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A 6-yr-old boy underwent a total body Ga-67 citrate imaging study because of a large mass of Hodgkin's lymphoma in the left neck and the left anterior chest wall region. The images showed intense uptake in the left neck extending anteroinferiorly to the left upper chest wall corresponding to the left neck and chest region. In addition, there was mild cervical-upper thoracic scoliosis with convexity to the right and mild scoliosis of the lower lumbar scoliosis with concavity to the left. After three cycles of chemotherapy, in the follow-up Ga-67 citrate total body images seven months after his first Ga-67 citrate imaging, the intense uptake in the left neck and the left upper chest wall had been resolved and the scoliosis of the cervical-thoracic and lower lumbar spine had also been reversed to normal. This case shows that a Ga-67 citrate imaging study is useful for first diagnosis and subsequent monitoring of the therapeutic effects in a follow-up imaging. Also Ga-67 citrate imaging provided evidence that the scoliosis had been reversed. [ABSTRACT FROM AUTHOR]

Abstract: Objective. : To determine the efficacy of adjuvant platinum-based chemotherapy in Stage I uterine papillary serous carcinoma (UPSC). Methods. : A retrospective multi-institutional investigation was performed to identify surgically staged patients with Stage I UPSC who were (1) treated after surgery with 3–6 courses of platinum-based chemotherapy without radiation from 1990–2003, and (2) followed for a minimum of 12 months, or until recurrence. Results. : Six patients (IA—2, IB—3, IC—1) were treated with carboplatin (AUC 6) or cisplatin (50 mg/m2) alone. One patient recurred to the vagina, was treated with chemo-radiation, and is alive and well at 122 months. One patient recurred to the lung, liver, and brain, and died of disease at 24 months. The remaining 4 patients are alive with no evidence of disease 15–124 months (mean 62 months) after treatment. Two patients (IB-1, IC-1) were treated with cisplatin (50 mg/m2) and cyclophosphamide (1000 mg/m2), and both are alive and well with no evidence of disease 75 and 168 months after treatment. Twenty-one patients (IA—5, IB—13, IC—3) were treated with a combination of carboplatin (AUC 6) and paclitaxel (135 mg/m2–175 mg/m2). One patient recurred to the vagina after 3 cycles of carboplatin/paclitaxel, and was treated with chemo-radiation. She is now without evidence of disease 10 months after treatment. At present, all 21 patients with Stage I UPSC treated following surgical staging with carboplatin/paclitaxel chemotherapy are alive and well with no evidence of disease 10–138 months (mean 41 months) after treatment. Conclusion. : Combination carboplatin/paclitaxel chemotherapy following surgery is effective in the treatment of Stage I UPSC. [Copyright &y& Elsevier]

Background: There are a number of equally efficacious chemotherapy options for the treatment of women with endometrial cancer, all of which work in only a subset of those women with this disease. An in vitro assay performed before therapy initiation to identify the drug(s) most likely to be effective for the individual patient would have clinical utility. Such an assay should yield response rates similar to those found in treated patient populations. The purpose of this investigation was to determine whether the patterns of in vitro tumor response rates as determined by ChemoFx are consistent with expected population response rates., Methods: Nine hundred twenty-three tumor specimens from patients with high-risk early-stage, advanced stage, or recurrent endometrial cancer were sent for testing with the ChemoFx drug response marker from August 2, 2006, to August 31, 2009. Tumors were categorized as responsive (R), intermediately responsive (IR), or nonresponsive to each drug or combination tested. Response rates from clinical trials were identified and compared with the corresponding in vitro response rates., Results: Of the 923 specimens received, 759 (82%) were successfully tested by ChemoFx. Of these, 755 were tested for at least 1 of 5 National Comprehensive Cancer Network-recommended endometrial cancer drugs. The response rates (R+IR) for these drugs were as follows: 66% carboplatin-paclitaxel, 48% carboplatin, 37% cisplatin, 23% doxorubicin, and 36% paclitaxel. Moreover, 20% of tumors were pan-sensitive (R or IR) to all 5 regimens tested, 27% were pan-resistant (nonresponsive), and 53% showed different degrees of response to different drugs., Conclusions: ChemoFx in vitro response rates were consistent with published population response rates, and the ChemoFx drug response marker may provide clinically useful information to better optimize individual chemotherapy for treatment of women with endometrial cancer.

The decision whether to proceed with complete axillary node dissection based on sentinel node status is clear for patients with negative or macrometastatic disease. However, the course of action based on sentinel node micrometastasis remains controversial. We reviewed 358 cases from 6/1999 to 7/2003. All sentinel nodes were evaluated at three levels by frozen section, touch preparation, and scrape preparation. Micrometastasis was defined as tumor deposits between 0.2 and 2 mm. Size, grade, and lymphvascular invasion of the primary tumor, as well as number, status, size of metastatic disease, and presence of extranodal capsular extension of sentinel and nonsentinel nodes were recorded. Of the 358 cases, 89 had positive sentinel nodes, 29 of which represented micrometastases. Only one (3%) of the 29 cases contained a nonsentinel node with macrometastasis. In 60 of the 89 cases sentinel nodes contained macrometastases. Of these, 38 cases (63%) had metastatic tumor in nonsentinel nodes. Intraoperative consult was performed in 53 of the 89 cases with positive sentinel nodes. Only 1 of the 19 (5%) intraoperative consult cases with micrometastatic sentinel nodes had positive nonsentinel nodes, while 21 of 34 (62%) of macrometastatic sentinel nodes at intraoperative consult had tumor in nonsentinel nodes. No single variable studied discriminated between micro- vs macrometastatic disease. At intraoperative consult, macrometastatic disease was present in all three diagnostic preparations, while diagnostic material in micrometastatic sentinel nodes was usually present in only one modality. This analysis suggests that the risk of finding tumor in nonsentinel nodes differs significantly between cases with micro (3%)- vs macro (63%)-metastatic disease in sentinel nodes. This holds true for cases assessed by intraoperative consult. Considering the known morbidity of complete axillary dissection, assessments of risk vs benefit of undertaking this procedure should be performed on a case-by-case basis in patients with sentinel node micrometastases.

The ribonucleotide reductase inhibitor hydroxyurea (HU) has demonstrated some benefit as a component of drug cocktails for the treatment of HIV-1 infection. However, HU is notoriously myelosuppressive and often administered only as salvage therapy to patients with late-stage disease, potentially exacerbating the bone marrow toxicity of HU. In this report we have compared the antiviral effects of HU and two novel RR inhibitors trimidox (3,4,5-trihydroxybenzamidoxime) and didox (3,4-dihydroxybenzohydroxamic acid) in combination with didanosine (2,3-didoxyinosine; ddI) in the LPBM5 MuLV retrovirus model (murine AIDS). We also evaluated the effects of these drug combinations on the hematopoietic tissues of LPBM5 MuLV-infected animals. The combination of RR inhibitors and ddI was extremely effective (DX>TX>HU) in inhibiting development of retrovirus-induced disease (splenomegaly, hypergammaglobulinemia, activated B-splenocytes and loss of splenic architecture). In addition, relative levels of proviral DNA were significantly lower in combination drug-treated animals compared to infected controls. Evaluation of femur cellularity, numbers of marrow-derived myeloid progenitor cells (CFU-GM and BFU-E) and peripheral blood indices revealed that TX and DX in combination with ddI were well-tolerated. However, treatment with HU and ddI induced moderate myelosuppression. These data demonstrate that RR inhibitors in combination with ddI provide significant protection against retroviral disease in murine AIDS. Moreover, the novel RR inhibitors TX and DX appear to be more effective and less myelosuppressive than HU when administered with ddI in this model.

Purpose: To determine if circadian timed (CT) chemotherapy results in improved response, progression-free survival (PFS), overall survival (OS), and lower toxicity, when compared with standard timed (ST) chemotherapy., Materials and Methods: Eligibility criteria were stage III, IV, or recurrent endometrial cancer with poor potential for cure by radiation therapy or surgery; measurable disease; and no prior chemotherapy. Therapy was randomized to schedules of ST doxorubicin 60 mg/m2 plus cisplatin 60 mg/m2, or CT doxorubicin 60 mg/m2 at 6:00 am plus cisplatin 60 mg/m2 at 6:00 pm. Cycles were repeated every 3 weeks to a maximum of eight cycles., Results: The ST arm included 169 patients, and the CT arm included 173 patients. The objective response rate (complete responses plus partial responses) was 46% in the ST group compared with 49% in the CT group (P =.26, one tail). Median PFS and OS were 6.5 and 11.2 months, respectively, in the ST group; and 5.9 and 13.2 months, respectively, in the CT group (PFS: P =.31; OS: P =.21, one tail). Median total doses were 209 mg/m2 doxorubicin and 349 mg/m2 cisplatin in the ST group, versus 246 mg/m2 doxorubicin and 354 mg/m2 cisplatin in the CT group. Grade 3 or 4 leukopenia occurred in 73% of patients in the ST arm and in 63% of patients in the CT arm. There were eight treatment-related deaths., Conclusion: In this trial, no significant benefit in terms of response rate, PFS or OS, or toxicity profile was observed with CT doxorubicin plus cisplatin in patients with advanced or recurrent endometrial carcinoma.

We evaluated the ability of a short course of treatment with the ribonucleotide reductase (RR) inhibitor hydroxyurea (HU) and two novel RR inhibitors Trimidox (TX) and Didox (DX) to influence late-stage murine retrovirus-induced lymphoproliferative disease. LPBM5 murine leukaemia virus retrovirus-infected mice were treated daily with HU, TX or DX for 4 weeks, beginning 9 weeks post-infection, after development of immunodeficiency and lymphoproliferative disease. Drug effects on disease progression were determined by evaluating spleen weight and histology. Effects on haematopoiesis were determined by measuring peripheral blood indices (white blood cells and haematocrit) and assay of femur cellularity and femoral and splenic content of colony-forming units granulocyte-macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E). HU, TX and DX partially reversed late-stage retrovirus-induced disease, resulting in spleen weights significantly below pre-treatment values. Spleen histology was also improved by RR inhibitor treatment (DX>TX>HU). However, as expected, HU was significantly myelosuppressive, inducing a reduction in peripheral indices associated with depletion of femoral CFU-GM and BFU-E. In contrast, although TX and DX were moderately myelosuppressive, both drugs were significantly better tolerated than HU. In summary, short-term treatment in late-stage murine retroviral disease with HU, TX or DX induced dramatic reversal of disease pathophysiology. However, the novel RR inhibitors TX and DX had more effective activity and significantly less bone marrow toxicity than HU.

The purpose of this study was to assess the physical response of skin to laser resurfacing in a real-time, quantitative fashion. The study was designed to assess skin contraction from two opposite standpoints. First, change in tension was measured during laser application while samples were held at constant length. Second, change in length of a sample under no tension was measured during laser treatment. These two disparate analyses represent the two possible extremes of the clinical situation in which skin exists under some tension with some laxity to allow for decrease in length. A custom apparatus with digital interface for skin tension measurements was used to produce single sample tracings of change in skin tension with laser treatment. Length change was measured for individual samples by continuous sonomicrometer readings. Individual sample data were then plotted in a time versus tension/length graph. Skin contracts immediately to a peak level and then relaxes to a sustained plateau level for both CO2 and erbium:YAG lasers. Increased contraction was noted when the beam penetrated into the dermis. Greater peak and plateau contraction is observed after the beam has penetrated into the dermis. Skin contraction varies directly with energy for CO2 and erbium:YAG laser. Findings were similar when skin tension was measured with the sample held at constant length and when length change was measured with the sample under no tension. Char left on the skin after a pass with CO2 laser substantially decreases skin contraction. High-density settings with CO2 laser yield pulse stacking, which effectively irradiates the same portion of tissue with char on it. Skin contraction varies inversely with computer pattern density settings for CO2 laser due to this pulse stacking effect. Density has little effect on skin contraction for the erbium:YAG laser because little char is generated. Histologic analysis identified a zone of coagulated dermis that correlates linearly with skin contraction.

Transforming growth factor beta (TGF-beta) can promote late stage tumor progression in a number of model systems. In the present study, we have examined whether expression of a truncated soluble extracellular domain of TGF-beta type III receptor (sRIII) in human breast cancer MDA-MB-231 cells can antagonize the tumor-promoting activity of TGF-beta by sequestering active TGF-beta isoforms that are produced by the cancer cells. The secretion of sRIII reduced the amount of active TGF-beta1 and TGF-beta2 in the conditioned medium. This led to a significant reduction of the growth-inhibitory activity of the medium conditioned by sRIII-expressing cells on the growth of mink lung epithelial CCL64 cells in comparison with the medium conditioned by the control cells. The tumor incidence and growth rate of all of the three sRIII-expressing clones studied were significantly lower than those of the control cells in athymic nude mice. Four of five control cell-inoculated mice showed spontaneous metastasis in the lung, whereas none of the sRIII-expressing cell-inoculated mice had any lung metastasis. Thus, our results suggest that the sRIII may be used to antagonize the tumor-promoting activity of TGF-beta.

This article reviews the "state of practice" with regard to sentinel lymph node biopsy, a new and evolving technique currently used most commonly for staging of malignant melanoma and adenocarcinoma of the breast. Sentinel lymph node biopsy has the potential to both increase the accuracy of lymph node sampling as a prognostic tool and to decrease the need for unnecessary and morbid extensive lymph node dissection in such patients. The need for close cooperation and planning involving the surgeon and pathologist is stressed, and gross room tissue handling, radiation safety, microscopic examination, and the use of ancillary diagnostic techniques are discussed.

The role of surgery in the treatment of Stage I and II non-Hodgkin's thyroid lymphoma (NHTL) is not well defined. At our institution, we have treated seven patients (six women and one man) with NHTL during the past 6 years. Three patients (43%) had a prior history of thyroid disease, usually lymphocytic thyroiditis. Clinical symptoms included a rapidly enlarging neck mass (86%), dysphagia (71%), dyspnea (71%), and hoarseness (71%). Five patients (71%) had hypothyroidism; one patient, hyperthyroidism; and one patient, normal thyroid function. Five patients underwent fine-needle aspiration (FNA) at our institution. In three instances, FNA results were indicative of NHTL; the remaining FNA tests yielded no diagnosis. Surgical procedures were varied: incisional biopsy (n = 4), limited tumor debulking with tracheostomy (n = 2), and thyroidectomy (n = 1). Each of the seven patients was found to have large cell lymphoma. Treatment consisted of combination chemotherapy with consolidative irradiation. All tumors dramatically decreased in size soon after the initiation of therapy. One patient refused radiotherapy. All patients except one are still alive (median follow-up, 24 months). In conclusion, 1) a diagnosis of NHTL, although rare, should be considered when patients have rapidly growing goiters; 2) FNA is a useful first step in diagnosing NHTL; 3) NHTL is exquisitely sensitive to both chemotherapy and radiation; 4) surgical intervention is generally confined to incisional biopsy with occasional limited pretracheal tumor debulking; and 5) when a biopsy is obtained from a patient suspected of having NHTL, immediate processing by the pathologist is recommended so that material can be obtained for special studies as needed.

We studied the expression of p53 gene product in pancreatic adenocarcinomas of the usual ductal type to determine its relationship to cigarette smoking and its usefulness as an independent prognostic indicator. Twenty-six resection specimens of pancreatic adenocarcinoma were examined by immunohistochemistry using an antigen retrieval solution and monoclonal PAb1801 and polyclonal CM1 antibodies on paraffin-embedded material. Specific nuclear p53 expression for both PAb1801 and CM1 was identified in seven cases (27%). In all cases immunoreaction was confined to neoplastic cells. Three of four (75%) tumors from patients who had never smoked showed immunoreaction, whereas only three of 14 (21%) tumors from smokers showed positive staining. Cases with positive staining had shorter mean survival (6.3 mo) than cases that failed to stain (9.8 mo), but the difference was not statistically significant in this small study. There was no statistically significant association between p53 immunoreactivity and other clinicopathologic parameters. Our findings indicate that abnormalities of p53 gene in pancreatic adenocarcinomas may not be directly related to cigarette smoking. Those patients who survived the longest tended to have tumors negative for p53 immunostaining. p53 immunoreaction may be a useful feature in distinguishing adenocarcinoma from chronic pancreatitis in small biopsies.

To investigate the etiologies for discrepancies between cervicovaginal smear and corresponding cervical biopsy results, 615 patients with cytologic diagnoses of dysplasia or malignancy during 1 year were reviewed. Sixty-nine patients (11%) were identified in which the cytologic and histologic diagnoses differed. Utilizing an algorithm developed for the study, these cases were assigned an etiologic category for discrepancy: colposcopic biopsy or cytologic sampling, cytologic screening, histotechnical processing, histologic or cytologic interpretation. The most common cause for a discrepancy was colposcopic biopsy sampling (36 cases, 51%). There were nine errors (13%) in biopsy interpretation, with seven underdiagnoses and two overdiagnoses. Eight errors (11%) in cytologic interpretation occurred with half of these representing underdiagnoses. The other causes for discrepancy were less common--cytologic sampling (6 cases), histotechnical processing (3 cases), cytologic screening (2 cases), and a combination of factors (5 cases). Use of this algorithm allows laboratories to identify problem areas and design specific corrective protocols to improve diagnostic accuracy and patient care.

Histologic grading of adenocarcinoma of the prostate gland is a reliable predictor of extension and metastasis. Studies involving correlation of grade between biopsy and prostatectomy specimens have traditionally involved biopsies using a large-bore (14-gauge) cutting needle. However, common practice has shifted to the use of biopsy cores with a smaller caliber (18 gauge). This study was undertaken to determine the degree of correlation of tumor grade between 18-gauge core biopsy samples and excised glands. Sixty-seven patients with stage A or B adenocarcinoma of the prostate gland who had previously undergone 18-gauge core biopsy, who underwent radical prostatectomies, were studied. The Gleason score was determined by referred consensus among three pathologists. There was exact agreement between biopsy and excision in 39 cases (58%), whereas 24 cases (36%) differed by one digit. Three cases (4.5%) were undergraded, and one case (1.5%) was overgraded by two or more points. Only six tumors (8.9%) would have been incorrectly specified by the degree of differentiation. Discrepancies in grade of two points or more were not more frequent in cases with a small tumor volume (< or = 10%) in the biopsy specimens. We concluded that with careful histologic evaluation, the grade of tumor identified in these smaller biopsy cores correlates well with that seen at prostatectomy.

Background: Primary small cell carcinoma of the head and neck is rare. Although the larynx is the most prevalent site of head and neck small cell carcinoma (SCC), this report will concentrate on SCC of the major salivary glands and paranasal sinuses. In all, 33 cases of paranasal sinus and 43 cases of major salivary gland SCC have been reported in the literature., Methods: We report two patients, one with submandibular gland SCC and the other with maxillary sinus SCC. A literature review of all known paranasal sinus and major salivary gland SCC with inclusion of data from these two new cases is undertaken. Discussion of all past and present cases concentrates on sites of metastasis, treatment, and survival., Results: Paranasal sinus SCCs predominantly arise from the nasal cavity, whereas the parotid gland is the primary site in three fourths of major salivary gland SCCs. One half of major salivary gland and three fourths of paranasal sinus SCCs have only local disease at presentation. Both patients in this report developed bone marrow metastases, a feature heretofore not observed in SCC from these primary sites. The patient with maxillary sinus SCC developed the syndrome of inappropriate antidiuretic hormone (SIADH)., Conclusion: The paranasal sinus and major salivary glands are rare primary sites for SCCs. Long-term survival with local therapy in patients with local disease can occur, but in patients with metastatic disease survival mirrors metastatic pulmonary SCC.

Objective: The utility of an antibody to proliferating cell nuclear antigen (PCNA), a growth-specific nuclear protein, was assessed as a prognostic variable for prostatic adenocarcinoma. Its expression was correlated with established prognostic indicators, including tumor grade, stage, prostatic-specific antigen (PSA), and percent of tumor in the gland at excision., Methods: Forty archival needle biopsies containing a minimum of four hundred tumor cells were analyzed. Immunoperoxidase staining of paraffin sections was performed for PCNA (PC10) after pretreatment in antigen retrieval solution. A proliferative index (PI) for each case was derived using image analysis with measurement of at least four hundred twenty-five nuclei., Results: PI values ranged from 2.4 to 31.3 percent. Mean PI values varied significantly (ANOVA, p = 0.005) among cases with dominant Gleason grade (DGG) of 3 (mean PI = 9.3%), 4 (mean PI = 13.7%), and 5 (mean PI = 18.8%). By t test, significant differences were noted for PI in cases with DGG 2 and 3 versus those with DGG 4 and 5 (p = 0.0065). PI for cases with DGG 3 versus 5 showed significant difference (p = 0.0017). Tumors of Gleason scores 5 to 7 differed significantly from those with scores 8 to 10 (p = 0.014). A statistical relationship for PI and PSA, clinical stage, and percent tumor at resection could not be established by linear regression., Conclusions: These findings suggest that additional study of the PI, as determined by PCNA immunohistochemistry and image analysis, may be warranted to determine its usefulness as an adjunctive parameter in prostate adenocarcinoma. This technique may be particularly useful in needle biopsies where limited tumor may render assessment of grade difficult.

Fifty-six specimens of gastric carcinoma were examined for the localization of HER-2/neu oncoprotein (HER-2/neu) and epidermal growth factor receptor (EGFR) by immunohistochemistry using polyclonal antibodies on paraffin-embedded material. Strong membrane staining for HER-2/neu was noted in 14 cases (25%), all of which were of the intestinal type. Only cytoplasmic staining was found in an additional 21 cases (37.5%), including seven diffuse tumors. Twenty-four cases (nine diffuse and 15 intestinal) showed cytoplasmic staining with accentuation on the cell membrane for EGFR. Patchy staining was common for HER-2/neu, while EGFR immunoreactivity was always diffuse. Twenty cases (35.7%) showed positive staining for both, 15 cases (26.8%) for HER-2/neu only, four cases (7.1%) for EGFR only, and 17 cases (30.4%) for neither. Expression of HER-2/neu was more commonly associated with intermediate-grade and high-stage tumors. Cases with positive (either membrane or cytoplasmic) staining for HER-2/neu showed poorer overall mean survival (308 days) than cases that failed to stain (763 days). The EGFR-positive cases showed shorter mean survival (387 days) than the negative cases (547 days), but this difference did not reach statistical significance. The EGFR positivity did not further reduce survival in HER-2/neu-positive cases (362 days). The results of this study support the hypothesis that the expression of HER-2/neu may be a significant predictor of prognosis in patients with gastric carcinoma. Our findings also suggest that expression of these two closely related protooncogenes in malignant and benign gastric tissues is independent of each other and that EGFR does not potentiate the oncogenic effect of HER-2/neu.

The effect of phenobarbital (PB) and beta-naphthoflavone (beta-NF) on acetaminophen (APAP)-induced hepatotoxicity was evaluated in obese and lean Zucker rats. In addition, the consequences of APAP overdose on hepatic CYP2B1/2B2 enzyme activities following PB treatment were assessed. A single oral dose of APAP 3 g/kg (total body weight) was administered to both littermates 24 hr after the last dose of PB or beta-NF. Histologic evidence of hepatocellular necrosis and serum hepatic aminotransferase enzymes 48 hr after APAP administration was utilized to evaluate hepatic damage. Hepatic microsomal total cytochrome P450 concentrations, alkoxyresorufin O-dealkylase activities, and 16 beta-testosterone hydroxylase activities were determined to evaluate the effect of APAP overdose on cytochrome P450 enzyme-substrate activities in the presence and absence of PB treatment. APAP overdose produced lower hepatotoxicity in the obese Zucker rat compared to lean controls. A similar trend was observed in animals treated with PB prior to APAP administration. In contrast, beta-NF treatment produced potentiation of APAP toxicity and/or death of both obese and lean Zucker rats. Generally, APAP overdose produced reduction of hepatic cytochrome P450 enzyme-substrate activities. However, obese Zucker rats retained a higher percentage of their pre-APAP-treated enzyme activities which is consistent with the observation that obese Zucker rats are less affected by the hepatotoxic effects of APAP overdosage.