Quantitative ultrasonic assessment of normal and ischaemic myocardium with an acoustic microscope: relationship to integrated backscatter.

PURPOSE OF INVESTIGATION: The aim was to study ultrasonic propagation properties of normal and ischaemic myocardium with a scanning laser acoustic microscope and to correlate these changes with ultrasonic backscatter. DESIGN: Myocardial ischaemia was produced by total occlusion of left anterior descending coronary artery in anaesthetised open chest dogs. Myocardium supplied by left circumflex coronary artery served as normal control. IBR5, an optimum weighted frequency average (4-6.8 MHz) of the squared envelope of diffraction corrected backscatter, was measured in vivo. Ultrasonic attenuation coefficient, an index of loss per unit distance, the propagation speed and heterogeneity index were measured from normal and ischaemic regions with a scanning laser acoustic microscope which operates at 100MHz in vitro. Myocardial water content of normal and ischaemic myocardium was also estimated. SUBJECTS: Were five anaesthetised mongrel dogs. RESULTS: Attenuation coefficient of 33.8(SD4.2) dB.mm-1 in the ischaemic tissue was lower than 63.8(17.2) dB.mm-1 in the normal tissue (p less than 0.01). Ultrasonic speed was lower in ischaemic than normal myocardium at 1584(25) v 1612(35) m.s-1 (p less than 0.05). Heterogeneity index of 11(7) m.s-1 in the ischaemic region was lower than 14(8) m.s-1 in the normal region (27% reduction, p less than 0.05). IBR5 and myocardial water content were higher in the ischaemic than the normal myocardium: -37.2(SEM1.8) dB v -46.6(0.6) dB, (p less than 0.01) and 80.9(0.0)% v 78(0.2)%, (p less than 0.05) respectively. CONCLUSION: Ultrasonic properties of the myocardium are significantly altered during acute ischaemia.

Histologic spectrum of diversion colitis.

Biopsy specimens taken from six patients with diversion colitis, an inflammatory process that occurs in the bypassed colonic segment after diversion of the fecal stream, showed a spectrum of histologic changes ranging from mild colitis to those seen in severe active chronic ulcerative colitis. Histologic abnormalities included aphthous ulcers, crypt distortion, atrophy and abscesses, a villous colonic surface, and a mixed acute and chronic inflammatory infiltrate with patchy lymphoid hyperplasia. Accurate pathologic diagnosis is dependent on clinical history, comparison of histologic morphology in both colonic segments, and response to therapy with local application of short chain fatty acids.

Hyperplastic gastropathy. Clinicopathologic correlation.

Assessment of gastric histology in patients with hyperplastic gastritis is now possible using new endoscopic biopsy techniques that obtain a full-thickness gastric mucosal biopsy. Thirty-one patients with hyperplastic gastropathy and full-thickness gastric mucosal biopsies or gastric resections were seen during a 13-year period. Six patients had Zollinger-Ellison syndrome (ZE) with gastric gland hyperplasia; six had Menetrier's disease with foveolar hyperplasia and gland atrophy; and a single patient with hyperplastic hypersecretory gastropathy (HHG) was seen. The majority of patients, 18 of 31 with large folds, had peptic disease. The enlarged gastric folds were due to edema and inflammation. Discordant clinical findings and gastric pathology were seen in four patients: three of the 18 patients with peptic disease had histology typical of ZE (two patients) or Menetrier's disease. None of the three patients have developed a syndrome on follow-up ranging up to 5 years. Also, the patient with HHG had the gastric histology seen in Menetrier's disease. One patient with Menetrier's disease had areas of atrophic gastritis interspersed between the hyperplastic gastritis. In summary, the majority of patients with endoscopic hyperplastic gastropathy had gastritis on histologic examination. Most patients with a clinical syndrome associated with hyperplastic gastritis showed histology typical for the syndrome; however, clinical-histologic concordance was not absolute. In a small minority of cases, a patient with one clinical syndrome had the histology typical of another.

Assessment of ampulla of Vater pathology. An endoscopic approach.

One hundred eighty-nine endoscopic biopsies of the papilla of Vater were obtained from 125 patients during a 10-year period. Chronic inflammation was the most common histologic change identified. Of the 44 patients with papillary neoplasia, 42 were diagnosed by endoscopic biopsy. Sixteen of the 18 patients with invasive carcinoma were diagnosed by biopsy. Follow-up biopsies in patients endoscopically managed demonstrated recurrent tumors in 6 of 11 patients. With advances in instrumentation and techniques, pathologists can expect to see increasing numbers of ampullary biopsies. When multiple biopsy fragments are obtained and step sectioned, the diagnostic reliability of endoscopic biopsies in patients with tumors and carcinoma is greater than 90%. The morphologic spectrum of papillary lesions is similar to that seen in the colon with some significant exceptions. Tumor morphology varied considerably from area to area. Variations were seen in the basic architecture (villous-tubular), grade of dysplasia, presence of malignancy, and invasion from fragment to fragment, and in some cases from microscopic field to field. Another notable difference between the ampulla and colon is the rich mucosal lymphatic network of the ampullary region. Thus, any carcinoma invading the lamina propria was diagnosed as invasive carcinoma.

Severe bleeding diathesis associated with invasive aspergillosis in transplant patients.

A severe bleeding disorder developed in eight renal transplant patients with invasive aspergillosis. The hemorrhagic diathesis was characterized by wound oozing, severe upper and lower gastrointestinal tract hemorrhage, and mucosal bleeding at other sites. This unusual coagulopathy was characterized by a prolonged thrombin time, which was corrected with protamine sulfate, and an abnormal Reptilase time. The bleeding disorder antedated the diagnosis of invasive aspergillosis in all cases. The probability that the coagulopathy was due to proteolytic enzymes elaborated by Aspergillus sp. is discussed.

Occult thyroid pathology in the young adult: an autopsy study of 138 patients without clinical thyroid disease.

Thyroid glands from autopsies on 138 adults, ages 20 to 40 years, with no known clinical or laboratory evidence of thyroid disease, were serially sectioned at 2 mm intervals and microscopically examined for occult thyroid disease and anatomic variations. Occult papillary carcinoma was found in 3% of the glands, along with a single case of medullary carcinoma. The prevalence of occult thyroid carcinoma in this group of young adults is significantly less than that reported in the literature in people over forty (P less than .001). The glands demonstrated a number of other morphologic changes of importance to surgical pathologists. The thyroid capsule was incomplete in 62% of the glands. Thyroid follicles were found in the capsule in 14% of cases and thyroid follicles or nodules were outside the gland in perithyroid connective tissue in 88% of cases. Thyroid follicles were identified in 7% of cases in perithyroid strap muscles attached to the pyramidal lobe. A number of other, less common anatomic variations were also seen.

Thyroglossal duct carcinoma.

Primary carcinoma of the thyroglossal duct is rare. This discussion reports two cases and reviews the 50 previously reported in the literature. The criteria for diagnosis include evidence of a thyroglossal duct remnant and a normal thyroid gland. The differentiation from cystic metastases to lymph nodes is pointed out. The histologic types parallel those of carcinoma of the thyroid gland, papillary carcinoma being the most common and having a generally favorable prognosis. The clinical presentation of these tumors is similar to that with benign cysts and thus is of limited value in the diagnosis.

Porokeratosis of mibelli in transplant recipients.

Four of 602 renal and hepatic transplant recipients had porokeratosis of Mibelli develop in the posttransplant period. Porokeratosis is an uncommon, autosomally dominant inherited disorder that presents in adolescence as a proliferation of an abnormal clone of epidermal cells. Clinically, it is characterized by nonhealing plaques that develop most commonly on the limbs. Porokeratosis, a premalignant condition, must be added to the list of potential cutaneous complications seen in immunosuppressed organ transplant recipients.

Cutaneous microabscess formation from Alernaria alternata.

A 69-year-old farmer with acute lymphocytic lymphoma developed multiple ulcerated hemorrhagic cutaneous lesions. Alternaria alternata was cultured from the lesions and hyphae were seen in biopsies of the lesions. The potential role of Alternaria as a human pathogen is discussed.

Cutaneous complications in renal transplant recipients.

Systematic review of the histologic characteristics of skin lesions biopsied and/or resected in a group of 580 renal transplant recipients collected over a 16-year period showed a total of 170 specimens from 120 patients. In this group there were 41 benign tumors, 22 infections, 35 inflammatory dermatoses, and 13 miscellaneous lesions. Fifty-nine lesions were malignant, and half of these were squamous cell carcinomas (SCCs). None were lethal or metastasized, although deeply invasive local recurrences and multiple lesions were common. Comparison with SCCs from a control group showed no clearcut differences with respect to level of invasion, grade, pattern, or presence of actinic change. Most of these lesions were found in sun-exposed areas, were associated with actinic changes, and with actinic keratoses. Problems in differentiating SCC from keratoacanthoma and the clinical implications of these difficulties are discussed in conjunction with a review of the literature.

Anaplastic thyroid carcinoma following low-dose irradiation.

Low-dose irradiation of the neck in childhood is associated with a markedly increased incidence of thyroid cancer. Such carcinomas have almost all been well differentiated, papillary or follicular types. This paper describes the development of metastatic anaplastic thyroid carcinoma in cervical lymph nodes a year after subtotal thyroidectomy for well-differentiated papillary carcinoma in a 32-year-old man who had had low-dose cervical irradiation at the age of 7 years. It appears that irradiation-related thyroid carcinomas, in at least a very small number of people, may be associated with aggressive carcinoma.

Gastrointestinal complications in renal transplant recipients.

In a 16-year study, 101 gastrointestinal (GI) lesions (16 fatal) developed in 580 renal transplant recipients seen in the authors' institution. Lesions were seen at all levels of the GI tract, but colonic lesions were the most common (42 patients) and were fatal in 8. Segmental ischemic colitis was the single most common morphologic diagnosis (14 patients). Seven of these patients had an unusual syndrome that clinically, at surgery, and on gross examination resembled inflammatory bowel disease. Lesions were segmental; involved bowel was thickened and erythematous with creeping peritoneal fat. Histologically, mucosa adjacent to the frank necrosis showed simplification and striking epithelial atypia. Specific identifiable viral infections caused 28% of the GI complications in this series. This incidence is higher than that in other reported series. Most of these infections can be diagnosed from endoscopically obtained material. These findings have therapeutic implications.

Unexpectedly high incidence of cytomegalovirus infection in apparent peptic ulcers in renal transplant recipients.

Gastroduodenal ulcers in renal transplant recipients are usually accepted as being acid-peptic in origin. In a series of 573 renal transplant recipients there was histologic material available for examination from eight patients with gastroduodenal ulcers and three patients with gastric erosions. All ulcers had originally been diagnosed as peptic or stress ulcers. However, on review, five of them proved to contain cytomegalovirus (CMV); CMV was also present in all the stomachs with erosions. We suggest that CMV infection plays as important a role in upper gastroduodenal ulcers and erosions in renal transplant recipients as it does in similar lesions elsewhere in the gastrointestinal tract of these immunosuppressed patients.

DNA content in radiation-associated thyroid cancer.

DNA content has been reported to be of prognostic significance in differentiated thyroid carcinoma. Since malignant tumors with irradiation as an initiator often contain DNA aberrations, the DNA content of well-differentiated thyroid carcinoma in patients with a prior history of low-dose head and neck irradiation was determined and compared with similar nonradiation-associated lesions. The DNA content of thyroid cancers from 53 patients was determined with use of flow cytometry. Sixteen radiation-associated thyroid carcinomas (11 papillary, 3 follicular, and 2 medullary) all were diploid. In a group of 37 nonradiation-associated tumors, 10 were aneuploid (10 of 29 papillary carcinomas and 0 of 2 follicular or 6 medullary carcinomas). This difference in DNA content is significant (p less than 0.02, Fisher's exact test). These findings were unexpected and suggest that if the initiating irradiation causes a DNA aberration, this aberration is not reflected in DNA content as measured by means of flow cytometry.

Total or near total thyroidectomy versus limited resection for radiation-associated thyroid nodules: a twelve-year follow-up of patients in a thyroid screening program.

Controversy continues regarding the extent of thyroidectomy appropriate for patients with radiation-associated thyroid nodules. The incidence of cancer in this group of patients is more than 50% when near total or total thyroidectomy is done and all thyroid tissue is serially sectioned and examined. Tumor multicentricity is common. Is total or near total thyroidectomy warranted in all of these patients? A prospective study and follow-up program of 2118 patients with prior low-dose head and neck irradiation who entered into a thyroid screening program allowed us to examine how the extent of thyroidectomy influenced the clinical course of these patients. Near total or total thyroidectomy was performed in 59 patients (36 had cancer), and limited thyroid resection, that is, lobectomy or less, was done in 78 patients (four of whom had cancer). During follow-up, only three patients have developed recurrent cancer; two had near total thyroidectomy and one had total thyroidectomy at first operation. Two patients with limited thyroid resection have had reoperation for new thyroid nodules, both of whom had benign nodules. We conclude that although limited thyroid resection may leave occult malignancies in unresected thyroid tissue, there is no significant difference in outcome between patients with limited resection and those with near total or total thyroidectomy after a 12-year follow-up of the program. Significant differences in cancer recurrence rats may occur with longer follow-up.

Thyroid gland morphology in young adults: normal subjects versus those with prior low-dose neck irradiation in childhood.

Thyroid glands obtained at autopsy from young adults were studied to establish more accurately the "normal" morphology in the groups 20 to 40 years of age. A total of 56 autopsy specimens (many obtained from trauma victims) were examined in detail by totally embedding and sectioning the thyroid glands. The morphology of these thyroid glands also was compared to that of surgically removed thyroid glands from 47 young adult patients with prior low-dose neck irradiation. The "normal" thyroid specimens frequently showed morphologic features, such as thyroid tissue outside the recognizable capsule of the gland (40 of 56 patients) and in the strap muscles of the neck (six of 56 patients), which are conditions commonly considered as evidence for invasive thyroid carcinoma. The thyroid glands from the "normal" young adult population were significantly different from those thyroid glands surgically removed from patients who had received irradiation. The irradiated thyroid glands invariably showed multiple nodules of a wide variety of histologic types, extensive lymphocytic infiltrates, and distorting fibrosis as well as a high incidence of malignancy (27 of 47 patients). A single 0.1 cm focus of papillary carcinoma was found in one specimen in the nonirradiated thyroid group. This study suggests that "occult" thyroid carcinomas in the group 20 to 40 years of age are rare and are significantly fewer in number than in the older population (P less than 0.02).

p21WAF1 expression is associated with improved survival after adjuvant chemoradiation for pancreatic cancer.

BACKGROUND: Cell cycle arrest after DNA damage is partly mediated through the transcriptional activation of p21(WAF1) by the p53 tumor suppressor gene. p21(WAF1) and p53 are both critical in maintaining cell cycle control in response to DNA damage from radiation or chemotherapy. Therefore, we examined the role of p21(WAF1) and p53 in the determination of outcome for patients who receive radiation and/or chemotherapy for pancreatic cancer. METHODS: p21(WAF1) and p53 protein expression were determined (with the use of immunohistochemistry) in specimens from 90 patients with pancreatic cancer. Forty-four patients underwent surgical resection, and 46 patients had either locally unresectable tumors (n = 9 patients) or distant metastases (n = 37 patients). Seventy-three percent of the patients who underwent resection and 63% of the patients who did not undergo resection received radiation and/or chemotherapy. RESULTS: p21(WAF1) expression was present in 48 of 86 tumors (56%) and was significantly (P<.05) associated with advanced tumor stage. Median survival among patients with resected pancreatic cancer who received adjuvant chemoradiation with p21(WAF1)-positive tumors was significantly longer than in patients with no p21(WAF1) staining (25 vs. 11 months; P = .01). Fifty of 89 tumors (56%) stained positive for p53 protein. p53 overexpression was associated with decreased survival in patients who did not undergo resection. CONCLUSIONS: Normal p21(WAF1) expression may be necessary for a beneficial response to current adjuvant chemoradiation protocols for pancreatic cancer. Alternate strategies for adjuvant therapy should be explored for patients with pancreatic cancer who lack functional p21(WAF1).

Molecular metastases in stage I pancreatic cancer: improved survival with adjuvant chemoradiation.

BACKGROUND: Reports of improved survival rates for patients with resected adenocarcinoma of the pancreas coincide with the adoption of adjuvant chemoradiation protocols. The impact of nodal micrometastases demonstrated by molecular assays and adjuvant therapy on survival of patients with stage I pancreatic cancer has not been adequately assessed. METHODS: A retrospective analysis of postoperative chemoradiation on survival in 61 patients undergoing resection of pancreatic adenocarcinomas from 1984 to 1997 was performed. Archival tumors and regional nodes from 25 patients with stage I cancers were tested for a Kiras oncogene mutation using polymerase chain reaction and analysis for restriction fragment length polymorphisms (PCR/RFLP). RESULTS: Adjuvant chemoradiation was associated with improved survival for stage I (P < .01), but not stage III, disease. Seventeen (68%) of 25 patients with stage I disease tested had evidence of mutant Kiras in one or more regional nodes. Survival did not differ for patients with molecular micrometastases. Six of 17 (35%) patients with micrometastases received adjuvant chemoradiation and had improved survival (P < .05). CONCLUSIONS: The majority of patients with stage I pancreatic cancer have PCR/RFLP evidence of lymph node micrometastases. Adjuvant chemoradiation improves survival in these patients by treating micrometastases not detected by histology. Adjuvant chemoradiation should be used for patients with stage I pancreatic cancers.

Borderline microinvasive carcinoma of the cervix.

This study identifies borderline microinvasive carcinoma of the cervix as a subgroup of microinvasive carcinoma. We define borderline microinvasive carcinoma of the cervix as the infiltration of neoplastic squamous epithelial cells into the stroma where the depth of infiltration is 1 mm or less from the basement membrane of the epithelial surface immediately adjacent to the site of infiltration without capillary-like or lymphatic-like space involvement. In a 20-year review of cervical neoplasia in our institution, 29 cases of borderline microinvasion were identified. None of these 29 patients had recurrent carcinoma. Of our in situ carcinomas, 4.8% were found to be borderline lesions on review. Of our cases initially interpreted as microinvasion, 27.1% were, in fact, borderline lesions. There are better data to establish the criteria for borderline microinvasive carcinoma than there are to establish the absolute depths of invasion that would be unequivocally acceptable as "microinvasion." Borderline microinvasive carcinoma of the cervix is a lesion which is not metastatic and can be treated by nonradical methods.

Bilateral pheochromocytoma and islet cell adenoma of the pancreas.

An 18-year-old woman with bilateral pheochromocytomas and an asymptomatic islet cell adenoma of the pancreas represents the 11th patient to be described with this combination of endocrine tumors. No other components of any multiple endocrine adenomatosis (MEA) syndromes were present. Because of this "overlap syndrome," in which tumors that have traditionally been considered to be components of separate and mutually exclusive MEA syndromes have occurred concomitantly in the same patient, a question is raised regarding the validity of a rigid classification of these various MEA syndromes. The possibility of a pancreatic tumor should be kept in mind in any patient with a pheochromocytoma, especially if it is bilateral of multicentric in origin.