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From Conventional to Stealth Liposomes a new Frontier in Cancer Chemotherapy
Tumori - Tập 89 Số 3 - Trang 237-249 - 2003
Luigi Cattel, Maurizio Ceruti, Franco Dosio

Many attempts have been made to achieve good selectivity to targeted tumor cells by preparing specialized carrier agents that are therapeutically profitable for anticancer therapy. Among these, liposomes are the most studied colloidal particles thus far applied in medicine and in particular in antitumor therapy. Although they were first described in the 1960s, only at the beginning of 1990s did the first therapeutic liposomes appear on the market. The first-generation liposomes (conventional liposomes) comprised a liposome-containing amphotericin B, Ambisome (Nexstar, Boulder, CO, USA), used as an antifungal drug, and Myocet (Elan Pharma Int, Princeton, NJ, USA), a doxorubicin-containing liposome, used in clinical trials to treat metastatic breast cancer. The second-generation liposomes (“pure lipid approach”) were long-circulating liposomes, such as Daunoxome, a daunorubicin-containing liposome approved in the US and Europe to treat AIDS-related Kaposi's sarcoma. The third-generation liposomes were surface-modified liposomes with gangliosides or sialic acid, which can evade the immune system responsible for removing liposomes from circulation. The fourth-generation liposomes, pegylated liposomal doxorubicin, were called “stealth liposomes” because of their ability to evade interception by the immune system, in the same way as the stealth bomber was able to evade radar. Actually, the only stealth liposome on the market is Caelyx/Doxil (Schering-Plough, Madison NJ, USA), used to cure AIDS-related Kaposi's sarcoma, resistant ovarian cancer and metastatic breast cancer. Pegylated liposomal doxorubicin is characterized by a very long-circulation half-life, favorable pharmacokinetic behavior and specific accumulation in tumor tissues. These features account for the much lower toxicity shown by Caelyx in comparison to free doxorubicin, in terms of cardiotoxicity, vesicant effects, nausea, vomiting and alopecia. Pegylated liposomal doxorubicin also appeared to be less myelotoxic than doxorubicin. Typical forms of toxicity associated to it are acute infusion reaction, mucositis and palmar plantar erythrodysesthesia, which occur especially at high doses or short dosing intervals. Active and cell targeted liposomes can be obtained by attaching some antigen-directed monoclonal antibodies (Moab or Moab fragments) or small proteins and molecules (folate, epidermal growth factor, transferrin) to the distal end of polyethylene glycol in pegylated liposomal doxorubicin. The most promising therapeutic application of liposomes is as non-viral vector agents in gene therapy, characterized by the use of cationic phospholipids complexed with the negatively charged DNA plasmid. The use of liposome formulations in local-regional anticancer therapy is also discussed. Finally, pegylated liposomal doxorubicin containing radionuclides are used in clinical trials as tumor-imaging agents or in positron emission tomography.

Radiation Therapy for Pituitary Metastasis: Report of Four Cases
Tumori - Tập 98 Số 1 - Trang e1-e6 - 2012
Aruna Turaka, Rosaleen B. Parsons, Mark K. Buyyounouski
Aims and Background

To report the clinical outcomes of four patients with pituitary metastases treated with radiotherapy.

Methods

Retrospective chart review of four cases.

Results

The mean age of the patients was 66 years; two were women and two were men. The mean duration of symptoms at initial presentation of the primary tumor was 2.25 months. The location of the primary tumor was the breast in one case and the lung in three. Magnetic resonance imaging of the brain revealed sellar masses in all cases. The mean interval between the primary tumor diagnosis and the development of pituitary metastases was 22.5 months. The metastases were treated with radiation therapy (palliative/stereotactic/intensity modulated) at a mean dose of 3219 cGy. At the last follow-up, three patients were dead and one was alive.

Conclusions

Treatment with three-dimensional conformal radiotherapy or stereotactic radiotherapy is a suitable non-surgical option for patients with pituitary metastases.

Pituitary Metastasis Mimicking a Macroadenoma from Carcinoma of the Larynx: A Case Report
Tumori - Tập 87 Số 6 - Trang 451-454 - 2001
M.C. Uzal, Zafer Koçak, Latife Doğanay, Fusun Tokatlı, Murat Çaloğlu, Cumhur Kılınçer

Metastatic tumors of the pituitary gland are not commonly diagnosed during life in cancer patients. The occurrence of symptomatic lesions is also very unusual and difficult to differentiate clinically and radiologically from pituitary adenomas. Furthermore, a single intrasellar metastasis from laryngeal carcinoma mimicking a pituitary adenoma is an extremely rare pathological finding. We report on the clinical, radiological, and pathological findings in a patient with laryngeal carcinoma who had a symptomatic solitary pituitary gland metastasis that was recognized antemortem.

Neoadjuvant volumetric modulated arc therapy in rectal cancer and the correlation of pathological response with diffusion-weighted MRI and apoptotic markers
Tumori - Tập 104 Số 4 - Trang 266-272 - 2018
Necla GÜRDAL, Merdan Fayda, Nijat Alishev, Barış Bakır, Didem Taştekin, Nuri Faruk Aykan, Uğur Gezer, Emre Balık, Esra Sağlam, Ethem Nezih Oral, Mine Güllüoğlu, Ahmet Kızır
Purpose:

In this prospective observational study, we aimed to report the applicability and tolerability of neoadjuvant volumetric modulated arc therapy with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in patients with locally advanced rectal cancer (LARC), and to evaluate the correlation of pathological response with apparent diffusion coefficient (ADC) measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and apoptotic markers.

Methods:

The study enrolled 30 patients with T3 to T4 and/or N+ rectal cancer who preoperatively received SIB-VMAT and concurrent chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers including the nucleosomes and cell-free DNA fragments in the serum samples were examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC measurements on the DW-MRI were analyzed.

Results:

No patients had acute or chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in 8 patients (27%), while in 10 patients (33%) near-complete pathological response was obtained. Posttreatment ADC was significantly higher in patients with pCR compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3% for distinguishing the patients with pCR from other responders. On the other hand, posttreatment DNA integrity values were revealed lower than the pretreatment values (p = 0.36). Also, the results revealed an insignificant increase in the posttreatment serum level of nucleosomes (p = 0.72).

Conclusions:

Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible treatment regimen in LARC with tolerable side effects, and improved local control rate and pCR rate.

Sentinel Lymph Node Biopsy in Breast Cancer: Review on Various Methodological Approaches
Tumori - Tập 99 Số 2 - Trang 149-153 - 2013
Baha Zengel, Ülkem Yararbaş, Ahmet Sirinocak, Güliz Özkök, Ali Galip Deneclı, Hakan Postacı, Adam Uslu
Aims and background

Sentinel lymph node biopsy has been accepted as a standard procedure for early stage breast cancer. In this retrospective analysis, the results obtained with different methodological approaches using radiocolloid with or without blue dye were examined.

Methods

A total of 158 sentinel lymph node biopsies were performed in 152 patients. Group A (85 patients) underwent lymphatic mapping using a combination of periareolar intradermal radiocolloid and subareolar blue dye injections. Group B (73 patients) underwent only periareolar intradermal radiocolloid injection. One large tin colloid and two small radiocolloids (nanocolloid of serum albumin -NC- and colloidal rhenium sulphide -CS-) were used.

Results

Successful lymphatic mapping was attained in 157 of 158 procedures (99.4%). Radiocolloids localized sentinel lymph nodes in 99.4% and blue dye in 75.3% of the cases. The number of sentinel lymph nodes removed was greater in nanocolloid and colloidal rhenium sulphide groups ( P ≤0.05). Among 60 metastatic sentinel lymph nodes, frozen section analysis using hematoxylin and eosin staining failed to detect 1 macro- and 10 micrometastasis. Radiocolloid uptake was higher in sentinel lymph nodes accumulating blue dye (1643 ± 3216 counts/10 sec vs 526 ± 1284 counts/10 sec, P <0.001). Higher count rates were obtained by using larger sized colloids (median and interquartile range: tin colloid, 2050 and 4548; nanocolloid, 835 and 1799; colloidal rhenium sulphide, 996 and 2079; P = 0.01). Only 2 extra-axillary sentinel lymph nodes were visualized using periareolar intradermal injection modality.

Conclusions

Radiocolloids were more successful than blue dye in sentinel lymph node detection. More sentinel lymph nodes were harvested with small colloids, but different sized radiocolloids were similarly successful. Sentinel lymph nodes having higher radiocolloid uptake tended to accumulate blue dye more frequently. Sentinel lymph nodes manifested higher count rates when a larger colloid was used. Frozen section was very successful in detecting macrometastatic disease in sentinel lymph nodes, but the technique failed in most of the micrometastates.

Medical Management of Colorectal Carcinomas
Tumori - Tập 80 Số 1 - Trang 1-11 - 1994
Claire F. Verschraegen, Richard Pazdur

Current information on the medical treatment of colorectal cancer was reviewed after a search of the literature through Medline. Publications from 1984 to present were surveyed. Appropriate adjuvant therapy increases overall survival and disease-free intervals. The treatment modalities of unresectable or metastatic tumors are disappointing, with at best 40% of patients experiencing short-lasting responses. Whenever possible, patients with advanced colorectal cancer should be enrolled in clinical trials.

Detection of somatostatin receptor subtypes 2 and 5 by somatostatin receptor scintigraphy and immunohistochemistry: Clinical implications in the diagnostic and therapeutic management of gastroenteropancreatic neuroendocrine tumors
Tumori - Tập 97 Số 5 - Trang 620-628 - 2011
Francesco Sclafani, Carlo Carnaghi, Luca Di Tommaso, Marcello Rodari, Annarita Destro, Lorenza Rimassa, Laura Giordano, Arturo Chiti, Massimo Roncalli, Armando Santoro
Aims and background

Somatostatin receptor scintigraphy (SRS) is the standard method for the detection of somatostatin receptors (SSTRs). It is commonly used in gastroenteropancreatic neuroendocrine tumor (GEP-NET) staging, and represents the criterion of choice for treatment with somatostatin (SST) analogs. Immunohistochemistry (IHC) was reported as a reliable method for the detection of SSTRs with theoretically superior sensitivity over SRS.

Methods and study design

We retrospectively analyzed the sensitivity and specificity of IHC in the detection of SSTRs in a cohort of consecutive patients with GEP-NETs attending our Institute from 1997 to 2007. IHC analysis was restricted to SSTR2 and SSTR5, and the results were interpreted according to two different scoring systems. SRS was used as the gold standard.

Results

Forty-four patients were enrolled; 24 (55%) had foregut carcinoids, 9 (20%) midgut carcinoids, 2 (5%) hindgut carcinoids, and 9 (20%) had GEP-NETs of unknown primary sites. A high concordance rate between IHC and SRS was shown, irrespective of the IHC scoring system applied (73% and 70%). The sensitivity of IHC was 89.3% and 78.6% and the specificity 43.8% and 50%, depending on the scoring system used.

Conclusions

Although SSTR2 was shown to be expressed by IHC in up to 50% of tumors not visualized by SRS, SRS still remains the method of choice in the diagnostic and therapeutic management of GEP-NETs. More pathological and clinical data are needed to properly understand the clinical relevance of immunohistochemical detection of SSTR expression in the absence of tumor uptake at SRS.

Ovarian Function Suppression with the Gonadotrophin-Releasing Hormone (GnRH) Analogue Goserelin in Premenopausal Advanced Breast Cancer
Tumori - Tập 80 Số 1 - Trang 28-32 - 1994
Emilio Bajetta, Luigi Celio, Nicoletta Zilembo, Aldo Bono, Domenico Galluzzo, Maria Giulia Zampino, Alessandra Longhi, Leonardo Ferrari, Roberto Buzzoni
Aims and background

Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue that induces the suppression of gonadal steroidogenesis, and it could therefore be a medical alternative to irreversible surgical castration. We report the clinical and endocrine results from 40 goserelin-treated premenopausal patients with advanced breast cancer.

Methods

A depot formulation of the drug (3.6 mg s.c.) was administered fortnightly for the first 4 doses, and monthly thereafter. Gonadotrophins and estradiol (E2) levels were measured before and at specific times during the treatment.

Results

Objective responses were observed in 17 of the 38 evaluable patients (45%), six of whom achieved complete remission. The best responses were observed on soft tissues (65%). Castration E2 levels were achieved in all of the patients.

Conclusions

Our results confirm that goserelin is as effective as surgical oophorectomy in premenopausal advanced breast cancer.

Peritoneal Cystic Mesothelioma: A Case Series
Tumori - Tập 89 Số 1 - Trang 31-35 - 2003
Kayomarz Sethna, Faheez Mohamed, Pierre Marchettini, Dominique Élias, Paul H. Sugarbaker
Background

Cystic peritoneal mesothelioma is a rare disease associated with a favorable short-term prognosis. Longer follow-up documenting a persistence of symptoms and a high rate of recurrence after debulking surgery along with an uncertain natural history prompt a re-evaluation of prior treatment recommendations. No prior long-term clinical study of these patients is available.

Methods

The experience with five cases of cystic peritoneal mesothelioma, four females and one male, are reviewed. All of these patients were treated with cytoreductive surgery with peritonectomy procedures and heated intraoperative intraperitoneal chemotherapy. CT, pathology and current status were investigated in order to learn more about the natural history of this disease.

Results

All patients were symptomatic from abdominal distention and three of the four complained of severe pain. Female patients complained of long periods of recurrent abdominal and pelvic pain poorly managed by oral analgesics. In one patient prolonged conservative management over ten years resulted in transition to an invasive process with extensive lymph nodal metastases. Her prognosis for long-term survival is guarded because of mesothelioma extension into the chest. Disease control of both ascites and pain in the abdomen and pelvis was achieved in all five patients treated with cytoreductive surgery plus intraperitoneal chemotherapy.

Conclusions

Cystic peritoneal mesothelioma should no longer be referred to as “benign” cystic mesothelioma. An aggressive approach with complete disease eradication is the correct goal of treatment. From our experience, cytoreductive surgery to remove all visible tumor and intraperitoneal chemotherapy to control microscopic residual disease will help patients with peritoneal cystic mesothelioma to remain symptom- and disease-free over an extended time period with a single surgical intervention. Disease eradication may prevent the transition to an aggressive and fatal disease process.

Thin-Walled Cysts as a Pathognomonic CT Finding in Cystic Mesothelioma
Tumori - Tập 94 Số 1 - Trang 14-18 - 2008
Paul H. Sugarbaker, Tristan D. Yan, Luis Zappa, Namik Haveric, Erwin A. Brun
Aim

Cystic mesothelioma is a rare disease that results in abdominal distention and poorly defined abdominal pain. Diagnosis has always been made by tissue biopsy rather than by radiologic studies.

Materials and methods

Our experience with 7 patients with cystic mesothelioma includes 4 patients who had not had prior surgery before the performance of a high resolution CT scan. A special review of the radiology of these cases was performed in order to identify any pathognomonic signs of this disease.

Results

In all patients who did not have a distortion of the radiologic images (as a result of surgical interventions) prior to the performance of a high resolution CT scan at our institution, a pathognomonic thin-wall cystic structure located within the gelatinous appearing mass was observed. These thin-walled cysts were of variable size and preferentially located within the greater omentum, pelvis and beneath the right hemidiaphragm.

Conclusion

Cystic mesothelioma can be diagnosed preoperatively by a high resolution abdominal and pelvic CT. The thin-walled cysts with great variation in size are located beneath the right hemidiaphragm, within the greater omentum and in the pelvis. No other disease with these radiologic findings has been identified.

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