[Multilocular thymic cyst].

We describe a case of multilocular thymic cyst with severe acute inflammation. A 23-year-old man was admitted to our hospital with a sudden onset of chest pain and high fever. A computed tomography scan showed multilocular cystic lesion at anterior mediastinum. We resected the tumor with the thymus by median sternotomy. Macroscopically, the mediastinal mass showed thick-walled multiloculated cavities filled with turbid yellow fluid. Histological examination revealed that the tumor was a multilocular thymic cyst which is reported by Suster.

[Tension hemothorax associated with congenital pulmonary arteriovenous fistula].

We describe a case of intrapleural rupture of pulmonary arteriovenous fistula A 37-year-old woman was admitted to our hospital with a sudden onset of right chest pain. A computed tomography scan showed massive pleural effusion and tension hemothorax. Subsequently the patient went into shock. Partial resection of the lung was performed emergently. Pulmonary arteriovenous fistula is often associated with Rendu-Osler-Weber disease (ROW). Because of her brain arteriovenous malformation and family history, we could not exclude the possibility of ROW.

Multiple sectioning and immunohistochemical staining of sentinel nodes in patients with breast cancer.

BACKGROUND: The aim of the present study was to investigate whether focused analysis of sentinel nodes is more useful than routine haematoxylin and eosin examination of axillary lymph nodes obtained by axillary lymph node dissection. METHODS: One hundred and fifty-two patients with breast cancer with clinically negative axillary nodes underwent successful sentinel node biopsy using a combination of dye and radioisotope, followed immediately by standard level I and II axillary lymph node dissection. Multiple sectioning, with haematoxylin and eosin and immunohistochemical analysis of sentinel nodes using cytokeratin antibody, was compared with single section and haematoxylin and eosin analysis of sentinel and non-sentinel nodes (routine examination). RESULTS: A mean of 1.9 (range 1-12) sentinel nodes and 11.2 (range 4-24) non-sentinel nodes were excised per patient. Metastases were detected in 44 patients (29 per cent) by single section and haematoxylin and eosin analysis of sentinel and non-sentinel nodes. An additional five patients (3 per cent) with metastases were detected by multiple sectioning and haematoxylin and eosin analysis of sentinel nodes. A further 20 patients (13 per cent) with metastases were identified by multiple sectioning and immunohistochemical analysis of sentinel nodes. Both haematoxylin and eosin and immunohistochemical analysis of sentinel nodes missed one patient with node metastases, which led to a false-negative rate of 1 per cent. CONCLUSION: Multiple sectioning and immunohistochemical staining of sentinel nodes identified 16 per cent more patients with positive axillary lymph nodes than routine haematoxylin and eosin examination.

Human stomach-specific gene, CA11, is down-regulated in gastric cancer.

To reveal the implication in gastric cancer pathogenesis of the novel human gene referred to as CA11, which was recently isolated by a differential display technique using normal gastric mucosa and gastric cancer tissue, we examined CA11 expression in 50 primary gastric cancers and also introduced the CA11 gene into gastric cancer cells. RNA dot blot analysis against various human organs and developmental stages demonstrated that CA11 was intensively expressed especially in normal stomach tissue. Northern blot analysis showed that expression of the CA11 gene in cancer tissue was down-regulated compared with normal tissue. Semi-quantitative RT-PCR also demonstrated that CA11 gene expression was decreased in 41 out of 50 (82%) of the gastric cancer tissues, when compared with normal stomach tissues, while no relationship was found between CA11 expression and various clinicopathological characteristics including histological type, depth of invasion, lymph node metastasis, and clinical stage. Immunohistochemical analysis with anti CA11 antibody showed that CA11-positive staining was observed in the surface regions of normal gastric epithelium, but was found faintly or not at all in cancer tissues. CA11 transfected MKN28 cells also displayed a marked decrease in the number of colony formations when compared to double normal controls. These findings suggest that the loss of CA11 expression in gastric tissues may play an important role in gastric carcinogenesis.

Quantitative analysis of estrogen receptor-alpha and -beta messenger RNA expression in human pancreatic cancers by real-time polymerase chain reaction.

Recent studies have disclosed the presence of a second estrogen receptor (ER; ER-beta) in addition to a classical ER-alpha. ER-beta mRNA expression has yet to be studied in pancreatic cancers. Thus, we studied the expression of ER-alpha and ER-beta mRNA in pancreatic cancers (n=29) by real-time quantitative reverse transcriptase-polymerase chain reaction, and compared the expression levels in pancreatic cancers with those in breast cancers (n=116) which are typical estrogen-dependent tumors. Breast cancers were divided into two groups, ER-positive and ER-negative, according to the ER status determined by enzyme immunoassay. ER-alpha mRNA levels were significantly (P<0.01) higher in ER-positive (679.4+/-74.7 fmol/microg RNA) than ER-negative (159.7+/-33.4) breast cancers, and pancreatic cancers showed significantly (P<0.01) lower ER-alpha mRNA levels (17.5+/-10.0) than ER-negative breast cancers. On the other hand, ER-beta mRNA levels were significantly (P<0.01) higher in ER-negative (14.1+/-1.6) than ER-positive breast cancers (7.9+/-1.0), and pancreatic cancers showed significantly (P<0.01) higher ER-beta mRNA levels (28.1+/-5.1) than ER-negative breast cancers. Accordingly, ER-alpha/ER-beta mRNA ratios were significantly (P<0.01) lower in pancreatic cancers (0.94+/-053) than in ER-positive (203.9+/-34.5) and ER-negative (21.9+/-5.2) breast cancers. ER-beta2 mRNA variant expression was significantly (P<0.05) higher in pancreatic cancers than in ER-positive and ER-negative breast cancers, and, on the contrary, ER-beta1 mRNA variant expression was significantly (P<0.01) lower in pancreatic cancers than in ER-positive and ER-negative breast cancers. These results suggest a possibility that ER-beta (ER-beta2) plays a more important role than ER-alpha in pancreatic cancers.

Clinicopathologic analysis of breast carcinoma with chromosomal aneusomy detected by fluorescence in situ hybridization.

BACKGROUND: The clinicopathologic characteristics of breast carcinoma with chromosomal aneusomy detected by fluorescence in situ hybridization (FISH) have yet to be clarified. METHODS: Fine-needle aspiration biopsy (FNAB) samples were obtained from 113 breast tumors and were subjected to FISH analysis using centromeric probes for chromosomes 1, 11, and 17 to study a numerical aberration of these chromosomes and its correlation with various clinicopathologic features of breast tumors. RESULTS: Polysomy was observed in 77.0%, 50.5%, and 37.2% of breast carcinoma samples for chromosomes 1, 11, and 17, respectively, and monosomy was observed in 1.8%, 8.8%, and 22.1% for chromosomes 1, 11, and 17, respectively. High histologic grade showed a significant correlation (P < 0.05) with polysomy of chromosome 11. Lymph node metastasis showed a significant correlation (P < 0.05) with polysomy of all three chromosomes, and positivity of lymph node metastasis increased as the number of polysomic chromosomes increased. In addition, estrogen receptor negativity was correlated significantly (P < 0.05) with monosomy of chromosome 17, and progesterone receptor negativity was correlated significantly (P < 0.05) with polysomy of chromosomes 11 and 17. CONCLUSIONS: Aneusomy of chromosome 1, 11, or 17 detected by FISH is correlated significantly with various clinicopathologic features of breast carcinoma. Because FISH analysis of chromosomal aneusomy can be done using FNAB samples, this technique seems to have the potential to be used for a better, preoperative definition of the biologic characteristics of breast tumors.

Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients.

AIM: The purpose of the present study was to evaluate the usefulness of gamma probe and ultrasonographically-guided fine-needle aspiration biopsy (FNAB) in the pre-operative detection of sentinel node (SN) metastasis in breast cancer patients. METHODS: Sentinel node biopsy (SNB) was performed in patients with stage I or II breast cancer with clinically negative nodes using dye and radio-isotope. Axillas of 60 patients in whom a hot spot was detected by gamma probe were examined by ultrasonography. Pre-operative diagnosis of SN metastasis by gamma probe and ultrasonographically-guided FNAB was compared with the histological results of SN. RESULTS: The sensitivity, specificity and overall accuracy of ultrasonography in the diagnosis of SN metastasis were 50.0%, 92.1% and 76.7%, respectively. SNs were visualized by ultrasonography in 29 of 60 patients. Of 14 patients with positive results by ultrasonography, four had positive and two had negative cytology. The combination of ultrasonography and ultrasonographically-guided FNAB for visualized nodes had a sensitivity of 78.5%, specificity of 93.3% and overall accuracy of 86.2%. Blind FNAB in the hot spot was not useful in the detection of SN metastasis in patients whose SNs failed to be detected by ultrasonography. CONCLUSIONS: Gamma probe and ultrasonographically-guided FNAB is a potentially useful method for pre-operative detection of SN metastasis. In patients with positive SNs, SNB is not indicated and complete axillary lymph-node dissection can be performed as a primary procedure.

Combination technique is superior to dye alone in identification of the sentinel node in breast cancer patients.

BACKGROUND: The purpose of the present study was to evaluate whether the combination of dye and radioisotope would improve the detection rate of sentinel nodes (SN) and the diagnostic accuracy of axillary lymph node status over dye alone in patients with breast cancer. METHODS: Sentinel node biopsy (SNB) was performed in stages I or II breast cancer patients with clinically negative nodes using dye alone (indocyanine green) or a combination of dye and radioisotope (99mTc-radiolabelled tin colloid). RESULTS: SNB guided by dye alone was performed in 93 patients and SNB guided by a combination of dye and radioisotope was performed in 138 patients. The detection rate of SN was significantly (P = 0.006) higher in the combination group (94.9%) than in the dye alone group (83.9%). The sensitivity, specificity, and overall accuracy of SNB in the diagnosis of axillary lymph node status were 100, 100, and 100%, respectively, for the combination group, and 81.0, 100, and 94.9%, respectively, for the dye alone group. There were no false negatives in the combination group, but four false negatives (19.0%) in the dye alone group. The combination method was significantly superior to the dye alone method for sensitivity (P = 0.011) and accuracy (P = 0.018). CONCLUSIONS: The addition of a radioisotope to the dye in SNB increases the detection rate of SNs in breast cancer patients, and SNs detected by the combination method predict the axillary lymph node status with greater accuracy than those detected by the dye alone method.

K-ras point mutation in the nerve plexuses around the superior mesenteric artery in resectable adenocarcinoma of the pancreatic head: distribution pattern and related factors.

BACKGROUND: Adenocarcinoma of the pancreas is likely to spread into the nerve plexuses around the superior mesenteric artery (SMA) at a microscopic level. Since there has been no detailed report on how minute cancer invasion is distributed among the peri-SMA plexuses or which cases are more vulnerable to such an event, it has long been controversial how to treat this area when resecting the pancreatic head cancer. HYPOTHESIS: The K-ras mutation assay is more sensitive than the conventional histologic diagnosis in detecting minute cancer invasion around the SMA. DESIGN: Prospective consecutive series. SETTING: Cancer center hospital. PATIENTS AND METHODS: The entire circle of the peri-SMA tissues was obtained from 24 patients who had received an extended pancreatectomy for adenocarcinoma of the pancreatic head. They were divided into right and left hemicircular samples (48 samples), and each sample was used for both histologic and genetic diagnoses. Since all patients' primary tumors were positive for point mutation at codon 12 of the K-ras gene, the presence or absence of the mutation was determined for the peri-SMA plexuses using the mutant allele specific amplification method. RESULTS: Compared with results of the histologic examination, the K-ras mutation assay was more sensitive in detecting positive findings in the peri-SMA plexuses (12 samples from 9 patients). According to the distribution of the K-ras mutation into the right- and left-half samples, 24 patients were classified into the following 4 patterns (right/left): negative/negative in 15 patients; positive/negative in 6 patients; positive/positive in 3 patients; and negative/positive in 0 patients. In 3 patients who showed a positive/positive pattern in the genetic diagnosis, their right-half samples included more cancer cells that were detectable by routine microscopy. There was no relation between K-ras mutation and lymphatic invasion, while K-ras mutation was particularly related with the invasion of portal vein (P =.04) and posterior peripancreatic tissues (P =.002). All 3 patients with K-ras mutation in bilateral plexuses were classified by the TNM staging system as T4 using Union Internationale Contre le Cancer classification. CONCLUSIONS: The K-ras mutation (at codon 12) assay indicated a simple and regular pattern of cancer extension into the nerve plexuses around the SMA from adenocarcinoma of the pancreatic head: (1) The left half of the plexus was unlikely to be involved by cancer in cases in which the right half was intact. (2) Cancer extension into the peri-SMA plexuses occurred after the posterior confine of the pancreas had been involved by direct invasion from the primary pancreatic tumor. (3) The left half was not involved in cancerous tumors classified as T1 to T3 but was occasionally involved in those classified as T4 tumors. These data seem to provide a useful indicator of some additional treatments (resection, irradiation, etc) for the peri-SMA region when a locally advanced pancreatic head cancer is treated with a curative intent.

Demonstration and diagnostic significance of pro-gastrin-releasing peptide in medullary thyroid carcinoma.

The expression of pro-gastrin-releasing peptide (proGRP) in medullary thyroid carcinoma (MTC) and other histological types of thyroid carcinoma was studied by an immunohistochemical technique, using polyclonal anti-proGRP antiserum. Immunoreactivity for proGRP was detected exclusively in MTC (n = 7); other histological types (n = 12) were all negative for proGRP. In addition, serum proGRP levels were elevated in patients with primary or recurrent MTC (n = 3), and they changed in parallel with serum calcitonin (CT), and carcinoembryonic antigen (CEA). These results show that proGRP, which is considered to be a specific marker for small-cell lung carcinoma, may be also a potential tumor marker for MTC, in addition to CT and CEA.

Intraoperative sentinel lymph node examination by imprint cytology and frozen sectioning during breast surgery.

BACKGROUND: The purpose of the present study was to evaluate the usefulness of intraoperative imprint cytology and frozen sectioning of sentinel lymph nodes in patients with clinically node-negative breast cancer. METHODS: Sentinel node biopsy was performed in 101 patients with stage I or II breast cancer with clinically negative nodes using a dye-guided method. Intraoperative evaluation of sentinel node involvement by imprint cytology and frozen sectioning was compared with the final histopathological results of permanent sections. Tumour-negative nodes in paraffin sections stained by haematoxylin and eosin were further studied using an anticytokeratin antibody. RESULTS: The results of imprint cytology and frozen-section analysis were compared with those of haematoxylin and eosin-stained sections. The sensitivity, specificity and overall accuracy of imprint cytology were 96.0, 90.8 and 92.1 per cent respectively, and those of frozen-section examination were 52.0, 100 and 88.1 per cent. Ten sentinel nodes were tumour positive on imprint cytology and tumour negative on stained paraffin sections. Micrometastasis was found in eight of these nodes on immunohistochemistry. Taking these immunohistological results into consideration, the final sensitivity, specificity and overall accuracy of imprint cytology were 90.9, 98.5 and 96.0 per cent respectively. CONCLUSION: Intraoperative imprint cytology is a useful method for evaluating the status of sentinel nodes and is more accurate than frozen-section analysis. In addition, imprint cytology can detect micrometastasis more accurately than conventional haematoxylin and eosin-stained sectioning.

Malignant seeding of the lumpectomy cavity upon breast-conserving surgery.

One of the etiologic factors involved in local recurrence after breast-conserving surgery may be malignant seeding of the wound during the lumpectomy procedure. A total of 340 patients with stage I and II breast cancer were entered into the study. Of these, 270 patients received breast-conserving surgery (BCS group), and the other 70 patients underwent mastectomy (control group). After resection, lavage cytology was performed at the surgical wound. There were 55 patients (20.4%) who showed positive lavage cytology in the BCS group. In the control group, there were only 3 patients (4.3%) with positive cytology. Positivity was significantly higher in the former group (p = 0.00064). Patients with evidence of cutting across cancer lesions showed significantly higher positive rates in lavage cytology (p < 0.00001). Positivity in lavage cytology was significantly higher in patients with positive surgical margins evaluated by frozen sections (p = 0.0017), touch cytology (p < 0.0001) and formalin-fixed, paraffin-embedded sections (lateral or medial margin; p = 0.0036, anterior and posterior margin: p = 0.0210). The positivity was also significantly higher in patients with an extensive intraductal component (p < 0.0001), and less than or equal to 50 (p = 0.0061) years of age. Multivariate analysis revealed that the highest relative risk factor for positive cytology was evidence of cutting across cancer lesions (relative risk = 8. 166; p < 0.00001).

Ground-glass opacity on thin-section CT: value in differentiating subtypes of adenocarcinoma of the lung.

OBJECTIVE: The purpose of this study was to determine whether thin-section CT could be used to differentiate small localized bronchioloalveolar carcinoma from peripheral adenocarcinoma having a bronchioloalveolar (replacement) growth pattern of alveolar lining cells and from adenocarcinoma not having a replacement growth pattern on the basis of the extent of ground-glass opacity revealed by thin-section CT. MATERIALS AND METHODS: One hundred twenty-four small, surgically resected, peripheral adenocarcinomas from 119 patients (67 men and 52 women; mean age, 60 years) were studied. Lesion diameters were 0.4-2.0 cm (median, 1.5 cm). The extent of ground-glass opacity within lesions on preoperative thin-section CT was reviewed retrospectively by three thoracic radiologists. On the basis of replacement growth of alveolar lining cells, small adenocarcinomas were classified histologically as localized bronchioloalveolar carcinomas (n = 42) or as adenocarcinomas with (n = 53) or without (n = 29) a replacement growth pattern of alveolar lining cells. RESULTS: The percentage of lesions that had ground-glass opacity was significantly greater in localized bronchioloalveolar carcinomas (mean, 56.7%+/-33.0%) than in adenocarcinomas with a replacement growth pattern (mean, 26.3%+/-25.3%, p < .001) or in adenocarcinomas without a replacement growth pattern (mean, 8.3%+/-4.7%, p < .001). CONCLUSION: Determination of the ground-glass opacity area in each tumor as revealed on thin-section CT was useful for differentiating small localized bronchioloalveolar carcinomas from small adenocarcinomas not having a replacement growth pattern.

Clinicopathologic analysis of BRCA1- or BRCA2-associated hereditary breast carcinoma in Japanese women.

BACKGROUND: The purpose of this investigation was to elucidate the clinicopathologic characteristics of BRCA1- and BRCA2-associated hereditary breast carcinomas (HBCs) in Japanese women. METHODS: Various clinicopathologic characteristics of HBCs arising in patients with BRCA1 or BRCA2 germline mutations were compared with those of the control group (sporadic breast carcinomas). RESULTS: The mean age at the time of diagnosis of BRCA1-associated HBCs and that of BRCA2-associated HBCs (44 years for both) were significantly younger than that of the control group (54 years) and the incidence of bilateral tumors was significantly higher in the BRCA1-associated HBCs (32%) and BRCA2-associated HBCs (29%) than in the control group (6%). BRCA1-associated HBCs showed a tendency (P = 0.06) toward an increase in solid-tubular type tumors and a significant increase in histologic grade 3 tumors (P < 0.01) and lymphatic invasion positive tumors (P < 0.05) compared with the control group. BRCA1-associated HBCs were significantly more estrogen receptor negative (P < 0.01), c-erb B-2 negative (P < 0.05), and p53 positive (P < 0.01), and they also showed a significant increase in MIB-1 staining grades (P < 0.01) as well as microvessel counts (P < 0.05) compared with the control group. However, there was no significant difference in these parameters between the BRCA2-associated HBCs and the control group. CONCLUSIONS: BRCA1-associated HBCs in Japanese women have biologically aggressive phenotypes. However, BRCA2-associated HBCs are without distinctive clinicopathologic features compared with sporadic breast carcinomas.

Comparison of computed tomography and pathologic examination for evaluation of response of primary lung cancer to neoadjuvant therapy.

Twenty-four patients (nine with squamous cell carcinoma, 14 with adenocarcinoma, and one with large cell carcinoma) underwent neoadjuvant therapy followed by surgical resection. The authors studied changes in tumor size, shape, and contrast enhancement on computed tomography (CT), and compared them with results of pathologic examination of surgical specimens. The size of tumors on CT was evaluated according to the criteria of the World Health Organization. Surgical specimens were evaluated histologically on the basis of the area of viable cancer cells. Of 14 patients considered to have a partial response on the basis of World Health Organization criteria, five had pathologic changes of complete response. After therapy, the residual tumors in these five patients showed irregular shapes with concave tumor margins on CT images and no enhancement. The authors found that CT size criteria tended to underestimate the therapeutic effect demonstrated by pathologic examination. On the basis of these results, the authors propose three CT criteria for complete response: 1) more than 50% size reduction, 2) a change in tumor morphologic features from round or oval to irregular after neoadjuvant therapy, and 3) disappearance of contrast enhancement.

Sentinel Node Biopsy in Breast Cancer Patients with Clinically Negative Lymph-Nodes.

BACKGROUND: The purpose of the present study is to evaluate the usefulness ofdye-guided sentinel node biopsy in breast cancer patients with clinically negative nodes and to clarify the anatomic distribution of sentinel nodes in the axilla. METHODS: Sentinel node biopsy was performed in patients with T1 or T2 breast cancer who had clinically negative nodes, using an indocyanin green dye-guided method. Thereafter, complete axillary dissection was performed. Sentinel node andcomplete axillary lymph-node dissection specimens were examined separately, andthe incidence of metastases was compared. RESULTS: We identified sentinel nodes in 115 (76.7%) of 150 patients with clinically negative nodes. The mean number of sentinel nodes was 1.7 (range, one toeight nodes). The mean size of sentinel nodes was 9.0 mm (range, 2.0 to 28.0 mm). Of the 31 patients who had a tumor-positive sentinel node, 14 (45.2%) patients had only the sentinel node involved. There was concordance on histological examination between sentinel node and axillary node status in 111 (96.5%) of 115 cases. Of the sentinel nodes 89.1% were located cranially to the intercostobrachial nerve and within 2 cm of the lateral edge of the pectoralis minor muscle. CONCLUSIONS: Sentinel node biopsy guided by indocyanin green dye is an easy technique with an acceptable detection rate of sentinel nodes for breast cancer patients with clinically negative nodes. Most of the sentinel nodes were locatednear the lateral edge of the pectoralis minor muscle and cranial to the intercostobrachial nerve.

Sentinel Node Biopsy in Breast Cancer.

Axillary lymphnode dissection (ALND) for breast cancer patients provides local control and information for the determination of the type of adjuvant therapy.The benefit of axillary surgery itself for survival is considered to be limitedto patients with positive nodes. Sentinel node biopsy is a recently developed, minimally invasive technique for precisely predicting axillary nodal status. As this technique has less morbidity and greater accuracy than ALND, it replaces ALND for patients with node negative breast cancer. In this report, we outline thecurrent status of sentinel node biopsy for breast cancer patients and introduceour preliminary results.