Quality of life after extended pelvic exenterations.

BACKGROUND: The aim of the study was to compare health-related quality of life (QoL) and oncological outcome between gynaecological cancer patients undergoing pelvic exenteration (PE) and extended pelvic exenteration (EPE). EPEs were defined as extensive procedures including, in addition to standard PE extent, the resection of internal, external, or common iliac vessels; pelvic side-wall muscles; large pelvic nerves (sciatic or femoral); and/or pelvic bones. METHODS: Data from 74 patients who underwent PE (42) or EPE (32) between 2004 and 2019 at a single tertiary gynae-oncology centre in Prague were analysed. QoL assessment was performed using EORTC QLQ-C30, EORTC CX-24, and QOLPEX questionnaires specifically developed for patients after (E)PE. RESULTS: No significant differences in survival were observed between the groups (P > 0.999), with median overall and disease-specific survival in the whole cohort of 45 and 49 months, respectively. Thirty-one survivors participated in the QoL surveys (20 PE, 11 EPE). No significant differences were observed in global health status (P = 0.951) or in any of the functional scales. The groups were not differing in therapy satisfaction (P = 0.502), and both expressed similar, high willingness to undergo treatment again if they were to decide again (P = 0.317). CONCLUSIONS: EPEs had post-treatment QoL and oncological outcome comparable to traditional PE. These procedures offer a potentially curative treatment option for patients with persistent or recurrent pelvic tumour invading into pelvic wall structures without further compromise of patients´ QoL.

Iodine seed localisation of non-palpable lesions in breast surgery first experience.

Surgical therapy of non-palpable malignant breast lesions requires precise preoperative localisation. Recently, radioactive iodine seed localisation has excelled among the number of localisation methods. We present our first experience with this method at our department. We describe the structure of the radioactive iodine seed, the principles of preoperative localisation and peroperative detection of the seed, the specimen transport process, histopathological examination, storage and disposal of the seed, as well as aspects of radiation protection.

Targeted axillary dissection and sentinel lymph node biopsy in breast cancer patients after neoadjuvant chemotherapy - a retrospective study.

INTRODUCTION: No consensus exists as yet regarding the optimal extent of surgery on the lymph nodes in breast cancer patients after neoadjuvant treatment. In addition to axillary dissection and sentinel lymph node biopsy (SLNB), a new approach called Targeted Axillary Dissection (TAD) was introduced. It requires the marking of metastatic nodes before the neoadjuvant treatment. METHOD: A retrospective observational study on patients with breast cancer and neoadjuvant chemotherapy treated surgically at a single institution in 2017. RESULTS: The analysis included 121 cancers in 120 patients. Clinical regression of lymphadenopathy occurred in 29 out of 74 cases. Axillary dissection was performed 34x, SLNB 52x and TAD 35x. In TAD procedures, the marked lymph node was found 30x and was among the sentinel nodes in 19 cases. No case occurred in which the marked node was assessed as negative with a metastasis found in the other nodes. On the contrary, there were 3 cases with negative sentinel nodes whereas the marked node was positive. Out of 74 cases with initially pathologic nodes, 23 patients were spared axillary dissection. CONCLUSION: Clinical assessment of the lymph node status is rather inaccurate. In cases with initially pathologic nodes we recommend marking of the most explicit metastatic node to enable TAD. The marked node is likely to reflect the status of the lymph nodes after neoadjuvant treatment more accurately than common sentinel nodes. A considerable proportion of patients can be spared axillary dissection in this way. However, the long-term oncologic safety of TAD still needs to be verified. Key words: breast cancer - neoadjuvant treatment - axillary dissection - sentinel lymph node biopsy - targeted axillary dissection.

[Magnetic resonance imaging in preoperative diagnosis of invasive lobular carcinomas of the breast - analysis of 230 cases]. / Magnetická rezonance v predoperacní diagnostice invazivních lobulárních karcinomu prsu - analýza 230 prípadu.

INTRODUCTION: In breast cancer patients, magnetic resonance imaging (MRI) is a supportive method characterized by high sensitivity. Its indications in the preoperative assessment are not clearly defined. More likely to benefit from preoperative MRI are younger women, women with a dense breast on mammography and patients with invasive lobular carcinoma (ILC). The aim of this study was to assess utilization of MRI and resulting benefits in preoperative tumour staging of ILC in patients treated in our institution. METHODS: A retrospective evaluation of medical records of all patients with bioptically proven and primarily surgically treated ILC through the years 20142016. RESULTS: Overall, 230 patients were evaluated, among them 131 (57.0%) underwent MRI. These patients were significantly younger than patients without MRI. The results of MRI were as follows: in 28.2% a small unicentric lesion, in 41.2% large infiltration or multifocality, and in 30.5% suspicion of multicentricity. The proportion of conservative surgeries and re-resections did not differ between the patients with and without MRI. The subgroup of patients with a small unicentric lesion on MRI showed a higher proportion of conservative surgeries and fewer re-resections compared to the other subgroups. In 41 women (31.3%) the MRI finding resulted in further assessments; in 29 (22.1%) an additional biopsy was done, with a malignant result in the ipsilateral breast in 8 cases and in the contralateral breast in 3 cases. The MRI finding had a substantial impact on surgery in 35 patients (26.7%) of whom it was evaluated as clinically beneficial in 23 (65.7%) cases. CONCLUSION: At our institution, more than a half of patients with ILC undergo MRI preoperatively. The finding has an impact on the scope of the surgery in approximately one fourth of the cases, being clinically beneficial in most of them. However, a high frequency of additional imaging assessments and biopsies should be taken into account. Due to the low specificity of MRI, every suspicious lesion has to be bioptically verified to avoid inappropriate surgery and patient harm.Key words: breast cancer - invasive lobular carcinoma - magnetic resonance imaging - occult lesion - biopsy.

Pelvic floor reconstruction by modified rectus abdominis myoperitoneal (MRAM) flap after pelvic exenterations.

OBJECTIVE: To describe the technique and report experiences with pelvic floor reconstruction by modified rectus abdominis myoperitoneal (MRAM) flap after extensive pelvic procedures. METHODS: Surgical technique of MRAM harvest and transposition is carefully described. The patients in whom pelvic floor reconstruction with MRAM after either infralevator pelvic exenteration and/or extended lateral pelvic sidewall excision was carried out were enrolled into the study (MRAM group, n=16). Surgical data, post-operative morbidity, and disease status were retrospectively assessed. The results were compared with a historical cohort of patients, in whom an exenterative procedure without pelvic floor reconstruction was performed at the same institution (control group, n=24). RESULTS: Both groups were balanced in age, BMI, tumor types, and previous treatment. Substantially less patients from the MRAM group required reoperation within 60days of the surgery (25% vs. 50%) which was due to much lower rate of complications potentially related to empty pelvis syndrome (1 vs. 7 reoperations) (p=0.114). Late post-operative complication rate was substantially lower in the MRAM group (any grade: 79% vs. 44%; grade≥3: 37% vs. 6%) (p=0.041). The performance status 6months after the surgery was ≤1 in the majority of patients in MRAM (81%) while in only 38% of patients from the control group (p=0.027). There was one incisional hernia in MRAM group while three cases were reported in the controls. CONCLUSIONS: Pelvic floor reconstruction by MRAM in patients after pelvic exenterative procedures is associated with a substantial decrease in postoperative complications that are potentially related to empty pelvis syndrome.

INTRAOPERATIVE FAT GRAFTING INTO THE PECTORALIS AND LATISSIMUS DORSI MUSCLES-NOVEL MODIFICATION OF AUTOLOGOUS BREAST RECONSTRUCTION WITH EXTENDED LATISSIMUS DORSI FLAP.

BACKGROUND: The latissimus dorsi flap is a reliable and one of the most commonly used methods of both immediate and delayed breast reconstruction. Its disadvantage is the limited volume of transferred tissue. The authors present their experience with the use of extended latissimus dorsi flap associated with immediate fat grafting into the pectoralis and latissimus dorsi muscles for secondary breast reconstruction. METHODS: From 2013 to 2016, 14 patients underwent secondary unilateral total breast reconstruction with extended latissimus dorsi flap associated with primary fat grafting into the pectoralis major and latissimus dorsi muscles. Fat was injected under visual control between muscle fibers. Fat injected into the pectoralis muscle formed an apparent bulging - autoprosthesis. RESULTS: Mean patient age was 48.2 years (range, 34 to 64 years). Mean injected fat volume was 86.4 ml (range, 50 to 160 ml) and majority of this volume was injected into the pectoralis muscle. All flaps healed uneventfully and no fat grafting-related complications were observed. The most common complication was donor site seroma, which occurred in 57.1%. Results of postoperative ultrasound examination were evaluated. Incidence and the size of oil cysts and fat necroses were significantly lower in muscular layer in comparison with the subcutaneous layer of the reconstructed breast. CONCLUSIONS: Immediate fat transfer into the pectoralis and latissimus dorsi muscle increases the breast volume during the reconstruction with extended latissimus dorsi flap avoiding implant-related complications when abdominal tissue is not available. Pectoralis and latissimus dorsi muscles were shown as reliable and safe recipients for fat grafting.

Molecular profile of 5-fluorouracil pathway genes in colorectal carcinoma.

BACKGROUND: This study addresses involvement of major 5-fluorouracil (5-FU) pathway genes in the prognosis of colorectal carcinoma patients. METHODS: Testing set and two validation sets comprising paired tumor and adjacent mucosa tissue samples from 151 patients were used for transcript profiling of 15 5-FU pathway genes by quantitative real-time PCR and DNA methylation profiling by high resolution melting analysis. Intratumoral molecular profiles were correlated with clinical data of patients. Protein levels of two most relevant candidate markers were assessed by immunoblotting. RESULTS: Downregulation of DPYD and upregulation of PPAT, UMPS, RRM2, and SLC29A1 transcripts were found in tumors compared to adjacent mucosa in testing and validation sets of patients. Low RRM2 transcript level significantly associated with poor response to the first-line palliative 5-FU-based chemotherapy in the testing set and with poor disease-free interval of patients in the validation set irrespective of 5-FU treatment. UPP2 was strongly methylated while its transcript absent in both tumors and adjacent mucosa. DPYS methylation level was significantly higher in tumor tissues compared to adjacent mucosa samples. Low intratumoral level of UPB1 methylation was prognostic for poor disease-free interval of the patients (P = 0.0002). The rest of the studied 5-FU genes were not methylated in tumors or adjacent mucosa. CONCLUSIONS: The observed overexpression of several 5-FU activating genes and DPYD downregulation deduce that chemotherapy naïve colorectal tumors share favorable gene expression profile for 5-FU therapy. Low RRM2 transcript and UPB1 methylation levels present separate poor prognosis factors for colorectal carcinoma patients and should be further investigated.

Lipomodelling - advanced technique for the correction of Congenital hypoplastic breast malformations and deformities.

A variety of surgical techniques has been used to correct hypoplastic breast malformations and deformities, including tissue expanders, breast implants, custom chest wall implants, mammary gland remodelling, as well as locoregional or free flap. Case series of successful breast reconstruction using lipomodelling technique in one patient with severe Polands syndrome and two patients with tuberous breasts are reported together with literature review. No surgical complications were observed and ultrasound examination did not reveal any pathology in breast tissue other than oil pseudocysts postoperatively. In both malformations, submammary fold was moved downwards. Moreover, the lower part of the breast and areolar herniation was corrected in tuberous breast, and in Polands syndrome, the areolar complex was significantly shifted downwards and laterally. In comparison with other reconstructive techniques, lipomodelling allows for the breast correction to begin in early adolescence. Further growth of the unaffected breast may be effectively corrected by subsequent lipomodelling session. This technique appears to change the overall approach to the management of hypoplastic breast and chest wall malformations.

[Hereditary Breast and Ovarian Cancer Syndrome]. / Syndrom hereditárního karcinomu prsu a ovarií.

Population with hereditary breast and ovarian cancer syndrome, i.e. BRCA1/2 mutation carriers, are at higher risk of developing breast and ovarian cancer as well as other solid tumours such as pancreatic cancer, prostate cancer and melanoma. With the increasing experience, screening recommendations and preventive strategies including prophylactic surgery are being settled. Surveillance of women with hereditary breast cancer syndrome comprises clinical breast examination every six months, breast ultrasound and MRI in patients aged 25 to 29 and MRI and mammography in women aged 30 to 65. Screening of pancreatic cancer should be considered in BRCA1/2 mutation carriers, who have two cases of pancreatic cancer in their family lineage or one first-degree relative with pancreatic cancer. Prostate cancer screening should be recommended to BRCA2 carriers from the age of 40 onwards and it should be considered in BRCA1 carriers as well. Screening for melanoma should be recommended on an individual basis with regards to a family history.

[Diagnostics of breast cancer in high-risk women - our own experience]. / Diagnostika nádoru prsu ve skupine rizikových zen - vlastní zkusenosti.

Preventive oncology clinic of MMCI provides complex preventive care for women with high hereditary risk of breast and ovarian cancer due to germline mutations in BRCA1 and BRCA2 genes. Clinical follow-up is also provided to women with mutations in other genes causing a higher risk of different tumors, and also to women with increased lifetime empirical risk of breast cancer due to positive family history. Our clinic was established in 2000 and takes care for about 700 women. The goal of the clinic is to extend the life expectancy of these women to the level of the regular population. The risk of breast cancer can be reduced by prophylactic surgeries. Prophylactic mastectomy and oophorectomy are offered to women at a high risk. Other modality in breast cancer risk reduction is a chemoprevention by Tamoxifen. Most women accept only secondary prevention with the goal of the detection of breast cancer in clinical stage I, where the tumor is smaller than 1 cm and the risk of recurrence is less than 10%. The algorithm of prevention care was changed over the time and our diagnostic methods were improved by magnetic resonance imaging of breasts. During the 11 years of clinical follow-up 32 breast cancers in 31 women were detected. High risk women are examined every 6 month by physical examination, breast ultrasound and MRI plus mammography yearly.

[Multimodal treatment of glioblastoma multiforme: results of 86 consecutive patients diagnosed in period 2003-2009]. / Výsledky multimodální lécby glioblastoma multiforme: Konsekutivní série 86 pacientu diagnostikovaných v letech 2003-2009.

BACKGROUNDS: Glioblastoma multiforme is the most common malignant primary tumor of the brain in adults. Standard therapy consists in maximal surgical resection and adjuvant concurrent chemoradiotherapy and adjuvant therapy with temozolomid. This approach improves survival in comparison with postsurgical radiotherapy alone. PATIENTS AND METHODS: Consecutive patients with histologically confirmed glioblastoma multiforme in the period from January 2003 to December 2009 underwent postoperative radiotherapy (1.8-2.0 Gy/d, total of 60 Gy) plus concurrent daily chemotherapy (temozolomide 75 mg/m2/d), followed by 6 cycles of temozolomide (150 to 200 mg/m2 for 5 days, every 28 days) and were analyzed retrospectively. The primary end point was to describe the correlation between known clinical factors, treatment and progression free survival (PFS) and overall survival (OS). We assessed the toxicity and safety of the chemoradiotherapy. RESULTS: Eighty-six patients (median age, 56 years; 60% male) were included. Most of them (> 80%) were of performance status (PS) 0-1 at the beginning of chemoradiotherapy. Total macroscopic resection was performed in 20% of the patients, subtotal in 65%, partial in 9%, and just biopsy in 6%. Median PFS was 7.0 months (2.0-35.5), median OS was 13.0 months (2.5-70). Postoperative performance status (PS), the extent of resection, and administration of planned treatment without reduction had statistically significant influences on PFS and OS. Median PFS and OS were 22.0, 7.0 and 6.0 months for PFS (p = 0.0018) in patients with PS O, 1 and 2 respectively and 32.0, 13.0 and 9.0 months for OS (p = 0.0023). Patients with total removal of tumor had longer PFS (14.0 vs 6.0 months, HR = 0.5688; p = 0.0301) and OS (23.0 vs 12.0 months, HR 0.4977; p = 0.0093), as did patients without dose reduction of radiotherapy and/or chemotherapy. Patients with radiotherapy dose of over 54 Gy had PFS 8.0 vs 3.0 months (HR = 0.3313; p = 0.0001) and OS 15.0 vs 5.0 months (HR = 0.1730; p < 0.0001). Similarly, treatment with concurrent chemotherapy for more than 40 days was also important: PFS 8.0 vs 5.0 months (HR = 0.5300; p = 0.0023) and OS 17.0 vs 9.5 months (HR = 0.5943; p = 0.0175). Age, gender and position of tumor had no significant influence. Treatment-related hematology toxicity grades 3 and 4 occurred relatively often: thrombocytopenia (9%), leukopenia (6%), neutropenia (6%) and lymphopenia (25%). Thrombo-embolic events were dominant in non-hematology toxicity. Serious toxicity occurred mainly in the subgroup of patients with PS 2. Treatment of progression was useful in selected patients. Second surgery was of the most benefit (OS 24.0 vs 12.5 months, HR = 0.5325; p = 0.0111). CONCLUSION: Postoperative performance status, extent of resection, successful administration of the majority of planned concurrent chemoradiotherapy and possibility of surgical treatment at the time of recurrence correlate with better prognosis for our patients with glioblastoma. Our experience indicates that performance status should be the main factor in decisions about treatment intensity. Treatment of malignant glioma requires a multidisciplinary team.

Genetic testing and prevention of hereditary cancer at the MMCI--over 10 years of experience.

Hereditary cancer syndromes are frequently seen in young cancer patients and patients with a positive family history. Genetic testing is important for the identification of high-risk individuals, and for the early introduction of specialized preventive care or prophylactic surgeries. High-risk tumour suppressor genes (BRCA1 and BRCA2) and DNA repair genes (MLH1, MSH2 and MSH6) are responsible for a substantial part of hereditary breast, ovarian and colorectal cancer. Other hereditary cancers are seen less frequently, but genetic testing has increased for many other site-specific cancers and complex syndromes. Genetic centres and molecular genetic laboratories are located mostly within university or regional hospitals. Some genetic centres are private. It is highly recommended (Czech Society for Medical Genetics) that all laboratories are accredited according to ISO 15,189 and that genetic testing of hereditary cancer syndromes is indicated by medical geneticists. The indication criteria and prevention strategies were published in Supplement 22 of Clinical Oncology 2009 (in Czech). Preventive care for high-risk individuals is organized by thirteen Oncology Centres, which provide most of the oncology care in the Czech Republic. Genetic testing and preventive care for high-risk individuals and mutation carriers is covered by health insurance. The molecular genetic laboratory at the MMCI provides molecular genetic testing of BRCA1, BRCA2, CHEK2 for hereditary breast/ovarian cancer, MLH1, MSH2, MSH6 for Lynch syndrome,TP53 for Li-Fraumeni syndrome, CDKN2A for familial malignant melanoma syndrome and CDH1 gene for hereditary diffuse gastric cancer. Other syndromes are tested in specialized laboratories elsewhere.The use of genetic testing is increasing because of more frequent referrals from oncologists and other specialists and the increasing variety of genes tested. However, in some patients the testing is not recommended and other family members are dying because of the late diagnosis of hereditary syndrome. Greater awareness of the importance of genetic testing in oncology is needed.

[Mammotomy, new technique not only for breast cancer]. / Mamotomie, jedna z nových vysetrovacích metod nejen pro diagnostiku tumoru prsu.

BACKGROUND: Vacuum biopsy device (mammotome) was primary developed for invasive diagnosis of the mammary gland. METHODS AND RESULTS: In Radiological department of Masaryk Memorial Cancer Institute we use the mammotome not only for breast tissue sampling. CONCLUSIONS: The device is used also for extraction of tumor specimens in advanced epithelial, mesenchymal or the other histological type of tumors for further chemoresistance testing.