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To determine whether lymphangiogenesis was associated with the development of colorectal carcinoma and whether the mean maximal diameter of lymphatic microvessels (LMMMD) or lymphatic microvessel density (LMVD) is associated with lymph node metastasis in early stage invasive colorectal carcinoma (T1 carcinoma), we used immunohistochemical staining with podoplanin to measure LMMMD and LMVD in intratumoral (LMMMDit, LMVDit) and peritumoral areas (LMMMDpt, LMVDpt) of T1 carcinomas (n=87). By comparing the LMMMD and LMVD in normal large intestine (n=10), adenoma (n=15), and Tis carcinoma (n=15), we found out that the LMVDpt in T1 carcinoma with lymphatic vessel invasion (LVI) was significantly high (P<0.001), and there was a significant decrease in LMMMDpt in T1 carcinoma (P=0.031). Both LMMMDpt and LMVDpt were significantly increased in the T1 carcinomas, with LVI compared with the T1 carcinomas without LVI (P=0.018, P=0.003). Multivariate analysis revealed that LVI and combined greater LMMMDpt and greater LMVDpt were associated with lymph node metastases (P=0.005, P=0.036). These results indicate that lymphangiogenesis might be induced in the surrounding tumor areas of the T1 colorectal carcinoma with LVI; thus, evaluation of the diameter and density of lymphatic microvessels is important in T1 colorectal carcinoma to predict lymph node metastases.

We report a case of acute myelogenous leukemia (AML) developing just after surgery for advanced gastric cancer, before adjuvant chemotherapy was started. Immature white blood cells were recognized in the peripheral blood from postoperative day (POD) 1. The patient's clinical status and bone scintigraphy showed no evidence of bone metastasis. Acute myelogenous leukemia was diagnosed by an aspiration biopsy of the bone marrow. If the AML had developed later and had become remarkable during or after adjuvant chemotherapy, the differential diagnosis between de novo and therapy-related leukemia would have been very difficult. Most leukemias that develop during the course of chemotherapy or radiotherapy, or both, are indisputably considered to be therapy-related. Thus, we report the clinical course of this patient with reference to the related literature to warn surgeons of the possibility of this unusual manifestation.

We report a case of spinal destruction caused by chronic contained rupture of an abdominal aortic aneurysm (AAA). The patient was a 73-year-old man who had undergone coronary artery bypass grafting, sigmoidectomy for colon cancer, and axillofemoral bypass with AAA resection within months of each other, 3 years earlier. Abdominal computed tomography and magnetic resonance imaging showed destruction of the 12th thoracic and 1st lumbar vertebrae. The possibility of a metastatic spine tumor prompted us to consult the orthopedic surgeons, who recommended a spinal percutaneous needle aspiration biopsy. However, the cardiovascular surgeons diagnosed chronic contained rupture of an inflammatory AAA. The patient gradually improved with antimicrobial treatment, but died of disseminated intravascular coagulation the following year. The definitive diagnosis was confirmed by autopsy. We report this case for its educational value, considering the serious consequences that might have occurred had we attempted to biopsy the lesion.

Our objective was to clarify intracranial cerebrospinal fluid (CSF) flow dynamics in normal-pressure hydrocephalus (NPH). Frequency analyses of CSF flow measured with phase-contrast cine MRI were performed. The CSF flow spectra in the aqueduct were determined in patients ( n=51) with NPH, brain atrophy or asymptomatic ventricular dilation (VD), and in healthy volunteers (control group; n=25). The changes in CSF flow spectra were also analyzed after intravenous injection of acetazolamide. Moreover, a phase transfer function (PTF) calculated from the spectra of the driving vascular pulsation and CSF flow in the aqueduct were assessed. These values were compared with the pressure volume response (PVR). The amplitude in the NPH group was significantly larger than that in the VD or control group because of a decrease in compliance. The phase in the NPH group was significantly different from that in either the VD or the control group, but no difference was found between the VD and control groups. The amplitude increased in all groups after acetazolamide injection. The PTF in the NPH group was significantly larger than in the control group, and a positive correlation was noted between PTF and PVR. Frequency analyses of CSF flow measured by cine MRI make it possible to noninvasively obtain a more detailed picture of the pathophysiology of NPH.

We herein report a case of postoperative fecal fistula following an appendectomy which was successfully treated by the use of autologous fibrin glue. An 82-year-old man had acute appendicitis and underwent an appendectomy. Later, a fecal fistula developed and he underwent drainage treatment twice. After 4 weeks of drainage and during the third recurrence, the remaining fistula was successfully treated using autologous fibrin glue, instead of surgery, due to potential complications and the risks of associated with advanced age. No recurrence has been observed for 5 months. In conclusion, autologous fibrin gluing for fecal fistula was found to be a safe, economical, and effective treatment. A search of Medline from 1980 until 2002 revealed no other report of this treatment for postoperative fecal fistula following an appendectomy.

Mixed aeciospore isolates of Cronartium flaccidum and Peridermium pini were obtained from single-tree infections in Britain, Italy and Greece. The 5.8s ribosomal RNA gene and flanking intergenic transcribed spacer regions ITS1 and ITS2 were found to be highly similar between C. flaccidum and P. pini. Within samples heterogeneity was detected at three nucleotide loci in the ITS1 and at four loci in the ITS2 suggesting that several fungal genotypes may occur at a single infection court. The heterogeneity was confirmed by heteroduplex polymorphism analysis of mixed aeciospore products. RFLP of the ribosomal intergenic spacer region 1 (IGS1) amplified from the same templates indicated limited sequence polymorphism in some copies of this repeated locus. Both the sexual and asexual forms of C. flaccidum show evidence of sequence polymorphism in two independent, non-coding regions of the ribosomal gene array. Variation appears to be greater in the sexual form C. flaccidum, than in the monoaecious form P. pini.

Using conserved fungal ribosomal gene sequences the internal transcribed spacer (ITS) regions one and two (ITS1, ITS2) and the 5.8s ribosomal RNA gene (rRNA) of Heterobasidion annosum were amplified by the polymerase chain reaction (PCR). The nucleotide sequence was determined in three European intersterility groups (ISG-S, -F and -P). Three sequence variants of the ITS were found in ISG-S isolates. The sequence of the ITS of ISG-F differed by two residues from the major ISG-S sequence variant. The ISG-P sequence differed from ISG-S and ISG-F at 15-16 and 16 residues, respectively. Amplified intergenic spacer elements were informative for ISG fingerprinting following digestion with various 4-cutter restriction endonucleases. All differences in the restriction fragments between the ISGs were because of sequence differences in the ITS regions. The fingerprint patterns of isolates from the same intersterility group but from different European localities were identical. These results show that ribosomal DNA fingerprinting is a rapid technique to identify ISGs in Heterobasidion annosum.

The expression of proliferating cell nuclear antigen (PCNA) was examined in formalin-fixed paraffin-embedded tissue sections from 41 lesions (27 melanocytic nevi, 3 atypical nevi and 11 malignant melanomas) to determine the proliferative activity of primary cutaneous melanocytic tumours. Most of the malignant melanomas had more than 7% PCNA-positive cells (9.2 +/- 0.5%), while the melanocytic nevi manifested less than 1% PCNA-positive cells (0.4 +/- 0.1%). Atypical nevi exhibited an intermediate, but still significantly lower, labelling ratio when compared with malignant melanomas (0.8 +/- 0.2%). The proliferative activity of the lesions was compared between portions at different depths in the skin (epidermal, upper dermal and lower dermal location). In cases of malignant melanoma, the proliferative activity was higher in the deeper portion of dermis whereas PCNA-positive cells in melanocytic nevi were located in the upper dermis predominantly. Thus the PCNA labelling ratio of malignant melanoma and/or melanocytic nevus cells located in the epidermodermal junction was not necessarily higher than that of malignant melanoma and/or melanocytic nevus cells in the dermis. These results indicate that staining with PCNA would be very useful in the differentiation of malignant melanoma from melanocytic nevi manifesting cellular and/or structural atypia by virtue of a significant difference in the proportion of PCNA-positive cells. Although malignant melanomas have higher proliferative activity than melanocytic nevi in the deeper dermis, junctional activity in melanocytic tumours does not indicate cell proliferation.

Data on 35 patients with oral malignant melanomas were pooled and the pathological features and the clinical course were examined in detail. Of these 35 cases, 27 (77.1%) showed a two-phase growth pattern, with both a vertical and a radial growth phase. Moreover, these 27 cases were classified into three subtypes according to gross features of the vertical growth phase; nodular, flat elevated and ulcerated types. Almost two-thirds of the cases were of the melanotic type. Malignant melanomas without a radial growth phase were found in 8 instances, all of which showed a nodular growth pattern, 1 being of melanotic type and 7 amelanotic. Mean latent insidious periods were evaluated for the cases with different growth phases. Cases with a radical growth phase exhibited the longest mean latent period (35.7 months), and a median survival time of 23.5 months. Cases without a radial growth phase showed a short mean latent period (2.1 months), and a median survival time of 7.5 months. The thickness of invasion ranged from 2 to 9 mm. Although 77.1% of the cases depicted similar pathological patterns to acral lentiginous melanomas of the skin, oral malignant melanomas demonstrated heterogeneity in morphological features, developmental process and biological behaviour. The histogenesis of oral melanomas is briefly discussed.

This communication reviews the clinical and pathological features of coronary artery lesions in Takayasu arteritis. The incidence of coronary artery involvement has been reported to be 9% to 10%, and is observed mainly in autopsy cases because coronary artery disease is usually not evident until the occurrence of angina pectoris or myocardial infarction, or after the onset of congestive heart failure. On the basis of pathological features, the following three types of coronary artery lesions can be distinguished: type 1, stenosis or occlusion of the coronary ostia and the proximal segments of the coronary arteries; type 2, diffuse or focal coronary arteritis, which may extend diffusely to all epicardial branches or may involve focal segments, so-called skip lesions; and type 3, coronary aneurysm. Most of the coronary artery lesions in Takayasu arteritis are of type 1. Narrowing of the coronary arteries is mainly due to the extension of the inflammatory processes of proliferation of the intima and contraction of the fibrotic media and adventitia from the ascending aorta. In some cases, coronary stenosis may be caused by coronary arteritis as skip lesions in Takayasu arteritis, but even in these cases the lesions have been reported to affect mainly the proximal segments of the coronary arteries. Diffuse lesions of the coronary artery and coronary artery aneurysm seem to be very rare in Takayasu arteritis. Other causes of coronary ostial stenosis, coronary arteritis and coronary artery aneurysm are also discussed.

The incidence of atypical bronchioloalveolar cell hyperplasia (ABH) of the lung was investigated to evaluate the possibility of this lesion being a precancerous stage in the histogenesis of adneocarcinoma. Lobectomy and pneumonectomy specimens of 165 primary and 45 metastatic tumour cases were step-sectioned horizontally and examined histologically. An average of 51 blocks were taken in each case. Sixty-seven ABHs up to 10 mm in diameter were detected, only 2 lesions being associated with scar tissue. Age was one factor apparently related to ABH development, although not the major one. There was no correlation between smoking index and ABH occurrence. In males, the incidence was highest in association with adenocarcinoma (25.5% of cases, 0.8% of sections), followed by large cell carcinoma (25.0% of cases), squamous cell carcinoma (10.5% of cases) and metastatic tumours from other sites (4.8% of cases). In females, ABH was also more common together with adenocarcinoma (8.3% of cases) than with metastatic tumours (4.0% of cases). The differences in male incidences by case and by section between the adenocarcinoma and metastatic tumour categories were statistically significant (P less than 0.05, P less than 0.01 respectively) indicating that ABH may be a precancerous lesion capable of transformation of adenocarcinoma.

Little attention has been paid to the pathological features of the pulmonary artery in Takayasu arteritis. Autopsy specimens of 6 cases of this disease were studied. Lesions were found in the aortic arch and its brachiocephalic branches in all cases and in both the aortic arch and thoracoabdominal aorta in 5 cases. The pathohistologic characters of the pulmonary artery were very similar to those of the systemic artery. Stenosis-recanalization, so-called blood vessels-in-blood vessels, of the pulmonary elastic arteries were found in four cases. These lesions were not observed in the systemic arteries, and most of the newly formed channels in them seemed to be branches of bronchial arteries. Luminal obstruction of pulmonary muscular arteries was observed in 4 cases, cellular arteritis of muscular arteries in 2 cases, and angiomatoid dilatation of small blood vessels in 2 cases. Thus in this study we found peculiar stenosis-recanalization lesions of the pulmonary elastic arteries, and also showed that the pulmonary elastic and muscular arteries are frequently involved in Takayasu arteritis. These findings suggest that pulmonary hypertension could influence morbidity and long-term mortality in this disease.

Foci of stromal melanocytes (FSM) of the uterine cervix have been known as extra-cutaneous "blue naevus". However macroscopic and histological findings suggest that FSM of the cervix are analogous to dermal melanocytosis, rather than to cutaneous blue naevus and the lesions are more appropriately called stromal melanocytosis. FSM of the cervix have been considered rare, but our study showed that they are not uncommon in Japanese women occurring in 8.6% (42/486). The lesions were initially observed in the third decade of life and became most prevalent in the fifth decade (15/86 cases, 17.4%). In stroma of the cervix, stromal melanocytes (SM) were present where many peripheral nerve fibres were seen. SM of the cervix were positive for S-100 protein in immunohistochemical studies and were sometimes observed close to peripheral nerve fibres. Melanocytes were never observed in the ectocervical and endocervical epithelium, but only in the stroma of the cervix. We suggest that malignant melanoma of the uterine cervix may originate from SM.

Normal oesophagus specimens taken from 65 autopsy cases and surgical specimens from 127 oesophageal carcinoma cases were examined histopathologically to determine melanocyte incidence and distribution. Melanocytes were found in the epithelio-stromal junction in 7.7% of normal oesophagus specimens examined at autopsy, and in 29.9% of surgical cases with oesophageal carcinoma. Positive specimens in the latter groups, especially from pre-operatively irradiated individuals, showed a more remarkable increase of melanocytes than was evident in any of the normal oesophageal samples. There were no significant differences in incidence between males and females, or between age groups. In cases where the cancer invaded into deeper stroma, the melanocytes were mainly observed in the normal epithelium around the carcinomas. Epithelial and stromal elements of the melanotic mucosa commonly showed hyperplastic changes such as acanthosis or basal cell hyperplasia, and chronic oesophagitis. Melanocytes were observed most commonly in the lower part of the oesophagus, the site where malignant melanoma of the oesophagus, most often originates. These results strongly suggest that the melanocyte increase observed in areas of hyperplastic epithelium and chronic oesophagitis may play an important role as a precursor lesion for malignant melanoma in the oesophagus.

Two cases of angiosarcoma of the scalp were reported. The patients were elderly men and died from pulmonary complications, including pneumothorax, pulmonary haemorrhage and pneumonia, associated with metastatic tumours in the lungs. The data recorded from 95 autopsies of patients with angiosarcoma in Japan during 1980-1984 were analyzed. According to the anatomical distribution of the primary tumour, the patients could be subdivided into a scalp group and non-scalp group. In both groups, the most common metastatic site was the lung. The patients of the scalp group had more frequent pulmonary complications such as pneumonia, haemothorax, atelectasis and pneumothorax, when compared with the patients of the non-scalp group. In particular, pneumothorax was observed only in the patients of angiosarcoma of the scalp. The results indicate that angiosarcoma of the scalp tends to metastasize to the lung, especially to the subpleural or surface pleural area and these metastatic tumours are prone to necrosis, causing characteristic pulmonary complications.

The association of progressive multifocal leukoencephalopathy (PML) with prolonged hemodialysis treatment (PHT), not previously reported, was observed in a 56-year-old Japanese man who received PHT for 11 years. He suffered from recurrent bouts of fever and progressive neurological signs, such as irritability, speech disturbance, gait disturbance and dysphagia for seven months, and finally fell into a deep coma and died. Clinical signs and symptoms were highly suggestive of progressive dialysis encephalopathy. Necropsy revealed that the PML mainly involved the brainstem and cerebellar white matter. The aluminium content of the brain tissue was lower than that of controls. Possibly the virus causing PML is one of the causes of progressive dialysis encephalopathy, since clinically PML is not easily distinguished from progressive dialysis encephalopathy. It is essential to differentiate PML of viral etiology from progressive dialysis encephalopathy of unknown cause.

The pathological changes in the lungs of six patients who were treated by an artificial ventilation with a Bird or Bennett type respirator for three days to six months with oxygen concentrations of 24-100% were examined by light microscopy, studies on thick-sections, reconstruction models and vascular casts, and morphometric methods. After prolonged inhalation of high concentrations of oxygen the lungs showed thickening of the alveolar wall, marked deposition of reticulin fibers and fibroblastic proliferation in the alveolar wall, reduction in the number of capillaries, an abnormal configuration of the capillary network and hyperplasia of alveolar lining cells. These lesions are not specific to this condition, and seemed to be less marked than similar lesions in cases of chronic forms of fibrosing alveolitis, chronic interstitial pneumonia, usual interstitial pneumonia and so-called pulmonary fibrosis. Morphometric results confirm these histological observations and show not only the concentrations of oxygen but also the duration of high and pure oxygen inhalation have important roles for these pulmonary lesions. The main reasons for these lesions seemed to be repeated damage to the capillaries and loss of the normal configuration of the capillary network, accompanied by rearrangement and reconstruction of the two types of reticulin fibers.