Bevacizumab treatment before resection of colorectal liver metastases: safety, recovery of liver function, pathologic assessment.

Patients with metastatic colorectal cancer receive chemotherapy prior liver resection more and more frequently. This preoperative treatment has many effects which have to be analysed, like the safety of liver resection, toxicity, tissue regeneration, radiological and pathological response and survival data. The aim of the study was to evaluate the safety of bevacizumab containing preoperative chemotherapy and functional recovery of the liver after resection for colorectal liver metastases (CLM) and to analyse radiological and pathological data. Data of three groups of 120 consecutive patients-(1) CTX + BV: cytotoxic chemotherapy + bevacizumab, (2) CTX: cytotoxic chemotherapy, (3) NC: no treatment before liver resection-were analysed. Postoperative liver function and complications were compared, clinical, radiological and pathological data were evaluated. Between 01.12.2006 and 31.12.2010 41 resections was performed after chemotherapy + bevacizumab (CTX + BV) and 27 resections was performed after preoperative chemotherapy without bevacizumab (CTX). There were 60 hepatic resections in this period without neoadjuvant treatment (NC). 8 patients had repeated resections. The postoperative complication rate was 40 % but there was no statistical difference between the groups (P = 0.72). Only the type of resection was associated with a significantly higher complication rate (p = 0.03). The subgroup of patients, who received irinotecan had a higher complication rate in the CTX group than in the BV + CTX group (55 % vs 41 %). Preoperative administration of bevacizumab was associated with higher peak postoperative AST, ALT levels but did not affect functional recovery of the liver. The RECIST system was not able to predict the outcome after chemotherapy in every patient and in many cases this system overestimated the effect of chemotherapy. On histopathological examination the presence of necrosis was not associated with chemotherapy or pathological response. Use of chemotherapy before hepatic resection of CLM was not associated with a significant increase in complication rates. The functional recovery of the liver was not affected by the preoperative administration of chemotherapy. The use of combined neoadjuvant chemotherapy is safe before hepatic resection.

Clinical validity of new ultrasound methods in the differential diagnosis of breast diseases.

The clinical application of the extended-field-of-view (EFOV) technique, 3D ultrasonography (3D US) and a newly developed US method using a homogeneous tissue equivalent phantom, the so-called attenuation in phantom (AIPH) method, was evaluated in 200 patients with breast disease. These methods improved differentiation both in the preoperative diagnostic and in the postoperative follow-up. EFOV made possible to see large or multiple lesions and also their vasculature in a single image, allowing exact measurement, comparison and better assessment of traditional criteria. In addition, costs and examination time were also reduced. The possibility of viewing the spatial arrangement and the internal and external surfaces of the lesions improved preoperative decision making. Finally, the newly developed AIPH method allowed excellent evaluation of the posterior acoustic pattern of the lesions even when the mass was near the chest wall. For this reason, it was easier to distinguish malignant lesions from benign lesions of the breast.

Allelic imbalance and microsatellite instability in BRCA1 associated breast and ovarian tumors.

We have investigated the involvement of microsatellite instability (MSI) and allelic imbalance (AI) at chromosome 13q and 17 in 41 breast and 41 ovarian carcinomas and their association with BRCA1 and BRCA2 gene mutations. MSI was detected in 20% of ovarian and 7% of breast tumors. AI at the BRCA1 locus was detected in 59% and 32% of ovarian and breast tumors, respectively. At the BRCA2 locus, AI rates were 49% and 44% for ovarian and breast tumors, respectively. Germline BRCA1 mutations, identified in 5 (12%) ovarian tumors and in one (2%) breast tumor were not associated with MSI. In only 2/5 BRCA1 positive tumors loss of the wild-type allele was observed. We conclude that BRCA1 mutation status is not associated with MSI and that MSI found in a fraction of ovarian tumors may reflect possible mutations in one of the DNA mismatch repair genes.

Surgery in Hungary.

After providing data on the geography and demographics of Hungary, the 1100 years of Hungarian history are briefly surveyed. The introduction, development, and present state of medical education and, in particular, surgical education, including specialty training, are discussed. Attention is devoted to the organization of the surgical community and of surgical manpower in the country. Various disease patterns and their influence on surgical practice are discussed. Attention is also devoted to health care provision and research activity. Finally, the future of surgery, especially general surgery, is outlined.

Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary.

We have investigated the impact of BRCA1 and BRCA2 mutations that were frequently identified among Hungarian high-risk breast-ovarian cancer families (Ramus et al., 1997b, AJHG), on the development of breast and ovarian cancer in the general Hungarian population. The prevalence of 3 BRCA1 mutations (185delAG, 300T-->G and 5382insC) and 2 BRCA2 mutations (6174delT and 9326insA) was evaluated in a hospital-based consecutive series of 500 female breast cancer patients and 90 ovarian cancer patients, not selected for age at diagnosis or family history of cancer, as well as in 350 controls. Among breast cancer patients, 3.6% (18/500) carried a founder mutation: 9 BRCA1 300T-->G, 7 BRCA1 5382insC, 1 BRCA1 185delAG and 1 BRCA2 9326insA. Among ovarian cancer patients, 11% (10/90) carried a founder mutation: 5 BRCA1 185delAG, 4 BRCA1 300T-->G and 1 BRCA1 5382insC. One control carried a mutation, BRCA1 5382insC. Inherited breast cancer was more frequent among women with younger age at diagnosis: 6.1% of women younger than age 50 but 2.4% of women diagnosed at age 50 or older carried one of the founder mutations. There was no association between mutation status and age at diagnosis of ovarian cancer. Three of 23 medullary breast cancers were inherited (p = 0.038). Carrier status was also associated with a non-significant trend toward advanced tumor stage at diagnosis. These mutations could be evaluated among all ovarian cancer patients and breast cancer patients younger than age 60 and of Hungarian ancestry.

Influence of hormonal status of patients with cystic disease on the composition of cyst fluid and breast cancer risk.

The relationship between the composition of breast cyst fluid (BCF), the menstrual status and in addition some endocrine events in the history of patients (n = 131) with gross cystic breast disease was investigated. The dehydroepiandrosterone (DHA) levels in type II (K+/Na+ < 1) cysts of the follicular group were significantly higher compared to the type II cysts of the luteal or postmenopausal groups. For testosterone a significant difference existed between the type I (K+/Na+ > or = 1) follicular and type I postmenopausal groups. Estrone levels were significantly higher in type I BCF of patients in the luteal phase compared to both the follicular and postmenopausal type I cysts. Progesterone levels were lowest in the postmenopausal subgroups (both in type I and II cyst). Significant correlations were found between the number of pregnancies and the levels of DHA-sulfate and also progesterone in BCF. DHA levels were correlated with the period of lactation. The K+/Na+ ratios were the lowest in women who lactated for the longest period. The estrone was lowest in BCF of current oral contraceptive (o.c.) users while the estradiol was lowest in patients who had never used o.c. A history of previous o.c. use was associated with a significantly high mean DHA level. A significantly higher DHA and lower testosterone level were demonstrated in BCF of patients who had some previous gynecological interventions. The composition of BCF and the "life of cysts" and thus the rate of breast cancer risk may depend on hormonal status during the menstrual cycles or postmenopause and also on endocrine history of patients.

[Morphological parameters of breast cancers detected by mammography with and without organized screening; a comparative study]. / Mammográfiával felismert rákok morphologiai paramétereinek összehasonlítása a területileg szervezett szürés során és alkalomszerüen vizsgáltaknál.

Some pathological findings and prognostic indices recorded in breast cancer cases, detected, on one hand, by a provider-initiated mammography screening program (Group 1), and, opportunistically, in self-referred symptomatic women (Group 2) on the other, are compared. In 8877 symptom-free women, aged 50-65 years, individually invited to attend the screening offered for the residents of the III., XII. and XIII. districts of Budapest, 67 cancer cases were detected (7.5 in 1000 screenees), in accordance with the cancer detection rate of the first, "prevalence" round of organised screening programmes. In the other group of 1593 symptomatic, self-referred women of the same age, 113 cancer cases were diagnosed by mammography. As far as the pathological parameters are concerned, the number of cases with invasive cancer less than 15 mm in diameter, and those with axillary nodes present was found to be significantly higher in the screened group as compared to the self-referred one (p < 0.01). In "small" cancers (i.e. less than 15 mm in diameter), no significant difference was found in the proportion of histologic grade III tumours among the two groups. In screen-detected cancers both the morphometric prognostic index (as calculated by Baak et al.) and the Nottingham Prognostic Index (NPI) proved to be more favourable, as compared to those in the self-referred group. The p-value as determined by Mann-Whithey test was 0.000003 in the screened group, and 0.000015 in the other one. These findings provide convincing evidence in support of the public health importance of provider-initiated, organised mammography screening for breast cancer, therefore, the introduction on service basis of organised breast screening into the health care system in Hungary is strongly recommended by the authors.

Correlation of biochemical tumor markers with conventional pathological features in primary breast cancer.

In this prospective study the correlation of pathological with biological prognostic factors and serum tumor markers has been investigated in 574 patients with primary invasive breast cancer. The p53 protein and Bax level correlated positively with tumor size, lymph node status and histological grade. The serum levels of CEA, CA 15.3, TPA-M and TK correlated with tumor extent. There was a significant difference between pre- and postmenopausal breast cancer patients in serum levels of TPA-M and cytosol levels of Bax. Whether these correlations can help in predicting the prognosis of breast cancer by providing additional information with respect to the conventional factors, will have to be investigated by several years of careful clinical follow-up.

[Amyloid goiter]. / Az amyloid golyváról.

Amyloid goitre is at an extremely rare occurrence. Authors review the origin of disease and its symptoms, diagnostic and therapeutic tools. The disease may be due to either primary or secondary systemic or local amyloidosis. Diagnosis may be made even before surgery on anamnestic data, on very rapid growth of thyroid glands, on diffuse appearance, on other symptoms of systemic amyloidosis, on findings of iconographic procedures and on detection of amyloid in aspirates. Final diagnosis is based on histology. Surgical therapy is aiming at avoidance of the existing and the threatening consequences of expanding mass. The outcome is independent from thyroid surgery, it is related to other manifestations of amyloidosis. Concerning with the present case the chronic superior vena cava syndrome and chylous pleural effusion as first described symptoms and asymptomatic hyperthyroxinaemia is emphasised. Neither other organ involvement, nor primary amyloidogenous molecula was found during the 18 months follow up, so patient has secondary and localised amyloidosis.

High frequency of germ-line BRCA2 mutations among Hungarian male breast cancer patients without family history.

To determine the contribution of BRCA1 and BRCA2 mutations to the pathogenesis of male breast cancer in Hungary, the country with the highest male breast cancer mortality rates in continental Europe, a series of 18 male breast cancer patients and three patients with gynecomastia was analyzed for germ-line mutations in both BRCA1 and BRCA2. Although no germ-line BRCA1 mutation was observed, 6 of the 18 male breast cancer cases (33%) carried truncating mutations in the BRCA2 gene. Unexpectedly, none of them reported a family history for breast/ovarian cancer. Four of six truncating mutations were novel, and two mutations were recurrent. Four patients (22%) had a family history of breast/ovarian cancer in at least one first- or second-degree relative; however, no BRCA2 mutation was identified among them. No mutation was identified in either of the genes in the gynecomastias. These results provide evidence for a strong genetic component of male breast cancer in Hungary.

[Malignant schwannoma of the breast]. / Az emlö malignus schwannomájáról.

Authors describe a malignant solitary schwannoma observed in the left breast of a 67-year old woman. Eight months after tumour removal the patient is symptom and complaint-free. The present case of breast schwannoma is the first clinical observation in the national and the 14th one in the world literature.

Changing diagnostic and therapeutic approaches to the 'Ogilvie syndrome'.

The only thing that has remained unchanged about the genuinely described 'Ogilvie syndrome' is its name. Recently it was considered to be an acute colonic pseudoobstruction, a clinical entity mimicking the mechanic ileus of the distal large intestine, without organic obstruction. It is almost always secondary to other diseases. Not all details of the pathogenesis are known, but it has become clear that the direct factor leading to the disturbance of the motility is a vegetative imbalance. X-ray findings are highly characteristic and critical in the planning of treatment. The danger for the patients is the progression of the state or the long duration of the process. Conservative treatment is suitable only for early cases, without complications. In case of failure non-invasive endoscopic or endoscopically assisted minimally invasive procedures may be mandatory. These methods have seen rapid advance in recent years. Uncertain diagnoses or complications call for open surgery. Cecostomy is the solution of choice anyway. The mortality is high in this group of elderly polymorbid patients. Authors compare six of their cases with data collected from the literature.

Surgical chemotherapy in the management of melanoblastoma of the lower extremities.

The therapy of advanced melanoblastomas of the lower extremities is limited. Surgery alone is insufficient due to the extent of the tumor, the radicality of mutilating surgery is questionable because of the existing or suspected subclinical metastasis. To avoid amputation, regional chemoperfusion and simultaneous hemofiltration may be the choice of treatment. Between 1993 and 1995 the authors performed surgical chemotherapy on 21 occasions in 14 patients with advanced melanoblastoma of the lower limb. Partial remission of 4 to 11 months developed in 10 patients, 3 patients achieved subjective improvement for 3 to 6 months, 1 patient had disease progression. Simultaneous application of surgical regional chemotherapy and hemofiltration offers an alternative approach in the management of patients suffering from advanced melanoblastoma.

[Pregnancy and colorectal cancer]. / Terhesség és colorectalis rák.

Among 1761 patients operated on for colorectal malignancies by the authors in a period of 20 years, four cases were diagnosed during pregnancy. Beside analyzing the case-histories they present the relevant literature data: the incidence of colorectal tumors during pregnancy is 4-5 cases/100,000 pregnancies, and most frequently they are situated in the rectum. The prognosis of primary colorectal malignancies diagnosed during pregnancy is unfavourable, and their biological behavior is more aggressive. Authors review the advised diagnostic and therapeutic approaches in different periods of pregnancy.

[Pseudomyxoma peritonei]. / Pseudomyxoma peritonei.

With reference to the clinical courses of three patients treated at the Department of Surgery, National Institute of Oncology, Budapest, the literature on the diagnosis and treatment of peritoneal pseudomyxoma has been reviewed. The disease is considered to be a rare low grade malignancy. Abdominal ultrasonography, computer tomography and laparoscopy are of significance in the diagnosis of this disease which is yet confirmed usually during surgery. The treatment is principally surgical, the results of chemotherapy are modest. The disease has a slow course and is susceptible to recurrence. Despite of early diagnosis and radical surgery cure can be reached rarely.

[Gigantomastia in pregnancy]. / Terhességi gigantomastia.

A 26 year old women presented with huge enlargement of breasts from 10th week of her first pregnancy. Both breast became very swollen and painful, more than tripled in size. The skin became oedematous, red, and subsequently ulceration and bleeding occurred. Interruption performed at the 12th week, it didn't stop the process. 3 months later bilateral mastectomy with free transplantation of the nipples and the areoles to the abdominal wall was performed. The pathologic diagnosis was hyperplasia of the connective tissue elements with fibroadenomas. 6 and 8 years later she delivered healthy babies. The authors review the literature of gigantomastia during pregnancy with discussion of the treatment.

[Multiple fibrous pseudotumor of the great omentum]. / A cseplesz multiplex fibrosus pseudotumora.

The authors describe a case of multiplex fibrous pseudotumor of the great omentum that developed in a 15 year-old man and was treated by surgical resection. They discuss the clinical and pathological differential diagnostic problems and give a review of the omental tumors and pseudotumors. The occurrence of pseudotumors in the abdomen is rare and these are mostly inflammatory variants. On our knowledge this case is one of the first of multiplex fibrous pseudotumor simulating fibroma that was localized in the great omentum.

An analysis of breast cancer in Hungary: experience of the National Institute of Oncology, Budapest.

Breast cancer is the most common type of cancer in women throughout the world (18%), with a yearly morbidity that is already over half a million. Its incidence in Hungary is increasing in each age group, and the mortality is strikingly high. This study was conducted to assess the effectiveness of breast-conserving surgery in comparison to more radical surgery on a large group of patients. During the 15 years between 1980 and 1994, a total of 6,358 patients with primary breast cancer underwent surgery at the National Institute of Oncology in Budapest, Hungary, as breast-conserving surgery in 2,026 patients (31.8%). Breast-conserving surgery is being performed in an ever-increasing number of patients, followed by adjuvant radiochemotherapy in premenopausal patients, or radiohormone therapy in menopausal patients. During follow-up, recurrence was found in only 5.9% of the patients who underwent breast-conserving treatment. Thus, according to our experience, breast conservation therapy for the management of breast cancer offers favourable results, provided that the preconditions to this treatment are adequately met.

Cancer of the breast in young women.

Between 1966 and 1986, 126 women below the age of 35 years were treated for cancer of the breast. The course of the disease in this group was compared to that in patients aged between 35 and 55 years, and in those aged 55 years and over. The 5-year survival was 51.7% below 35, 63% between 35 and 55, and 73.5% in patients aged > or = 55 years. Negative or positive findings of axillary lymph nodes decisively affect the survival. The authors found no interpretation for the poor prognosis of breast cancer of young women.

Thymic cysts. Report of 10 cases.

Among 984 mediastinal tumours in the authors' series, 10 thymic cysts were found; one of the cysts extended to the neck. The literature is reviewed in relation to the aetiology, pathogenesis, pathology, diagnostic features, differential diagnosis, therapy and prognosis of thymic cysts.