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Insulin is used as a therapeutic agent in patients with diabetes, and cutaneous lipohypertrophy (LH) and localized insulin-derived amyloidosis (LIDA) are well-known adverse effects associated with insulin injections. The clinical implications, management, assessment methods, and pathological differentiation of LH and LIDA have been recently updated. This review was to update our knowledge of the pathological differentiation, effects of insulin absorption, hypoglycemic events, and recent assessment methods for LH and LIDA. A scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta Analyses extension for Scoping Reviews guidelines. Original studies and case reports in English were also included. PubMed and Scopus databases were searched for keywords to identify papers published up to January 2022. A total of 113 studies were identified through a database search, and 31 were eligible for inclusion in this scoping review. In the 31 studies included in this review, patients with type 2 diabetes had high frequencies of LH and LIDA. LH outcome parameters were assessed using pathological findings and imaging. LIDA is mainly determined by pathological methods, such as hematoxylin and eosin and Congo red staining. Several in vitro and in vivo LIDA models of LIDA have been developed. These results suggest that pathological analysis is required to identify LH and LIDA. It is important to consider LIDA, as it likely influences insulin adsorption and glycemic control. Although several studies have evaluated the LIDA process, little is known about the mechanisms underlying the development of adverse effects associated with insulin injections., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Chronic Diseases and Translational Medicine published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

This study was to investigate the time course of changes to the antioxidant activity of milk from cows fed a trehalose-supplemented diet, and to determine possible underlying mechanisms for observed changes. Six Holstein cows were used, and subjected to two experimental feeding periods consisting of a 1% trehalose-supplemented diet for 10 days, followed by a basal diet only (no trehalose) for 10 days. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities in milk were gradually increased during the trehalose supplementation period and were highest at the end of the second period. However, trehalose was not detected in the milk and plasma of dairy cows fed a diet supplemented with trehalose for 10 days, indicating that the increased antioxidant activity in the milk of trehalose-fed cows is not due to the direct transfer of trehalose to the milk. Plasma DPPH activities exhibited a similar time course to that seen for milk. Relative superoxide dismutase (SOD) activities in the rumen were higher 3 days after the end of trehalose supplementation than at any other time during the experimental periods. These results suggested that the improved antioxidant activity in milk and plasma of cows fed a trehalose-supplemented diet was due to improved ruminal relative SOD activity., (© 2012 The Authors. Animal Science Journal © 2012 Japanese Society of Animal Science.)

Reasons for Performing Study: Several studies have indicated that even low-intensity warm-up increases O(2) transport kinetics and that high-intensity warm-up may not be needed in horses. However, conventional warm-up exercise for Thoroughbred races is more intense than those utilised in previous studies of equine warm-up responses., Objectives: To test the hypothesis that warm-up exercise at different intensities alters the kinetics and total contribution of aerobic power to total metabolic power in subsequent supramaximal (sprint) exercise in Thoroughbred horses., Methods: Nine well-trained Thoroughbreds ran until fatigue at 115% of maximal oxygen consumption (VO2max) 10 min after warming-up under each of 3 protocols of equal running distance: 400 s at 30% VO2max (LoWU), 200 s at 60% VO2max (MoWU) and 120 s at 100% VO2max (HiWU). Variables measured during exercise were rates of O(2) and CO(2) consumption/production (VO2,VO2), respiratory exchange ratio (RER), heart rate, blood lactate concentration and accumulation rate and blood gas variables., Results: VO2 was significantly higher in HiWU than in LoWU at the onset of the sprint exercise and HR was significantly higher in HiWU than in LoWU throughout the sprint. Accumulation of blood lactate, RER, P(a)CO(2) and PvCO2 in the first 60 s were significantly lower in HiWU than in LoWU and MoWU. There were no significant differences in stroke volume, run time or arterial-mixed venous O(2) concentration., Conclusions: These results suggest HiWU accelerates kinetics and reduces reliance on net anaerobic power compared with LoWU at the onset of the subsequent sprint., (© 2010 EVJ Ltd.)

Reasons for Performing Study: Accumulated O(2) deficit (AOD) and plasma lactate accumulation rate (PLAR) are alternative methods for estimating net anaerobic energy utilisation (NAEU) in exercising horses. How they compare or their accuracy is unknown., Objectives: We hypothesised net anaerobic energy utilisation calculated by PLAR (NAUE(PLAR)) is equivalent to NAUE estimated by AOD (NAUE(AOD))., Methods: Six Thoroughbred horses ran at identical supramaximal speeds (118% aerobic capacity) until exhaustion for 2 runs while breathing normoxic (NO, 21% O(2)) or hyperoxic (HO, 26% O(2)) gas. Jugular blood was sampled at 15 s intervals to measure plasma lactate concentration. Horses also ran at incremental submaximal speeds from 1.7-11.0 m/s to determine the linear relationship between speed and O(2) consumption to estimate O(2) demand for AOD calculations., Results: Maximum O(2) consumption of horses increased 11.6 ± 2.3% in HO and NAEU(PLAR) and NAUE(AOD) decreased 38.5 ± 8.0% and 46.2 ± 17.7%, respectively. The NAEU(PLAR) in NO was 114.5 ± 27.4 mlO(2) (STPD) equivalent/kg bwt contributing 23.5 ± 3.7% to total energy turnover and in HO was 70.9 ± 19.8 mlO(2) (STPD) equivalent/kg bwt contributing 14.6 ± 3.8% to total energy turnover. The NAUE(AOD) in NO was 88.6 ± 24.3 mlO(2) (STPD) equivalent/kg bwt contributing 19.9 ± 2.1% to total energy turnover and in HO was 56.2 ± 19.1 mlO(2) (STPD) equivalent/kg bwt contributing 10.9 ± 4.3% to total energy turnover. Overall, NAEU(AOD) was systematically biased -23.5 ± 16.8 mlO(2) (STPD) equivalent/kg bwt below NAEU(PLAR). Total energy demand estimated by PLAR was 11.1 ± 5.4% greater than that estimated by AOD and was higher in every horse., Conclusions: The NAUE(PLAR) estimates average 40.0 ± 29.6% higher than NAUE(AOD) and are highly correlated (r(2) = 0.734), indicating both indices are sensitive to similar changes in NAEU. Accuracy of the estimates remains to be determined. Multiple considerations suggest NAUE(AOD) may underestimate total energy cost during high-speed galloping, thus biasing low the AOD estimate of NAEU., (© 2010 EVJ Ltd.)

Reasons for Performing Study: Although the main cause of injury to the superficial digital flexor tendon (SDFT) is assumed to be high intensity loading of the tendon, to date the forces exerted on the SDFT during cantering have never been measured., Objective: To measure the force exerted on the SDFT at walk, trot and canter on a treadmill., Methods: Arthroscopically implantable force probes (AIFP) were implanted in the SDFT of the left and right forelimbs of 8 Thoroughbred horses (480-565 kg). The output of the AIFP was calibrated using the SDFT force calculated by inverse dynamics and an in vitro model of the lower forelimb at trot. The AIFP output was recorded at 1000 Hz at the walk, trot and canter (9 m/s) on a flat treadmill., Results: AIFP data were analysed successfully in 13 measurement sessions at the walk and trot, in the leading forelimb in 8 sessions at canter and in the trailing forelimb in 5 sessions at canter. The mean ± s.d. maximal force in the SDFT was 3110 ± 1787 N at the walk, 5652 ± 2472 N at the trot, 7030 ± 2948 N in the leading forelimb and 6453 ± 2940 N in the trailing forelimb at canter., Conclusions: The force in the SDFT increases with running speed from the walk to the canter. The force in the SDFT could not be measured at the gallop. Further study is needed to determine the force in the SDFT at high speed, because it is important for preventing injuries to the SDFT to limit overloading of this tendon., (© 2010 EVJ Ltd.)

Reasons for Performing Study: Thoroughbred racehorses often experience interruptions to their training. Identifying the effects of these changes and how they alter athletic performance might provide an insight on to how to prevent these changes from occurring., Hypothesis: Training and detraining young Thoroughbreds alters their aerobic capacities with correlated changes in circulatory capacities; if horses remained spontaneously active in a pasture during their detraining period, their decreases in aerobic capacity during detraining would be reduced., Methods: We trained 6 Thoroughbred yearlings for 6 months using a conventional yearling race training programme. They were then detrained for 10 weeks with free range on pasture for 8 h/day and stall rest at night. Treadmill measurements of O2 transport variables were made before training (PRE), after training (TR) and after detraining (DT). A step-test protocol identified each horse's aerobic capacity (VO2max) and speed to attain it, and a steady-state run at VO2max was used to quantify 02 transport variables at each time period., Results: The mass-specific and whole-body VO2max, cardiac output (Q) and stroke volume (Vs) increased from PRE to TR. All mass-specific values decreased significantly from TR to DT; however, because body mass increased by 8.3% from TR to DT, none of the variables changed significantly from TR to DT on a whole-body basis., Conclusions: Changes in aerobic capacity are highly correlated with changes in Vs and circulatory capacity during training and detraining. Exercise activity of trained young horses free at pasture for 8 h/day is sufficient to maintain VO2max, (Q and Vs during 10 weeks of DT., Potential Relevance: Aerobic and cardiovascular fitness may be maintained in young Thoroughbred horses during at least 10 weeks of detraining by maintaining modest spontaneous exercise activity.

Reasons for Performing Study: Heart rate (HR) recovery immediately after exercise is controlled by autonomic functions and the time constant (T) calculated from HR recovery is thought to be an index of parasympathetic activity in man., Objectives: To investigate whether it is possible to evaluate autonomic function using the time constant in horses., Methods: Five Thoroughbred horses were subjected to a standard exercise test. Following pre-medication with saline, atropine and/or propranolol, the horses ran for 2.5 min at a speed of 8 m/sec at a 10% incline and T was calculated from HR after the exercise. Secondly, 7 Thoroughbred horses were then trained for 11 weeks and T and maximal oxygen uptake (VO2max) measured at intervals of 1 or 2 weeks. In 6 horses, T with atropine pre-medication was also measured before and after the whole training period. Furthermore, the HR variability at rest was evaluated by power spectral analysis at intervals of 3 or 4 weeks., Results: Time constant was increased by atropine and/or propranolol pre-medication, decreased with the progress of training and inversely correlated with VO2max during training (r = 0.43, P<0.005). Parasympathetic blockade significantly decreased T only after and not before, the training; however, T was lower in post training than in pretraining, irrespective of parasympathetic blockade. On the other hand, parasympathetic activity at rest was attenuated and sympathetic activity became predominant following the training., Conclusion: Heart rate recovery is affected by sympathetic withdrawal and parasympathetic reactivation in horses and suggests that physical training hastened HR recovery by improving the parasympathetic function after exercise with aerobic capacity. However, the effects of other factors need to be considered because the training effect appeared on T even under parasympathetic blockade. The parasympathetic activity at rest is in contrast to that after exercise, suggesting that T does not reflect parasympathetic activity at rest., Potential Relevance: If demonstrated how HR recovery is controlled after exercise, its analysis will be important in the evaluation of physical fitness in horses.

Reasons for Performing Study: One cause of overstrain injury to the superficial digital flexor tendon (SDFT) in horses is the force loaded on the SDFT during repeated running. Therefore, decreasing this force may reduce SDFT injury. It has been reported that strain on the SDFT decreases with a toe-wedge shoe. Uphill courses are used for training of racehorses, and the angle of hoof-sole to the horizon during uphill running is similar to that of the toe-wedge shoe., Objectives: To determine the effects of uphill exercise on the force on the SDFT during trotting and cantering., Methods: Arthroscopically implantable force probes (AIFP) were implanted into the SDFT of the left or right forelimb of 7 Thoroughbred horses and AIFP output recorded during trotting and cantering on a treadmill inclined at slopes of 0, 3 or 8%, and then 0% again. Superficial digital flexor tendon force was calculated as a relative value, with the amplitude of AIFP output voltage at initial 0% slope equal to 100., Results: Out of 14 sets of experiments, AIFP data were analysed successfully in 9 at the trot, in 3 at the canter in the trailing forelimb on a slope of 3 and 8%, and in 2 at the canter in the leading forelimb on a slope of 3%. Increasing the incline from 0-8% tended to decrease peak force in the SDFT at the trot, and in the trailing forelimb at the canter. However, force in the SDFT was unchanged in the leading forelimb at the canter on the 3% incline., Conclusions: The force in the SDFT trotting or cantering uphill is unchanged or lower than that loaded at the same speed on a flat surface. Because at similar speeds the workload for uphill exercise is greater than on the flat, uphill running increases exercise intensity without increasing force in the SDFT., Potential Relevance: Uphill exercise may reduce the risk of SDFT injury as both running speed and SDFT force are decreased on an incline as compared to the flat, even when exercise intensity is the same. Further study is needed to confirm these findings at canter in a larger population of horses.

Background: A distinction between noninvasive, invasive, and metastatic thymoma on the basis of the cytologic features is difficult. The current study investigated whether the expression of MMP and TIMP was correlated with tumor invasiveness and prognosis in patients with thymoma., Methods: Tumor tissue samples were obtained from 42 patients with thymic epithelial tumors between 1974 and 2001 at Tokushima University Hospital. Three-micrometer-thick, formalin-fixed, paraffin-embedded tissue sections were immunostained using specific antibodies against MMP-2, MMP-9, TIMP-1, and TIMP-2., Results: MMP-2 expression was detected in 30 tumors (71%), and TIMP-2 expression was detected in 31 tumors (74%). MMP-9 expression was detected in 22 of 36 tumors (61%), and TIMP-1 expression was detected in only 7 tumors (19%). MMP-2 and TIMP-2 expression levels were very low (10% and 0%, respectively) in noninvasive tumors but were very high (91% and 97%, respectively) in invasive tumors. In thymic epithelial tumors, the more progressive the clinical stage of tumor, the higher the strongly positive rate of MMP-2 and TIMP-2 expression. There was no correlation between positivity for MMP-9 and stage. Twenty-five percent of Type AB thymomas and 50% of Type B1 thymomas expressed MMP-2 and TIMP-2. Most of Type A, Type B2, Type B3, and Type C thymomas expressed MMP-2 and TIMP-2. There were significant differences in disease-free survival at 5 years between patients without and with MMP-2 expression (91% vs. 55%, respectively) and patients without and with TIMP-2 expression (100% vs. 53%, respectively)., Conclusions: MMP-2 and TIMP-2 are key enzymes for invasiveness of thymic epithelial tumors. The expression of these proteins can predict a poor outcome in patients with thymoma., (Copyright 2003 American Cancer Society.)

Background: The differential diagnosis between reactive mesothelial cells (RMs), malignant mesotheliomas (MMs), and adenocarcinomas (ACs) is often difficult in cytologic specimens, and the utility of various immunohistochemical markers have been explored. Because recent immunohistologic studies have suggested that E-cadherin (E-cad) and calretinin (Cal) may be useful markers for epithelial and mesothelial differentiations, respectively, the authors investigated their utility in cytologic diagnosis., Methods: In this retrospective study, immunostaining was performed on smears retrieved from Papanicolaou-stained slides of effusions using the labeled streptavidin-biotin method. Sixteen cases of RM, 9 cases of MM, and 52 cases of AC from various sites, including 13 pulmonary primaries, were examined with primary antibodies against E-cad and Cal., Results: The positive rates for E-cad and Cal, respectively, were as follows: RM, 0/16 (0%) and 16/16 (100%); MM, 9/9 (100%) and 8/8 (100%); and AC, 45/52 (86.5%) and 0/51 (0%). The E-cad expression by neoplastic cells was strongest in the intercellular junctions, and poorly differentiated neoplastic cells in the single cell form showed the weakest expression., Conclusions: In contrast to the results of previous immunohistochemical studies, the current study indicates that MMs constantly express E-cad, whereas RMs lack its expression in cytologic specimens, which would be useful in the differential diagnosis between the two. On the other hand, E-cad expression is not reliable for distinguishing AC from MM. The Cal expression can be a very useful marker for the distinction between AC and the mesothelial lineage. The combined immunostaining for E-cad and Cal has utility in differential diagnosis among RM, MM, and AC.

Background: The authors examined somatic mutations of the adenomatous polyposis coli (APC) gene in 84 human aberrant crypt foci (ACF) to determine whether APC gene mutations were involved in the histologic progression of ACF., Methods: Mutation cluster regions of the APC gene were subjected to polymerase chain reaction single-strand conformation polymorphism analysis and direct sequencing., Results: Four kinds of deletion were detected in the mutation cluster regions of APC gene in five ACF. APC mutation was detected in 1 of 18 ACF with Stage I abnormalities (6%). Four of 10 adenomatous ACF (40%) harbored the mutation. There were no mutations in 56 hyperplastic ACF., Conclusions: These results suggest that APC mutations may be involved initially in only a limited number of adenomas in ACF.

Background: The incidence of cervical metastases after surgery for Stages I/II carcinoma of the tongue is 30-40%. Postoperative cervical metastases are an adverse prognostic factor for patients with this malignancy. The purpose of this study was to evaluate the clinicopathologic factors associated with late cervical metastases in patients with carcinoma of the tongue., Methods: The clinicopathologic features of 44 patients with previously untreated Stage I/II carcinoma of the tongue were reviewed. All patients were treated with partial glossectomy only., Results: Cervical metastases developed in 21 of 44 patients within 5 years. Factors significantly associated with the development of cervical metastases were invasive growth, differentiation, nuclear polymorphism in the deep portion, tumor border, nest formation, infiltrative growth ratio, depth, and thickness. No statistical correlations between cervical metastases and age, gender, tumor location, clinical stage, Brinkman index, alcohol index, mitosis, connective tissue, lymphocytic infiltration, or perineural invasion were found. Multivariate analysis demonstrated that only tumor thickness > 4 mm had a predictive value for cervical metastasis (risk ratio 9.4; 95% confidence interval, 1.5-57.7)., Conclusions: The current study data indicate that patients with Stage I/II carcinoma of the tongue > 4 mm in thickness are at increased risk for subsequent cervical metastasis. Thus, conservative supraomohyoid neck dissection is indicated in patients with Stage I/II carcinoma of the tongue > 4 mm in thickness.

Background: The authors previously found specific mutations of the K-ras gene at codon 12 in the pancreatic juice of 67% of patients (6 of 9) with pancreatic ductal carcinoma, and the detection of these mutations was useful for diagnosis. This study was performed to detect and evaluate K-ras mutations in pancreatic juice from patients with intraductal papillary mucinous tumor of the pancreas, which is considered a low grade malignancy. The results were interpreted from the viewpoint of clinical significance., Methods: K-ras mutations were examined using seminested polymerase chain reaction analysis combined with restriction enzyme digestion, followed by nonradioisotopic single strand DNA conformation polymorphism., Results: Twelve of thirteen cases (92%) of intraductal papillary mucinous tumor of the pancreas, confirmed histologically (9 adenomas and 4 carcinomas), and 26 of 43 cases (60%) of ductal carcinoma showed specific K-ras gene mutations in the pancreatic juice. Furthermore, 4 of 22 patients (18%) with chronic pancreatitis, followed for more than 1 year without a sign of pancreatic tumor, showed K-ras mutations. In contrast, no mutations of the K-ras gene were detected in the pancreatic juice from 28 normal controls., Conclusions: K-ras mutations were found in the pancreatic juice of all but one patient with intraductal papillary mucinous tumor of the pancreas, but they were not useful for distinguishing carcinoma from adenoma. The authors concluded that K-ras mutations are not a specific marker for pancreatic neoplasms because similar mutations were detected in the pancreatic juice from patients with chronic pancreatitis. At the present time, the detection of K-ras mutations in pancreatic juice should be used clinically as an adjunct diagnostic modality for pancreatic diseases.

Background: To the authors' knowledge, there has been no previous report of primary malignant melanoma of bone., Methods: A 33-year-old woman presented with a tumorous lesion in the olecranon of the right ulna. The histologic diagnosis was malignant melanoma with close similarity to clear cell sarcoma. To exclude the possibility of malignant melanoma metastatic to the bone, clinical investigations including gallium 67-citrate scintigraphy, brain, chest, and abdominal computed tomography, and upper and lower gastrointestinal endoscopic examinations were performed. Conventional histopathologic, immunohistochemical, and electron microscopic studies were also performed., Results: Clinical investigations showed no lesion suggestive of a primary melanoma other than that in the right ulna. Histologically, the tumor was comprised of polygonal or fusiform cells with clear or granular cytoplasm and vesicular nuclei containing one or two prominent nucleoli. The features were similar to those of clear cell sarcoma (malignant melanoma of soft parts). Fontana preparations and immunohistochemical staining for S-100 protein and HMB-45 (melanoma specific antigen) also revealed that the tumor cells had the characteristics of malignant melanoma. The patient has remained alive and well for more than 5 years after the initial treatment., Conclusions: The clinicopathologic findings in this case strongly suggested that the lesion was a primary malignant melanoma of bone. Therefore, this is the first report to indicate that malignant melanoma and related diseases can occur even in bone tissue.

Background: Prognosis of patients with adenocarcinoma of the pancreatic body and tail is extremely poor. Anatomically, this part of the pancreas is thin, and cancerous invasion to the retropancreatic structures occurs easily. The majority of patients have residual tumor in the retroperitoneal tissues after conventional distal pancreatectomy., Methods: Between 1962 and 1979, 10 patients with carcinoma of the pancreatic body underwent simple distal pancreatectomy. Between 1980 and 1990, 22 patients including 7 with distant metastasis underwent a more aggressive approach intended to achieve longer survival: distal pancreatectomy with extended dissection of the lymph nodes and adjacent structures, especially into the retropancreatic space. After 1984, intraoperative ŕadiation (IORT) by electron beam and chemotherapy by hepatic infusion plus systemic injection of mitomycin C (MMC) were added for 7 patients without distant metastasis., Results: The 10 patients who underwent pancreatectomy between 1962 and 1979 all died within 20 months after their operations. Conversely, the patients treated with an aggressive approach between 1980 and 1990 survived longer; the 5-year survival rate for 15 patients without distant metastasis was 29%, though the 7 patients with distant metastasis died within 10 months of their operations. There were 4 long term survivors (> or = 5 years); 3 of whom received IORT and chemotherapy with MMC. Invasion to the retropancreatic soft tissues was present in 95% of the resected specimens from the 22 patients. However, invasion to the surgical margin at the posterior surface of the resected specimen was present in only 36% after extended resection of the retropancreatic structures., Conclusions: Survival improved for this disease after distal pancreatectomy with extended dissection, especially of the retropancreatic structures, adjuvant IORT, and chemotherapy had been performed.

Background: It is now well documented that patients with squamous cell carcinoma of the upper aerodigestive tract frequently develop additional squamous cell carcinoma in the same field., Methods: p53 expression in 95 patients with multicentric squamous cell carcinoma and in squamous epithelia surrounding multicentric squamous cell carcinomas of the upper aerodigestive tract in 20 patients was examined by immunohistochemistry. In addition, p53 expression in 129 patients with supposedly unicentric squamous cell carcinoma and in squamous epithelia surrounding unicentric squamous cell carcinoma in 22 patients was also examined by immunohistochemistry., Results: Among the 95 patients with multicentric squamous cell carcinoma, 62 (65%) had a clearly positive reaction for p53 protein, whereas 56 (43%) of 129 patients with unicentric squamous cell carcinoma had a positive reaction for p53 protein. The frequency of positive nuclear p53 staining in multicentric squamous cell carcinoma appeared higher than that in unicentric squamous cell carcinoma. However, there was no significant difference between the two groups. Among the nondysplastic squamous epithelia surrounding multicentric squamous cell carcinomas in 20 patients, 12 (60%) were p53 positive, whereas only five (22%) of 22 patients with nondysplastic squamous epithelia surrounding unicentric squamous cell carcinomas were positive. The difference between the two groups was significant (P < 0.05)., Conclusions: The present results suggest that nuclear accumulation of p53 in the squamous epithelium surrounding multicentric squamous cell carcinoma is probably due to heavier exposure and increased susceptibility to mutagens of the affected individuals, although this remains to be verified.

Background: Tumor suppressor gene p53, located on the short arm of chromosome 17, frequently mutates in various types of cancers and plays a critical role in the multiple stages of carcinogenesis. However, there is little information about the clinicopathologic significance of alterations of the p53 gene in soft tissue sarcomas (STS)., Methods: Because it is known that nuclear accumulation of p53 protein correlates closely with the presence of mutations in the p53 gene, immunohistochemical detection of this protein was performed. A polyclonal antibody (RSP-53) raised against synthetic human p53 peptide was used to detect nuclear accumulation of the protein. Pathologic specimens of 96 patients with STS were collected from the surgical pathology files of the National Cancer Center Hospital and examined., Results: Nuclear accumulation of p53 protein was detected in 31 (32.3%) patients. The percentage of patients with a positive immunoreaction was high in patients with malignant schwannoma (100%), rhabdomyosarcoma (71.4%), and synovial sarcoma (50.0%), whereas it was low in patients with liposarcoma (13.6%) and 0% in those with fibrosarcoma. It was closely associated with the histologic grade of malignancy (grade 1, 12.0%; grade 2, 30.8%; grade 3, 44.4%) and the patient's age (younger than 40 years, 46.9%; 40 years of age or older, 25.0%). Both overall and metastasis-free survival rates were significantly lower for patients with a nuclear p53 immunoreaction than for those without it., Conclusions: The nuclear p53 immunoreaction is considered a marker of tumor aggressiveness and appears to be a useful prognostic factor for STS.

Retrospective immunocytochemical study of prolactin, growth hormone, ACTH, TSH and gonadotropins was performed on 150 pituitary adenomas from 142 patients and the results were correlated with clinical manifestations. There were 60 prolactin-positive tumors, 13 growth hormone-positive tumors, nine ACTH-positive tumors and seven gonadotropin-positive tumors. Seven tumors showed positivity for both prolactin and growth hormone, one tumor was positive for prolactin and ACTH and another was positive for prolactin and TSH. Fifty-two tumors were negative for all the hormones. In the hormone secreting tumors, the results of immunocytochemical study correlated very well with clinical manifestations, while most of the hormone-negative tumors were nonfunctioning clinically. This study demonstrates the reliability of the immunocytochemical method in clinicopathologic study of pituitary adenomas.

Two new cases of pilomatrix carcinoma are reported. They were studied immunohistochemically for the presence of high and low-molecular weight cytokeratins, beta-2-microglobulin, S-100 protein, carcinoembryonic antigen, epithelial membrane antigen, blood group isoantigens, and peanut agglutinin binding. Results of these studies were compared with those obtained in immunohistologic analysis of 13 typical pilomatrixomas, and 4 other benign lesions with hair follicle differentiation. An attempt was made to correlate antigenic expression with malignant transformation; however, there were no consistent differences between the 2 groups. It would seem that immunocytochemistry is of no assistance in differential diagnosis between benign and malignant hair matrical tumors. Hence, the pathologist must rely on morphological criteria alone to make a diagnosis of pilomatrix carcinoma.

The nuclear DNA content of tumor cells in imprint smears prepared from 72 surgically resected adenocarcinomas of the lung was determined prospectively by means of cytofluorometry, and its relationship to pathologic stage, degree of histologic differentiation, and nuclear atypia represented by the mean nuclear area (MNA) and standard deviation of the nuclear area (SDNA) was studied. The mean nuclear DNA content (MNDC) of poorly differentiated adenocarcinomas was significantly larger than that of well-differentiated adenocarcinomas both in Stages I + II and III + IV (P less than 0.001, each), and the MNDC of Stages III + IV was significantly larger than that of I + II in poorly differentiated adenocarcinomas (P less than 0.01). There was a tendency for histogram Patterns III and IV, in which more aneuploid cells were present than in I and II, to be more common and for the incidence of the aneuploid stem cell line to be higher in less differentiated and more advanced adenocarcinomas, although the differences were not significant statistically. Furthermore, there were significant positive correlations between MNDC and MNA (P less than 0.01) and between MNDC and SDNA (P less than 0.05). The averages of the MNA according to the histogram pattern increased significantly in the increasing order of Patterns I to IV. These results indicate that the nuclear DNA content increases in less differentiated and more advanced adenocarcinomas, and that the nuclear atypia is reflected in abnormal nuclear DNA content (DNA aneuploidy).

Five cases of the recently characterized cystic mesothelioma of the peritoneum are presented. The patients, all women, ranged in age from 23-50, and were seen with large, solitary or multiple, multicystic masses involving the abdominal and pelvic peritoneum. Histologically, they consisted of interconnecting cystic cavities lined by a single layer of flattened to cuboidal cells with variable nuclear atypia. These cells in one case showed ultrastructural features consistent with mesothelial origin. In follow-up periods ranging from 1-13 years, two patients have had recurrence of disease, but all patients are still alive. When these cases are combined with the ten previously reported, the recurrence rate in patients followed for two years or more is 50% (four of eight). This lesion may represent a clinically "borderline" variant between the better known benign (adenomatoid tumor) and malignant mesotheliomas of the peritoneum.

Forty-nine cases of cutaneous malignant lymphoma were reviewed in order to analyze the clinicopathological features of these neoplasms. Excluding 13 cases of mycosis fungoides and 4 cases of cutaneous involvement of proven adult T-cell lymphoma/leukemia, the remaining 32 cases were further classified according to their pathological and clinical features. There were 12 primary cutaneous lymphomas, 15 cases of secondary cutaneous involvement of systemic lymphoma, and 5 cases of concurrent skin and lymph node involvement. Histologically, large cell lymphoma predominated in both primary and secondary cutaneous lymphomas. Immunohistochemical study using monoclonal antibodies reactive with B- and T-cells in paraffin sections revealed the cellular lineage in 30 cases. Nineteen cases were of T-cell origin and 11 cases were of B-cell derivation. The prognosis of these patients was rather poor; 25 patients died within 5 years. The predominance of T-cell lymphoma contrasts with a higher frequency of cutaneous B-cell lymphoma in Western countries. As the clinicopathological features of cutaneous lymphomas are diverse, it is suggested that cutaneous lymphomas should be classified and studied in a similar way to their nodal counterparts.

To investigate the effect of arginine-enriched solution on tumor growth and metastasis, rats were infused with solutions containing 5.5 and 0.66% arginine for 8 days. Infusions were started at the same time of subcutaneous transplant of Yoshida sarcoma. Arginine-rich solution suppressed tumor growth at an early stage and prevented metastases to the liver and kidney. In addition, arginine supplements enhanced the phagocytic activity of alveolar macrophages. It also resulted in maintenance of a positive nitrogen balance and prevented the increases in the levels of several amino acids observed in the control group. The suppressive effect of arginine-enriched solution on tumor growth may be due to its activation of the immunologic system, in which the phagocytic activity of macrophages probably participates.