Photodynamic therapy of the intact breast.

As breast cancer is diagnosed in over a million patients a year it is a significant oncological issue. Treatment paradigms have shifted to emphasize breast preservation protocols. However, due to a lack of equipment and facilities this option is only rarely offered to poverty stricken patients and those in the developing world. Photodynamic therapy may play a role in allowing for greater breast conservation based in part on the emerging success of partial breast radiation. This paper will review the rationale behind and technical aspects for intact breast photodynamic therapy.

Clinical photodynamic therapy of head and neck cancers-A review of applications and outcomes.

As local control is tantamount to cure in head and neck cancer, an aggressive regimen of surgery and radiation remains the standard of care for most patients. Despite significant technical advances, these treatments are highly morbid. Further, patients who fail treatment have limited salvage options. Photodynamic therapy (PDT) and photodiagnosis (PD) of head and neck cancer offer significant potential for improved outcomes in a myriad of clinical indications ranging from in situ to recurrent disease. However, despite promising results, these modalities remain at the fringe of head and neck treatment options. Photofrin(®), Photosan and Foscan(®) are photosensitizers used clinically in head and neck PD/PDT. In addition, aminolevulinic acid (ALA), which gives origin to Protoporphyrin IX, an endogeneous photosensitizer, is also used for PD/PDT. We review the clinical literature on these photosensitizers to assist in the integration of these important modalities into the mainstream of head and neck oncological therapy.

Colovaginal anastomosis: a unique complication of end-to-end anastomosis stapler use in low anterior resection.

Anastomotic staplers have been used in colorectal surgery for several years. End-to-end stapler use for low anterior resection, as well as for other procedures, is common in surgical practice. These staplers have allowed more extended, lower resections of the colorectum without loss of bowel continuity or sphincter function. There have been reported complications of stapler use, with anastomotic stricture and leakage being the most common. We report here a unique complication of direct colovaginal anastomosis using the end-to-end stapler during a low anterior resection of an early-stage rectal adenocarcinoma.

Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts.

Liposomes containing polyethylene glycol-derivatized phospholipids are able to evade the reticuloendothelial system and thereby remain in circulation for prolonged periods. We report here that doxorubicin encapsulated in these sterically stabilized liposomes (S-DOX) suppresses the growth of established human lung tumor xenografts in severe combined immunodeficient (SCID) mice and inhibits the spontaneous metastases of these tumors. The enhanced therapeutic efficacy of S-DOX compared to free doxorubicin was demonstrated in two independent human/mouse models. In the first model, S-DOX inhibited the growth of a human non-small cell lung tumor xenograft established orthotopically in the lungs of SCID mice. Treatment of these mice with S-DOX, but not with free drug, suppressed the growth of the tumor in the lung, prevented metastasis from the lung, and enhanced survival percentage. In another model, the human lung tumor is engrafted into gonadal fat pad of SCID mice. Human tumor xenografts grow floridly in this site of engraftment, and the tumor spreads from this primary site into the peritoneal cavity and subsequently reaches the liver and lung. In this model, free drug suppressed the growth of the primary tumor but had no effect upon the subsequent spread of the tumor into the peritoneal cavity, liver, and lung. In contrast, treatment of the tumor-bearing mice with S-DOX (but not with doxorubicin in conventional liposomes) suppressed the tumor spread to the peritoneal cavity, completely arrested metastasis to the liver and lung, and suppressed the growth of the primary tumor xenograft. This report provides the first evidence that antitumor drugs delivered by sterically stabilized liposomes can arrest the metastasis of human tumor xenografts.

Endometrial carcinoma associated with breast carcinoma: low incidence with tamoxifen use.

BACKGROUND: Women treated with tamoxifen for breast cancer are at increased risk of endometrial cancer. This study examines the experience at Roswell Park Cancer Institute (RPCI) with women diagnosed with both endometrial carcinoma (EC) and breast carcinoma (BC) to determine the risk and stage of endometrial carcinoma among women treated with tamoxifen. METHODS: The tumor registry was searched for women with diagnoses of both BC and EC between 1980 and 1993. Systemic therapy was classified for all analytic cases of breast carcinoma (women who received primary BC treatment at RPCI). Medical records of all women with both BC and EC were reviewed, including all analytic and nonanalytic cases. RESULTS: There were 1947 analytic and 1534 nonanalytic BC cases and 877 analytic and 239 nonanalytic EC cases. Thirty-six women in the nonanalytic breast cancer group also had endometrial carcinoma. Fifteen had endometrial carcinoma before breast carcinoma, and 20 of 21 women with breast cancer first had no record of tamoxifen use. Thirty-seven women in the analytic breast carcinoma group had endometrial carcinoma. Endometrial carcinoma preceded breast carcinoma in 29 women. Breast carcinoma preceded endometrial carcinoma in eight women, and two of these developed endometrial carcinoma during or after tamoxifen therapy. Therefore, a total of three women developed endometrial cancer during or after tamoxifen therapy (two analytic and one nonanalytic). The EC was classified as International Federation of Gynecology and Obstetrics (FIGO) Stage IA (1 patient) and IB (2 patients) with one patient each with histologic Grade I, II, and III after 1, 2, and 5 years of tamoxifen therapy, respectively. No patients had recurrence or died from endometrial carcinoma. The risk of endometrial carcinoma with tamoxifen was determined from the number of women in the breast cancer analytic group receiving tamoxifen. Hormonal therapy was coded as part of systemic treatment in 652 of 1947 analytic patients (33%; 510 as adjuvant therapy and 142 for metastatic cancer). Of these patients, 172 of 652 women (26%) had undergone hysterectomy prior to breast cancer diagnosis, and another 71 women (11%) received nontamoxifen hormone therapy (e.g., prednisone). Tamoxifen therapy was documented in 402 women in the analytic group. (The median age of these women at BC diagnosis was 63 years). Therefore, the maximum estimate of endometrial carcinoma risk is 2 of 402 cases (0.5%). CONCLUSIONS: The risk of endometrial carcinoma with tamoxifen use is low. The value of routine invasive screening for endometrial carcinoma for women receiving tamoxifen should be determined by prospective study.

Orthotopic engraftment of human lung tumours in SCID mice for the study of metastasis.

This study presents a new technique for the orthotopic engraftment of human lung tumours in SCID mice and demonstrates the importance of a more clinically relevant route of tumour propagation for the study of metastatic potential. The orthotopic engraftment of human lung tumour biopsy specimens was performed via an anterior thoracotomy into SCID mice. Engraftment of non-small cell lung cancer specimens from nine patients into 52 SCID mice yielded a 31% engraftment rate and a 50% metastasis rate. Unlike subcutaneous inoculation, the engraftment rates following the orthotopic inoculation did not vary between squamous cell carcinomas and adenocarcinomas. Direct visceral pleural invasion was seen in most cases. Orthotopically placed tumours grew 5-fold by 4 to 6 months. Unique to this model was the observation of metastasis to clinically relevant sites, such as the adrenal gland and supraclavicular lymph nodes. Contralateral lung metastases were also noted in 37.5%, and one ovarian metastasis occurred. The procedure was well tolerated, with survival rates of 98%.

Characterization of GRO alpha, beta and gamma expression in human colonic tumours: potential significance of cytokine involvement.

The GRO genes, isolated from transformed fibroblasts, belong to a superfamily of genes such as platelet factor 4 and neutrophil activating peptide/IL-8. Three related GRO genes are described which are closely linked on chromosome 4: GRO alpha, GRO beta, and GRO gamma: GRO beta and GRO gamma share 90 and 86% sequence homology with GRO alpha. The GRO alpha gene product shares homology with, and is melanocyte growth stimulatory activity (MGSA). The MGSA/GRO alpha has potent chemotactic, growth regulatory and transformative functions. The function of GRO beta and gamma is unknown. Expression of GRO alpha is well characterized in vitro; studies in actual human tissues are not reported. We chose to determine the specific expression of GRO alpha, beta and gamma in both normal and transformed human colonic tissues and to assess the role of exogenous cytokines on their induction. Tissues from ten patients with colonic neoplasia were obtained at the time of colectomy. All specimens underwent Northern analysis for GRO gene expression, comparing normal colonic mucosa with neoplastic mucosa. Differential GRO alpha, beta and gamma expressions were determined by polymerase chain reaction (PCR). GRO alpha expression was evaluated in the tumour specimens compared with normal, while there was constitutive expression of GRO gamma in both normal and neoplastic colonic mucosa. Expression of GRO beta was minimal in all tissue specimens. In addition, HT29 colon carcinoma cells stimulated with IL-1 beta and TNF alpha demonstrated induction of GRO alpha and IL-8. Thus, GRO alpha is differently elevated in in vivo colon carcinoma specimens. GRO gamma was constitutively expressed in colonic tissues; GRO beta was not similarly expressed.

Transoral repair of a rare basioccipital meningocele in a neonate: case report.

An extremely rare case of a basioccipital meningocele causing obstruction of the upper airway in a neonate is described. A transoral approach was used to remove the meningocele and repair the dural fistula. Bilateral posterior lateral pharyngeal releasing incisions were made to allow mucosal and muscle coverage over the dural repair. This report demonstrates and emphasizes the use of lateral pharyngeal releasing incisions to cover midline full thickness defects in the posterior oropharyngeal wall that might be encountered during transoral transclival operations.

Bromine levels in human serum, urine, hair. Short communication.

Much is known about the essentiality of the halogens fluorine (F), chlorine (Cl), and iodine (I), but very little has been discussed with respect to bromine (Br). As a member of the halogen family its chemical properties are comparable to those of other halogens, but its presence has been masked by the presence of I and Cl in chemical analyses. By virtue of new technology and a special computerized machine called the Kevex Model 0600 Energy Dispersive X-Ray Induced X-Ray Fluorescence Spectrometer (EDXRF), we can specifically identify bromine in different compartments and verify its concentration accurately. In order to establish standard values of Br concentrations and evaluate the nature of its presence in humans, samples of serum, urine, and hair were collected from ten healthy adult males and analyzed for bromine content. Our samples had normal distributions, with serum bromine levels ranging from 3.2 to 5.6 micrograms/mL, urine levels between 0.3 to 7.0 micrograms/mL, and hair levels determined from 1.1 to 49.0 micrograms/mL. These levels, especially those of serum bromine, have been encountered by other examiners whose samples also had normal distributions. These findings suggest to us that bromine may well be an essential trace element, as are its other halogen family members.

Incest and physician responsibility.

This paper examines the epidemiologic, psychologic, and clinical aspects of incest, and emphasizes the need for action by physicians. The apparent increase in the incidence of this emotionally damaging experience makes it essential for the physician to understand the dynamics of incest, individually and in the family, so as to be prepared to meet the needs of the patient and the community. This paper stresses the responsibility of the physician in the intervention of the immediate trauma and in the prevention of its continuation or recurrence. Ways in which the physician, because of his close contact with the family, may fill this role are discussed.