Adjuvant aromatase inhibitor therapy in patients with stage I breast cancer at a regional oncology center in Israel: implementation of a 'switching' policy in postmenopausal patients after initial tamoxifen.

OBJECTIVE: To analyze the implementation of a switching policy of adjuvant aromatase inhibitor (AI) therapy sequentially after tamoxifen in consecutively treated stage I (T1N0M0) hormone receptor (HR)-positive breast cancer (BC) patients. METHODS: The records of 279 consecutive HR-positive BC patients diagnosed between 2002 and 2006 and followed at the Soroka Medical Center were reviewed. RESULTS: Two-hundred-seventeen patients who initially received tamoxifen were suitable for switching and 28 received an AI as initial adjuvant treatment. The switch was accomplished in 82.5% of the 217 patients. Those who switched to an AI had a higher proportion of T1c stage than patients eligible who were not switched, but did not differ in age, histologic grade, or having received chemotherapy. Of the 179 patients who switched, 155 (86.6%) completed at least 4.5-5 years of adjuvant tamoxifen/AI therapy. Eighteen patients discontinued AI therapy prematurely because of toxicity. CONCLUSIONS: In this stage I BC population, despite the toxicities of AI therapy, >84% of eligible patients received an AI as adjuvant therapy. Measures to improve the management of AI toxicity, such as changing to a different AI, may reduce early stopping.

The impact of the 21-gene recurrence score assay on decision making about adjuvant chemotherapy in early-stage estrogen-receptor-positive breast cancer in an oncology practice with a unified treatment policy.

BACKGROUND: The 21-gene recurrence score (RS) assay has been validated in retrospective studies as prognostic of distant disease recurrence and predictive of the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). There is limited published data on the impact of the assay on clinical practice, particularly in the context of a single practice with a unified treatment policy. PATIENTS AND METHODS: Between 2006 and 2009, RS was obtained on 135 patients in a single practice with a uniform treatment policy. Treatment recommendations before and after RS result were analyzed retrospectively. Pre-RS treatment recommendations were based on clinicopathological features and Adjuvant! Online (AO) calculated survival advantage. RS and AO survival advantage for adding chemotherapy were compared for each patient. RESULTS: The distribution by risk group of RS was low- 49.6%, intermediate-37.8%, and high-12.6%. In 34 patients (25.2%, 95% confidence interval 17.9% to 32.5%), recommendation for chemotherapy was changed after obtaining assay result. Most changes (70.6%) were from chemotherapy to no chemotherapy. The RS correlated poorly with AO predictions. CONCLUSION: The 21-gene assay, when applied in a consistent manner in early-stage BC, changes treatment recommendations in one-quarter of patients tested.

Stage I breast cancer in a regional oncology practice in Israel 2002-2006: clinicopathologic features, risk estimation and planned therapy of 328 consecutive patients.

We present the clinicopathologic features and treatment plans of 328 consecutive stage I (T1N0M0) breast cancer patients seen at a regional medical center in Israel. Predicted 10-year mortality risk was calculated using the Adjuvant! Online website. The 21-gene recurrence score (RS) (OncotypeDx) was obtained on a minority of patients. Eighty-nine per cent of patients had estrogen receptor (ER) and/or progesterone receptor (PgR) positive tumors. In 43.3% of patients history of an invasive malignancy was reported in a first degree relative and in 15.5% specifically breast and/or ovarian cancer was reported. Chemotherapy was added to endocrine therapy in 59 ER/PgR positive patients, decreasing predicted 10-year mortality risk by a median of 1.8%. Individualized risk estimation by genetic analysis may further decrease the use of chemotherapy in stage I patients. Breast cancer screening may provide an opportunity to identify cancer prone families.

Small cell carcinoma of the breast: case report.

BACKGROUND: Small cell neuroendocrine carcinoma of the breast is a rare tumor with fewer than 30 cases reported in the literature. The reported age of incidence of mammary small cell carcinoma is similar to that of breast carcinoma of the usual types. CASE: The clinicopathologic findings of a primary mammary small cell neuroendocrine carcinoma occurring in a 28-year-old female are presented with a review of pertinent literature. She was treated with lumpectomy and sentinel node biopsy as well as chemotherapy and radiotherapy. CONCLUSIONS: To the best of our knowledge, this is the youngest patient with primary small cell carcinoma of the breast reported in the English literature, indicating that these tumors occur in a wide age range.

Role of wire-guided breast biopsy for diagnosis of malignant nonpalpable mammographic lesions.

Biopsies of mammographically detected nonpalpable lesions have resulted in increased numbers of diagnosed early breast malignancies. From June 1992 to September 1996 a total of 433 consecutive patients underwent 438 biopsies. The mean age was 55.7 years (range 30-82 years); 150 patients were younger than 50 years. Mammographic findings were classified as microcalcifications (C), masses (M), masses with microcalcifications (MC), architectural distortions (A), and stellate lesions (S). In 30 women two needles were placed to localize a lesion in the ipsilateral side and in 5 on the contralateral side. There were 182 (41.6%) biopsies performed for M, 144 (32.9%) for C, 78 (17.8%) for A, 25 (5.7%) for MC, and 9 (2.1%) for S. The overall malignancy rate was 34% (149/438). Thirty-four women (23%) who presented malignancy were younger than 50 years of age. From year to year, it increased from 27% during the first year to 51% during the fourth year. Altogether 100 (67%) patients had invasive carcinoma, 40 (27%) ductal carcinoma in situ (DCIS), 6 (4%) lobular carcinoma in situ, and 3 (2%) tubular carcinoma. Four patients had simultaneous bilateral palpable and nonpalpable carcinoma. Among the patients, 9 of 20 with previously operated breast carcinoma and 9 of 19 with other previous malignancies were found to have early breast carcinoma. The mammographic finding with high rates of malignancy were S 67%, MC 40%, M 34%, C 33%, and A 28%. A group of 11 of 110 (10%) patients had histologically proven axillary lymph node metastasis. Results from this large retrospective study of wire-guided localization biopsies showed a relatively high rate of malignancy (34%) and DCIS (27%).

Abdominal wall pain in pregnant women caused by thoracic lateral cutaneous nerve entrapment.

Three pregnant women presented with disabling lower abdominal wall pain unresponsive to conventional therapies. The striking similarities among the clinical signs and symptoms prompted a review of the literature and led to the suspicion of thoracic lateral cutaneous nerve entrapment, a syndrome reported in other conditions, including after surgery, but not during pregnancy. Treatment by nerve block with local anesthetics was rapidly and completely successful in relieving the symptoms.

Double seton--a new modified approach to high transsphincteric anal fistula.

Despite the fact that complicated extrasphincteric anal fistulas have been recognized and treated for many years, there is still a lack of consensus among colorectal surgeons as to the optimum surgical approach. We have devised a modification of the seton technique, which we used in 23 patients without complications or recurrence.

Granulocytic sarcoma of the chest wall at site of Hickman catheter tract.

Insertion of a Hickman central venous catheter before administration of induction chemotherapy is a common practice in treatment of patients with acute myeloblastic leukemia (AML). Granulocytic sarcoma associated with AML may be the initial clinical manifestation of newly diagnosed or relapsed AML, heralding systemic involvement by weeks to months. A case of granulocytic sarcoma of the chest wall occurring as subcutaneous nodules along a scar of a previous Hickman catheter tract in a 45 year old female patient with AML is described. The patient who was in first complete remission, developed granulocytic sarcoma simultaneously with complaints associated with leukemic CNS infiltration. This is the second case described of granulocytic sarcoma of the chest wall at the site of a Hickman catheter tract. The simultaneous CNS and chest wall manifestations raise the interesting question whether both sites behaved as sanctuaries for resistant leukemic cells, in this case.

Preoperative irradiation and fluorouracil chemotherapy for locally advanced rectosigmoid carcinoma: phase I-II study.

From June 1988 to July 1991, 20 patients with locally advanced rectal or rectosigmoid cancer were treated prospectively with a strategy of combining preoperative irradiation and fluorouracil chemotherapy before surgical resection. The preoperative radiation dose was 5,000 cGy, and fluorouracil chemotherapy was administered on the first and last 3 days of irradiation in an intravenous bolus dose of 500 mg/m2. In a median follow-up of 25 months, the local regional failure rate was 10%. The 3-year actuarial overall survival and disease-free survival were 92% and 82%, respectively. Twenty percent of the surgical specimens showed no residual tumor, and only 10% showed positive lymph nodes. Significant leukopenia occurred in 10% of patients. Preoperative irradiation and fluorouracil chemotherapy increased surgical downstaging and improved local regional control. The overall toxicity was acceptable. The results of this particular multimodality approach was encouraging and warrant further investigation in phase III trials.

Hickman catheter malposition in central venous tributaries: an avoidable error?

We report three cases of erroneous positioning of Hickman catheters into central venous tributaries. The malposition was not diagnosed intraoperatively because of proximity of such veins to the superior vena cava. Suspicion of misplacement raised by early postoperative catheter malfunction should allow for correction by percutaneous vascular catheters.

Randomized study of interleukin 2 (IL-2) alone vs IL-2 plus lymphokine-activated killer cells for treatment of melanoma and renal cell cancer.

The purpose of this study was to evaluate the efficacy and safety of a continuous-infusion interleukin 2 (IL-2) regimen for patients with metastatic melanoma and renal cell cancer. To investigate the contribution of adoptively transferred lymphokine-activated killer cells, patients were randomized to receive either IL-2 alone or IL-2 plus lymphokine-activated killer cells. Twenty-three patients with renal cell carcinoma and 20 with melanoma were entered into the protocol. There were no objective responses noted in the 38 assessable patients (20 with renal cell carcinoma, 18 with melanoma). Most patients demonstrated progressive disease following one 31-day cycle of weekly continuous-infusion IL-2. Grade I and II toxic reactions, including fever, rash, anorexia, and weight gain, were common and treated symptomatically. Significant in vivo stimulation of lymphokine-activated killer and natural killer cell activity was noted in most patients. This continuous-infusion IL-2 regimen with or without lymphokine-activated killer cells was ineffective in the treatment of melanoma and renal cell carcinoma.

Emergency abdominal surgery for complications of metastatic lung carcinoma.

Acute intra-abdominal conditions due to metastatic primary lung cancer have been reported rarely in the literature, with a very high associated operative mortality noted. We report on 13 patients with metastatic lung cancer who underwent exploratory celiotomy from 1976 through 1988. Twelve were men, and their ages ranged from 43 to 68 years. All but 1 of the patients had known extra-abdominal metastases (primarily brain) at the time of the abdominal symptoms. In 11 patients the small bowel was the site of metastases. One patient had cecal involvement, while the 13th had common bile duct obstruction. The most common histologic type was a large-cell carcinoma. The extent of surgery was dependent on the pathologic findings encountered; most patients underwent resection of obstructed or perforated intestine. Eight of the 13 patients survived and were discharged from the hospital after a mean stay of 17 days. We conclude that acute intra-abdominal conditions from metastatic lung cancer can often be treated successfully by prompt surgical exploration, including bowel resection or bypass if necessary.

Induction of the expression of differentiation-related antigens on human colon carcinoma cells by stimulating protein kinase C.

This study was undertaken to determine whether the phorbol diester, phorbol 12-myristate 13-acetate (PMA), causes differentiation of the human colon carcinoma cell line, SW 48. Under routine growth conditions, the cells are round, have a high nuclear-to-cytoplasmic ratio, and lack cytoplasmic vacuoles. After treatment for 1 hour with 100 nmol/L of PMA at 37 degrees C, the cells assumed a spread-out, flasklike shape, displayed a low nuclear-to-cytoplasmic ratio, and exhibited cytoplasmic vacuoles. An inert but lipophilic phorbol diester, 4 phorbol 12,13-didecanoate, failed to induce these morphological changes. Cell kinetic studies showed that whereas SW 48 cells have a doubling time of 35 hours, those incubated with 100 nmol/L of PMA have a doubling time of 90 hours. Although the flow cytometry histograms were similar until 8 hours into the cell cycle, the PMA-treated cells ultimately spent proportionately less time in S and more in G2/M. Finally, under routine growth conditions, SW 48 cells express neither carcinoembryonic antigen nor G7 antigen. These antigens, which are present on the surface of well-differentiated cells, were expressed after treatment of SW 48 with PMA. The data suggest that PMA causes profound changes in structure, cell growth kinetics, and antigen expression, consistent with induction of differentiation of the cell line SW 48.

Primary adenocarcinoma of the jejunum.

Experience with primary adenocarcinoma of the jejunum at the Union Memorial Hospital is reviewed. Six patients treated from 1968 to 1986 with this interesting but rare tumor were identified. Although symptoms appeared to be of long duration, all patients were diagnosed with advanced disease, with only one patient surviving long-term. Data on primary jejunal adenocarcinoma reported in the medical literature were reviewed. The survival figures appear to correlate with stage at presentation, and therefore early and aggressive diagnostic and therapeutic intervention seems indicated to improve the outlook in these patients with historically poor survival rates.

Intraoperative ultrasound of the liver affects operative decision making.

The surgeon operating upon patients with primary or metastatic hepatic cancers must determine if resection is feasible and, if it is, the magnitude of required resection. In an attempt to determine which tests best aid the surgeon in these determinations, the authors prospectively compared preoperative computed tomography (CT) of the liver and intraoperative ultrasound (IOU) in 42 patients with liver tumors who underwent 45 exploratory operations. The primary diseases included colorectal cancer metastases in 27 patients, hepatoma in 11 patients, and metastatic cancers of other origins in 4 patients. In the 42 patients there were 89 identified hepatic lesions that were confirmed to be malignant by resection, biopsy, or continued growth on follow-up CT. The sensitivity of either test for detecting these lesions was 69/89 (77%) for CT and 87/89 (98%) for IOU. Resection was not feasible in 13 patients. Five had extrahepatic disease, 4 had more nodules discovered by IOU, 3 were found by IOU to have involvement of all three hepatic veins by tumor and 1 patient had portal-vein invasion. Alternatively, in four patients tumors thought to involve all three hepatic veins by CT were shown to be free of at least one hepatic vein, thereby permitting resection. In one patient who had been previously operated upon, a tumor thought to involve the remaining right hepatic vein was seen to be free of the vein, also permitting resection. Regarding the extent of resection, IOU was also helpful. Lesser procedures than anticipated were proved possible by IOU in seven patients. A more extensive resection was shown to be necessary by IOU in two patients. Thus, IOU affected the operative management in 22 of 45 operative episodes (49%). It was conclude that IOU is superior to both preoperative CT and surgical exploration in assessing both the feasibility and the extent of resection required for primary and secondary hepatic cancers. In the authors' experience, IOU is the most sensitive indicator of number of lesions present in the liver. In addition, the ability of IOU to determine hepatic venous anatomy is a helpful adjunct in determining resectability of liver tumors.

Extrarenal adult Wilms' tumor.

Extrarenal Wilms' tumor is a very rare disease, occurring mostly in children. Sixteen cases have been reported in the world medical literature. A case of retroperitoneal extrarenal Wilms' tumor is reported in a 36-year old white male and the literature reviewed. Pathologic examination revealed both undifferentiated renal blastoma plus differentiated areas containing immature tubules and glomeruli. No evidence of extrarenal teratomatous tissue was seen. Theories for the histogenesis of this rare tumor are discussed.