Olaf Horstmann

Sentinel lymph node biopsy in colon cancer: A prospective multicenter trial

Introduction:The clinical impact of sentinel lymph node biopsy (SLNB) in colon cancer is still controversial. The purpose of this prospective multicenter trial was to evaluate its clinical value to predict the nodal status and identify factors that influence these results. Methods:Colon cancer patients without prior colorectal surgery or irradiation were eligible. The sentinel lymph node (SLN) was identified intraoperatively by subserosal blue dye injection around the tumor. The SLN underwent step sections and immunohistochemistry (IHC), if classified free of metastases after routine hematoxylin and eosin examination. Results:At least one SLN (median, n = 2) was identified in 268 of 315 enrolled patients (detection rate, 85%). Center experience, lymphovascular invasion, body mass index (BMI), and learning curve were positively associated with the detection rate. The false-negative rate to identify pN+ patients by SLNB was 46% (38 of 82). BMI showed a significant association to the false-negative rate (P < 0.0001), the number of tumor-involved lymph nodes was inversely associated. If only slim patients (BMI ≤24) were investigated in experienced centers (>22 patients enrolled), the sensitivity increased to 88% (14 of 16). Moreover, 21% (30 of 141) of the patients, classified as pN0 by routine histopathology, revealed micrometastases or isolated tumor cells (MM/ITC) in the SLN. Conclusions:The contribution of SLNB to conventional nodal staging of colon cancer patients is still unspecified. Technical problems have to be resolved before a definite conclusion can be drawn in this regard. However, SLNB identifies about one fourth of stage II patients to reveal MM/ITC in lymph nodes. Further studies must clarify the clinical impact of these findings in terms of prognosis and the indication of adjuvant therapy.

Pylorus Preservation Has No Impact on Delayed Gastric Emptying After Pancreatic Head Resection

Objectives Delayed gastric emptying (DGE) has been specifically attributed to pylorus-preserving pancreaticoduodenectomy (PPPD). As PPPD has been shown to be comparable with the classic Kausch-Whipple pancreaticoduodenectomy (KWPD) in terms of oncological radicality, DGE has advanced to be the leading argument for hemigastrectomy in PD. Methods A prospective, nonrandomized comparison of patients undergoing PPPD (n = 113), KWPD (n = 19), and duodenum-preserving, pancreatic head resection (DPPHR, n = 18) for various diseases was performed. First, groups were analyzed with regard to structural similarity; then, they were compared with special emphasis on DGE and other postoperative complications. Finally, further prognostic factors were sought that had an impact on DGE. Results The PPPD group was comparable with the KWPD group, but not to the DPPHR population. The in-clinic course after DPPHR compared favorably with PPPD as well as KWPD, and, here, no DGE occurred. The overall morbidity rates of PPPD and KWPD were comparable; 1 patient died in hospital (mortality rate, 0.7%). The gastric tube after PPPD and KWPD could be withdrawn at a median of 2 and 3 days, respectively, a liquid diet was started after 4 and 5 days, respectively, and a full diet was tolerated after 10 days each (n.s.). DGE was distributed evenly among PPPD (12%) and KWPD patients (21%, n.s.), and it was noted almost exclusively when other postoperative complications were present (P < 0.0001). No further prognostic factors influencing DGE could be identified. Conclusion Pylorus preservation does not increase the frequency of DGE. DGE almost exclusively occurs as a consequence of other postoperative complications. Therefore, DGE should not be used as an argument to advocate hemigastrectomy in PPPD.

Prevalence of familial pancreatic cancer in Germany

Based on several case‐control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit‐model and the Kaplan‐Meier method. Twenty‐three of 479 (prevalence 4.8%, 95% CI 3.1–7.1) patients reported at least 1 first‐degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3–2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9–3.5) and by standardized interviews of first‐degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1–5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1–3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer.

IS DELAYED GASTRIC EMPTYING FOLLOWING PANCREATICODUODENECTOMY RELATED TO PYLORUS PRESERVATION

Abstract  Background: Delayed gastric emptying (DGE) is the most frequent postoperative complication after pylorus-preserving pancreaticoduodenectomy (PPPD). This prospective, non-randomized study was undertaken to determine whether the incidence of DGE may be reduced by modifying the original reconstructive anatomy with a retrocolic duodenojejunostomy towards an antecolic duodenojejunostomy. Patients and methods: The study was comprised of 51 patients who underwent PPPD between August 1994 and November 1997. The operation was carried out as originally described but was modified by performing the duodenojejunostomy antecolically. Clinical data were recorded prospectively, with special regard to DGE. Results: After PPPD, the nasogastric tube could be removed at a median of 2 days (range 1–22 days) postoperatively; in two patients, the nasogastric tube was reinserted because of vomiting and nausea. A liquid diet was started at a median of 5 days (3–11 days); the patients were able to tolerate a full, regular diet at a median of 10 days (7–28 days). The overall incidence of DGE was 12% (n=6). No postoperative complications other than DGE were exhibited by 36 patients (71%). In this group, DGE was only seen in one patient (3%). In the second group, where postoperative complications other than DGE occurred (n=15), five patients (30%) exhibited DGE (P=0.002). Conclusions: DGE after PPPD seems to be of minor clinical importance following uncomplicated surgery. When taking the results into consideration, it can be said that, despite the lack of a control group, antecolic duodenojejunostomy might be the key to a low incidence of DGE after PPPD. In our experience, DGE is linked to the occurrence of other postoperative complications rather than to pylorus preservation.

Significance of isolated tumor cells in lymph nodes among gastric cancer patients.

PurposeTo determine the frequency and prognostic impact of isolated tumor cells (ITC) in regional lymph nodes judged to be tumor free in conventional histopathology among gastric cancer patients.MethodsAmong 161 patients who underwent gastrectomy and D2-lymphadenectomy, 56 were staged pN0(35%). Archival paraffin blocks of 1148 resected regional lymph nodes of those pN0 patients were reevaluated for ITC using monoclonal antibody Ber-EP4. Patients with and without ITC were compared with regard to the distribution of various clinicopathological factors. Prognostic impact of ITC was tested in uni- and multivariate analysis.ResultsOf 56 pN0 patients, 33 (59%) exhibited single Ber-Ep4 immunoreactive cells or small cell clusters in at least one lymph node. The occurrence of ITC was not dependent on other clinicopathological factors. ITC impaired patients’ prognoses significantly in uni- as well as multivariate analyses [estimated 5-year survival rate: 82% for pN0(i−) vs 58% for pN0(i+) (p=0.059) and 15% for pN1/2 (p=0.0005 and p<0.0001, respectively)].ConclusionITC are a frequent event in apparently tumor-free lymph nodes of gastric cancer patients and are overlooked by conventional histopathology. They are encountered even in limited stages of disease and impair patients’ prognoses. This should be borne in mind when advocating local resection for early gastric cancer.

Signals from embryonic fibroblasts induce adult intestinal epithelial cells to form nestin-positive cells with proliferation and multilineage differentiation capacity in vitro

The intestinal epithelium has one of the greatest regenerative capacities in the body; however, neither stem nor progenitor cells have been successfully cultivated from the intestine. In this study, we applied an “artificial niche” of mouse embryonic fibroblasts to derive multipotent cells from the intestinal epithelium. Cocultivation of adult mouse and human intestinal epithelium with fibroblast feeder cells led to the generation of a novel type of nestin‐positive cells (intestinal epithelium‐derived nestin‐positive cells [INPs]). Transcriptome analyses demonstrated that mouse embryonic fibroblasts expressed relatively high levels of Wnt/bone morphogenetic protein (BMP) transcripts, and the formation of INPs was specifically associated with an increase in Lef1, Wnt4, Wnt5a, and Wnt/BMP‐responsive factors, but a decrease of BMP4 transcript abundance. In vitro, INPs showed a high but finite proliferative capacity and readily differentiated into cells expressing neural, pancreatic, and hepatic transcripts and proteins; however, these derivatives did not show functional properties. In vivo, INPs failed to form chimeras following injection into mouse blastocysts but integrated into hippocampal brain slice cultures in situ. We conclude that the use of embryonic fibroblasts seems to reprogram adult intestinal epithelial cells by modulation of Wnt/BMP signaling to a cell type with a more primitive embryonic‐like stage of development that has a high degree of flexibility and plasticity.

The genetic basis of sporadic pancreatic cancer

Adenocarcinomas of the pancreatic gland are the fifth leading cause of cancer death in the USA and western Europe with a 5-year survival rate of less than 5% and a median survival of less than 6 months [76]. They bear histological resemblance to the pancreatic ducts and are referred to as pancreatic ductal adenocarcinoma [5,34,53]. Due to the late occurrence of symptoms and the high metastatic potential, pancreatic adenocarcinomas have a dismal prognosis. Since the pancreaticoduodenectomy, a surgical resection that includes the pancreatic head, the duodenum, common bile duct and the gallbladder was introduced in 1912 by Kausch, surgery still remains the primary curative treatment. However, the 5-year survival for patients undergoing resection, is only about 20% [76] and about 80% of all cancers are unresectable at the time of diagnosis [2]. In order to improve the clinical management of cancer patients, it is mandatory to understand the genetic basis of pancreatic cancers. This review describes the histological progression of pancreatic adenocarcinomas and summarizes the underlying chromosomal and genetic alterations.

Simulation von Operationstechniken in der Weiterbildung zum ChirurgenEine Analyse über Nutzen und Effekt

ZusammenfassungPer Simulation von Operationstechniken haben Weiterbildungskurse in der Viszeralchirurgie zum Ziel, Naht-, Resektions- und Rekonstruktionstechniken am Gastrointestinaltrakt zu vermitteln. Vor, nach und 5 Jahre nach erstmaligem Stattfinden des Weiterbildungskurses für gastrointestinale Chirurgie in Norderstedt wurde eine Befragung der Teilnehmer hinsichtlich der Ausbildungssituation, des Lernerfolges und der Umsetzung des Erlernten in der eigenen Klinik durchgeführt. Während bei gut 1/3 der Teilnehmer die Ausbildungssituation als unzureichend beschrieben wird, ist die Zufriedenheit mit diesem Kurs mit 94% sehr hoch: 27% der Teilnehmer trauten sich nach dem Kurs zu, selbstständig eine Anastomose zu nähen. Gründe für die Ablehnung neuer Techniken waren in nur 7% bei den Teilnehmern selbst zu finden, in 41% konnten die Vorgesetzten nicht überzeugt werden. Mehr noch als die Vermittlung neuer Techniken liegt die Bedeutung eines solchen Kurses in der Übung von Fähigkeiten, die im Operationssaal aus verschiedenen Gründen zu kurz kommen.AbstractThe course in Gastrointestinal Surgery (GISC) aims at teaching and training resection, reconstruction and suture techniques of the upper gastrointestinal tract. Prior to, after and 5 years following the first course, participants were asked to answer a questionnaire requesting information regarding the adequacy of surgical training in their residency program and how much they had benefited from the GISC. While 1/3 of the participants described the surgical training during their residency as inadequate, more than 90% benefited from the GISC. Although the single-layer-continuous suture technique was implemented by only 8% of the participating surgeons, other techniques such as cross-section gastroenterostomy were accepted by 38%. Only 7% of the participants rejected these new techniques, while 41% of the senior surgeons at home could not be convinced. Besides the teaching of new techniques, participants benefited above all from the repetitive training in surgical procedures.

‘Cross-section gastroenterostomy’ in patients with irresectable periampullary carcinoma

BACKGROUND The most frequent complication following gastroenterostomy (GE) for gastric outlet obstruction is delayed gastric emptying (DGE), which occurs in roughly 20% of patients. There is evidence that DGE may be linked to the longitudinal incision of the jejunum and that a transverse incision (cross-section GE) may decrease the incidence of DGE following GE. PATIENTS AND METHODS In contrast to the orthodox GE, the jejunum is severed transversely up to a margin of 1.5 cm at the mesenteric border and the anastomosis is created with a single running suture. A Braun anastomosis is added 20-30 cm distally to the GE. Patients were followed prospectively with special regard to the occurrence of DGE. RESULTS Between 1 August 1994 and 1 August 1998, 25 patients underwent cross-section GE, mostly because of an irresectable periampullary carcinoma. Eight patients exhibited clinical signs of gastric outlet obstruction preoperatively, while in 17 the GE was performed on a prophylactic basis. A biliary bypass was added in 15 patients. There was no disruption of the GE, but one patient died in hospital (4%). The nasogastric tube was withdrawn on the first postoperative day (range 0-6 days), a liquid diet was started on the fifth day (range 2-7 days) and a full regular diet was tolerated at a median of 9 days (6-14 days).The incidence of DGE was 4%: only the single patient who died fulfilled the formal criteria for DGE. DISCUSSION In contrast to orthodox GE, DGE seems to be of minor clinical importance following cross-section GE. As the technique is easy to perform, is free of specific complications and leads to a low incidence of DGE, it should be considered as an alternative to conventional GE.

NEUROTENSIN-RELATED REGULATION OF THE POSTPRANDIAL LOWER-OESOPHAGEAL-SPHINCTER PRESSURE

Abstract Background: Ingestion of food has been shown to modulate the lower-oesophageal-sphincter pressure (LESP). Fat is especially effective in decreasing the postprandial LESP. As there is good evidence that neurotensin (NT) is able to decrease the LESP, we conducted the present trial to determine whether NT could possibly be a mediator of the fat-induced decrease of the LESP. Methods: Six half-breed dogs were fitted for cervical side-to-side oesophagostomy to allow repeated oesophageal intubation; plasma NT immunoactivity was recorded during infusion of NT and after intragastric instillation of 200 ml of a fat solution. Experiments were repeated, with the specific NT antibody GN25 administered intravenously. Results: The optimal dose of NT required to simulate a postprandial situation was 50 pmol/kg/h. Infusion of this NT dose led to a statistically significant decrease of the LESP. Simultaneous administration of the NT antibody (immunoneutralisation) significantly inhibited this effect. Intragastric fat decreased the LESP and increased plasma NT. Immunoneutralisation of endogenously released NT led to an earlier restoration of baseline LESP, but this effect was not statistically significant. Conclusions: NT and intragastric fat modulate the LESP. NT appears to mediate the postprandial, fat-induced decrease of the LESP. Research with specific NT-receptor antagonists is necessary to determine the exact role of NT and other regulatory peptides in this context.