Increased activity of nm23-H1 gene in squamous cell carcinoma of the head and neck is associated with advanced disease and poor prognosis.

The present study was undertaken to determine whether the nm23-H1 gene is expressed in squamous cell carcinoma of the head and neck (SCCHN) and whether the level of nm23-H1 protein or mRNA in cells vary as they progress to a more malignant phenotype. Of the 120 SCCHN studied 54 (45%) stained positively for nm23-H1 protein. Protein expression was significantly higher in more advanced stages of disease. Expression of nm23-H1 was significantly higher in cancer tissues than in normal, adjacent tissue, dysplasia, or carcinoma in situ. The nm23-H1 rate increased with progression of synchronous lesions from dysplasia to carcinoma in situ and finally to carcinoma (P<0.05). Northern blot analyses of tissues with various clinicopathological characteristics also revealed differences in nm23-H1 mRNA expression. When levels of nm23-H1 mRNA were compared to tumor stage, intensity of expression was found to be higher in stages 3 and 4 than stages 1 and 2 (P<0.01). Malignant tumors had a higher level of mRNA nm23-H1 expression than normal or premalignant tissues. The nm23-H1 negative patients survived significantly longer than nm23-H1 positive ones (P<0.05). To study the possible relationship between nm23-H1 gene expression and cell growth rate in tumor cells, the mRNA level in each tumor was compared to proliferative activity. The nm23-H1 gene expression levels were directly related to the [3H]thymidine labeling index in tumor cells (R=0.6681). Our results strongly indicate that the nm23-H1 gene is involved in progression of SCCHN. Together with results obtained on lung cancer, our observations suggest that increased expression of nm23-H1 in cancers of the upper aerodigestive tract may have different implications than elsewhere in the body.

Expression of cyclooxygenase-2 in fine-needle aspirates from breast carcinoma and benign breast diseases.

Numerous studies have demonstrated that the levels of cyclooxygenase (COX), the enzyme that catalyzes the conversion of arachidonic acid to prostaglandin H(2), and of prostaglandins are higher in various tumors and cells during inflammation than in normal tissues. The aim of the present study was to analyze whether COX-2 isoform expression was noticeably higher in fine-needle aspirates (FNA) from breast carcinoma than in FNA from fibroadenoma and fibrocystic breast tissue. COX-2 expression was detected by immunocytochemical (IC) staining and was analyzed by microscopic scoring and computer gray-scale analysis. Evaluation of COX-2 IC positivity in FNA from three groups of patients (nine with breast carcinoma, nine with fibroadenoma, eight with fibrocystic breasts) revealed high COX-2 IC positivity in the majority of patients with breast carcinoma and low or absent COX-2 IC positivity in patients with fibrocystic breast changes. In addition, low or medium COX-2 IC positivity was found in the majority of patients with fibroadenoma, only three of these patients having high COX-2 IC positivity.

The management of war wounds to the extremities.

We present our experience in the treatment of war wounds in 174 patients treated in the Institute of Plastic and Reconstructive Surgery, Department of Surgery, Clinical Hospital Center in Zagreb. The wounds were divided into four categories depending on the type of injury and the extension of the soft tissue defect which showed the differences in primary excision and reconstruction of wounds. Patients were placed in one of two groups depending on their primary treatment and time of definitive reconstruction. Group A comprised 79 patients who were initially treated by plastic surgeons and whose reconstructive procedure was done within five days. Group B comprised 95 patients who were initially treated in a field hospital and referred later to the plastic surgery unit for definitive reconstruction more than five days after the injury. Sixty-nine (87%) of the patients in group A had only one or two debridements before definitive closure and stayed in hospital 20 days or less. In group B, 59 (62%) of the patients required three or more debridements before definitive closure and remained in hospital more than 21 days (p < 0.001). Proper primary treatment and early reconstruction result in significantly shorter duration of hospital stay and lead to more effective rehabilitation and recovery of the patients. A knowledge in terminal ballistics is important in the understanding of the pathophysiology of war wounds.

Early diagnosis and treatment of ectopic pregnancy.

During the period from 1995 to 1999, 64 patients were treated for ectopic pregnancy. All patients admitted to the department passed the same procedure including (complete preoperative laboratory findings, Beta HCG, serum progesterone and transvaginal colour Doppler). In patients who had ultrasound finding typical for ectopic pregnancy in combination with positive Beta HCG, conservative treatment was primarily done. In the rest of the patients, Beta HCG was tested every second day and in combination with the clinical and vaginosonographical findings the patients underwent diagnostic or operative laparoscopy. Out of 64 patients 36 had visible ectopic pregnancy when admitted to the clinical department. Three patients had no visible ectopic pregnancy neither at the time of their admission to the department nor at the time of laparoscopy. One of them had cervical pregnancy and the other two had pregnancies in the uterine part of the tube. The patient with cervical pregnancy was treated with metrotrexat (MTX) 12 mg daily in 5 doses. One patient with cornual pregnancy was treated with high doses of oxytocin infusion in combination with MEB intravenously 3 x 1 amp. The other patient with cornual pregnancy underwent laparoscopy with cornual resection and salpingectomy. Four of other tubar pregnancies were treated with metrotrexat 12 mg/day for 5 days. Other ectopic pregnancies were treated as follows: 36 laparoscopic salpingectomies, 10 laparoscopic salpingotomies with ovum expression, 9 adnexectomies by laparotomy, and 2 laparoscopic adnexectomies.

Surname as 'cancer risk' in extreme isolates: example from the island of Lastovo, Croatia.

The aim of this study was to analyze whether there are surnames which appear more frequently among the ancestors of cancer cases in a small isolate, in comparison to the ancestral surnames of the healthy controls, using the classic case-control design. The chosen setting was the island of Lastovo, Croatia, located more than 100 kilometers from the nearest coastal region. The period of study was 1970-1995, during which a total of 76 cancer cases were recorded in a population of approximately 800. The comparison of surname frequencies was performed in current and in five ancestral generations. The leading hypothesis was that, if inbreeding and common ancestry contributed to the development of the disease, then those phenomena should be reflected in increasing frequency of some surnames among ancestors, identifying the 'hidden' consanguinity, or 'following' cancer-promoting genes on the Y-chromosome. The results imply that there are surnames representing a classic "risk" for cancer, but also those "protecting" from its development, which all underscores the importance of founder effect and genetic predisposition to the disease in a small, reproductively isolated population. All of the results become more evident and increasingly significant when analyzed in more distant ancestral generations.

[Current use of bisphosphonates in clinical oncology]. / Primjena bifosfonata u internistickoj onkologiji.

Bisphosphonates represent nowadays a standard therapy of tumor induced hypercalcemia and are progressively more used in the treatment of tumor bone metastatic disease. Among several bisphosphonates, pamidronate is one of the most commonly used in clinical practice, so we also used it in succesful treatment of patients with breast cancer bone metastases. It has been shown that pamidronate reduces the frequency of hypercalcemia, bone pain and pathological fractures, although the mechanisms by which these effects are achieved are not completely clarified. Bisphosphonates are also important not only in treating patients with present metastases but also in prevention, or at least, delay of bone metastases onset. Recently, there are clinical trials examining the so called adjuvant therapy, that means the use of bisphosphonates in prevention of bone metastases in high risk breast cancer patients without distant metastases. In addition to breast cancer, multiple myeloma is another area of successful bisphosphonate application. In this paper we present some of the clinical results following the use of pamidronate in breast cancer- and hypernephroma-patients with hypercalcemia.

[Microdochectomy with perioperative dye localization of ducts in patients with nipple secretion]. / Mikrodohektomija s perioperativnim bojenjem izvodnih kanala kod sekrecije iz dojke.

A series of 1321 women having a discharge from the nipple were examined at the outpatient clinic. Of seven basic types of discharge: milky, multicolored, purulent, watery, yellow (serous), serosanguineous and bloody, only the last four represent and indication for surgery. Galactography was performed in 55 patients as a necessary element in the surgical plan of management. In 36 women, the operation of microdochectomy was indicated, but only 24 accepted to be subjected to that procedure. The authors describe a new technique of colour mammary ductal localization which identifies the duct from which the discharge is emerging and assures its complete excision. The procedure combines preoperative methylen blue dye injection followed by periareolar incision of the involved duct using a pair of binocular loops for magnification of the nipple. In all tissue specimens, the cause of a pathological discharge was found: 15 (62.5%) cases presented with fibrocystic disease, and in 6 carcinoma was present. This technique provides a safe and effective method of complete excision of the pathologically involved mammary duct with good cosmetic results.

[Hormonal therapy with aromatase inhibitor in advanced breast cancer]. / Hormonsko lijecenje uznapredovalog raka dojke blokatorom aromataze.

We investigated the aminogluthetimide therapy effect on 30 postmenopausal women with advanced breast cancer previously treated with tamoxifen as a first-line hormonal treatment. Aminogluthetimide exhibits anticancer effect by inhibition of aromatase enzyme which plays a key role in the conversion of androgen to estrogen in peripheral adipose tissue. This pathway presents the main source of estrogen in postmenopausal women. Mean duration of the treatment was 14.3 months. Complete remission has been achieved in 10% of all patients, and partial remission in 16.6%. Mean duration of free intervals was 16.1 months in the group with ER+/PgR+ hormonal status, which is significantly longer compared to the ER+/PgR- and ER-/PgR+ groups where it was 11.8 months (p < 0.01). Aminogluthetimide treatment led to significant decrease in estradiol (E2) and dehydroepiandrosterone-sulphate (DHAS) levels in plasma. Thus, the effect of aminogluthetimide therapy as a second-line hormonal therapy has a benefit in the treatment of metastatic hormon-dependent breast cancer patients.

[Surgical management of war injuries involving soft tissue defects]. / Kirurski postupak kod ratne rane s manjkom mekog tkiva.

In this article, the authors emphasize that the knowledge of terminal ballistics is important for understanding of the pathophysiology of war wounds. They present their own experiences in the treatment of war wounds in 126 casualties, treated in the Institute of Plastic and Reconstructive Surgery, Department of Surgery, Clinical Hospital Center, Zagreb. About 96% of the wounded sustained extremity injuries, while head, neck and thoracoabdominal injuries appeared in a significantly smaller number of cases. War wound were divided into four main categories with regard to type of injury and extension of soft-tissue defect, thus showing the differences in primary excision and in reconstruction of the wounds; 78.6% of head and neck injuries were treated by primary or early primary reconstruction (within three to five days after the injuries have been sustained), while 45.4% of thoracoabdominal injuries were treated by a secondary closure. The greatest number of sophisticated reconstructions were used in extremity injuries (15 wound were reconstructed by local flaps, while free flaps were used in 8 cases). The authors emphasize the importance of proper primary treatment which enables an early reconstruction. This results in significantly shorter hospitalization, so that 87.5% of patients were treated within 20 days and then transferred to early rehabilitation.

[Developmental and involutional breast disorders]. / Razvojna i involucijska poremecenja dojke.

The majority of benign breast disorders may be classified as developmental and involutive. Mastalgia and breast nodularity represent the greatest groups of these disorders, while epithelial hyperplasia is a complex benign disorder which is most difficult to be evaluated. Sixty women with diagnosis of cyclic mastalgia and 30 with noncyclic breast pain were followed-up. Patients were administered bromocryptine, danazol or a local progestogel. Better treatment results were achieved in cyclic mastalgia than in women with noncyclic mastalgia. One hundred and forty-five biopsies of the benign breast tissue were examined histologically. Nonproliferative forms were found in 66.9% of the women, proliferative without atypia in 29.65%, and proliferative with atypia in 3.45% of the patients. Atypical ductal hyperplasia and atypical lobular hyperplasia increase four-to fivefold the risk for breast cancer. Prophylactic subcutaneous or total mastectomy is not as a rule indicated in atypical epithelial hyperplasia, only regular follow-up is required.

[An anatomic study of the septofascial layer in the forearm]. / Anatomsko istrazivanje septofascijalnog sloja podlaktice.

In the anatomical investigation the authors dissected 20 fresh cadaveric forearms to study septofascial layers. It's vascularization was based on radial artery and concomitant veins. We perfused those flaps with methylene blue in the proximal part of radial artery. In 10 cases we found fine vascular network colored in blue. In the second group we isolated free septofascial tissue which was perfused with radiopaque contrast Hexabrix. Five flaps were perfused in the proximal part of vascular pedicle and five in the distal part. Afterwards the radiographs confirmed good vascular network, independent of flow direction. Fascia dimension in the proximal part of the forearm varied from 7-15 cm and in the distal part from 6-10 cm, depending on the forearm size. Fascia length varied from 21-27 cm. The authors found thicker and stronger fascia in the ulnar part of the forearm. The length of vascular pedicle was reversely proportional with the flap dimension. This anatomical investigation may find it's greatest application in plastic and reconstructive surgery.

One-stage reconstruction of war wounds with free osteocutaneous flaps.

Thirty-one patients with traumatic osteocutaneous defects of the extremities sustained during the war in Croatia and Bosnia and Herzegovina were treated at the Institute of Plastic-Reconstructive and Breast Surgery in Zagreb. Injuries were categorised using the Mangled Extremity Syndrome Index (MESI). The average length of bone defect was 5.9 cm (range 4-12 cm). Patients were divided in two groups according to the time they had reconstruction with a free osteocutaneous flap: group 1, within 6 days after injury, and group 2, after more than 6 days. The mean time to reconstruction in group 2 was 5.2 weeks. Average time to solid bone union was 13.3 weeks in group 1 and 16.6 weeks in group 2. Functional outcome was better in group 1 with fewer complications, smaller number of operations and shorter hospital stay. One-stage reconstruction of osteocutaneous defects with free composite flaps provides reliable treatment solution with good functional outcome.

Metronidazole in the treatment of chronic radiation proctitis: clinical trial.

AIM: To evaluate the effectiveness of metronidazole in combination with corticosteroids in enema and mesalazine (5-aminosalicylic acid) in comparison with the same protocol without metronidazole in the treatment of chronic radiation proctitis. METHODS: Sixty patients with rectal bleeding and diarrhea were randomly divided into two groups. Patients in the first group were treated with metronidazole (3x400 mg orally per day), mesalazine (3x1 g orally per day), and betamethasone enema (once a day during 4 weeks). Patients in the second group were treated with mesalazine and betamethasone enema, but without metronidazole. The efficacy of metronidazole was assessed on the basis of rectal bleeding, diarrhea, and rectosigmoidoscopy findings in all patients. RESULTS: The incidence of rectal bleeding and mucosal ulcers was significantly lower in the metronidazole group, 4 weeks (p=0.009), 3 months (p=0.031), and 12 months (p=0.029) after therapy. There was also a significant decrease in diarrhea and edema in the metronidazole group, 4 weeks (p=0.044), 3 months (p=0.045), and 12 months (p=0.034) after treatment. CONCLUSION: Metronidazole in combination with mesalazine and betamethasone enemas successfully treats rectal bleeding and diarrhea in chronic radiation proctitis.

High-energy war wounds: flap reconstruction.

In this article, we emphasize that knowledge of terminal ballistics is essential for understanding the pathophysiology of war wounds. We present our own experiences in treatment of high-energy war wounds in 75 patients treated in the Institute of Plastic and Reconstructive Surgery, Department of Surgery, Clinical Hospital Center in Zagreb. Patients were divided into three groups with regard to the time of definite reconstruction, using local or free microvascular flaps. About 12% of patients underwent flap reconstruction in the acute phase, associated with low complication rate and the shortest hospital stay. Group II was comprised by 18% of the patients and, considering the number of complications, presented the most unfavorable time for reconstruction. Flap reconstruction in the chronic phase resulted in a substantial prolongation of the hospital stay in 82% of patients. Therefore, we advocate proper primary treatment of wounds aimed at early flap closure. This type of management results in a significantly shorter hospitalization and leads to more effective rehabilitation and recovery of patients.