Influence of differences in tumor vascularity upon the effects of hyperthermia

Summary Utilizing two types of human renal carcinoma heterotransplanted in nude mice, we investigated the variations in hyperthermic effects (42.5°C for 30 min) caused by differences in tumor type with special reference to variations in tumor vascularity. In the hypovascular JRC1 strain, sporadic vascular dilation was observed throughout the tumors after heating. Destruction of tumor cells was observed mainly in the region of dilation. In the hypervascular JRC11 strain, homogenous vascular dilation was observed immediately after heating, mainly at the periphery of tumors. There was a decrease in the viability of cells in the center of the tumor. Therefore, the hypervascular tumors showed greater destruction mainly at the center where blood circulation was reduced. The range of necrosis was also greatly affected by the extent of vascular dilation caused by heating in hypovascular tumors.     

A poptosis of hypertrophic chondrocytes in rat cartilaginous growth plate

Calcifying cartilages undergo endochondral ossification, a process in which cartilage is replaced by bone. These tissues contain chondrocytes that proliferate, leading, to differentiation and hypertrophy. Recent histological and biochemical studies suggest that hypertrophic chondrocytes undergo apoptosis. We investigated the process of this cell death to determine when fragmentation of DNA, a hallmark of apoptosis, occurs during cellular commitment to hypertrophy, and to test the hypothesis that the chondrocytes are intrinsically programmed to undergo apoptosis. End-labeling of fragmented DNA of rat proximal tibiae revealed that a majority of hypertrophic cells bore fragmented DNA, indicating that apoptosis was in progress in this zone. In pelleted chondrocyte cultures isolated from, rat rib growth plates and employed in an in vitro model of a growth plate, hypertrophic cells were also positive for end-labeling. Gel electrophoresis of DNA isolated from the chondrocyte cultures at 1–3 weeks yielded the ladder formation characteristic of apoptosis. We conclude that the chondrocytes in the growth plate are programmed to self-annihilate by apoptosis and that the apoptotic process is closely associated with the commitment to hypertrophy.     

Radiotherapy to bone metastases from renal cell carcinoma with or without zoledronate

OBJECTIVE

To investigate the rate of objective response and the skeletal‐related event (SRE)‐free survival after combined therapy with radiotherapy (RT) and zoledronate in patients with bone metastases from renal cell carcinoma (RCC).

PATIENTS AND METHODS

In all, 23 patients with RCC metastatic to bone were included in this retrospective study, of whom 13 had RT to bone metastases with no bisphosphonate therapy between 2000 and 2006, while the remaining 10 had combined therapy with RT and zoledronate (RT + Z) in 2006 and 2007. Significant calcifications of osteolytic metastases and/or shrinkage of bone lesions, as measured by computed tomography, were defined as a partial response. SREs were defined as any of pathological fracture, spinal cord compression, bone surgery, or additional RT to the bone.

RESULTS

In the RT + Z group, six patients had a partial response, showing evidence of calcification of their osteolytic bone metastases, while in the RT group, only one patient did (P = 0.019). One patient in the RT + Z group had an SRE, while 10 in the RT group had SREs (P = 0.003). The median SRE‐free survival time was not reached in the RT + Z group, but in the RT group it was 18.7 months (P = 0.046).

CONCLUSION

Combined therapy as RT + Z achieved a higher objective response rate (six of 10) and prolonged SRE‐free survival than RT alone in patients with bone metastases from RCC.     

Interferon treatment on glomerulonephritis associated with hepatitis C virus

We report on a 10-year-old girl with glomerulonephritis associated with hepatitis C virus infection, who was treated with interferon-α. On the first renal biopsy at 8 years of age, mild mesangial hypercellularity in a segmental to semiglobal pattern was present in all glomeruli. After 6 months interferon-α therapy, proteinuria diminished completely. However, mesangial proliferation was advanced on the second biopsy at 10 years of age. We concluded that the interferon-α was effective in the treatment of proteinuria despite the lack of pathological improvement. Received: 15 March 2000 / Revised: 11 July 2000 / Accepted: 14 July 2000     

The protective effect of thromboxane A2 synthetase inhibitor against ischemic liver injury

To evaluate the role of thromboxane A₂ (TXA₂) in ischemic liver injury, the serum changes in thromboxane B₂ (TXB₂) and 6-keto-prostaglandin F₁ alpha (6-K-PGF₁) following warm ischemia of the total canine liver were examined, and the protective effect of a TXA₂ synthetase inhibitor was assessed. Total liver ischemia was performed for 60 min on two groups of dogs: a control group, in which ischemia alone was performed, and an OKY-046 group, which received a TXA₂ synthetase inhibitor. A temporary active portacaval shunt was used to eliminate the effects of splanchnic venous stasis during clamping of the hepatic pedicle. Postoperative changes in liver function, assessed by the transaminase enzyme levels, and in prostaglandins were recorded and the histologic liver findings of both groups 1 week after ischemia were compared. The levels of 6-K-PGF₁ increased after reperfusion in both groups, while those of TXB₂ increased in the control group but maintained low levels in the OKY-046 group. Liver function was better and histologic changes less marked in the OKY-046 group than in the control group, suggesting the important role of TXA₂ in ischemic liver injury and the usefulness of a TXA₂ synthetase inhibitor for protecting the liver against ischemic injury.     

ADULT HEPATOBLASTOMA: CASE REPORT AND REVIEW OF THE LITERATURE

We report a case of hepatoblastoma in a 24 year old woman. The tumour was removed by an extended right lobectomy after transcatheter hepatic arterial embolization. A survey of the literature revealed 31 cases of adult hepatoblastoma. According to these reports there are no characteristic clinical features of the tumour, making a correct diagnosis before surgery or autopsy extremely difficult. Complete removal of the tumour is the only treatment which is potentially curative provided that lesion is confined within the liver capsule.     

Hemiarch replacement during pregnancy (19 weeks) utilizing normothermic selective cerebral perfusion

A 20-year-old woman with Marfan syndrome in the 19 weeks of pregnancy was admitted for a dissecting aneurysm of the ascending aorta to the proximal arch. She wanted to continue with pregnancy. A cardiotocography and a trans-esophageal echo probe which allowed visualization of the fetal heart contraction were attached on the abdomen. A cardio-pulmonary bypass was established via the right axillar and femoral arteries with bicaval drainage. The aortic isthmus and arch branches were clamped. After opening the ascending aorta, selective cerebral perfusion was initiated by quick cannulation into the left carotid and left subclavian arteries. Peripheral pressure was maintained above 80 mmHg with the flow of the selective cerebral perfusion at 1.0 L/min and flow from the femoral artery at 3.5 L/min. Hemi-arch replacement was performed using a Dacron graft. The body temperature passively descended to 35 °C. She normally delivered a healthy female baby after 37 weeks’ of gestation.     

Fecal stream is essential for adaptive induction of glucose-coupled sodium transport in the remnant ileum after total proctocolectomy

Our previous studies demonstrated that sodium glucose cotransporter 1 (SGLT-1) was induced in the remnant ileum of total colectomized rats via the action of factors other than hyperaldosteronism. The aim of the present study was to clarify whether fecal stream is required for the enhancement of SGLT-1-mediated sodium transport. Twenty-seven pairs of ileal tissues were obtained from the proximal and distal side, respectively, of loop ileostomy after total proctocolectomy. Mucosae were mounted in an Ussing chamber to evaluate glucose-coupled sodium transport. Levels of SGLT-1 mRNA in proximal and distal mucosae were compared by Northern blotting. Villous height and crypt depth were measured to test for correlations between mucosal structure and SGLT-1-mediated sodium transport or mRNA expression levels. Both glucose-coupled sodium transport and expression of SGLT-1 mRNA were significantly lower in distal mucosae relative to proximal mucosae. In distal mucosae, villous height, but not crypt depth, was significantly lower than in proximal mucosae, demonstrating a positive correlation between villous height and SGLT-1 function and expression. Comparative studies of proximal and distal mucosae demonstrated that in addition to hormonal changes, fecal stream is required for full induction of the sodium transport system (which includes SGLT-1-mediated transport) in the remnant ileum following total proctocolectomy. Presented in part at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–19, 2005 (poster presentation). This work was supported by Grants-in-Aid for Scientific Research 10557118 and 14657295 from the Ministry of Education, Science and Culture of Japan to K. Fukushima, and by Kanae Foundation to K. Fukushima.     

Perioperative complications after hepatectomy with or without intra-arterial chemotherapy for bilobar colorectal cancer liver metastases

BACKGROUND: We investigated perioperative complications of hepatic arterial infusion chemotherapy preceding major hepatectomy for multiple bilobar colorectal cancer metastases. No consensus exists concerning operative feasibility or perioperative course in patients undergoing major liver resection with neoadjuvant chemotherapy--partly because such chemotherapy is considered hepatotoxic, increasing the risk of postoperative liver failure. METHODS: Clinicopathologic data were available for 41 consecutive patients with 5 or more bilobar liver metastases from colorectal cancer who underwent major liver resection with or without prior hepatic arterial chemotherapy. Data concerning operative feasibility, postoperative liver function, complication rates, and histologic findings in the non-neoplastic liver were analyzed retrospectively. RESULTS: Prehepatectomy and postoperative day 1 platelet counts were lower (P < .01 and P < .05), alkaline phosphatase on postoperative day 3 was higher (P < .01), and prothrombin time on day 1 was more prolonged (P < .01) in the chemotherapy group. No significant difference was seen between groups in intraoperative data, morbidity, or duration of hospitalization. Histologic examination of adjacent non-neoplastic liver confirmed mild to severe fatty degeneration in 91% of the patients undergoing neoadjuvant chemotherapy, compared with 53% in those without neoadjuvant chemotherapy (P = .023). Although the number of neoplasms in chemotherapy patients was greater than that of the other group, overall and disease-free survival rates were comparable between groups. CONCLUSIONS: Despite mild postoperative liver dysfunction, pre-resection hepatic arterial chemotherapy did not increase morbidity.