Current trends of sentinel lymph node biopsy for breast cancer--a surgeon's perspective.

Sentinel lymph node biopsy (SLNB) is standard care for patients with early-stage breast cancer, and axillary lymph node dissection (ALND) is considered unnecessary when sentinel lymph nodes (SLNs) are tumor-free. Additional non-SLN metastasis in patients with positive SLNs can be estimated using several risk factors such as primary tumor size, metastatic tumor size in SLNs, lymphatic vessel invasion, and so on. All patients with positive SLNs may be treated with further ALND based on their own risk for non-SLN metastasis. Recent randomized clinical trials have already proved less surgical morbidity and better QOL for SLNB alone compared with ALND. However, trials concerning the efficacy of ALND in positive SLNB patients in preventing local regional recurrence and improving overall survival compared with no ALND, and also, concerning the effectiveness of ALND compared with axillary radiation therapy (RT), have not yielded clear results. The prognostic significance of micrometastasis in SLNs or bone marrow also remains to be determined. So far SLNB is not acceptable for patients with positive nodes in the axilla at initial diagnosis even if their axillary metastases are down-staged to negative by neoadjuvant chemotherapy. Although basically SLNB does not need to be performed for patients with pure ductal carcinoma in situ (DCIS), it is recommended for patients with an initial diagnosis of DCIS which is large, palpable, high grade, or found in younger patients. Because these types of DCIS have higher incidences of accompanying invasive lesions. In addition if patients will undergo mastectomy, SLNB is recommended because of the inability to perform SLNB after mastectomy. SLNB may be acceptable for patients with T3 or T4b tumors, even though SLN identification is lower yet SLN involvement is higher compared with T1 or T2 tumors, and systemic adjuvant therapy is more important for patients with T3 or T4b tumors. SLNB is a bridge to further axillary treatment such as ALND or axillary RT, and which strategy, including no further treatment, is best considered individually based on recurrence risk, treatment responsiveness and use or non-use of systemic therapy.     

Homing, proliferation and survival sites of human leukemia cells in vivo in immunodeficient mice.

The cellular components of the hematopoietic stem cell niche have been gradually identified. However, the niche for malignant hematopoiesis remains to be elucidated. Here, using human leukemia cells, which could be transplanted to immunodeficient mice, we studied the in vivo homing, proliferation and survival sites by immunohistopathology, compared with the corresponding sites for cord blood CD34(+) (CBCD34(+)) cells. The human leukemia cells initially localized on the surface of osteoblasts in the epiphysial region, and expanded to the inner vascular and diaphysial regions within 4 weeks. The percentage of CD34(+) leukemia cells in the bone marrow was transiently increased up to 50%. In vivo 5-bromo-2'-deoxyuridine labeling revealed that the epiphysis was the most active site for leukemia cell proliferation. CBCD34(+) cells showed the similar pattern of homing and proliferation to leukemia cells. After high-dose administration of cytosine-1-beta-D-arabinofuranoside, residual leukemia cells were localized in the perivascular endothelium as well as in contact with the trabecular endosteum. These findings suggest that xenotransplantation into immunodeficient mice provides a useful model to study the leukemia niche.     

Early infectious complications after peripheral blood stem cell autografts in children

Seventeen children underwent marrowablative high-dose chemotherapy with peripheral blood stem cell autografts and were studied retrospectively to determine the type, frequency, and outcomes associated with infectious complications 3 months postgraft. The patients were kept in isolated rooms with a laminar air flow facility, but no decontamination procedures, such as gut sterilization with nonabsorbable antibiotics, nonmicrobial diet, and skin cleansing, were used. They were under their mothers' daily care to maintain good psychological conditions. After the completion of marrow-ablative chemotherapy and the infusion of stem cells, the absolute granulocyte count exceeded 0.5 × 10⁹/liter with a mean of 17.9 days (range 6–65 days), Fifteen patients developed a total of 16 febrile episodes during the first 4 week period, and the confirmed diagnoses were mucositis (12), enterocolitis (nine), septicemia (four), central venous catheter-associated infection (three), pneumonia (one), perianal abscess (one), and possible invasive fungal infection (one). All episodes were successfully treated with parenteral antibiotic therapy, and no patient died of infectious complications. The observations suggest that high-dose chemotherapy can be performed safely with simple and efficient patient management protocol followed by peripheral blood stem cell autografts.     

Epidemiologic Survey of Children with End-Stage Renal Disease

We performed an epidemiologic study on the basis of a questionnaire survey of 162 children with end-stage renal disease (ESRD). Sixty-nine (43%) of our 162 children, including 25 detected at mass screening of urine, were found by chance hematuria and/or proteinuria. The three major causes of ESRD in our children were chronic glomerulonephritis (CGN) in 56, congenital anomalies of the urinary tract in 30, and nephrotic syndrome (NS) in 27. The renal pathology in 39 children with CGN or NS was focal glomerular sclerosis in 15, diffuse mesangial GN in 7, IgA GN in 5, membranoproliferative GN in 3, membranous GN in 3, and unclassified in 6. Forms of dialysis initiated were hemodialysis in 91 children, continuous ambulatory peritoneal dialysis (PD) in 66, and intermittent PD in 5. Renal transplantation was performed on 38 children, and the graft and the patient survival rates were 76% and 89%, respectively. The survival rate of our 162 children for a mean follow-up of 8.1 years was 77%. In conclusion, an integrated program of maintenance dialysis and transplantation provides a favorable life for children with ESRD.     

Renal handling of carnitine in children with carnitine deficiency and hyperammonemia associated with valproate therapy

Free and acylcarnitine in serum and urine samples were measured in five patients with hyperammonemia associated with anticonvulsant therapy including sodium valproate, of whom three had a Reye-like syndrome. All had considerable reduction in serum free carnitine and slight increase of acylcarnitine concentrations, suggesting increased conversion of free to acylcarnitine by valproate administration. Urinary excretion of both free and acylcarnitine was increased, accompanied by depressed reabsorption of free carnitine and decreased acylcarnitine/free carnitine clearance ratio. These results indicate a decreased threshold for free carnitine. The combination of these several factors may be responsible for carnitine deficiency in patients with hyperammonemia taking valproate.     

Pharmacokinetics of a benzodithiin (RD3-0028) following aerosol treatment in rat

1. RD3-0028, a benzodithiin compound, has potent antiviral activity against respiratory syncytial virus (RSV) in cell culture. The compound also inhibits growth of RSV and improves pathologic changes of interstitial pneumonia in the immunosuppressed mouse when delivered by small-particle aerosol. 2. In the present study, the absorption, distribution and excretion of 14C-RD3-0028 were compared in rat following either a single aerosol treatment or oral administration. 3. The plasma concentration was maintained at the same level from 5 min to 1 h, and decreased with a half-life of 2.2 +/- 0.1 h for 1-8 h. 4. The excretion of radioactivity in the urine and faeces at 24 h after aerosol treatment was 89.3 and 4.5%, respectively, indicating that almost all the radioactivity was rapidly excreted in the urine. The excretion of total radioactivity was 98.9% within 168 h. 5. The concentrations of radioactivity in the lung and trachea following aerosol treatment were higher than those in other tissues, and were detected even at 72 h. 6. These results suggest that the aerosol treatment might be useful for delivering RD3-0028 to the respiratory tract of RSV-infected patients.     

Sentinel lymph node biopsy without axillary dissection after an intraoperative negative histological investigation in 358 invasive breast cancer cases

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an important treatment option for breast cancer patients, as it can accurately predict axillary status. Our previous study using dye with or without radioisotope showed the accuracy and sensitivity of SLNB to be 97% and 94%, respectively. Based on these results, axillary lymph node dissection (ALND) was eliminated starting in January, 1999 in patients with intraoperatively negative SLNB at our institution. The present study shows the results and outcomes of SLNB as a sole procedure for patients with invasive breast cancer. PATIENTS AND METHODS: Three-hundred-fifty-four patients and 358 cases of invasive breast cancer (4 bilateral breast carcinoma) treated with SLNB alone after an intraoperative negative SLNB were studied prospectively from January 1999 to December 2001. RESULTS: The number of the identified SLNs per case ranged from 1 to 8 (mean, 2.5). Of a total of 358 cases, 297 (83%) were treated with hormone therapy and/or chemotherapy, and 281 (78%) were treated with radiotherapy to the conserved breast (50 Gy+/-10 Gy boost), the axilla (50 Gy), or the both sites. After a median follow-up of 21 (range 6-42) months, no patient developed an axillary relapse. Four cases initially recurred in distant organs and one case in the conserved breast. CONCLUSIONS: Our results indicate that an intraoperative negative SLNB without further ALND may be a safe procedure when strict SLNB is performed. To better assess the safety, however, may require longer follow-up.     

A report of two cases in which radiation therapy was effective for distant lymph node metastases after curative resection of gastric cancer

Long-term survival is difficult after manifestation of distant lymph node metastasis following curative resection for advanced gastric cancer. Two patients who achieved long survival with linac therapy after curative treatment of gastric cancer, are reported. Case 1: 45 years old, male. Distal gastrectomy with D2 dissection was carried out for such gastric cancer as L.M, less.Post.Ant, fType 3, T2 (MP), fStage II, on July 13, 1994. As paraaortic lymph nodes metastases was observed with CT examination on October 12, 1995, irradiation therapy using linac was conducted, and CR was achieved. Though Virchow's lymph nodes metastases was followed that episode, PR was achieved with 4,750 cGy of linac therapy. Finally, however, the patient died with metastases to lung and bone on May 19, 2002. Case 2: 62 years old, male. Distal gastrectomy with D2 + No.8p and also No.16b1 interaorticocaval dissection was conducted for such advanced gastric cancers as M, less, fType 3, T3 (SE), fStage III B on June 7, 1995. Paraaortic lymph nodes metastases were observed through CT examination on October 12, 1995. Irradiation therapy using linac resulted in CR. Virchows lymph node metastasis, which appeared on December 12, 1997, was also treated with 5,000 cGy of linac, and CR was also achieved. The patient is surviving today without recurrence.