Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.     

Leberresektionen wegen primärer lebermalignome Eigene ergebnisse und literaturanalyse

Zusammenfassung Im Rahmen einer retrospektiven Untersuchung wurden 50 Resektionen wegen primärer Lebermalignome, die vom 1. 6. 1979 bis zum 31. 12. 1991 an der Chirurgischen Universitätsklinik Köln durchgeführt wurden, analysiert. Die Resektionsrate betrug 28 %. Die Kliniksletalität betrug insgesamt 22 % und konnte in den letzten 5 Jahren auf 4% gesenkt werden. Die Ein-, Dreiund Fünfjahresüberlebensraten betrugen unter Einschluß der Kliniksletalität 55%, 30% und 24%. Wichtigster Prognosefaktor war die chirurgische Radikalität. In einer Literaturanalyse wurden die Ergebnisse von 8725 Leberresektionen wegen primärer Lebermalignome, die zwischen 1980 bis 1992 publiziert wurden, untersucht. Die Resektionsrate betrug im Durchschnitt 32 ± 17%. Die Kliniksletalität konnte von 15 ± 5% (Resektionen vor 1970) auf 6 ± 2% (Resektionen nach 1980) gesenkt werden. Die Ein-, Drei- und Fünfjahresüberlebensraten betrugen 66 ± 17%, 39 ± 15% und 27 ± 10%. Bis auf eine geringere Kliniksletalität asiatischer Studien (4 % vs. 7%) waren die Resektionsraten und Langzeitergebnisse von asiatischen, amerikanischen und europäischen Studien durchaus vergleichbar. Die Langzeitprognose wird in erster Linie durch die erreichte chirurgische Radikalität sowie die Größe und Ausdehnung des Tumors zum Zeitpunkt der Resektion beeinflußt. Die Effektivität adjuvanter Therapien ist noch nicht ausreichend untersucht.

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Liver resection for primary liver tumors. Our own results and an analysis of the literature

In a retrospective study we analysed 50 resections for primary liver tumors performed between 1 July 1979 and 31 December 1991 at the Department of Surgery of the University of Cologne. The mean resectability rate was 28 %. Hospital mortality after resection was 22% and could be reduced to 4% during the last 4 years. The overall survival rates after 1, 3 and 5 years were 55%, 30% and 24% respectively. The surgical radicality is the most important prognostic factor. In a review of the literature the results of 8,725 resections for primary liver malignancies published between 1980 and 1992 were analyzed. The mean resectability rate was 32 ± 17%. The hospital mortality after resection could be reduced from 15 ± 5% (resections before 1970) to 6 ± 2 % (resections after 1980). The overall survival rates after 1, 3 and 5 years were 66 ± 17%, 39 ± 15% and 27 ± 10%, respectively. Apart from a lower hospital mortality in Asian studies (4 % vs. 7 %) the resection rates and long-term results of Asian, American and European studies were similar. Long-term prognosis predominantly depended on the surgical radicality and on the size and extension of the tumor at the point of resection. The effectivity of an adjuvant tumor therapy is not analyzed sufficiently.

     

雌激素对内膜癌细胞中FAK基因转录的影响

目的定量观察雌激素刺激后内膜癌细胞的焦点粘连激酶（Focal—adhesion kinase，FAK）转录水平。方法不同浓度的17β-雌二醇体外刺激雌激素敏感的内膜癌细胞株RL95—2。加用三苯氧胺或ICI 182，780雌激素拮抗剂的细胞及未加雌激素的细胞设为阴性对照。经不同作用时间后，采用实时RT—PCR方法测定处理后的细胞内FAK的mRNA水平。结果在给予不同浓度的雌激素共培养1d或5d后，细胞的FAK基因的转录水平对比阴性对照细胞无明显改变。结论雌激素对内膜癌细胞的FAK转录可能无显著影响。FAK基因在内膜癌组织中的过度表达的机理需要进一步深入研究。     

Chronic renal failure and its treatment in tuberous sclerosis

BACKGROUND.: Chronic renal failure is rare in tuberous sclerosis, but itsprecise frequency is not known and treatment modalities havenot been evaluated. METHODS.: A questionnaire was addressed to the 260 French dialysis centresand the characteristics of 65 patients with tuberous sclerosisand chronic renal failure were analysed. RESULTS.: In France the approximate prevalence of tuberous sclerosis withend-stage renal failure is 0.7 cases per million and that ofend-stage renal failure in tuberous sclerosis 1 per 100. Tuberoussclerosis with chronic renal failure was more frequent in females(63.1%) and was diagnosed at a mean age of 29 years. Renal impairmentwas the first manifestation of tuberous sclerosis in about halfthe cases. Renal tumours were frequent, with angiomyolipomasin 15 cases (23.1%), cysts in 12 cases (18.5%), and both in35 cases (53.8%). Malignancies were associated in nine cases(13.8%). Nephrectomy was done before dialysis in 21 cases (32.3%),and after the start of dialysis in six cases (9.2%). All butone of the 48 patients with end-stage renal failure were treatedby dialysis; 20 were transplanted, with good results. CONCLUSIONS.: Tuberous sclerosis with end-stage renal failure is rare. Thesepatients require dialysis and renal transplantation, but werecommend binephrectomy after starting dialysis and before transplantation,given the risk of cancer and bleeding related to angiomyolipomas.     

Stromal changes in early invasive and non-invasive breast carcinoma: an ultrastructural study

Six examples of histologically diagnosed, non-invasive breast carcinomas were studied by electron microscopy to elucidate the ultrastructural features for an accurate diagnosis of in situ carcinoma. The results obtained revealed two patterns of basal lamina/stromal cells relationship. One pattern showed intact basal lamina with associated periductal stromal cells consisting entirely of fibroblasts, the other pattern showed disruption of basal lamina by gaps and malignant cell protrusions with associated stromal cells consisting of both fibroblasts and myofibroblasts. As myofibroblasts are not a component of normal breast stroma but are known to be a prominent feature in the stroma of infiltrating breast carcinoma, the present observations suggest that myofibroblastic proliferation around in situ carcinoma represents an early sign of carcinomatous infiltration. Hence the definitive diagnosis of non-invasive carcinoma of the breast requires an intact basal lamina and a complete absence of a myofibroblastic reaction.     

Neuroendocrine differentiation in carcinoma of the breast. Tyramide signal amplification discloses chromogranin A-positive tumour cells in more breast tumours than previously realized

The aim of the study was to determine if, by means of tyramide signal amplification (TSA), the presence of chromogranin A (CgA)-positive tumour cells could be demonstrated in breast cancer cases found to be negative by conventional immunohistochemical staining. Sections from 44 cases of breast cancer (28 infiltrating ductal carcinomas, 2 lobular carcinomas, 4 ductal carcinomas in situ (DCIS), 7 lobular carcinomas in situ (LCIS), and 3 mucinous carcinomas) were stained for CgA by conventional immunohistochemical methods and by immunohistochemistry with TSA. The sections were also histologically graded and their oestrogen receptor (ER), progesterone receptor (PgR) and HER-2 oncogene status was recorded. Five of the tumours showed CgA-positive staining with the polyclonal antibody 430 with conventional methods. Thirty cases showed CgA-immunoreactive tumour cells after immunohistochemical staining with the polyclonal antibody 430 with TSA. However, eight of these also showed faint staining with the negative control antibody X0936 with TSA. One case showed immunopositivity for CgA using a monoclonal antibody without tyramide amplification and only a further two cases were positive when TSA was applied. The presence of CgA appears to be associated with a lower histological grade and may be more often found in oestrogen receptor-positive tumours.     

p21 ras protein expression in benign and malignant

The ras oncogenes encode for GTP binding and GTPase active proteins of relative molecular mass 21 000 (p21^ras) which are involved in the transduction of stimuli for cell proliferation. There have been conflicting reports about the detection and significance of expression of p21^ras protein in human breast disease as determined by immunohistochemistry. The antibody Y13-259, which detects a single protein of M_r 21 000, has been applied immunohistochemically to frozen sections of normal, benign proliferative breast, fibroadenomas, and carcinomas. Uniform staining of normal breast epithelium and myoepithelium was found, with occasional stronger staining in areas of epithelial hyperplasia in benign breast disease. Contrary to previous reports, decreased expression, usually heterogeneous, was found in half of the carcinomas examined. Thirty per cent of the carcinomas exhibited heterogeneous staining stronger than that of normal breast, interpreted as increased expression of p21^ras protein. This did not relate to tumour grade or node status but showed a significant correlation with proliferation rate as determined by the monoclonal antibody Ki-67. This study confirms previous reports that p21^ras protein expression is a feature of normal cells, and has identified increased expression in 30 per cent of tumours associated with higher proliferation rates, which is a lower incidence than previously claimed when a different antibody was employed.     

Epstein-Barr virus and carcinomas: undifferentiated carcinomas but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus.

The Epstein-Barr virus (EBV) is consistently associated with undifferentiated nasopharyngeal carcinoma (NPC). There is, however, conflicting evidence as to whether squamous cell NPCs are also EBV-associated. Moreover, it has been proposed that other epithelial tumours, particularly thymomas and thymic carcinomas, should be included in the group of EBV-associated neoplasias. However, since the viral DNA in these studies was demonstrated only in extracted DNA, the cellular origin of the viral DNA is uncertain. We have therefore investigated 152 epithelial tumours from various sites for the presence of EBV-DNA by in situ hybridization with 35S-labelled probes. Sixty-eight of 77 undifferentiated NPCs showed an EBV-specific autoradiographic signal, thus confirming the strong association of this tumour type with EBV even in geographical areas where undifferentiated NPC is not endemic. None of eight squamous cell NPCs showed an EBV-specific signal. All of 15 carcinomas with a similar morphology to undifferentiated NPC but from different anatomic sites (thymus, tonsil, breast) were EBV-negative as were 9 thymomas, 26 squamous cell carcinomas of the palatine tonsil, and 14 cervical carcinomas. Our results therefore suggest a unique association of EBV with undifferentiated NPC and support concepts assigning different biological properties to undifferentiated NPC as compared with squamous cell NPC.