Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT).

BACKGROUND: Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS. PATIENTS AND METHODS: An open-label prospective phase II trial ('PREDICT') in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma. RESULTS: Of 123 subjects who received the MAGE-A3 immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS+). The 1-year OS rate was 83.1%/83.3% in the GS+/GS- populations. The rate of progression-free survival at 12 months was 5.8%/4.1% in GS+/GS- patients. The median time-to-treatment failure was 2.7/2.4 months (GS+/GS-). There was one complete response (GS-) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was similarly immunogenic in both populations and had a clinically acceptable safety profile. CONCLUSION: Treatment of patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an overall 1-year OS rate of 83.5%. GS- and GS+ patients had similar 1-year OS rates, indicating that in this study, GS was not predictive of outcome. Unexpectedly, the objective response rate was lower in this study than in other studies carried out in the same setting with the MAGE-A3 immunotherapeutic. Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3 immunotherapeutic treatment is ongoing in another melanoma study.This study is registered at www.clinicatrials.gov NCT00942162.

The pharmacokinetics of oral oxycodone in patients after total gastric resection.

OBJECTIVE: Oxycodone is a semi-synthetic opioid with a stronger analgesic effect than morphine and codeine. The efficacy of this opioid in the treatment of postoperative pain has been proved in different groups of patients. The drug has a favourable adverse reaction profile, which encourages doctors and patients to use it more and more widely. The drug is also used in the patients who underwent an abdominal surgery, e.g. stomach resection. Gastrectomy leads to pathophysiological changes within the gastrointestinal tract, which may cause changes in the drug absorption. In consequence this leads to a change in the pharmacokinetics and effect of the drug. The aim of the research was an analysis of the pharmacokinetics of oxycodone from prolonged release tablet in patients after total gastrectomy. PATIENTS AND METHODS: The research was carried out on patients after gastrectomy with Roux-en-Y reconstruction. The patients (n=24; mean [SD] age, 67.6 [9.8] years; weight, 69.1 [13.6] kg; and BMI, 25.2 [4.0] kg/m(2)) received oxycodone in a prolonged release tablet in a single orally administered dose of 10 mg. Blood samples were collected within 12 h after the drug administration. The plasma concentrations of oxycodone and noroxycodone were measured with validated high-pressure liquid chromatography coupled with triple tandem mass spectrometery method. RESULTS: The main pharmacokinetic parameters for oxycodone in men (n = 14) and women (n = 10) were as follows: Cmax, 14.40 (3.76) and 11.54 (6.98) ng/ml (p = 0.2066); AUC0-∞, 157.87 (56.89) and 106.44 (61.31) ng´h/ml (p = 0.0460); tmax, 2.18 (0.58) and 2.15 (0.58) h (p = 0.8008), respectively. CONCLUSIONS: Total gastrectomy did not affect the pharmacokinetics of oxycodone administered in prolonged release tablets, but the exposure to the drug was significantly lower in women.

Indocyanine green angiography for evaluation of gastric conduit perfusion during esophagectomy--first experience.

BACKGROUND: A complication of esophageal surgery is leakage at the anastomosis site and one of the factors involved in this complication is poor blood flow in the distal portion of the tube. The aim of this study was to evaluate the feasibility of indocyanine green fluorescence imaging as a method of determining the perfusion of the gastric conduit after esophagectomy. METHODS: We analysed 15 consecutive patients who underwent transhiatal esophagectomy (THE) due to cancer. All of the patients had reconstruction of the gastrointestinal tract using the gastric conduit. Before performing the anastomosis, the blood flow in the area of the tube was evaluated using intravenous indocyanine green and observing its vascular flow with a camera equipped with an infrared laser. RESULTS: In all cases it was possible to visualize the vascular flow of indocyanine green within the region of the gastric tube. The fluorescence imaging system showed vascular insufficiency of the distal gastric conduit in 4 patients--in all of these patients the anastomosis was performed end-to-side and there was no subsequent leak. Leakage at the anastomosis site was observed in 1 patient (6.66%). The leak was observed in the 9th postoperative day, despite visualization of a good vascular supply of the tube. CONCLUSIONS: Indocyanine green fluorescence imaging of gastric tube allows for intraoperative modifications, but it must be noted that the patient's comorbidities and general health may also increase the risk of anastomosis leakage.

Breast cancer sentinel lymph node mapping using near infrared guided indocyanine green and indocyanine green--human serum albumin in comparison with gamma emitting radioactive colloid tracer.

AIMS: Recently, a novel method of using near infrared (NIR) guided indocyanine green (ICG) and ICG conjugated with human serum albumin (ICG:HSA) for sentinel lymph node biopsy (SLNB) of breast cancer patients has shown true potential. The aim of this study was to compare the usefulness of NIR guided ICG and ICG:HSA against the gamma emitting radiocolloid (RC). METHODS: A group of 49 consecutive breast cancer patients underwent SLNB using RC. From this group, the first 28 patients were compared against ICG, while the next 21 patients were compared against ICG:HSA. The number of patients with visible fluorescent path was recorded. Furthermore, the number of SLNs detected by fluorophores percutaneously and total number of intraoperative SLNs detected by fluorophores and/or RC was noted. RESULTS: NIR guided real time lymphatic flow was observed in 47/49 patients (96%). In all cases except one, SLNs detected by the RC tracer were also detected by their respective fluorophore. Additionally, ICG detected 10 additional SLNs in 8 patients, while 3 additional SLNs were detected by ICG:HSA in 3 patients. Statistical analysis revealed no difference between the number of SLNs detected between ICG versus ICG:HSA and RC versus ICG:HSA. However, a significant statistical difference was observed between RC and ICG (p=0.0117), as well as between the combined NIR guided and RC method (p=0.0033). CONCLUSIONS: In conclusion, the use of either ICG or ICG:HSA with RC to obtain SLNB seems to be an effective alternative. Compared to RC alone, the use of ICG:HSA, more so than ICG alone, may provide additional benefits.

The role of sentinel node biopsy in ductal carcinoma in situ of the breast.

AIM: Sentinel node biopsy (SNB) is an accepted alternative to lymphadenectomy in the case of invasive breast carcinoma, although the sentinel node's role in ductal carcinoma in situ (DCIS) diagnosed on core needle biopsy has not been well defined nevertheless guidelines recommend this procedure. The purpose of this study was to determine the diagnostic value of sentinel nodes in female patients with primary DCIS using core needle stereotactic biopsy. MATERIAL AND METHODS: Between the years 2000 and 2005, 261 patients were diagnosed with DCIS by core needle biopsy. In this group, 183 patients underwent SNB to determine lymph node involvement. Those patients with metastases to the sentinel node underwent axillary lymphadenectomy. RESULTS: In the group of 183 patients that underwent SNB, 10 patients (5.5%) showed metastases to the sentinel lymph node. Histopathological studies of the primary lesions of these 10 patients revealed invasive ductal carcinoma in 6 cases (3.5%) and 1 case (0.5%) of invasive lobular carcinoma. Only 3 of the patients (1.5%) were given a final diagnosis of DCIS with metastases to sentinel lymph nodes, of which 2 cases were DCIS and 1 case was DCIS with microinvasion. Axillary lymphadenectomy performed on patients with abnormal SNB showed involvement of other axillary lymph nodes in 4 patients. CONCLUSIONS: SNB as a diagnostic tool in DCIS remains controversial as the number of cases of axillary lymph node metastases is minuscule. The biggest clinical challenge in this situation is a group of patients with primary diagnosis of DCIS in which invasive components are seen by mammotomic biopsy.

Evaluation of the sentinel node biopsy in colorectal carcinoma including the results of immunohistochemical examinations.

AIM: To evaluate the method and results of sentinel node biopsy including immunohistochemical examinations in resectable colorectal cancer. MATERIAL AND METHODS: From April 2004 to April 2005, sentinel node biopsy was carried out with the dye method in 27 patients operated on for colorectal cancer. The standard examination of sentinel nodes consisted in the evaluation of individual H&E-dyed specimens from bisection of the node. The negative sentinel nodes were examined with the use of immunohistochemistry against cytokeratins AE1/AE3. FINDINGS: The sentinel node was identified in 25 patients (92.6%). In a routine histopathological examination it included metastases in 3 cases. The sentinel node was clean in one patient whereas other regional nodes resected "en bloc" with the tumour included metastases. The sensitivity of the method was 75%, and the number of falsely negative results was 25%. Metastases (micrometastases) in the sentinel node were found in 2 other patients (8%) in the immunohistochemical examination. This examination did not change the results of the analysis in the patient with positive non-sentinel nodes and with the negative sentinel node in H&E dyeing. Nevertheless, the sensitivity of the method rose to 83.3% and the number of falsely negative results dropped to 16.7%. CONCLUSIONS: 1. The sentinel node biopsy using the dye method is a safe and relatively easy technique showing a high success rate (92.6%). 2. Low sensitivity of the method, as reflected in the literature, may result from lack of extended histopathological examinations performed on the sentinel node (e.g. immunohistochemistry). 3. Further research is necessary to determine the role and importance of the sentinel node biopsy in colorectal cancer.

[A case of primary lymphangiomyomatosis in retroperitoneal space and lungs]. / Przypadek pierwotnego naczyniaka chlonnego (lymphangiomyomatosis primaria) przestrzeni zaotrzewnowej i pluc.

Authors present a rare case of primary lymphangiomyomatosis. Diagnosis was based on histopathological evaluation. Diagnostic difficulties were caused by lack of pathognomonic symptoms in clinical examination, ultrasonography and CT. The patient has been treated with hormonal medicines (Provera, Megace) since 1997. Now she is in a good condition, She hasn't got any symptoms of progression disease.

[Cases of carcinoid tumor in stomach and retroperitoneal space]. / Przypadki rakowiaka zoladka i przestrzeni zaotrzewnowej.

Authors present two cases of carcinoid localized in stomach and retroperitoneal space. Diagnosis was based on clinical examination, endoscopy, CT and histopathological evaluation. The case of gastric carcinoid was an early lesion (penetrated only mucose and submucose layer of gastric wall). In opposition, second patient had inoperable large tumor localized in retroperitoneal space with multiple metastases to the liver.

Genetically modified tumour vaccines (GMTV) in melanoma clinical trials.

Since melanoma is a model immunogenic malignancy incurable in the disseminated phase of its natural course different immunotherapeutic approaches are tested in clinical trials. A number of tumour vaccines genetically modified (GMTV), with various immunostimulatory factors, are tested in phase I/II clinical trials. These factors include cytokines, tumour antigens (TA), costimulatory molecules or HLA antigens. We have designed a novel, mixed auto/allogeneic cellular melanoma vaccine modified with the IL-6 and the sIL-6R genes. Preclinical studies in a mouse model demonstrated that the IL-6/sIL-6R based vaccine is able to elicit efficient anti-tumour responses, mediated by CD8+ and NK cells, which resulted in inhibition of the tumour growth, metastases formation and prolonged survival of the animals treated. Irradiation of vaccine cells does not only lead to their sterilisation but also causes increased secretion of exogenous IL-6 and sIL-6R. Since January 1996 we have vaccinated more than one hundred metastatic melanoma patients. Promising clinical results (22% CR+PR, 32% SD) and the evidence of immune responses in the vaccinated patients have prompted us to design a phase III clinical trial which is to be open in 2000.

[Radiotherapy in the adjuvant therapy of rectal cancer: comparison of two treatment schedules]. / Radioterapia w leczeniu uzupelniajacym raka odbytnicy: porównanie dwóch schematów leczenia.

UNLABELLED: From 1988 to 1991 54 patient with carcinoma of the distal part of the rectum were cured in our Department. These patients were divided into two groups (similar with regard to sex, age and advance of disease). In group I (28 patients) abdomino-perineal resection was performed, accompanied (according to histo-pathological indications) by adjuvant radiotherapy to maximal dose 6000 cGy. In group II such procedure was preceded by "short" radiotherapy (4 x 500 cGy). Local recurrence rate was 17.8% in group I and 11.5% in group II. CONCLUSIONS: Preoperative radiotherapy (for example "short" schedule 4 x 500 cGy) may decrease number of local recurrences after abdomino-perineal resections in rectal cancer cases. This procedure effects no technical problems and complications during and after operations.

[The effect of regional lymphatic metastasis on the methods and results of treating stomach neoplasms]. / Wplyw zajecia regionalnych wezlów chlonnych na sposób i wyniki leczenia raka zoladka.

From I 1986 to I 1997 we have operated in our Department 333 patients with gastric cancer. Resection has been done in 204 cases (with total resection rate 97%). Mostly there were patients with advanced disease (totally 160 cases with III and IV stage according to UICC classification). Metastases to regional lymph nodes were confirmed at 186 patients (91%). In every resection for cure and in palliative operations, where it was possible, we have done lymphangiectomy contained D1 and D2 level of regional lymph nodes. We achieved 28.9% 5-year survival rate (according to Kaplan-Meier) with postoperative mortality 2% and low number of surgical complications. Total resection of the stomach with regional node dissection (levels D1 and D2) is good and safe procedure and should be performed in majority cases of gastric cancer particularly in early and middle stages of disease.

[Conservative treatment of breast cancer--indications and surgical technique]. / Oszczedzajace leczenie chorych na raka sutka--wskazania i technika chirurgiczna.

Comparison of the results of conservative surgery and radiotherapy with mastectomy in the treatment of the breast cancer are discussed. The indications, contraindications and surgical technique on conservative surgery are presented.

[Evaluation of the usefulness and technique of intraoperative large bowel lavage]. / Ocena przydatnosci i technika sródoperacyjnego plunkania jelita grubego.

The technique is presented of intraoperative large bowel lavage, making possible cleansing of the bowel in patients in whom this was impossible to perform in the preoperative period. This method in some patients enables abandoning of diverting fistula creation and thus avoiding of multistage treatment.

[Quality of life after total gastrectomy depending on the method of alimentary tract reconstruction]. / Jakosc zycia po resekcji calkowitej zoladka w zaleznosci od sposobu rekonstrukcji przewodu pokarmowego.

The quality of life was subjected to evaluation in two groups of patients after total gastrectomy depending on the method of alimentary tract reconstruction within at least nine months after the operation. One group included patients in whom the alimentary tract reconstruction was performed without creation of a reservoir according to Roux-Y (n = 10). The second group consisted of patients in whom a reservoir was created from the small intestine (jejunal pouch) according to Hunt-Lawrence-Rodino in Herfarth modification (n = 13). In both groups no statistically significant differences were found with respect to sex, age and time after the operation. The symptoms, body weight gain, amount of consumed food and the level of certain substances in blood were analysed. A higher quality of life was found in patients in whom in place of removed stomach, jejunal pouch was created.