed retrospectively. PATIENTS AND METHODS: All 33 patients were irradiated with a mean dose of 50 Gy after complete resection (16 patients), partial resection (9 patients) or biopsy (8 patients). Staging was done according to the Masaoka classification; there were 12 Stage II, 12 Stage III and 9 Stage IV patients. RESULTS: In patients with invasive thymoma Stage II to IV (median follow-up 54.4 months) Kaplan-Meier estimates of overall survival (OS), disease-specific (DSS) and disease-free survival (DFS) at 5 years were 63.7% (95% confidence interval [CI], 42 to 84%), 88.3% (CI, 75 to 100%) and 77.4% (CI, 58 to 95%), respectively. Among the prognostic factors tested, such as age, myasthenia gravis, completeness of surgery and histologic subclassification, total radiation dose, and Masaoka Stage, the latter was the only significant predictor of improved survival (p = 0.04). Considering local control, radiation dose was a significant prognostic factor (p = 0.0006). In patients with thymic carcinoma (median follow-up 43.4 months) 5-year DSS, and DFS were 22.2% (CI, 0 to 60%) and 16.7% (CI, 0 to 46%), respectively. Thymoma as compared to thymic carcinoma had a statistically significant better DSS (p = 0.007) and DFS (p = 0.0007). CONCLUSION: Postoperative radiotherapy with sufficient doses plays an important role as adjuvant treatment in complete or incomplete resected invasive Stage II to III thymoma. In unresectable thymoma Stage III to IV as well as in thymic carcinoma a multimodality approach should be considered to improve survival.

Is aggressive surgery in pleural empyema justified?

OBJECTIVE: High risk and a long hospitalization time are often quoted as negative aspects of aggressive surgery in pleural empyema. We did a retrospective analysis evaluating outcome and duration of hospitalization in patients treated according to an aggressive schedule. METHODS: Since 1989 we have treated 101 patients with pleural empyema (72 males, 29 females; mean age 50.3 years, range 11-91 years; 77 metapneumonic empyema, 24 empyema following trauma or abdominal surgery). Sixty-nine patients had had unsuccessful conservative pre-treatment (antibiotics, thorcozentses, drainage/irrigation, VATS). Thirty-one were critically ill patients. In eight cases a seropurulent stage of empyema was present, 17 patients had fibrinous membranes, 30 an organizing stage with and 46 without well identifiable dissection plane. Eighty-five patients proceeded to thoracotomy. Pulmonary abscesses or indurative pneumonia necessitated wedge-resection, lobectomy, or pneumonectomy in 29 cases. In the presence of gross necroses or callosities not amenable to decortication primary open-window thoracostomy (n = 22) was carried out. In six cases a secondary open-window thoracostomy was carried out because of persisting putrid secretion and sepsis persisting after decortication or after drainage. The thoracostomy was closed when clean granulative tissue developed. Sixteen patients underwent only drainage and irrigation because of an early stage or because of a general condition not permitting thoracotomy. RESULTS: Three patients died due to severe sepsis not responding to treatment, one had fatal bleeding from a duodenal ulcer (mortality rate 3.9%). The others were able to resume their preoperative activities. The median duration of hospitalization was 14 days (mean 21.1 days; SEM 1.7 days). CONCLUSION: Aggressive surgery for pleural empyema beyond the seropurulent stage ensures rapid relief from sepsis at a low mortality rate even in very ill patients.

Postoperative radiotherapy in radically resected non-small cell lung cancer.

PURPOSE: To evaluate the value of adjuvant postoperative external-beam radiation (EBR) in patients with radically resected non-small cell lung cancer (NSCLC) pT1-3 pN0-2 compared to patients with resected NSCLC without adjuvant EBR. MATERIALS AND METHODS: In 155 patients (121 male, 34 female; mean age, 59 years) 105 lobectomies, 12 bilobectomies, and 38 pneumonectomies with radical lymph node dissection of the contralateral [corrected] side were performed. Postoperative staging was done according to the TNM system and was as follows: pT1 (n=38), pT2 (n=89), pT3 (n=28); pN0 (n=39), pN1 (n=67) and pN2 (n=49). Histopathologic study revealed 68 squamous cell carcinomas, 53 adenocarcinomas, 21 large cell carcinomas, 6 adenosquamous cell carcinomas, and 7 bronchioloalveolar cell carcinomas. All patients were randomly assigned into two treatment groups: 72 patients with no further treatment (control group), and 83 patients (EBR group) with adjuvant postoperative EBR of the bronchial stump and mediastinum (50 to 56 Gy, 8 or 23 MV photons, 2 Gy/d, 5 d/wk) beginning 4 to 6 weeks after surgery. RESULTS: The overall 5-year survival rate (median observation time, 43 months) of all patients was 24.1% (EBR group, 29.7%; control group, 20.4%; p>0.05, not significant). The relative risk of the EBR group was 0.85 with a two-sided confidence interval of 0.66 to 1.09. The overall 5-year recurrence-free survival was 20.6% (EBR, 27.1%; control group, 15.6%; p=0.07). The relative risk of the EBR group was 0.80 with a confidence interval of 0.63 to 1.01. The rate of local recurrences at the bronchial stump and/or mediastinum was significantly smaller in the EBR group (n=5) than in the control group (n=17) (p<0.01). Multivariate analysis (chi2 test) demonstrated an independent influence of postoperative EBR on the incidence of local recurrences. The incidence of distant metastases was slightly but not significantly higher in patients without EBR (38 patients) compared to those who had EBR (32 patients). CONCLUSION: High-dose postoperative EBR to the mediastinum significantly reduces the risk of local recurrence at the bronchial stump and/or mediastinum. Age, sex, histologic subtype, tumor size, surgical approach, or extent of lymph node involvement had no prognostic value--only postoperative EBR had an independent influence on the risk of local recurrence. The effect of postoperative EBR was on the verge of significance with respect to recurrence-free survival and showed the same tendency in overall survival, however with an attenuated relative risk.

Life-saving muscle flaps in tracheobronchial dehiscence following resection or trauma.

OBJECTIVE: In the presence of acute inflammation and necrosis of the wall, tracheo-bronchial defects are difficult to manage. The absence of adequate vascularization and the contaminated area prevent successful direct re-suturing. METHODS: In order to restore a sufficient blood supply we used a pedicled latissimus dorsi or a pectoralis major flap that was entered into the thorax after a 10-cm resection of the second rib. A portion of the muscle was fitted into the tracheo/bronchial defect by reinforced sutures. The remaining muscle was sutured to the tissue surrounding the defect. This method was applied in various septic conditions: Bronchial defects; complete dehiscence of the right (n = 6) or left (n = 1) main bronchus at the carinal level following resection for lung cancer (n = 4) or for tuberculous (n = 2) on nontuberculous pleuropneumonia (n = 1). Tracheal defects; (1) destruction of one third of the tracheal circumference involving the cricoid down to the fourth ring following tracheotomy in presence of a septic sternum after intrathoracic goiter and Bechterew's disease; (2) 30% dehiscence of the anastomosis and septic sternum following tracheal resection; (3) Mediastinitis involving tracheal and esophageal wall following a 7 cm long iatrogenous laceration of the intrathoracic trachea. RESULTS: In one case the latissimus dorsi developed venous stasis on day 2 and was replaced by the pectoralis major muscle which showed uneventful healing. In all other patients the muscle flap resulted in an uneventful closure of the defect and recovery. CONCLUSIONS: Large, well vascularized, pedicled muscle flaps ensure a safe closure of tracheo-bronchial defects or dehiscences even in presence of gross necrosis and sepsis.

Iatrogenic ruptures of the tracheobronchial tree.

We did a retrospective study in 12 patients with iatrogenic tracheal or tracheobronchial ruptures treated since 1975. Ten female subjects, one male subject, and one child (age range, 8 to 72 years), all of whom had undergone intratracheal intubation, were admitted to the hospital. Four patients had been intubated with a double-lumen catheter (two Carlens type with carinal spur, two Robertshaw without spur), and seven had had "high volume-low pressure" tubes, placed under emergency conditions in three of those seven cases. In one further case, an unsuccessful attempt of percutaneous tracheostomy had been made. The localization of the ruptures (all of them longitudinally in the membranaceous wall; length, 2 to 13 cm; mean, 7 cm) comprised both cervical and intrathoracic trachea in seven, the intrathoracic trachea in three instances, and the left main stem bronchus in two cases. Ten patients had mediastinal and subcutaneous emphysema, seven presented with a pneumothorax, and nine had intratracheal bleeding. The interval until the onset of symptoms and diagnoses differed widely: twice diagnoses were made intraoperatively, during thoracic surgery. The longest interval until diagnosis was 5 days; only then did the patient show subcutaneous emphysema and have retrosternal pain. All patients had surgical repair. Nine recovered without sequelae, and three died of septic multiorgan failure.

"Adjuvant" external radiation of the mediastinum in radically resected non-small cell lung cancer.

OBJECTIVE: The effect of postoperative external beam radiation in MO non-small cell lung cancer resected with curative intention was evaluated in a randomized trial. METHODS: In 155 patients (121 males, 34 females; mean age: 59 years) 105 lobectomies, 12 bilobectomies and 38 pneumonectomies with radical lymph node dissection to the contralateral side were carried out. Histology revealed squamous cell (n = 68), adeno- (n = 53), large cell (n = 21), adenosquamous (n = 6) or bronchioloalveolar type (n = 7) carcinomas. The pathologic stages T1 (n = 38), T2 (n = 89), T3 (n = 28); NO (n = 39), N1 (n = 67), and N2 (n = 49) were evenly distributed between the two treatment groups: group A (72 patients) had no further oncologic treatment, while group B (83 patients) had external beam radiation to the mediastinum (50-56 Gy, 8 or 23 MeV photons, 2 Gy/day, 5 days a week) beginning 4 weeks after the operation. RESULTS: The overall 5-year survival rate of the whole collective was 24.1% without any significant difference between the radiotherapy group B (29.7%) and the control group A (20.4%) (log-rank test: P > 0.05). The overall 5-year recurrence-free survival rate was 20.1%, with no difference between groups B and A (radiotherapy: 22.7, controls: 15.6%, long-rank test: P > 0.05). There was no difference in the incidence of distant metastases (external beam radiation: n = 32; controls: n = 38). The rate of local recurrences at the bronchial stump or in the mediastinum, however, was significantly reduced in the radiotherapy group (n = 5) compared with 17 in the controls (P < 0.01 chi-square test). A multivariate analysis confirmed the independent influence of postoperative radiotherapy on the incidence of local recurrence. CONCLUSIONS: External radiation of the mediastinum in radically resected non-small cell lung cancer reduces the risk of local recurrence, but has no influence on distant metastastic spread and overall survival.

Is preoperative percutaneous fine-needle aspiration cytology of intrathoracic lesions advisable in resectable patients?

OBJECTIVE: The study addresses the clinical significance of percutaneous fine-needle aspiration (FNA) cytology in patients with intrathoracic lesions. METHODS: The diagnoses based on cytology in 101 patients (73 male, 28 female; age 21-78 years) with intrathoracic lesions were compared with a definitive histological diagnosis obtained by thoracotomy. Sixty-one lesions were localized in the right and 31 in the left lung, 5 bilaterally and 4 paramediastinally (maximum diameters: 0.8-12 cm; median: 3.5 cm). RESULTS: Upon FNA, 69 cases were graded malignant and 17 benign. In the remaining 15 cases the pathologists felt unable to define clearly the cell type or the biological properties, though the material was found representative. Histology yielded 80 malignant and 21 benign lesions, consistent with the cytological diagnosis in 70 cases. In 60 patients accordance between the cellular subtypes suspected after FNA and those found histologically was present. A significantly higher rate of correct FNA diagnoses was made in malignant lesions (chi-square test: p<0.05). The overall diagnostic accuracy of FNA was 0.77, the sensitivity 0.79 and the specificity 0.91 From the surgical point of view, nine resectable lung cancers, three metastases, three other malignancies and three tuberculomas would have been missed by relying on the FNA diagnoses. Eighteen pneumothoraces (nine requiring suction drainage) occurred after FNA. CONCLUSION: The indication for FNA in otherwise resectable patients should be made carefully, keeping in mind the rate of diagnostic errors and of complications, as well as the possibility for diagnostic VATS of peripheral lesions.

Rotating brush for video-assisted thoracoscopic pleural abrasion.

We present a simple device enabling parietal pleural abrasion during video-assisted thoracoscopic surgery (VATS). The rotating brush facilitates safe pleurodesis in patients with pneumothorax obviating the need for additional chemical agents or pleurectomy.

Evaluating intraoperative radiation therapy (IORT) and external beam radiation therapy (EBRT) in non-small cell lung cancer (NSCLC). Five years experience.

A pilot study on intraoperative radiation therapy (IORT) combined with external beam radiation therapy (EBRT) in nonresectable non-small cell lung cancer (NSCLC) was performed in 31 patients (mean age: 66.2 years, range: 51-80; 10 anatomically and functionally, 21 functionally, nonresectable; 20 squamous-cell, 11 adenocarcinoma). The tumor was exposed by lateral thoracotomy and a staging lymph node dissection was performed (final staging 7 T1, 16 T2, 8 T3; 11 nodal positive). Ten to 20 Gy IORT (energy: 7-20 MeV electrons) were delivered to the tumor. Unilateral continuous positive airway pressure ventilation of the diseased lung was used to reduce the amount of healthy lung tissue in the IORT port and to minimize the ventilatory movement. Secondary collimation and direct shielding of radio-sensitive structures within the IORT port by aluminium sheets were used to further reduce collateral damage. Four weeks after IORT, 46 Gy EBRT (2 Gy/day 5 times a week; 8-23 MeV photons) were administered to the mediastinum and to the tumor-bearing area on an outpatient basis. In nodal positive cases the mediastinal dose was increased to 56 Gy. Twenty-three patients were evaluable. In 13 complete, in 8 partial (50-97% regression) and in 2 minor response has been achieved. Five patients experienced a recurrence (local only: 2; local and distant: 1; distant only: 2). Twelve patients died of underlying cardio-respiratory disorders within 6 to 25 months after IORT; 7 died of cancer. The overall 5-year survival rate including the incidental deaths is 14.7%. The recurrence-free survival rate is 53.2%.

Closure of bronchial defects using a pedicled pericardial flap.

A technique for closure of lateral or terminal defects in the bronchial wall after tissue-saving procedures, which obviates the need for sleeve resection in few selected situations, is described. Its main advantages are a low risk of surgical complications at the suture line and easy performance.

Relationship of tumor cell motility and morphologic patterns. Part 1. Melanocytic skin tumors.

In the diagnosis of melanocytic skin tumors, the assessment of the overall architectural pattern (silhouette) is often essential. We have previously shown by a computer simulation model that tumor patterns are likely to depend on the relative degrees of proliferation and motility of the tumor cells. In this study, we examined the morphological pattern of 12 cases each of nevocellular nevi, primary melanoma, and metastatic melanoma by image analysis. The patterns of the individual melanocytic skin tumors were compared statistically with patterns generated by computer simulation, which facilitates estimates of biological properties of the tumor cells. Additionally, mitotic counts were made to measure tumor cell proliferation. A comparison of the three diagnostic groups revealed that the cells of nevocellular nevi show a low degree of motility, which, however, still exceeds the very low degree of proliferation. Thus, an "invasive" pattern with numerous small nests and single cells at the base of the lesion is common. In primary malignant melanoma, tumor cell motility and tumor cell proliferation are significantly increased in various proportions, thus leading to varying morphological patterns. In metastatic melanoma, a strikingly elevated degree of proliferation exceeds the only slightly elevated degree of motility and leads to sharply demarcated, "expansive" lesions. To check the validity of the technical procedure, estimates of proliferation based on pattern analysis alone were compared with the results obtained by mitotic counts. There was a significant correlation, indicating that the assumptions of the computer model and the image analysis procedure are in fact applicable to real-life melanocytic skin tumors.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracardiac malpositioning of a sternoclavicular fixation wire.

A case of intracardiac malpositioning of a sternoclavicular Kirschner pin is reported. After an uneventful closed wire-fixation of sternoclavicular subluxation and a normal postanesthetic recovery, a 17-year-old male patient developed opacification of the right hemithorax and signs of internal bleeding. The lateral chest roentgenogram showed one fixation wire protruding deeply into the anterior mediastinum. Sternotomy showed a large pericardial tear communicating with the right pleural cavity and a puncture hole of the right auricle that had caused a blood loss of 3 L into the pleural space. Although the surgical repair was uneventful, the patient eventually died as a sequelae to prolonged cerebral hypoxemia.