Experimental and clinicopathologic studies on the function of the HGF receptor in human colon cancer metastasis.

The organ-specific metastasis characterizes several human cancers, including colon carcinoma, a disease that frequently involves metastases in the liver. The data on the molecular mechanisms of liver metastasis would therefore be highly useful for prognostic purposes. Although the upregulation/amplification of the hepatocyte growth factor (HGF) receptor, c-met, has been frequently observed in colon cancer metastasis, the actual functional significance of the feature in the liver metastatization is not yet known. We have used three human colon carcinoma cell lines (HT29, HT25 and WiDr), characterized by different liver metastatic potentials in SCID mice, to analyze the expression of c-met and the biological effects of HGF. We found that HGF induces scattering in in vitro liver-metastatic cell lines (HT25 and WiDr) only at doses which are non-mitogenic (1-20 ng/ml). Analysis of the c-met expression revealed that the metastatic cell lines express authentic c-met gene and protein material, unlike the non-metastatic HT29 cell line, which expresses only the c-terminal cytoplasmic domain of the c-met beta-chain. Interestingly, c-met was found to be localized in the substrate-attached peripheral membrane and partially colocalized with phosphotyrosine-proteins in the metastatic cells only when kept on fibronectin. On the other hand, we have analyzed 86 primary human colon cancers in Dukes' B (invasive but non-metastatic) and C (invasive and lymph node metastatic) stages. Western blotting of the proteins isolated from the tumor tissues and immunohistochemical control study on the paraffin samples of a third of these cases (25/86) all indicated a significant upregulation of the c-met protein in the Dukes' C tumor glands compared to the Dukes' B stages (P < 0.001 and P < 0.05, respectively). Since the two stages differ in the involvement of the regional lymph nodes but not in the invasion depth, the clinicopathological data and our experimental findings further support the notion that the c-met expression in human colon cancer can be considered as a marker of the metastatic potential due to its involvement in the generation of the motility signal.

The time-course of metastases from breast cancer after mastectomy and breast-conserving surgery with and without isolated local-regional recurrence.

We have examined time intervals between events in 390 metastatic breast cancer (MBC) patients whose distant failure developed within 10 years from initial surgery of Stage I/II disease. All of the patients underwent axillary dissection and mastectomy (n=295) or breast-conserving surgery (BCS, n=95), between 1983 and 1987. Distinctions have been made between distant failure with (n=79) and without (n=311) isolated local-regional recurrence (LRR). The median survival time after first relapse was significantly longer with intrabreast (30 months) and chest wall (24 months) than with distant relapse (15 months), but with axillary (17 months) or with supraclavicular (17 months) relapse survival was similar. The delay between LRR and distant metastasis was shorter with axillary (7 months) and supraclavicular (9 months) than with breast (20 months) and chest wall (12 months) recurrences. The median postmetastatic survival time by site of first relapse was significantly shorter with supraclavicular (6 months) and axillary (9 months) than with distant site relapse (15 months) but with intrabreast (12 months) or with chest wall (11 months) recurrence survival was similar. In MBC, regional recurrences are associated with a shorter interval between events than with local recurrences. The shortened intervals for patients with regional recurrence suggest that metastases existed at the time of initial surgery. The question of whether prevention of local or regional recurrence or both improves cause-specific survival after mastectomy or BCS needs to be answered in randomized studies.

Male breast tumours.

The data of 63 male breast cancer patients treated between 1967 and 1990 in the Department of Surgery of the National Institute of Oncology are described. Beside the 59 breast cancer cases four tumours of other histologic type were also detected. As to surgical treatment, in addition to mastectomy, the axillary block dissection is regarded as important in each case. The prognosis is mainly determined by the time elapsed until treatment and by the lymph node status. The mean survival of the axillary node negative patients was 116 months, compared to that of 38.9 months found in axillary node positive cases. Metastases were the soonest detected 2 years following surgery, altogether in 36 cases (61%). Local recurrence developed in eight patients (14%). Steroid hormone receptor investigations have been performed since 1980; of the 27 patients examined estrogen receptor positivity was seen in 25 cases. The hormone receptor study of the tumour and the assessment of the hormonal status of the patient provide valuable information for the treatment. In case of tumour progression the life of the patient might considerably be prolonged by combined hormone and cytostatic therapy.

Correlation between colon adenoma and cancer.

In the course of 1301 colonoscopies performed by the authors, in cases of 127 patients (9.76%), 177 polyps were removed; 159 (89.83%) out of them proved to be adenomas by histology. In 23 adenomas (14.46%) malignant transformation was observed. The highest percentage of polyps was detected in the group of patients with tumours, and a somewhat lower proportion was found in the case of patients who underwent resection surgery because of tumours. A similar tendency could be seen concerning the malignant transformation of the removed adenomas. Our data seem to support the theory by Morson and Hermanek regarding the transformation from adenoma to cancer in the large bowel. Surgery is proposed in the following types of colon polyps: (1) polyps unremovable by endoscopic polypectomy, even by piecemal snare excision; (2) invasion (adenoma with invasive adenocarcinoma)--if the tumour is situated within a 3 mm distance from the resection line; (3) following endoscopic removal of polypoid adenocarcinoma (in this case the site of polypectomy can be marked by preoperative injection of ink or in the course of intraoperative colonoscopy); (4) in the case of complications of endoscopic polypectomy (perforation, bleeding uncontrollable by conservative or endoscopic means); (5) colotomy and polypectomy should be performed when the adenoma cannot be reached with the endoscope--for technical reasons--and the intraoperative method cannot be used under the conditions of an open abdomen but without the necessity of opening the bowel.

Ovarian metastases of colorectal tumours.

The authors, based on their own experience and review of the literature, discuss the incidence of ovarian metastases of patients with colorectal tumours. They take a stand for the prophylactic oophorectomy in the management of female patients over 40 years operated on for rectal cancer localized on the left colon side.

Intraoperative colonoscopy.

The authors performed intraoperative colonoscopy in 31 patients. This examination is done if preoperative colonoscopy was not performed or incomplete, and intraoperative difficulty occurs. In addition, it is indicated to localize non-palpable lesions, to perform polypectomy (if unsuccessful preoperatively but manageable intraoperatively), to define the site of endoscopic polypectomy, in certain instances to determine the resection plane, and after resection of constrictive tumours to look over the proximal intestinal section, to detect the synchronous lesions. It is emphasized that by their method the opening of the lumen becomes avoidable thus resulting in a decreased postoperative morbidity and mortality.

Comparative evaluation of manual and instrumental rectum resections.

The authors compared the perioperative results of 125 + 125 Dixon operations performed at two time intervals (1956-1979 and 1985-1990), the postoperative recurrences and the survival data. It is established that, from the anastomosis point of view, the instrumental resections--beside their rapidity and favourable sterility--are safer interventions associated with less complications. With respect to local recurrences the two methods do not differ significantly. A further advantage of the double stapling is that a larger number of patients can undergo a sphincter-saving resection, and a lower lying anastomosis can be performed than with hand-sewn sutures.

Immunohistochemistry and reverse transcriptase polymerase chain reaction on sentinel lymph nodes can improve the accuracy of nodal staging in breast cancer patients.

In this study the nodal staging sensitivity of sentinel lymph node biopsy (SLNB) with detailed pathological and molecular biological examination has been investigated and compared to that of axillary lymph node dissection (ALND) with routine histological evaluation. Sentinel lymph nodes (SLNs) were removed by the dual-agent injection technique in 68 patients with primary, clinically node-negative breast cancer. Forty-seven patients had negative SLNs according to hematoxylin and eosin (H&E) staining. These H&E-negative SLNs were serially sectioned and examined at 250 microm levels by anticytokeratin immunohistochemistry (IHC). In 14 patients the SLNs were also investigated by cytokeratin 20 (CK20) reverse transcriptase polymerase chain reaction (RT-PCR). SLNB with IHC increased the node-positive rate by 26% (by 40% in tumors less than or equal to 2 cm in size (pT1) and by 9% in tumors more than 2 cm but less than or equal to 5 cm in size (pT2)). The sensitivity of SLNB with IHC was superior to that of ALND with routine histology in pT1 tumors and identical in pT2 tumors. The concordance between histology and RT-PCR was only 21%, and in two of three cases with positive histological results RT-PCR was negative. In conclusion, SLNB with detailed pathological and/or molecular biological evaluation can improve the sensitivity of regional staging. ALND can probably be abandoned in patients with pT1 SLN-negative breast cancer. Further prospective studies are required to determine the clinical significance of these detailed SLN evaluation techniques, but at present these methods are still investigational.

Alterations of K-ras and p53 mutations in colorectal cancer patients in Central Europe.

Many molecular investigations of colorectal cancer (CRC) have suggested that the accumulation of specific mutations in proto-oncogenes and tumor suppressor genes regulating cell growth via signal transduction trigger the stagewise progression to malignancy. In this study, the frequency, location, and type of mutations of the K-ras proto-oncogene exon I and p53 tumor suppressor gene exons 5-8 were analyzed in colorectal carcinomas of 65 patients from Central Europe, using polymerase chain reaction (PCR)-cold single-strand conformation polymorphism (SSCP) screening and direct sequencing. The incidence of K-ras activating mutations in these Central European samples was lower (25%) compared to that obtained in American and western European populations (40-50% at least), while the incidence of p53 inactivating mutations was similar (58%). These results suggest that some other genetically linked mechanisms may play a role in CRC development and progression, and hence K-ras and p53 mutations cannot be considered to be universal genetic markers for CRC.

Inguinal sentinel lymph node biopsy for staging anal cancer.

BACKGROUND AND AIMS: The optimal treatment of clinically negative inguinal lymph nodes in patients with primary anal cancer has not yet been clearly defined. The presence of metastases in the inguinal lymph nodes is an adverse prognostic factor for anal cancer. In the present study the feasibility of sentinel lymph node biopsy (SLNB) for staging anal cancer was investigated. PATIENTS AND METHODS: From September 1999 to March 2002, 8 patients with biopsy proven primary anal cancer underwent lymphoscintigraphy and dual-agent guided inguinal SLNB for nodal staging before starting multimodality treatment. RESULTS: Inguinal SLNB was successful in all 8 patients (13 groins). A total of 20 hot and blue SLNs (mean 1,5 (1-2) per groins) were removed. In 2 patients (25%) the SLN was positive for metastasis. CONCLUSIONS: Lymphoscintigraphy followed by dual-agent guided inguinal SLNB is technically feasible for staging patients with primary anal cancer. The detection of metastases in the removed sentinel lymph node(s) may alter the treatment and thus may improve the locoregional control and overall survival of these patients.

Endoscopy and autopsy follow-up of biodegradable oesophageal anastomoses in dogs.

The biofragmentable Anastomosis Ring (BAR) is a mechanical device composed of absorbable material and creates an inverting, atraumatic compressive anastomosis with no foreign material at the anastomotic site after healing. The aim of the present experimental study was to assess the safety of oesophagoscopy in early days after oesophageal anastomoses performed with the BAR and to follow-up the healing of BAR anastomoses by in vivo endoscopy and autopsy examination. Thirty mongrel dogs divided into subgroups according to the time-points of endoscopy and autopsy (4th, 7th, 14th, 28th day) were used. There was no significant difference in the healing of anastomoses performed under or above the tracheal bifurcation. Pleural adhesions helped to cover and seal small subclinical leaks. The mortality was 13.3% (4 dogs) and the overall leakage rate 14.3%. We looked for bleeding, haematoma, erosion, ulceration and granulation tissue in the anastomosis. Due to the high mechanical strength of these anastomoses, oesophagoscopy was a safe, easy and feasible method for follow-up BAR intrathoracic anastomoses, with no significant difference between the number of lesions found with endoscopy as compared to the autopsy data. The overall sensitivity of oesophagoscopy to discover mucosal lesions was 73.1%. Endoscopy had no complications, therefore it is a useful method of follow-up and may help predict the normal or compromised healing of oesophageal anastomoses.

[CT examination of diverticular sigmoiditis]. / A sigmoiditis diverticularis CT-vizsgálata.

The authors deal with the incidence of sigmoid diverticulosis in Hungary. The pathomorphological types of the inflammatory complications (pericolic inflammation, abscess, abscess-phlegmon, chronic phlegmonic diverticulitis) are discussed in details. It is pointed out that besides the examinations available so far (irrigoscopy, colonoscopy), the clinical picture decided the question of whether or not the inflammatory complication required surgical treatment. CT examination offers a new possibility as well as an examination free of complication which furnishes more exact information as compared to every method used so far to the determination of the inflammation and thus to the decision of using surgical or conservative therapy.

[Giant lipoma of the ligamentum teres hepatic]. / A ligamentum teres hepatis nagy kiterjedésü lipomája.

The authors succeeded in removing a lipoma of 20 x 18 x 15 cm in size. It originated from the ligamentum teres hepatis of a 66-year old man. This is the first case described in the Hungarian and second in the world literature. Based on their observations the anatomy, physiology and pathology of the ligamentum teres hepatis are discussed.

[Surgical complications in colorectal tumors]. / Colo-rectalis daganatok mütéti szövödményei.

Complications of elective surgery on 510 colo-rectal cancer patients are reported. Mortality rate of the operations was 4.9% and complications were observed in 10% of the cases. Intraoperative and early postoperative (10%) as well as late (8.6%) complications have been differentiated. Causes and possibilities for preventing complications are analyzed.

[Surgical treatment of pulmonary metastases of colorectal tumors]. / A colo-rectális daganatok pulmonális áttéteinek sebészi kezelése.

In 22 cases of the 510 patients underwent surgery and followed up because of colorectal cancer, only pulmonary metastases were found. General problems in the surgery of pulmonary metastases are discussed and the possibilities and the expected results of the surgical therapy of pulmonary metastases in colorectal patients are analysed in details on the base of the data of their 8 patients underwent surgery and according to the literature. In carefully selected cases the surgical therapy of the metastases can be recommended.

[Experience in the treatment of breast sarcomas]. / Az emlösarcomák kezelésében szerzett tapasztalataink.

Authors operated on 6339 malignant breast tumors at the Department of Surgery, National Institute on Oncology between 1980 and 1994. The records of 14 patients with sarcomas of the breast were analyzed. These included 2 malignant phyllodes tumors, 3 malignant fibrous histiocytomas, 2-2 fibrosarcomas and carcinosarcomas and liposarcoma, angiosarcoma, leiomyosarcoma, osteosarcoma and dermatofibrosarcoma protuberans one of each. During this period 5 patients died, 9 are living without evidence of tumor. Analysing these 14 cases authors present their policy in surgical therapy of breast sarcomas compared with literature data. They emphasise the importance of wide resection margins for prevention of tumor progression. The above mentioned principle is valid for local recurrences so radicalization of the previous conservative breast surgery may be necessary in selected cases. Intraoperative histological examination is recommended to verify that the resection margins are tumor free. Axillary block dissection is not necessary except in cases when palpable, firm lymph nodes are present in the region. Depending on the histological grade adjuvant radiotherapy could be considered but its effectiveness is not proven.

[Aspiration cytology in the diagnosis of gastrointestinal tumors]. / A tápcsatorna daganatainak aspirációs citológiai vizsgálatáról.

Early experiences with the new endoscopic aspiration cytology method in the diagnosis of gastrointestinal malignancies are discussed. It was performed in five patients in case of gastric and cardiac cancers and in fifteen ones of colon tumours. Results are compared with those of biopsies and brush cytologies. The new method is quick, reliable and suggested to be widely used in the gastrointestinal endoscopy.

[Leiomyosarcoma in the male breast]. / Leiomyosarcoma férfi emlöben.

Leiomyosarcoma of a 61 y.o. male's breast was removed by the authors. This observation is the first in the Hungarian and third in the world literature. Short survey is taken of the aetiology, prognosis and therapeutic possibilities of male breast cancers.

[Diagnosis and therapy of metastatic and recurrent colorectal tumors]. / Metastatikus és recidiv colo-rectalis daganatok diagnosztikája és terápiája.

77 patients were treated by the authors because of recurrent or metastatic colorectal cancers. Follow-up protocol of elective surgery is discussed with respect to the two different types of surgery that is those performed because of colon and rectal cancer, respectively. The diagnostic and therapeutic principles as well as the results gained by the authors are discussed in details in case of the different types of recurrent and metastatic tumours (anastomotic recurrence, metachron tumour, local recurrence, hepatic, pulmonary, lymph node and osseal metastasis). In contrast to the previous principles a more active surgical therapy is advised by the authors in case of recurrence and metastases of colorectal cancers.

[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.