Determination of lidocaine and its two N-desethylated metabolites in dog and horse plasma by high-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry.

A sensitive method for the quantification of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), in animal plasma using high-performance liquid chromatography combined with electrospray ionization mass spectrometry is described. The sample preparation includes a liquid-liquid extraction with methyl tert-butylmethyl ether after addition of 2M sodium hydroxide. Ethylmethylglycinexylidide (EMGX) is used as an internal standard. For chromatographic separation, an ODS Hypersil column was used. Isocratic elution was achieved with 0.01 M ammonium acetate and acetonitrile as mobile phases. Good linearity was observed in the range of 2.5-1000 ng ml(-1) for lidocaine in both dog and horse plasma. For MEGX, linear calibration curves were obtained in the range of 5-1000 ng ml(-1) and 20-1000 ng ml(-1) for dog and horse plasma, respectively. In dog and horse plasma good linearity was observed in the range of 200-1500 ng ml(-1) for GX. The limit of quantification (LOQ) in dog plasma for lidocaine, MEGX and GX was set at 2.5 ng ml(-1), 20 ng ml(-1) and 200 ng ml(-1), respectively. For horse plasma a limit of quantification of 2.5 ng ml(-1), 5 ng ml(-1) and 200 ng ml(-1) was achieved for lidocaine, MEGX and GX, respectively. In dog plasma, the limit of detection (LOD) was found to be 0.8 ng ml(-1), 2.3 ng ml(-1) and 55 ng ml(-1) for lidocaine, MEGX and GX, respectively. In horse plasma the LOD's found for lidocaine, MEGX and GX, were 1.1 ng ml(-1), 0.5 ng ml(-1) and 13 ng ml(-1), respectively. The method was shown to be of use in pharmacokinetic studies after application of a transdermal patch in dogs and after an intravenous infusion in horses.

Surgical repair of a tibial fracture in a Belgian Landrace pig.

This paper reports the surgical treatment of a tibial fracture in a castrated adult male Belgian Landrace pig of 180 kg. The fracture was repaired using an intramedullary Steinmann pin, combined with cerclage wire and external transfixation. In contrast to other animal species, the fracture repair in the pig was hindered by the short and curved bones, the thick subcutaneous fat layer and the pronounced musculature. Postoperatively, the pig developed an osteomyelitis of the tibia due to pin tract contamination. Despite this complication, the fracture healed acceptably when all fixation material was removed two months after surgery. The infection resolved quickly and a satisfactory clinical result was obtained.

Pharmacokinetics of a lidocaine patch 5% in dogs.

Lidocaine is increasingly used in transdermal drug delivery systems for different pain conditions in human medicine whereby several pharmacokinetic studies have demonstrated minimal systemic absorption in men. In the present study, the pharmacokinetics of a lidocaine patch 5% was studied in six dogs. In the first experiment, one single lidocaine patch was applied for 12 h to the lateral side of the thorax after removing the hair either by clipping or by the application of a depilatory agent, according to a two-way crossover design. No potential adverse effects induced by the patches were observed in either group. In dogs with clipped hair, a mean peak plasma lidocaine concentration of 62.94 ng/ml was obtained after 10.67 h. In the depilatory group, a mean peak plasma concentration of 103.55 ng/ml was reached after 9.27 h. Significant differences in the AUC(0 --> infinity), C(max), k(a) and T(1/2a) were noticed between the two groups. No significant differences were found for the elimination parameters and for T(max). In the second experiment, the patches were applied for 60 h to the clipped skin in order to study the absorption kinetics after a prolonged application period. There, the mean peak lidocaine plasma concentration was 45.18 ng/ml achieved after 24 h and a final concentration of 29.37 ng/ml was obtained at 60 h. In conclusion, all dogs tolerated the transdermal lidocaine patch well. The results of this study suggest that there is an overall minimal absorption from the lidocaine patch. However, the application of a depilatory agent leads to a more rapid and increased absorption of lidocaine.

Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease.

BACKGROUND & AIMS: The aim of this study was to determine the risk of endoscopic/radiological recurrence of Crohn's disease postoperatively and the long-term outcome. METHODS: A randomized placebo-controlled trial was performed to determine the effectiveness of mesalamine in preventing recurrent Crohn's disease postoperatively. Patients in the control group were examined endoscopically/radiologically before entry into and annually during the trial. Findings were classified as minimal or severe. RESULTS: There were 76 patients (49 men and 37 women; mean age, 37.1 +/- 13.2 years). Fifty (61.7%) had terminal ileal resections. Overall, 55 endoscopic/radiological recurrences were observed in 51 patients (67.1%). Expressed actuarially, the recurrence rate was 27.5% at 1 year (95% confidence interval [CI], 15.8%-37.6%), 60.8% at 2 years (95% CI, 46%-71.3%), and 77.3% at 3 years (95% CI, 62.7%-86.3%). Nineteen (37%) were symptomatic and 12 (24%) were initially asymptomatic but later became symptomatic (mean, 13.0 +/- 8.8 months), whereas 20 (39%) remained asymptomatic (mean, 16.9 +/- 17.4 months). Patients with severe endoscopic/radiological disease were significantly more likely to be or become symptomatic than those with minimal disease (23 of 32 vs. 8 of 19, respectively; P = 0.0437). CONCLUSIONS: This study suggests that postoperative endoscopic/radiological recurrences occur later than previously reported. Furthermore, many of these patients, especially with minimal disease, will remain asymptomatic.

Malignant fibrous histiocytoma of the lung. Report of four cases and review of the literature.

BACKGROUND: Primary malignant fibrous histiocytoma (MFH) of the lung is a rare clinical entity. Only 23 reports of 49 cases have been reported in the literature. Surgery was the primary mode of therapy, with high rates of local and distant recurrence reported. The role of radiation therapy and chemotherapy has never been clearly defined. METHODS: The records of the Mayo Clinic in Scottsdale and Rochester from 1970 to 1990 were reviewed for cases of primary pulmonary MFH. A review of the literature was also undertaken. RESULTS: Four cases from the Mayo records and 49 cases from a review of the literature were identified. Eight patients were alive at 5 years from diagnosis; all had been treated with surgery as the primary modality. No definite relationship between histologic subtype of MFH and survival could be identified and no definite role of radiation therapy or chemotherapy could be defined. CONCLUSIONS: MFH of the lung should be treated by surgical resection if technically feasible. The role of adjuvant therapy remains undefined.

Salivary duct carcinoma. Clinicopathologic and immunohistochemical review of 26 cases.

BACKGROUND: Salivary duct carcinoma (SDC) is a high grade aggressive malignancy of the major salivary glands. Clinical and pathologic features that may be predictive of survival are not well delineated. The microscopic features of SDC are remarkably similar to those of mammary ductal carcinoma, raising the question of whether these tumors share antigenic or hormonal features. METHODS: We reviewed the clinical and pathologic characteristics of 26 cases of SDC treated at the Mayo Clinic from 1960 to 1989. Immunoperoxidase studies and flow cytometry were performed in 25 and 24 cases, respectively. RESULTS: The study population consisted of 22 men and 4 women (mean age, 66 years). The parotid gland was involved in 23 patients and the submaxillary gland in 3. Five of 24 tumors studied were diploid (21%), and 19 (79%) were nondiploid. Nine tumors (35%) recurred locally and 16 (62%) metastasized distantly; 20 patients (77%) died of disease at a mean interval of 3 years after diagnosis. Female sex was the only significant negative prognostic factor analyzed, but positive nodal status approached significance. Paraffin-section immunostaining showed positive reactions for epithelial membrane antigen (100%), keratin (AE1/AE3) (88%), alpha-lactalbumin (88%), GCDFP-15 (76%), and carcinoembryonic antigen (72%); S-100 protein was rarely detected (4%). Stains for estrogen receptor were uniformly negative, but one tumor was positive for progesterone receptors. CONCLUSIONS: The prognosis for SDC is dismal, and clinically useful prognostic factors were not found. Our results do not confirm hormonal concordance between SDC and breast carcinoma.

Trends in colorectal cancer over a half century in Rochester, Minnesota, 1940 to 1989.

Recent reports of increasing incidence, especially in men, led us to update through 1989 an earlier study of colorectal cancer incidence in Rochester that covered the period 1940 through 1979. The combined data reflected cancer trends in the community over half a century. Data resources of the Rochester Epidemiology Project were used to identify new cases of colon and rectal cancer among Rochester residents. Incidence rates were estimated using decennial census data, and 95% confidence intervals were based on the Poisson distribution. The GLIM statistical package was used to evaluate trends over time. Age-adjusted (US white 1970) incidence rates of colorectal cancer for men were 53.7, 61.3, 53.7, 54.2, and 52.5 per 100,000 person-years, respectively, for the decades 1940 to 1949, 1950 to 1959, 1960 to 1969, 1970 to 1979, and 1980 to 1989. Comparable rates for women were 42.7, 49.3, 42.9, 40.7, and 40.9 per 100,000 person-years. No statistically significant changes were seen in the incidence of colon and rectum cancer for men or women. There was no consistent trend in tumor stage at diagnosis and the mean size of the initial lesion did not change with time. The incidence of colorectal cancer has not changed over the past 50 years in this community where case ascertainment has been consistent and complete.

Upper aerodigestive tract cancers.

BACKGROUND: Cancers of the upper aerodigestive tract constitute approximately 4% of all malignancies. These include cancer of the lip, tongue, major salivary glands, gums and adjacent oral cavity tissues, floor of the mouth, tonsils, oropharynx, nasopharynx, hypopharynx and other oral regions, nasal cavity, accessory sinuses, middle ear, and larynx. METHODS: The histologically diagnosed cancers of the upper aerodigestive tract reported to the Surveillance, Epidemiology, and End Results program of the National Cancer Institute in 1973-1987 were tabulated by histologic type, sex, age, and racial group, and according to quinquennium (1973-1977, 1978-1982, 1983-1987). Frequencies, age-specific incidence rates, median age, and extent of spread at diagnosis, stage, and survival were examined. RESULTS: Cancer of the upper aerodigestive tract represented 3.5% of all microscopically proven malignant neoplasms. Except for salivary glands, gums, nasopharynx, and nasal cavity and accessory sinuses, epidermoid carcinomas accounted for greater than 95% of the cancers. For all aerodigestive sites combined, there was a 2-to-1 male-to-female ratio (greater for laryngeal cancer, which was approximately 5 to 1). Incidence in black males was often twice the levels recorded in white males, whereas rates for black and white females tended to be close. The 5-year relative survival was approximately 50% (90% for lip and 65% for larynx), was somewhat better for whites than for blacks, and did not improve significantly over the 15 years studied. Salivary gland adenocarcinoma carried a survival of approximately 80%. CONCLUSIONS: Because many of the cancers of the upper aerodigestive tract are caused by alcohol and tobacco use, the potential for prevention is considerable.

Mucous membrane plasmacytosis of the upper aerodigestive tract. A clinicopathologic study.

We report 9 patients with an unusual plasma cell proliferative disorder of the upper aerodigestive tract. Six patients were men and three, women. The age at presentation ranged from 40 to 67 years with a mean of 54 years. Symptoms at presentation included dysphonia, dysphagia, difficulty breathing, and oral pain. These plasma cell lesions typically produced a cobblestone or warty appearance of the upper aerodigestive tract mucosa including the larynx, pharynx, palate, lips, mouth, tongue, and trachea in varying combination of multiple sites in each patient. Histologically, all lesions were characterized by psoriasiform epithelial hyperplasia with dyskeratosis and dense subepithelial plasmacytosis. Plasma cells were mature but so expansive and diffuse in infiltration as to suggest extramedullary plasmacytoma. Immunohistochemistry for kappa and lambda light chain showed polyclonal immunoglobulin content in all cases examined. Microbial cultures and Warthin-Starry stains were negative for organisms. A variety of treatments including antibiotic therapy, corticosteroid administration, and surgical resection were unsuccessful. In two patients, the process required tracheostomy. This disorder has not been previously described with the exception of a single reported case, which is included in this series. The etiology, pathogenesis, and successful management of mucous membrane plasmacytosis remain unknown.

Pediatric surgical pathology of the head and neck.

Anatomically, the head and neck region is composed of a greater variety of structures than any other part of the body. Practically all the anatomic structures can be the site of the various pathological processes. Multiplying the anatomic structures by the various pathological processes produces an infinite number of pathological diagnoses that may be encountered in the head and neck region. The large number of pathological possibilities provides a challenge for the pathologist working in surgical pathology of the head and neck region in children. Whenever a specimen is submitted to the laboratory, it is necessary to have at one's disposal a list of differential diagnoses. Clinical information is of importance in interpreting specimens if excellence in patient management is to be achieved. Therefore, it is imperative that open communication exist between the clinician and the pathologist. Thus, a combination of knowledge of the pathological possibilities, the range of differential diagnoses, the ability to use newer technologies, such as cell marker determinations by flow cytometry and immunoperoxidase, and dialogue with clinical physicians will provide some assurance of the ultimate in patient care. Herein the authors discuss some of the more common and important neoplasms encountered in pediatric head and neck surgical pathology.

Middle ear adenoma and adenocarcinoma.

Adenomas and adenocarcinomas originating from the middle ear are few in number and have met with significant controversy in the literature. Our experience with 11 previously described patients is updated and five new cases are added. These tumors were seen in persons whose ages ranged from 7 to 77 years. The most common initial symptom was decreased hearing (11 cases), followed by otorrhea (4 cases), and otalgia (4 cases). At the time of diagnosis, facial nerve weakness was present in several patients (seven), and this was a poor prognostic sign. These glandular tumors engender controversy regarding histologic origin and the pathologic demarcation between adenoma and adenocarcinoma. In this review, we show that otorrhea, bone erosion, facial nerve involvement, and aggressive clinical behavior can be the result of lesions that appear microscopically benign. Furthermore, we present evidence of the similarity of these glandular lesions to paragangliomas and carcinoid tumors. Finally, pathologic data are presented to develop the previously unreported theory that the origin for this group of tumors is paraganglionic tissue.

Eosinophil-mediated bile duct stricture. A case studied by immunohistochemistry.

Major basic protein accounts for the majority of the protein within the eosinophilic granule. Utilizing immunohistochemical staining for major basic protein, we have demonstrated the dominant role of the eosinophil in a reversible bile duct stricture.

Increasing incidence of pancreatic cancer among women in Olmsted County, Minnesota, 1940 through 1988.

To determine trends in the incidence of pancreatic cancer and associated survival, we conducted a population-based study in Olmsted County, Minnesota. From 1940 through 1988, 219 residents of Olmsted County (120 men and 99 women) were diagnosed as having exocrine pancreatic cancer. All patients were Caucasians, and 92% had a histologically confirmed diagnosis. The mean annual adjusted incidence of pancreatic cancer per 100,000 population was 8.5 overall (11.3 for men and 6.6 for women). During the course of the study, the incidence rates increased in women (P < 0.05) and in both genders combined (P = 0.06) but not in men (P = 0.4). The male:female ratio decreased from approximately 2:1 for 1940 through 1949 to 1.5:1 for 1980 through 1988. The incidence was significantly associated with increasing age (P < 0.001) and male gender (P < 0.001) but not calendar period (P = 0.19). The overall median duration of survival was 2.8 months. The 1-year survival rate was only 14%, and no patient lived for more than 55 months after pancreatic cancer was diagnosed. Men and women had similar survival rates. The increased incidence of pancreatic cancer among women may be due in part to the increasing life span of women and the increasing occurrence of pancreatic cancer in the aged.

Evaluation of DNA nuclear pattern as a prognostic determinant in resected pancreatic ductal adenocarcinoma.

From a cohort of 72 patients who underwent radical resection for ductal adenocarcinoma of the pancreas between 1951 and 1980, 62 paraffin-embedded specimens were analyzed by flow cytometry. Patients were divided into two groups according to the length of survival: long-term survivors (19 patients who survived 3 or more years after operation) and short-term survivors (43 patients who died within 12 months after resection). In 30 specimens (48%), the nuclear DNA pattern was diploid, whereas 32 were nondiploid (two tetraploid and 30 aneuploid). There were no significant differences in the number of diploid/nondiploid patterns, the fraction of cells in DNA synthetic (S) phase, or the DNA index between the two groups. These data suggest that there is no difference in the DNA content analysis of patients with pancreatic ductal adenocarcinoma when comparing long-term with short-term survivors following resection.

Sinus histiocytosis involving the lacrimal sac and duct. A clinicopathologic case report.

A 17-year-old girl with right-sided epiphora and a lacrimal sac mass was found radiologically to have marked enlargement of her lacrimal sac and nasolacrimal duct and mucosal thickening of her right nasal turbinates and maxillary, ethmoid, and sphenoid sinuses. Biopsy specimens from all these sites showed chronic inflammatory infiltrates with a predominant population of large phagocytic histiocytes, some of which had engulfed lymphocytes and plasmacytes. The results of a systemic workup were normal. This is the first reported case, to our knowledge, of sinus histiocytosis involving the lacrimal sac and nasolacrimal duct as an extranodal focus.

Acinic cell carcinoma. Clinicopathologic review.

The authors reviewed 90 cases of acinic cell carcinoma treated at the Mayo Clinic to assess long-term follow-up and to study features predictive of disease progression. Sixty-three patients (55 females and 35 males) were seen for primary treatment; 27 had recurrent disease when first evaluated. Histologically, these tumors were composed of serous acinar cells and intercalated duct-type cells. Morphologic patterns included solid, microcystic, follicular, and papillary-cystic. All patients were followed for at least 10 years or until death. Of the primary treatment group, 44% had local recurrence, 19% had metastasis, and 25% died of disease. Disease first recurred locally up to 30 years after presentation and resulted in death after as many as 38 years. Poor prognostic features include pain or fixation; gross invasion; microscopic features of desmoplasia, atypia, or increased mitotic activity; and excision as initial treatment. Neither morphologic pattern nor cell composition was a predictive feature.

Laryngeal keratosis and carcinoma in the Rochester, MN, population 1935-1984.

An attempt was made to identify all laryngeal carcinomas (LSCC), carcinomas in situ (LCIS), and clinical keratoses (LK) in a defined community and to observe them retrospectively via medical records from 1935 to 1984. In Rochester, MN, 108, 7, and 52 cases of LK, LCIS, and LSCC, respectively, were diagnosed, providing mean annual incidence rates of 5.8, 0.4, and 3.3/100,000 person-years. LSCC and LK incidence rates increased more than threefold between 1935 and 1984, while LCIS incidence remained constant. A strong male predilection was noted for all three diseases. The peak age-specific incidence for LK (45 to 54 years of age) occurred a decade earlier than for LSCC. Although 16.2% of LKs had LSCC or LCIS at initial diagnosis over half of LK patients were followed without initial biopsy and only one cancer developed in that group. Clinicopathologic characterization is provided for all three diseases.

Carcinoid tumor of the appendix in the first two decades of life.

Carcinoid tumor of the appendix is the most common neoplasm of the gastrointestinal tract in childhood and adolescence. Sufficient long-term follow-up data after surgical treatment are not currently available for patients diagnosed during the first two decades of life. From 1936 to 1988, 23 patients were observed at this institution with histologically confirmed carcinoid tumors involving the vermiform appendix. In contrast to the adult experience, in which the tumor is most commonly encountered as the result of an incidental appendectomy, 18 of these patients presented with signs and symptoms of an acute abdomen directing the surgeon to the appendix. In the other five cases, surgery was performed for other reasons. Median age at presentation was 13.0 years (range, 6 to 20 years). Fourteen patients were female, nine were male. Simple appendectomy was the initial procedure for all patients. Tumor size ranged from "microscopic" to 2.5 cm in largest dimension. Three patients subsequently underwent right hemicolectomy, and one patient had removal of a residual appendiceal stump, but no residual or metastatic tumor tissue was found in any of the resected specimens. Nineteen patients underwent simple appendectomy alone. Eighteen available specimens were reviewed at the time of this study for confirmation of histology and degree of invasion. The tumor invaded to the serosa in nine of 23 (39%). The mesoappendix or periappendiceal fat was involved in seven of 23 (30%). Vessel invasion was not noted in any specimen. Our median follow-up time was very long, being 26 years (range, 9 months to 51 years). No patient has had evidence of recurrent or metastatic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Ureteroscopic visualization of a cavernous hemangioma of the renal pelvis.

We describe a 54-year-old man in whom a capillary hemangioma of the renal pelvis was suspected ureteroscopically before excision. To our knowledge, this is the first case reported of this entity managed in this fashion.