H. U. Baer

Increased expression of erbB3 in colorectal cancer is associated with concomitant increase in the level of erbB2

ErbB3 is a transmembrane signaling molecule that shares close structural homology with epidermal growth factor receptor (EGFR), erbB2, and erbB4. They have all been implicated in cell transformation and tumor pathogenesis, but very little is known about the role of erbB3 in normal colon and colorectal cancer. Therefore, in the current study, we determined whether erbB3 is found in normal human colon and whether its expression is altered in colorectal cancer. Because of some evidence that erbB3 might interact with erbB2 and EGFR, respectively, by heterodimerization, we also included erbB2 and EGFR analysis with special regard to coexpression. The study was performed on 35 patients operated on for colorectal carcinoma. The normal human colon showed weak erbB3 and erbB2 immunostaining, predominantly in surface epithelial cells. EGFR immunoreactivity in normal colon varied from weak to strong. In contrast, in 31 of 35 (89%) and in 29 of 35 (83%) colonic cancers, moderate to strong immunoreactivity for erbB3 and erbB2, respectively, was present in most epithelial cancer cells. A concomitant erbB3 and erbB2 immunostaining advantage could be found in 77% of cancerous tissues in comparison with the normal colon. No difference in EGFR immunostaining was evident between normal colon and cancer. Northern blot analysis showed an increase in erbB3 and erbB2 mRNA levels in 64% of cancers in comparison with normal colon samples. By densitometry, 2.3-fold and a 1.5-fold significant increases in erbB3 and erbB2 mRNA levels, respectively, were calculated in the cancerous tissues. Eighty-five percent of cancers with erbB3 mRNA overexpression showed an increase in erbB2 mRNA. Southern blot analysis did not indicate any gene amplification or rearrangement responsible for erbB2 or erbB3 overexpression. EGFR, however, was decreased in cancer on mRNA level. These findings indicate that erbB2 and erbB3, but not EGFR, may contribute to tumor growth and disease progression in colon cancer. The correlation between increased erbB2 and erbB3 expression in both Northern blots and immunohistochemical analysis suggests a co-overexpression of erbB2 and erbB3 and might support the hypothesis that these two growth factor receptors act together by heterodimer formation.

MOLECULAR ASPECTS OF HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. The success of its established treatment modalities is frequently limited by the advanced stage of the tumor at the time of diagnosis. Therefore, it is important to understand the mechanisms that control its growth behavior. In the present study, we review some aspects of molecular and cellular processes involved in growth control and metastatic potential of HCC. These include some growth factors and their receptors, oncogenes and tumor suppressor genes, and factors that control angiogenesis and extracellular matrix formation. These factors may be important targets for novel therapeutic approaches in the future.

Delayed gastric emptying occurs after both classical and pylorus-preserving whipple procedure

Background: Delayed gastric emptying (DGE) after pancreatic head resection confers a serious nutritional problem to patients who often already have faced substantial weight loss prior to surgery. The reasons for the disturbed gastric motility are not yet fully understood. Aim of the study and methods: We compared the incidence of gastric emptying delay after pancreatic resection in a prospectively collected, consecutive and recent material. All pancreatic resections were done with a well standardized technique and 95% of all procedures were carried out by 3 surgeons. DGE was defined if there was at least 500 ml gastric secretion per day through a nasogastric tube for more than 5 days. If the nasogastric tube drained less than 500 ml per day, the tube was removed and patients were allowed to drink ad libitum. Results: From 1111993 to 11/1997 271 patients underwent pancreatic resection (15 total pancreatectomies and 8 local excisions excluded). There were 44 classical Whipple, 95 pylorus-preserving Whipple, 92 duodanum-preserving and 40 left resections. Overall morbidity was 30% (patients) and mortality was 1.5% in the whole series. In total, 29 patients (11%) developed DGE; 20 had pancreatic neoplasm, 6 had periampullary tumors and 3 had chronic pancreatitis. In these patients, the nasogastric tube remained for 11 days on average (range 5 to 40 days). In the DGE group, morbidity (DGE excluded) was 34% (patients) and mortality was 0. The incidence of DGE was 25% (n=ll) after classical Whipple resection and 19% (n=lg) after pyloruspreserving resection (p = 0.41). There was no occurrence of DGE in patients undergoing duodenum-preserving or left resection. One patient was reoperated due to persistent DGE, all the other patients were treated conservatively. Conclusions: Despite well-standardized technique in an referral center, there is a substantial presence of DGE in patients undergoing classical or pylorus-preserving resection. There was no difference in the incidence of DGE between these two methods of resection. All DGEs were transient and could be treated by a conservative regime in all cases but one.

Totale Gastrektomie: Pouch-Rekonstruktion mit Duodenalpassage

Die ideale Rekonstruktion der Nahrungspassage nach totaler Magenresektion wird kontrovers diskutiert. Alle etablierten Formen (Roux-Y oder Hunt-Lawrence-Rodino) schalten das Duodenum aus, das in der Folge zu Pankreasfunktionsstorungen fuhrt mit Maldigestion/Steatorrhoe und pathologischer Glukosetoleranz. Die im vorliegenden Film beschriebene Rekonstruktionsmethode erhalt die Duodenalpassage mittels eines Jejunuminterponates, das zu einem 10 cm langen Pouch geformt und zwischen Oesophagus und Duodenum anastomosiert wird. Im Vergleich zu den anderen Rekonstruktionstechniken zeigte sich neben der physiologischeren Regulation der GI-Hormone ein besserer postoperativer Gewichtsverlauf und erhohte Lebensqualitat. Wir empfehlen diese Rekonstruktionsmethode nach Gastrektomie mit Lymphadenektomie beim Magenkarzinom der UICC-Klassifikation I und II.