Neuroendocrine differentiation in castration-resistant prostate cancer: A case report.

The most common type of prostate cancer is acinar adenocarcinoma, which is androgen-dependent and, therefore, treated with chemical or surgical castration and androgen receptor inhibition. However, the disease usually progresses to castration-resistant prostate cancer (CRPC). A neuroendocrine pattern is frequently observed in the cellular composition of CRPC, which is considered to emerge as an effect of androgen deprivation therapy. This is the case report of a 69-year-old patient with prostate adenocarcinoma, who, after an initial period of disease control with radiotherapy and antiandrogens, was diagnosed with CRPC with high levels of prostate-specific antigen (PSA), unresponsive to androgen inhibition, with accompanying lung and osseous metastases. Bronchial biopsy of the lung metastasis revealed infiltration by non-small-cell adenocarcinoma of prostatic origin with neuroendocrine characteristics. On somatostatin receptor scintigraphy with 99mTc-octreotide, there was high uptake by almost all known lung and osseous metastases. The patient was subsequently treated with a combination of docetaxel and octreotide, and a partial response was observed 6 months later, with reduction of the PSA level and the size of the lung metastasis. The aim of the present study was to provide a clinical example of the previously demonstrated, in vitro and in vivo, synergistic antitumor activities of docetaxel and octreotide in cases of CRPC selected by means of histological confirmation of their neuroendocrine nature and somatostatin receptor scintigraphy.

Samarium-153Sm-EDTMP as an equivalent variant to pharmaceutical analgesic treatment.

PURPOSE: Cancer pain is the most serious symptom for patients, especially during their terminal phase, when palliative medicine is needed. Our study tried to verify the usefulness of single-shot intravenous administration of Samarium (Sm)-153EDTMP in patients with bone metastases (group-A, N=53, males=25, females=28, age range: 30-69 years), as well as to compare a series of variables, using as a control group (group-B, N=37, males=17, females=20, age range: 30-69 years) with patients who were under drug treatment given from a physician specialized in palliative medicine. METHODS: Both groups answered the following questionnaires: Greek Brief Pain Inventory (GBPI), Brief Multidimensional Life Satisfaction Scale (BMLSS), Hospital Anxiety Depression Scale (HADS) and ECOG performance status. RESULTS: Pain severity and pain interference improvement p=0.0005 for both groups. HADS-anxiety: Samarium group, p= 0.397, drugs group p= 0.031. HADS-depression improvement for both groups p=0.031 and p=0.003, respectively. BMLSS improvement p=0.029 and p=0.265, while EGOG PS improvement was p=0.005 and p=0.014, respectively (numeric values). CONCLUSION: Intravenous administration of Sm-153EDTMP was equivalent to drug treatment against cancer pain for patients with multiple bone metastasis, an option for those patients who are intolerant or resistant to drug treatment. Samarium-treated patients needed less or not at all pain killers, having a better cost-effective result.

Management of metastatic bone pain with repeated doses of rhenium 186-HEDP in patients under therapy with zoledronic acid: a safe and additively effective practice.

PURPOSE: The aim of this study was to compare pain response and hematologic toxicity between single and multiple therapies with (186)Re-HEDP under zoledronic acid in patients suffering from painful osseous metastases from prostate or breast cancer. MATERIALS AND METHODS: Forty-five (45) patients received multiple therapies of (186)Re-HEDP (n = 77), under a stable regimen of analgesics and zoledronic acid, far off other therapeutic manipulations, and with no extraosseous disease progression. Hematologic status and pain indices were followed up regularly. RESULTS: Evaluable patients (n = 12), received 31 (186)Re-HEDP therapies. After the first treatment with (186)Re-HEDP, the mean percentile decrease for hemoglobin was 4.7%, for white blood cells was 21.4%, and for platelets was 12%. After multiple therapies, the respective declines were 7.0%, 16.0%, and 23.4%. With respect to baseline blood counts, only thrombocytes showed a tendency for greater decrease after repeated treatments, yet not of clinical significance. Favorable clinical response occurred after the first therapy in 10 of 12 patients (83.3%), after multiple doses in 15 of 19 (78.9%), and overall in 25 of 31 (80.6%) of (186)Re-HEDP therapies. Significant post-therapy improvement in pain indices was observed in all cases, regardless of the number of therapeutic doses. CONCLUSIONS: Retreatments with (186)Re-HEDP under zoledronic acid provide continuing effectiveness in metastatic bone pain and are safe enough, if an acceptable baseline hematologic status exists.

Trastuzumab plus paclitaxel or docetaxel in HER-2-negative/HER-2 ECD-positive anthracycline- and taxane-refractory advanced breast cancer.

Trastuzumab is considered effective against human epidermal growth factor receptor (HER)-2-positive breast cancer as assessed by immunohistochemistry (IHC) and fluorescence or chromogenic in situ hybridization (FISH/CISH) on biopsy material. Trastuzumab is now approved in both the adjuvant and metastatic settings for this patient population. Because HER-2 extracellular domain (ECD) levels have been correlated with disease progression in the metastatic setting, we considered trastuzumab salvage therapy plus a taxane in heavily pretreated trastuzumab-naive relapsed breast cancer patients with high serum levels of HER-2 ECD (> or =15 ng/ml). All patients had previously failed at least two lines of anthracycline- and taxane-based regimens and were HER-2 negative by IHC and FISH/CISH prior to a centralized reanalysis, and were serum positive for HER-2 ECD (> or =15 ng/ml) at baseline. Regular serum accounts of HER-2 ECD were recorded and compared with response and survival outcomes. Twenty-two patients were finally eligible for salvage therapy. Minor responses were observed in five (23%) and stable disease (SD) was observed in 11 patients, leading to a clinical benefit rate of 73% (16 of 22 patients). The median time to progression and overall survival time were 5 (6.5 months in minor responders and SD) and 12 months, respectively; 11 and eight patients remained progression free for >6 and >12 months, respectively. Eleven and seven patients were alive at 12 and 15 months, respectively, after treatment start. Furthermore, in total, 13 (59.1%) patients obtained a biochemical response. In our study, patients with conventionally HER-2-negative disease but with expression of HER-2 ECD above the normal limit (> or =15 ng/ml) displayed a rapid response, both biochemically and clinically, to the trastuzumab-taxane combination. This is the first study assessing anti-HER-2-based treatment in HER-2-negative advanced breast cancer according to HER-2 ECD positivity; if our results are confirmed, additional patients with "hidden" HER-2-positive breast cancer might benefit from anti-HER-2 treatment.

Jaw uptake of technetium-99 methylene diphosphonate in patients on biphosphonates: a word of caution.

Nitrogen-containing biphosphonates are a group of medications that are increasingly used in the management of Paget's disease, fibrous dysplasia, osteoporosis, multiple myeloma and metastatic prostate or breast cancer bone disease. On 2004 it was established that nitrogen-containing biphosphonates may induce jaw osteonecrosis and since then, a substantial number of publications has supported this finding. Jaw osteonecrosis may be asymptomatic, lasting for about a year or symptomatic, accompanied with mild or severe pain. Jaw osteonecrosis usually results in patients with poor dental hygiene, or subjected to invasive dental procedures. Its incidence increases with the length of nitrogen-containing biphosphonates treatment and appears to be higher for the Zometa(TM) users. It is important to early recognize this entity, since early intervention can make a significant difference to the outcome of this debilitating side effect. We here report three patients who had a positive technetium-99m methylene diphosphonate ((99m)Tc-MDP) bone scan. One of these patients also had osteomyelitis and was treated aggressively. The other two were treated in a more conservative manner. Detailed dental examination supported the scintigraphic findings. Biopsy was performed only in one patient and also offered specimens for antibiotic cultures. In discussion, jaw biopsy is a debatable procedure in the setting of jaw osteonecrosis and many consider that it should be avoided in most cases, except if it is necessary to establish the diagnosis and suggest antibiotic treatment by obtaining samples for bacterial cultures. Although axial tomography and magnetic resonance imaging are useful in defining the extent of the disease, 3-phase (99m)Tc-MDP bone scan is the most sensitive imaging modality pinpointing the disease at its early stages. In conclusion, a 3-phase (99m)Tc-MDP scan with anterior and lateral views of the skull is indicated in all symptomatic or asymptomatic patients, with a history of long-term nitrogen-containing biphosphonate treatment, since this may lead to an early detection of the disease.

Trapping of technetium-99m albumin macroaggregate and other four radiopharmaceuticals by blood clots in vitro.

Radiopharmaceuticals are known to interact with the blood components (i.e. the red blood cells, serum proteins etc) but so far, there have been no data regarding their purely mechanical trapping in thrombi. The experiments presented in this communication provide evidence that the technetium-99m labeled albumin macroaggregate ((99m)Tc-MAA), apparently due to its particle size, can be almost quantitatively retained in the in vitro model described. These results can be extrapolated in vivo and offer a plausible explanation for either the "hot spot" artifact, occasionally seen in lung perfusion imaging or for the partial trapping of (99m)Tc-MAA by a thrombus at the tip of a subclavian catheter, as has been recently reported. Control experiments were also run using (99m)Tc-methylene diphosphonate ((99m)Tc-MDP), (99m)Tc(III)-dimercaptosuccinic acid ((99m)Tc(III)-DMSA), (99m)Tc-methoxyisobutyl isonitrile ((99m)Tc-MIBI) and sodium pertechnetate (Na(99m)TcO(4)), in order to study the extent of trapping of these radiopharmaceuticals under identical incubation conditions. (99m)Tc-MDP and (99m)Tc(III)-DMSA exhibited the lowest blood clot uptake (partially non-specific and partially mechanical trapping), while in the case of (99m)Tc-MIBI and Na(99m)TcO(4), besides mechanical and non-specific clot-trapping, transport and retention inside the red blood cells was also observed.

[The importance of the tumor marker CYFRA 21-1 in patients with lung cancer after surgery or chemotherapy].

Lung cancer is the most common cancer worldwide with 900,000 new cases each year in men and 330,000 in women, being also the major cause of death from cancer. In Greece about 4,000 persons die every year due to lung carcinoma. One of the major problems in the follow up of these patients is the difficulty of early detection of recurrent disease. Tumor markers are of particular interest in this respect. Cytokeratines, especially fragment 19, are specified epithelial tissue-proteins that show increased levels in patients with carcinomas. CYFRA 21-1 assays determine the serum cytokeratin 19 fragment. The aim of our study was to evaluate the importance of serum CYFRA 21-1 studied by immunoradiometric assay in patients with various types of lung cancer after surgery or chemotherapy. Ninety-six consecutive patients were studied during a two years period. Forty-five of them had small cell lung cancer (SCLC) and 51 had non-small cell lung cancer (NSCLC). Moreover, 52 healthy individuals were studied to estimate the cut off value of CYFRA 21-1. Increased serum levels of the marker were found in patients with lung cancer compared to controls (P<0.001). The cut off value was estimated as 3.3 ng/ml with 96% specificity. Before the treatment there was no difference in the sensitivity of CYFRA 21-1 for patients with SCLC (21/45 patients had increased CYFRA 21-1 levels, 47%) and for patients with NSCLC (27/51 had increased levels, 52%). Also, before treatment there was a higher sensitivity in NSCLC than in SCLC and especially in SCC among other histotypes of NSCLC when different stages of the disease were compared. Patients with extended disease, metastatic or recurrent disease had also more increased levels of the marker (P<0.001). One month after surgical ablation of the primary lung lesion, 28/58 patients showed a drop in the levels of the marker as an indication of the tumor ablation. From the 58 operated patients 35 relapsed and 31/35 showed an increase in CYFRA-21-1 levels with a sensitivity of 92% and specificity of 95%. From the 38 patients that underwent chemotherapy treatment, 24 had a depravation of the disease and 21/24 had a great increase of serum CYFRA 21-1 with a sensitivity of 89% and specificity of 94%. In conclusion, CYFRA 21-1 is a useful tumor marker before and after surgical treatment in lung cancer.

A large intra-atrial thrombus detected during a lung perfusion scan with technetium-99m macroaggregated albumin injected through the subclavian venous line.

A sixty five year old female patient carrying a double lumen subclavian catheter, with severe right-sided heart failure, was subjected to lung perfusion scan in order to rule out pulmonary embolism. Administration of Tc-99m macroaggregate albumin ((99m)Tc-MAA), via a double lumen (Hickman) subclavian line, resulted in trapping almost half of the injected dose in the right atrium, at the tip of the subclavian catheter. There was no evidence of pulmonary embolism. This finding was interpreted as consistent with the presence of a large intra-atrial thrombus. This thrombus, despite the thrombolytic treatment that followed, was detached and caused cardiac arrest and eventually the death of the patient. Autopsy showed a massive pulmonary embolus. This report suggests, that injecting (99m)Tc-MAA for a lung perfusion study via the central venous line, may result in the early detection of a thrombus, as in this case at the tip of the catheter and this may be life saving for the patient. We have been unable to find in the literature a similar case of a thrombus detected by the iv administration of (99m)Tc-MAA.

[Serum levels of S-100b protein after four years follow-up of patients with melanoma].

The early detection of the recurrence and of distant metastases of melanoma can be supported by the detection of S-100 in the serum. In this study we have evaluated the diagnostic significance of the levels of S-100b as a tumor marker in the diagnosis and the follow-up of patients with melanoma. We have studied 27 patients (15 men and 12 women) aged 29-58 years (mean age +/- SD: 46 +/- 11 years) with melanoma in stages I-IV, as shown by histology. The thickness of the tumor was >0.75 mm according to Breslow. Thirty-two healthy individuals 19 men 13 women aged 29-52 years (mean age +/- SD: 44 +/- 9 years) were our control group. Serum samples of S-100b were measured by radioimmunoassay (RIA) every three months during the first and second year, and every six months for the next two years. All patients were operated after the first diagnosis. Our results have shown a cut-off of S-100b values between controls and patients of 0.2 micro g/l. The overall sensitivity and specificity for the diagnosis of melanoma for all stages was 71% and 94% respectively. Patients with recurrence or distant metastases had significantly higher levels of S-100b as compared to those without metastases or recurrence (P<0.05) and to healthy individuals (P<0.05). In 11 patients with elevated serum S-100b levels, after treatment and during the follow up period, these levels were reduced to normal. In conclusion, although the number of our patients was limited, serum S-100b showed after four years of follow up to be useful in stages III and IV of melanoma, in the diagnosis of relapse or metastases and in monitoring the response to treatment.

[Procollagen-I, collagen telopeptide I, CEA, CA 15-3 as compared to bone scintigraphy in patients with breast cancer].

UNLABELLED: The most common metastases of breast cancer (BC) are bone metastases. Serum pro-Iota collagen peptide (PICP) and I collagen telopeptide (ICTP) levels indicate the rate of bone collagen synthesis and bone resorption respectively and therefore indicate metastatic activity in the bone. We have studied the clinical importance of serum PICP and ICTP as well as CA 15-3 and CEA and compared them to bone scintigraphy findings indicating metastases from BC. Ninety seven women of mean age 58+/-8 years with BC were examined. The diagnosis of BC was histologically confirmed. Bone metastases were diagnosed in 68 of them by bone scans performed after the intravenous injection of 925 MBq of technetium-99m methylendiphosphonate, while 29 patients were free from bone metastases. We also examined 52 women of similar age, as controls. Serum PICP, ICTP, CA 15-3 and CEA were measured in both patients and controls. Serum levels of ICTP and CA 15-3 were significantly higher in patients with BC and bone metastases compared to patients without metastases (P<0.05), while PICP and CEA were only marginally higher. A statistically significant correlation was observed between the existence of bone metastases and ICTP serum levels (P<0.05). The sensitivity of PICP, ICTP, CEA and CA 15-3 was 28.1%, 48.6%, 78%, 42% respectively and their specificity was 83.9%, 94%, 65% and 86% respectively. IN CONCLUSION: ICTP and CA 15-3 are the most reliable markers of those studied for the diagnosis of bone metastases in BC. PICP alone or combined with ICTP were not sensitive enough. CA 15-3 showed sensitivity 78% and specificity 86%. When combining CA 15-3, ICTP and CEA the sensitivity and specificity increased to 82% and 96% accordingly.

Positive Tc-99m-MIBI scan in a patient with confirmed Paget's disease of bone.

A 46-year-old man was referred to our department for a Tc-99m MDP bone scan after he was admitted to our hospital with diffuse bone pain and the subsequent finding of multiple mixed type (lytic-blastic) lesions on routine x-rays. The Tc-99m MDP scan was highly suspicious for malignancy and, therefore, a Tc-99m MIBI scan was performed, which also revealed abnormal uptake in all regions with increased osteoblastic activity. Clinical chemistry and further workup revealed a highly elevated serum alkaline phosphatase and increased excretion of hydroxyproline in the urine. The presumed diagnosis of Paget's disease of the bone was further confirmed by biopsy.

The role of 99mTc(V)-DMSA scan as compared to 99mTc-MDP and CT scans in imaging the primary tumor and metastases of osteosarcoma.

The oncophilic complex of technetium-99m labeled pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) has been successfully used for the detection of primary and metastatic medullary thyroid cancer and for imaging various soft tissue tumors like lung, brain and prostate cancer. In this article, the role of 99mTc(V)-DMSA in the diagnosis of the primary tumor and metastases of osteosarcoma patients as compared to the 99mTc-MDP scan and the CT scan was studied. Twenty-eight patients with bone disease were referred to the Nuclear Medicine Department of Saint Savas Oncology Hospital in Athens from the Orthopedics Department of the same Hospital. From them, 18 (Group A) had osteosarcoma, 7 (Group B) osteomyelitis and 3 (Group C) bone fractures. The final diagnosis was made after fine needle aspiration biopsy. All patients were subjected to the 99mTc(V)-DMSA scan, the standard bone scan (99mTc-MDP) and CT scan. Group A patients showed a selective uptake of 99mTc(V)-DMSA in the primary tumor region. No abnormal 99mTc(V)-DMSA uptake was observed in the patients of Groups B and C. The 99mTc(V)-DMSA scan was found to be superior to the 99mTc-MDP and the CT scans in identifying metastases of osteosarcoma. Sensitivity was 100%, 86% and 98% respectively.

[Correlation of procollagen (I) with prostate specific antigen and bone scan for the diagnosis of bone metastases in patients with prostate carcinoma]. / In Process Citation.

Procollagen (I) carboxyterminal propeptide (PICP) is a metabolite of procollagen, a precursor molecule of collagen type I, which accounts for more than 90% of the organic matrix of the bones. Serum PICP levels indicate the rate of bone collagen synthesis and therefore the osteoblastic activity. In this study we evaluate the clinical usefulness of serum PICP as an indicator of bone metastases in patients with prostate cancer in relation to bone scan and to prostate specific antigen (PSA) measurements. We found no similar study in the literature relating these three tests. Seventy-eight patients (median age 63+/-4,3 years) with prostate adenocarcinoma were examined. The diagnosis was confirmed histologically. Bone metastases were diagnosed in 42 (54%) of them assessed by bone scans (Group A), while the remaining 36 patients (46%) had no bone metastases (negative bone scans and X-rays) (Group B). We also examined 21 patients with benign prostate hyperplasia as a control group (Group C). All patients had serum PICP measurements, bone scans with (99m)Tc-MDP and PSA measurements. None of them had a history of disease or of using drugs known to affect bone metabolism. Serum levels of PICP were assayed by a radioimmunoassay (RIA) kit (Orion Cooperation, Farmos Diagnostics, Finland). Serum PSA was also tested by a RIA kit (Tandem-R, Hybritech Inc, USA). PICP levels in Group A were 265+/-89 microg/l, in Group B 128+/-39 microg/l and in Group C patients 110+/-48 microg/l. High levels of PICP above 170 microg/l, were diagnostic of bone metastases with sensitivity 54%, specificity 93% and accuracy 84%. In comparison, PSA levels above 4 ng/ml were also diagnostic with a sensitivity of 68%, specificity of 91% and accuracy 88%. Patients with low levels of PICP, lower than 90 microg/l, n=31, had no bone metastases. The positive prognostic value of bone scan was 74% with a sensitivity of 76%, specificity of 58% and accuracy 71%. Positive bone scans combined with very high levels of PICP and PSA, had positive prognostic value 97%, with sensitivity of 78%, specificity of 96% and accuracy 97%, while bone scans with levels of PICP lower than 170 microg/l, had positive prognostic value of 32%. Levels of PICP and PSA were significantly higher in patients with prostate cancer and bone metastases in comparison to patients with benign prostate hyperplasia (P<0.0001) respectively. Also, levels of PICP and PSA were higher in patients with prostate cancer without metastases as compared to prostate hyperplasia (P<0.0005 and P<0.0001 respectively) (Wilcoxon-Mann-Whitney test). When metastases were more extensive, PICP levels were higher than PSA. It is concluded that PICP as a marker of osteoblastic activity is useful for diagnosing bone metastases of prostate adenocarcinoma but when co-evaluated with PSA and the bone scan, the diagnostic accuracy of these three diagnostic procedures is much higher.