Soft tissue sarcoma with ZC3H7B::BCOR fusion in a male mimicking low-grade fibromyxoid sarcoma - A case report.

Diagnosis of soft tissue tumors is often challenging, given the large number of entities, often with non-specific or overlapping morphology. Although morphology still plays an important part in diagnostic process, additional studies including immunohistochemistry and molecular genetics are often needed to arrive at correct diagnosis. We report a case of 61-year-old male with subcutaneous tumor in right hip area, that was surgically removed. The tumor was composed of uniform bland spindle cells in mild to moderately cellular myxoid nodules, with limited areas of collagenization and the diagnosis of low grade fibromyxoid sarcoma was made. The tumor recurred 3 years after the initial diagnosis and the new sample showed a high-grade round cell sarcoma with limited residual low-grade areas and non-specific immunoprofile after extended immunohistochemical work-up. Molecular analysis demonstrated ZC3H7B::BCOR fusion. Sarcomas with ZC3H7B::BCOR fusion occurring outside of uterus are exceedingly rare. A comprehensive review of previously published cases and a short discussion about classification of the entity is provided, together with data about morphology and immunoprofile of the lesions. The case also underscores the necessity of extended work up of soft tissue tumors with unusual immunohistochemical or morphological features in order to accurately assess their biological potential.

Prognostic significance of CD3+ tumor-infiltrating lymphocytes in patients with endometrial carcinoma.

AIM: The aim of the present study was to investigate tumor-infiltrating leukocytes in patients with endometrial carcinoma. PATIENTS AND METHODS: Cluster of differentiation (CD)3(+), CD8(+) and C20(+) tumor-infiltrating lymphocytes (TILs) and CD68(+) tumor-associated macrophages (TAMs) were evaluated retrospectively by immunohistochemistry in tumor specimen from 124 patients with endometrial carcinoma. RESULTS: A significant decrease of CD3(+) TILs and an increase of CD68(+) TAM count was associated with higher tumor stage. In patients with early-stage, high-risk tumors, low intraepithelial CD3(+) TIL counts were associated with significantly inferior survival. In multivariate analysis of patients with early-stage tumors, intraepithelial CD3(+) TIL counts were an independent predictor of survival. CONCLUSION: In patients with endometrial carcinoma a decrease of intraepithelial CD3(+) TIL counts is associated with advanced stage and high risk group. Intraepithelial CD3(+) TIL counts are an independent predictor of survival in patients with early tumors.

Prognostic significance of human papillomavirus (HPV) status and expression of selected markers (HER2/neu, EGFR, VEGF, CD34, p63, p53 and Ki67/MIB-1) on outcome after (chemo-) radiotherapy in patients with squamous cell carcinoma of uterine cervix.

The aim of the retrospective study was to evaluate prognostic significance of human papillomavirus (HPV) status and expression of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor type 2 (HER2/neu), vascular endothelial growth factor (VEGF), CD34 antigen, tumor suppressors p63 and p53, and Ki67/MIB-1 in squamous cell carcinoma of the uterine cervix (SCCC) treated with radiotherapy or chemoradiotherapy. Seventy-two consecutive patients with SCCC, diagnosed and treated with (chemo-) radiotherapy with a curative intent at the University Hospital Hradec Kralove between August 1998 and August 2008, were enrolled in the study. The median follow-up period was 57 months (range 5-152). The tested biological factors were evaluated by polymerase chain reaction (HPV status) and by immunohistochemistry (remaining above mentioned markers) from archival paraffin embedded original diagnostic tumor samples. A statistical significant correlation was observed between low expression of p63 and poor overall survival (p = 0.001), although the complete response probability was influenced with borderline statistical significance (p = 0.05). However, the results could be affected by the statistical error due to the small number of p63 negative patients. HPV positivity and EGFR staining intensity was associated with higher complete response probability (p = 0.038 and p = 0.044, resp.). All other results were not significant. Neither HPV positivity nor EGFR staining intensity were reflected in the overall survival evaluation. In conclusion, the presented study did not confirm any apparently significant association of the suggested markers with prognosis of SCCC in patients treated with (chemo-) radiotherapy.

Cutaneous recurrence of malignant mesothelioma of the tunica vaginalis testis: a rare case report.

BACKGROUND: Mesothelioma of the tunica vaginalis testis is a rare and aggressive cancer; fewer than 90 cases have been reported. It occurs in all age groups, but its highest incidence appears between 55 and 75 years of age. Less than 5% of all malignant mesotheliomas arise from the tunica vaginalis testis. CASE REPORT: The authors present a rare case of localized malignant mesothelioma of the tunica vaginalis testis. Diagnosis and treatment are described. CONCLUSION: Mesothelioma of the tunica vaginalis testis can be asymptomatic for a long time. In more than half of the cases, the clinical manifestations imitate a hydrocele or a tumor mass in the scrotum. Despite treatment, this tumor has a very poor prognosis with a median survival of 23 months.

Non-closure of peritoneum after abdominal hysterectomy for uterine carcinoma does not increase late intestinal radiation morbidity.

BACKGROUND/AIM: To evaluate whether non-closure of the visceral peritoneum after total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) in patients with uterine corpus carcinoma influences the volume of the small intestine within the irradiated volume during adjuvant radiotherapy or late radiation intestinal toxicity. MATERIALS AND METHODS: A total of 152 patients after TAH + BSO with adjuvant pelvic radiotherapy were studied. The state of peritonealization was retrospectively evaluated based on surgical protocols. The volume of irradiated bowels was calculated by CT-based delineation in a radiotherapy planning system. The influence of visceral peritonealization upon the volume of the small intestine within the irradiated volume and consequent late morbidity was analyzed. RESULTS: Visceral peritonealization was not performed in 70 (46%) of 152 studied patients. The state of peritonealization did not affect the volume of the irradiated small intestine (p = 0.14). Mean volume of bowels irradiated in patients with peritonealization was 488 cm(3) (range 200-840 cm(3), median 469 cm(3)); mean volume of bowels irradiated in patients without peritonealization was 456 cm(3) (range 254-869 cm(3), median 428 cm(3)). We did not prove any significant difference between both arms. Nor did we observe any influence of non-peritonealization upon late intestinal morbidity (p = 0.34). CONCLUSION: Non-closure of the visceral peritoneum after hysterectomy for uterine corpus carcinoma does not increase the volume of the small intestine within the irradiated volume, with no consequent intestinal morbidity enhancement.

Expression of p53, p21 and p16 does not correlate with response to preoperative chemoradiation in gastric carcinoma.

BACKGROUND/AIMS: A retrospective evaluation was oerformed to determine whether the intensity of p53, p21 or p16 expression predicts response to preoperative chemoradiotherapy in locally advanced gastric carcinoma. METHODOLOGY: Thirty-six patients (cT2-4 or N+) were studied. Preoperative treatment consisted of 30-45Gy of radiation with continuous 5-fluorouracil and weekly cisplatin. Expression of p53, p21 and p16 in pretreatment biopsies was assessed by immunohistochemistry. Level of expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level and/or finding of intense tumor regression in histopathologic examination. RESULTS: Seventeen patients responded to chemoradiation: 8 patients had pathologic complete response, 9 patients were downstaged. The multivariate analysis showed no significant influence of p53 (p = 0.76), p21 (p = 0.10) nor p16 (p = 0.70) expression upon tumor response. Response was found in 52% of patients with low, and in 40% of patients with high p53 staining (p = 0.21); in 54% of patients with low, and in 30% of patients with high p21 staining (p = 0.14); and in 48% of patients with low, and in 43% of patients with high p16 staining (p = 0.32). CONCLUSIONS: We found no significant influence of p53, p21 nor p16 expression upon response to preoperative chemoradiotherapy in gastric carcinoma.

Epidermal growth factor receptor as a predictor of tumor response to preoperative chemoradiation in locally advanced gastric carcinoma.

PURPOSE: The purpose of our study was a retrospective evaluation whether the intensity of epidermal growth factor receptor (EGFR) expression predicts tumor response to preoperative chemoradiotherapy in patients with locally advanced gastric carcinoma. PATIENTS AND METHODS: Thirty-six patients with gastric adenocarcinoma (cT2-4 or N+) were studied. Preoperative treatment consisted of 30-45 Gy of gastric irradiation with continuous 5-fluorouracil and weekly cisplatin. Surgical resection was performed 4-6 weeks later. EGFR expression in pretreatment tumor biopsies was assessed by immunohistochemistry. Level of EGFR expression was determined from the intensity and extent of staining. Tumor response was defined as a reduction of at least one T-stage level and/or finding of intense tumor regression in histopathologic examination. RESULTS: Seventeen patients responded to preoperative chemoradiation -- 8 patients (22%) had pathologic complete response, 9 patients (25%) were downstaged. Positive EGFR expression was found in 8 tumors (22%), and represented a significant predictive marker of poor tumor response in multivariate logistic regression analysis (p = 0.015). Response to chemoradiotherapy was found in 60% (16/28) of EGFR negative patients and in 13% (1/8) of EGFR positive patients (p = 0.044). None of the eight EGFR positive patients achieved pathologic complete response in comparison with 8/28 (29%) of patients with EGFR negative staining (p = 0.16). CONCLUSION: EGFR may represent a molecular marker predictive for poor response to preoperative chemoradiotherapy in locally advanced gastric carcinoma.

The influence of cisplatin dose upon survival in concurrent chemoradiotherapy of locally advanced cervical carcinoma with weekly cisplatin.

The objective of this study was to evaluate the influence of cisplatin dose upon 3-year overall and disease-free survival rate of patients with advanced cervical cancer treated with concurrent chemoradiotherapy with weekly cisplatin. Seventy-three patients with stage IIB-IVA cervical carcinoma were treated with pelvic (or pelvic + paraaortic) external-beam radiotherapy, high-dose rate brachytherapy and concomitant chemotherapy with weekly cisplatin of 40 mg/m2 in the time period form January 2000 to December 2006 at our department. The 3-year overall survival and disease-free suvival rates were evaluated with regard to the number of cisplatin cycles applied during the external radiotherapy. Only twenty-eight patients received the intended five doses of chemotherapy. The most frequent cause of chemotherapy delay was the acute hematological toxicity with leukopenia. The 3-year overall survival was 71 % and the 3-year disease-free survival was 61 %. Survival analyses didn't prove a statistically significant influence of cisplatin dose upon 3-year survival in cervical carcinoma patients treated by exclusive chemoradiation with weekly cisplatin.

IMRT with the use of simultaneous integrated boost in treatment of head and neck cancer: acute toxicity evaluation.

Acute toxicity has been evaluated in head and neck cancer patients treated with intensity-modulated radiotherapy using simultaneous integrated boost (SIB-IMRT). The basis of the treatment protocol is an irradiation in 30 fractions with a total dose: 66 Gy to the region of macroscopic tumor, 60 Gy to the region of high-risk subclinical disease and 54 Gy to the region of low-risk subclinical disease. Between December 2003 and September 2005, 38 patients with carcinoma of different locations in the head and neck region were irradiated. Five patients underwent concurrent chemotherapy (weekly cisplatin). Acute toxicity was evaluated according to Radiation Therapy Oncology Group toxicity scale for skin, mucous membrane, salivary glands, pharynx and esophagus and larynx. All 38 patients completed the therapy without urgency of interruption due to acute toxicity of radiotherapy. No patient experienced grade 4 toxicity. More severe toxicity was observed in patients with concurrent chemotherapy. The results confirm that the irradiation according to our SIB-IMRT protocol is a therapy with acceptable toxicity and there is a space for radiobiological enhancement of this regimen by concurrent chemotherapy, e.g. weekly cisplatin.

Is it reasonable to consider second-line chemotherapy in patients with hormone-refractory prostate cancer?

At present, no consensus exists regarding the use of second-line chemotherapy in patients with hormone-refractory prostate cancer (HRPC). A total of 23 patients with evidence of disease progression during or after first-line chemotherapy (epirubicin, etoposide, and dexamethasone) were included in this study. Two second-line treatments were administered throughout the study period (2000-2004) with 15/23 patients receiving carboplatin AUC 3 on day 1 and vinblastine 5 mg/m2 on day 1 of a 21-day cycle and 8/23 patients treated with docetaxel 50 mg/m2 on day 1 of a 21-day cycle. The latter regimen has been used since 2003. The prostate-specific antigen (PSA) level decreased by > or =50% in 3 of 23 patients, corresponding to an overall PSA response rate of 13% (95% confidence interval, 3-34%). The median time to biochemical progression was 9, 24 and 33 weeks, respectively. The median overall survival was 39 weeks (range, 15-73 weeks) with no difference between the two chemotherapy groups (p=0.08). A significant reduction of analgesic use was observed in 2 of 10 patients (20%) who required analgesics for cancer pain upon study entry. The major toxicity was grade 3 thrombocytopenia in 2 of 23 patients (9%). Both second-line treatments, a combination of carboplatin and vinblastine and a monotherapy with docetaxel, showed modest activity at subtoxic doses in patients with HRPC.

[Intensity-modulated radiotherapy in the treatment of thyroid cancer]. / Radioterapie s modulovanou intenzitou v lécbe karcinomu stítné zlázy.

The main problem of the conventional radiotherapy in postoperative or curative irradiation in thyroid cancer is to achieve a sufficient dose in the planning target volume with acceptable dose distribution homogeneity and at the same time not to exceed tolerance doses in the organs of risk. Our study presents the advantages of intensity-modulated radiotherapy over conventional radiotherapy on an example of dosimetric comparisons of isodose plans of three patients treated at our department. The intensity-modulated radiotherapy in thyroid cancer offers an improvement of dose homogeneity and better sparing of organs at risk (spinal cord and lungs). Furthermore, dose escalation is feasible in the whole initial planning target volume up to 60 Gy with a simultaneous sparing of healthy tissues and organs at risk.

Bi-weekly epirubicin, etoposide and low-dose dexamethasone for hormone-refractory prostate cancer.

BACKGROUND: Recent studies have demonstrated the efficacy and favorable toxicity profile of chemotherapy regimens given at lower doses and frequent intervals. The aim of our study was to evaluate the efficacy and toxicity of a bi-weekly chemohormonal regimen consisting of epirubicin, etoposide, and low-dose dexamethasone (EED) in patients with hormone-refractory prostate cancer (HRPC). METHODS: We treated a total of 32 patients who had failed hormonal therapy and antiandrogen withdrawal. Chemotherapy was given every 2 weeks and consisted of epirubicin (30 mg/m2 intravenously, day 1) and etoposide (50 mg/m2 orally, days 1-7). Dexamethasone (1.5 mg orally, every other day) was given continuously until disease progression. Twenty patients (63%) had received prior treatment with estramustine phosphate. Each patient's pain response was evaluated according to analgesic use. Toxicity was graded using the Common Toxicity Criteria (version 2.0). RESULTS: Prostate-specific antigen (PSA) levels showed a decline of 50% or greater in 16 of 32 patients (50%, 95% confidence interval [CI], 32-68%) with a median time to biochemical progression of 5 months (range, 4-9 months). The median survival for all patients was 10.5 months (range, 3-35 months). Four of 10 patients (40%) with measurable soft tissue lesions achieved partial response according to standard criteria. Eleven of 23 symptomatic patients (48%, 95% CI, 27-69%) experienced an improvement in pain with a median duration of 6 months. The regimen was tolerated well by the patients, with only four patients (12%) having grade 3 leukopenia. CONCLUSION: Chemohormonal EED regimen proved to be active and well-tolerated in patients with HRPC.

Transduodenal intraluminal high dose rate brachytherapy in the treatment of carcinomas of the subhepatic region.

BACKGROUND/AIMS: The prognosis of carcinomas of the subhepatic region is poor, and therapeutic efforts are limited mostly to palliation. The aim of this study was to retrospectively evaluate the effectiveness of transduodenal administration of intraluminal high dose rate brachytherapy in the palliative treatment of bile duct and pancreatic head carcinomas. METHODOLOGY: Twelve patients with inoperable bile duct and pancreatic head carcinomas were treated by transduodenal brachytherapy using high dose rate remote afterloading system. Eleven patients were treated by intraluminal brachytherapy inserted via a nasobiliary drain and one patient by intraluminal brachytherapy via a nasopancreatic drain inserted in the duct of Wirsung. RESULTS: After transduodenal intraluminal brachytherapy, a control of icterus was observed in all patients. The treatment was well tolerated with the mean survival of 284 days. CONCLUSIONS: Transduodenal intraluminal brachytherapy is technically feasible. The addition of intraluminal brachytherapy may be beneficial to patients in whom drainage can be established. Transduodenal insertion of brachytherapy is not competitive to the percutaneous approach but spreads the possibilities of the treatment of bile duct carcinoma. Intraluminal brachytherapy of pancreatic head carcinoma is feasible only via transduodenal approach.

Intraluminal high dose rate brachytherapy in the treatment of bile duct and gallbladder carcinomas.

BACKGROUND/AIMS: The prognosis of biliary tract carcinomas is poor, and therapeutic efforts are limited mostly only to palliation. The aim of this study was to retrospectively evaluate the effectiveness and tolerability of intraluminal high dose rate brachytherapy in the treatment of bile duct and gallbladder carcinomas. METHODOLOGY: Thirteen patients with bile duct and gallbladder carcinomas were treated by brachytherapy administered through high dose rate remote afterloading system. Five patients after Roux-en-Y hepaticojejunoanastomosis were treated by intraluminal brachytherapy inserted via a diahepatal drain, and 8 inoperable patients were treated by intraluminal brachytherapy via a percutaneous biliary drain. RESULTS: After intraluminal brachytherapy, a control of icterus was observed in all patients. The treatment was well tolerated and mean survival was 275 days. CONCLUSIONS: The addition of intraluminal brachytherapy may be beneficial to patients with carcinomas causing biliary obstruction in whom bile drainage can be established.

Pegylated liposomal doxorubicin in combination with hyperthermia in the treatment of a case of advanced hepatocellular carcinoma.

BACKGROUND: Currently, there is no standard treatment of inoperable advanced hepatocellular carcinoma. STUDY: A patient with advanced hepatocellular carcinoma was treated with intravenous infusion of pegylated liposomal doxorubicin (PLD, Caelyx) in combination with ultrasound hyperthermia of the liver. Each cycle consisted of infusion of 60 mg of PLD followed by two fractions of hyperthermia 41 degrees C to 43 degrees C for 45 minutes 1 and 48 hours after infusion, respectively. RESULTS: A substantial regression of the tumor was observed on computed tomography scans. No toxicity of combined treatment was noted. CONCLUSIONS: This may be the first report of the combination of PLD and hyperthermia in the treatment of advanced hepatocellular carcinoma. Our observation suggests that the combination of PLD with hyperthermia is technically feasible, well tolerated, and could have synergistic potential.