Yoshihiko Kamada

Human papillomavirus DNA in squamous cell carcinoma of the lung.

AIM: To compare the incidence of squamous cell carcinoma (SCC) of the lung in Okinawa with that in Niigata on the mainland. METHODS: All patients presenting with SCC of the lung in Okinawa and Niigata in 1993 were included in the study. Diagnoses were confirmed by conventional histological examination of paraffin wax sections. Human papillomavirus (HPV) was detected by non-isotopic in situ hybridisation (NISH) and polymerase chain reaction (PCR) amplification with primers specific for the E6 and E7 regions of the HPV genome. PCR products were analysed by Southern and dot blotting. RESULTS: The incidence of well differentiated SCC of the lung was high in patients from Okinawa compared with moderately and poorly differentiated types, and compared with the incidence of SCC in patients from Niigata. This is despite similar patterns of age, sex (predominatly male), and smoking habit. More patients from Okinawa, however, were positive for HPV DNA by PCR (79%) and NISH (53%). Many patients haboured HPV types 6, 16, and 18. Only 30% of patients from Niigata were positive for HPV DNA by PCR and 20% by NISH. These patients all harboured one HPV type only. CONCLUSION: Surprisingly large numbers of patients from Okinawa were positive for HPV DNA. The detection of HPV DNA was strongly associated with well differentiated SCC. This was particularly true for HPV types 6 and 16. There was no correlation between either smoking and detection of HPV DNA, or smoking and histological differentiation.

Extremely high Langerhans cell infiltration contributes to the favourable prognosis of HPV‐infected squamous cell carcinoma and adenocarcinoma of the lung

Aims: The infiltration of Langerhans cells in adenocarcinomas and squamous cell carcinomas of the lung was examined in relation to prognostic implications and human papillomavirus (HPV) infection.

Prognostic Implication of Human Papillomavirus Infection in Squamous Cell Carcinoma of the Lung

On the subtropical island of Okinawa, squamous cell carcinoma (SCC), particularly the well-differentiated form, is the most frequent type of lung cancer, while this form is relatively rare on the Japanese mainland and in other countries. Furthermore, in Okinawa, in 1993, 80% of SCC cases of the lung were found to be infected with human papillomavirus (HPV). We studied the prognosis of SCC of the lung with HPV infection (n = 25) and compared it with non-HPV-infected SCC (n = 16). Using the Kaplan-Meier method (Wilcoxon analysis), the prognosis of HPV-infected cases was found to be better than that of the non-infected cases. In the virus-infected cases, apoptosis and infiltration of a large number of Langerhans cells were demonstrated. In addition to these findings, the virus-infected tumors were demonstrated to be histologically well-differentiated, perhaps contributing to the favorable prognosis. However, among the virus-infected cases, the type 16 virus-infected cases showed a poorer prognosis, compared to those infected with other HPV types. p53 gene mutation was also examined, and was considered to be an unfavorable prognostic factor, as reported elsewhere. However, in Okinawa, HPV-positive cases with p53 mutations showed a slightly better prognosis than did non-viral infected cases with p53 mutations. The TNM staging system was also useful for categorizing the virus-infected cases. The prognosis of stage III (A and B) cases was poor. All of our present cases received surgical treatment. Chemotherapy and radiation therapy were not performed. Such treatment, however, might be effective, because virus-infected uterine cervical carcinomas have been routinely treated with chemotherapy and radiation. Furthermore, if the immunological basis of increased Langerhans cell infiltration in HPV-infected cases is elucidated, a clinical trial with immunotherapy may be favorable for the clinical outcome.

Carcinoma of the lung in Okinawa, Japan: With special reference to squamous cell carcinoma and squamous metaplasia

In Okinawa, a subtroplcal Island In southern Japan, squamous cell Carcinoma (SCC), especially the well‐differentiated form, Is prevalent, while this form is relatively rare in both the mainland and other countries (e.g. United States of America). More patlents with SCC from Okinawa, moreover, were positive for human papillomavlrus (HPV) DNA by polymerase chain reaction (PCR) (79%), and harbored HPV types 6, 16 and 18, In combination. On the other hand, less than 30% of the mainland patlents were positive for HPV DNA by PCR. Those patients who were positive all harbored only one HPV type. Furthermore, in Okinawa, there were a signiflcant number of cases with adenosquamous carcinoma, and they too were positive for HPV DNA. The SCC and the adenocarcinoma cells adjacent to the SCC component In these cases were also positive for HPV DNA, and such adenocarcinoma cells were enlarged In size with relatively wide cytoplasm. The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasla. In this report, HPV DNA was transfected to adenocarclnoma cells (cultured cell fines) and this showed that HPV causes squamous metaplasla. In addition, aberrant expression of p53 was demonstrated In a large number of the SCC cases In Okinawa. The enlarged adenocarclnoma cells adiacent to the SCC components In adenosquamous carcinomas also showed aberrant expression of p53.The recent advances In the studies of anti‐oncogenes, p53, etc. and oncogenes are outlined. It Is to be noted that the molecular mechanisms of carcinogenesis in the lung have been studied In general, classifying lung tumors Into two groups, namely, small cell carcinoma (SCLC) and non‐small cell carcinoma (NSCLC). However, because human lung cancer is represented by a wide variety of histological types, molecular genetic studies according to a more detailed histological subclasslflcatlon is needed.

The relevance of intrinsic subtype to clinicopathological features and prognosis in 4,266 Japanese women with breast cancer

BackgroundEstrogen receptor (ER), progesterone receptor (PgR), and HER2 expression status in breast cancer function as prognostic and predictive factors that enable individualized treatment. Intrinsic subtype classification has also been performed based on these and other biological and prognostic characteristics. However, clinical analysis of such subtypes in a large number of Japanese breast cancer patients has not yet been reported.MethodsBetween January 2003 and December 2007, 4,266 patients with primary breast cancer were registered. Four subtypes based on immunohistochemically evaluated ER/PgR/HER2 status, clinicopathological features, and prognosis were analyzed retrospectively.ResultsThe following subtype distribution was observed: luminal A type (ER+ and/or PgR+, HER2−), 3,046 cases (71%); luminal B type (ER+ and/or PgR+, HER2+), 321 cases (8%); HER2 type (ER−, PgR−, HER2+), 398 cases (9%); and triple negative (TN) type (ER−, PgR−, HER2−), 501 cases (12%). The HER2+ subtypes (luminal B and HER2 types) had a significantly higher incidence of lymph node metastasis and lymphatic permeation, while the hormone receptor negative subtypes (HER2 and TN types) showed a significantly higher nuclear grade. Overall, patients with HER2-type and TN-type disease had a significantly poorer prognosis than other subtypes.ConclusionIntrinsic breast cancer subtypes are associated with clinicopathological features and prognosis in Japanese women. Long-term clinical observation of the relationship between each subtype and therapies used should provide useful information for selecting appropriately tailored treatments.

Coxsackievirus B4 Myocarditis in an Orangutan

A 37-year-old female orangutan died at the zoological garden. Autopsy examination demonstrated severe coxsackievirus B4 myocarditis immunohistochemically as a cause of the death. Apoptosis of the cardiac muscle cells was observed using the TdT-mediated dUTP-biotin nick endo labeling method and was considered to play a role in the myocarditis. Congestion of the liver and both lungs due to cardiac failure was also observed. Coxsackievirus infection is found frequently in the Okinawan human population. The present orangutans infection might have come from visitors who were allowed to go near the orangutan. Malignant tumors, severe suppurative infections, and intestinal parasite infections were not observed. Epstein-Barr virus DNA was detected in lymph nodes, but there was no Burkitts lymphoma.

Acute ascending necrotizing myelitis in Okinawa caused by herpes simplex virus type 2.

A case of rapidly progressing ascending myelitis was necropsied. Necrosis was present throughout the whole length of the spinal cord and involved both the grey and white matter randomly. The perivascular lymphocytic infiltration in the spinal cord in the present case was more pronounced than that in the previously reported two cases of necrotizing myelopathy associated with malignancy. Using immunoperoxidase staining the presence of herpes simplex virus type 2 (HSV 2) antigen was demonstrated. Electron microscopic examinations revealed large numbers of HSV particles in the spinal cord. HSV 2 may be a common aetiological agent of necrotizing myelopathy and myelitis in Okinawa, an HSV 2 endemic area. In the present case, the necrosis was mainly found in the spinal cord but was also observed, to a very limited extent, in the brain.

Successful Treatment of Bilateral Deep Femoral Aneurysms and Multiple Iliac Aneurysms Associated with Severe Aortic Valve Disease: Report of a Case

We report herein the case of a patient in whom aneurysms of the bilateral deep femoral arteries (DFA) and multiple iliac aneurysms associated with severe aortic valve disease were successfully treated by a two-staged operation. The patient was a 74-year-old man who had dense calcification of the ascending aorta and aortic arch. Prior to aortic valve replacement (AVR), the aneurysms of the DFA and internal iliac arteries were resected. The terminal end of the abdominal aorta and bilateral common iliac arteries were then reconstructed with a Y graft to be used as a possible alternative arterial input route in place of the ascending aorta for extracorporeal circulation during the AVR. The inferior mesenteric artery (IMA) was well developed, and the external iliac arteries and their branches were preserved at aneurysmectomy. Postoperatively, there was no ischemia of the pelvic organs or the hip muscles. The AVR was subsequently performed 5 weeks after the first operation, and the patient was discharged after an uneventful postoperative course.

Evaluation of inflammatory-response-induced thoracoscopic surgical stress

OBJECTIVE Due to the paucity of reports evaluating stress induced by thoracoscopic surgery with minithoracotomy, we assessed this stress based on the inflammatory response to surgery. METHODS Differences in pre- and postoperative peripheral white blood cell (WBC) count, serum C-reactive protein (CRP), and serum interleukin-6 (IL-6) were evaluated, defined as dW, dCRP, and dIL-6. Thoracoscopic partial lung resection cases were divided into 2 groups by access route: Group A patients in which surgery was concluded via several small access ports. and Group B patients going surgery via small access ports plus minithoracotomy. We also compared dW in standard lobectomy with exploratory thoracotomy (thoracotomy without lobectomy) cases. RESULTS No significant difference was seen in dW, dCRP, or dIL-6 between groups. dW in response to exploratory thoracotomy was lower than that in standard lobectomy (p = 0.06). CONCLUSIONS Surgical stress induced by thoracoscopic partial lung resection does not increase significantly when minithoracotomy is added. Postoperative inflammatory response may, however, be influenced by the extent of surgical trauma.

Massive spinal cord necrosis associated with adult T-cell leukaemia caused byAspergillus

A man with adult T-cell leukaemia (ATL) underwent massive spinal cord necrosis caused byAspergillus infection. Leukopaenia due to anti-cancer chemotherapy resulted in pulmonaryAspergillus infection. The aspergilloma was reduced in size by anti-fungal chemotherapy, but paraplegia occurred. At autopsy, the pulmonary aspergilloma was encapsulated and showed no contiguous extension of the infection to the epidural or subdural spaces or spinal cord. However, at the T5 level of the spinal cord, there was marked necrosis with haemorrhage caused byAspergillus infection, but without leukaemic cell infiltration of the spinal cord. Dichotomously branchingAspergillus hyphae filled the blood vessels of the T5 level of the spinal cord.