Ulrich Adam

The Lymph Node Ratio is the Strongest Prognostic Factor after Resection of Pancreatic Cancer

IntroductionSurvival after surgery of pancreatic cancer is still poor, even after curative resection. Some prognostic factors like the status of the resection margin, lymph node (LN) status, or tumor grading have been identified. However, only few data have been published regarding the prognostic influence of the LN ratio (number of LN involved to number of examined LN). We, therefore, evaluated potential prognostic factors in 182 patients after resection of pancreatic cancer including assessment of LN ratio.MethodsSince 1994, 204 patients underwent pancreatic resection for ductal pancreatic adenocarcinoma. Survival was evaluated in 182 patients with complete follow-up evaluations. Of those 182 patients, 88% had cancer of the pancreatic head, 5% of the body, and 7% of the pancreatic tail. Patients underwent pancreatoduodenectomy (85%), distal resection (12%), or total pancreatectomy (3%). Survival was analyzed by the Kaplan–Meier and Cox methods.ResultsIn all 204 resected patients, operative mortality was 3.9% (n = 8). In the 182 patients with follow-up, 70% had free resection margins, 62% had G1- or G2-classified tumors, and 70% positive LN. Median tumor size was 30 (7–80) mm. The median number of examined LN was 16 and median number of involved LN 1 (range 0–22). Median LN ratio was 0.1 (0–0.79). Cumulative 5-year survival (5-year SV) in all patients was 15%. In univariate analysis, a LN ratio ≥ 0.2 (5-year SV 6% vs. 19% with LN ratio < 0.2; p = 0.003), LN ratio ≥ 0.3 (5-year SV 0% vs. 18% with LN ratio < 0.3; p < 0.001), a positive resection margin (p < 0.01) and poor differentiation (G3/G4; p < 0.03) were associated with poorer survival. In multivariate analysis, a LN ratio ≥ 0.2 (p < 0.02; relative risk RR 1.6), LN ratio ≥ 0.3 (p < 0.001; RR 2.2), positive margins (p < 0.02; RR 1.7), and poor differentiation (p < 0.03; RR 1.5) were independent factors predicting a poorer outcome. The conventional nodal status or the number of examined nodes (in all patients and in the subgroups of node positive or negative patients) had no significant influence on survival. Patients with one metastatic LN had the same outcome as patients with negative nodes, but prognosis decreased significantly in patients with two or more LN involved.ConclusionsNot the lymph node involvement per se but especially the LN ratio is an independent prognostic factor after resection of pancreatic cancers. In our series, the LN ratio was even the strongest predictor of survival. The routine estimation of the LN ratio may be helpful not only for the individual prediction of prognosis but also for the indication of adjuvant therapy and herein related outcome and therapy studies.

Postoperative morbidity and long-term survival after pancreaticoduodenectomy with superior mesenterico-portal vein resection

The role of superior mesenteric-portal vein resection (SM-PVR) for vein invasion or tumor adherence during pancreatoduodenectomy (PD) is still under debate. We investigated morbidity, mortality, and long-term survival in patients who underwent PD with or without SM-PVR. Between July 1994 and December 2004, 222 PD (78% pylorus preserving, 19% Whipple, and 3% total pancreatectomy) were performed for malignant disease. Fifty-three patients (24%) had PD with SM-PVR. Sixty-eight percent of the venous resections were performed as wedge excisions and 32% as segmental resections. Long-term survival was analyzed in 165 patients with pancreatic (n=110), ampullary (n=33), or distal bile (n=22) duct cancer using univariate (log-rank) and multivariate (Cox regression) methods. In patients undergoing PD with SM-PVR and conclusive histologic examination of the resected vein specimen (n=42), 60% had true tumor involvement of the venous wall, whereas 40% had no proven tumor infiltration. In the complete study group, negative resection margins were obtained in 69% of patients with SM-PVR and in 79% of patients without SM-PVR (P=0.09). Median duration of surgery was 500 minutes (SM-PVR) versus 440 minutes (no SM-PVR; P<0.001). Volume of intraoperatively transfused blood was 600 ml (median) in both groups. Postoperative surgical complications/mortality occurred in 23%/3.8% (SM-PVR) versus 35%/4.1% (no SM-PVR); P=0.09/0.9. Analysis of long-term survival in all 165 patients included 41 with SM-PVR. Five-year survival rates were 15% in cancer of the pancreatic head, 22% in ampullary cancer, and 24% in distal bile duct cancer (P=0.02). Long-term survival was not influenced by the need for SM-PVR in any of the different tumor entities. In multivariate analysis, a positive resection margin (P<0.01, relative risk [RR]: 1.8, 95% confidence interval [CI]: 1.2–2.7), a histologically undifferentiated tumor (P=0.01, RR: 1.7, 95% CI: 1.1–2.5), and the tumor entity (P<0.01) were significant predictors of survival. Univariate survival analysis of the 110 patients with cancer of the pancreatic head revealed that a histologically undifferentiated tumor (P=0.05) and positive resection margins (P=0.02) were associated with a poorer survival. In multivariate analysis, the resection margin (P=0.02, RR: 5.1, 95% CI: 1.1–2.8) and a histologically undifferentiated tumor (P=0.05, RR: 3.8, 95% CI: 1.0–2.5) significantly influenced survival. After PD, perioperative morbidity and long-term survival in patients with SM-PVR were similar to those of patients without vein resection. In case of tumor adherence or infiltration, combined resection of the pancreatic head and the vein should always be considered in the absence of other contraindications for resection.

Delayed gastric emptying after pylorus-preserving pancreatoduodenectomy is strongly related to other postoperative complications

Patients undergoing pylorus-preserving pancreatoduodenenectomy (PPPD) have a risk of up to 50% for developing delayed gastric emptying (DGE) in the early postoperative course. From 1994 to August 2002, a total of 204 patients underwent PPPD for pancreatic or periampullary cancer (50%), chronic pancreatitis (42%), and other indications (8%). Retrocolic end-to-side duodenojejunostomy was performed below the mesocolon. DGE was defined by the inability to tolerate a regular diet after day 10 (DGE10) or day 14 (DGE14) postoperatively, as well as the need for a nasogastric tube at or beyond day 10 (DGE10GT). Postoperative morbidity was 38%, 30-day mortality was 2.9%, and median postoperative length of stay was 15 days. DGE occurred in 14.7% (DGE10), 5.9% (DGE14), and 6.4% (DGE10GT), respectively. After further exclusion of 21 patients (10.3%) with major complications and no possible oral intake (because of death, reoperation, or mechanical ventilation), the frequencies of DGE10, DGE14, and DGE10GT in the remaining group of 183 patients were 9%, 2%, and 2%, respectively. Multivariate analysis revealed postoperative complications (P < 0.001), the presence of portalvenous hypertension (P < 0.01), and tumors as indications for surgery (P < 0.01) as independent risk factors for DGE10. The overall incidence of DGE was low after PPPD. In those patients experiencing DGE, however, other postoperative complications were the most important factor associated with its occurrence.

Management of delayed visceral arterial bleeding after pancreatic head resection.

Despite low mortality, postoperative complications are still relatively frequent after pancreatic head resection. The occurrence of delayed visceral arterial bleeding from erosions or pseudoaneurysms of branches of the celiac trunk or from the stump of the gastroduodenal artery is a rare but life-threatening complication and is probably underreported in the literature. During a 10-year period, we diagnosed and treated 12 patients (three referred from other hospitals) with severe visceral arterial bleeding, presenting 7 to 85 days after pancreatic head resection. Clinical presentation was gastrointestinal bleeding (seven patients) or abdominal bleeding (five patients). The bleeding source was identified by angiography in 10 of the 12 cases. Definitive bleeding control was achieved by angiography in six of the 12 patients (stent 2, coiling 4), or by surgery in five patients. None of the six patients with successful angiographic intervention required further surgery for bleeding control. One patient died due to hemorrhage before bleeding was controlled. Median transfusion requirement was 12.5 (range 3–37) units. Of five patients with interventional or surgical occlusion of the common hepatic artery, three developed hepatic abscesses and two had complications of the hepaticojejunostomy. One of those five patients died four months after definitive bleeding control because of recurrent hepatic abscesses. All other patients eventually recovered completely. We conclude that delayed arterial bleeding from visceral arteries is a rare but life-threatening complication after pancreatic head resection. Angiographic stenting with preservation of hepatic blood flow, if technically possible, represents the best treatment option.

Short- and long-term results of duodenum preservation versus resection for the management of chronic pancreatitis: a prospective, randomized study.

BACKGROUND Individualization of operations for chronic pancreatitis (CP) offers tailored operative approaches for the management of complications of CP. For the management of the inflammatory head mass and its complications, duodenum-preserving procedures (Frey and Beger operations) compete in efficacy and quality of life with pancreatoduodenectomy procedures (PPPD and Whipple operations). Our aim was to compare the short- and long-term results of duodenum-preserving and duodenum-resecting techniques in a prospective, randomized trial. METHODS Eighty-five patients with CP were randomized to undergo either pylorus-preserving (PPPD) or duodenum-preserving pancreatic head resection (DPPHR). Perioperative and long term results were evaluated. RESULTS Although the duodenum-preserving operations had a lesser median operating time (360 vs 435 minutes; P = .002), there were no differences in the need for intraoperative blood transfusion (76% vs 79%) or the duration of hospital stay (13 vs 14 days). Postoperative complications in general (33% vs 30%), surgical complications (21% vs 23%), and severe complications such as pancreatic leakage (10% vs 5%) or the need for reoperation (2% vs 2%) did not differ between the DPPHR and the PPPD groups, and there was no mortality (0%). The long-term outcome after a median of >5 years showed no differences between the DPPHR and PPPD regarding quality of life, pain control (67% vs 67%), endocrine status (45% vs 44%), and exocrine insufficiency (76% vs 61%). CONCLUSION Both types of pancreatic head resections are equally effective in pain relief and eventual quality of life after long-term follow-up (>5 years) without differences in endocrine or exocrine function.

Subcutaneous Redon drains do not reduce the incidence of surgical site infections after laparotomy. A randomized controlled trial on 200 patients

PurposeSurgical site infections (SSI) cause excess morbidity and mortality in modern surgery. Several different approaches to reduce the incidence of SSI have been investigated with variable results.MethodThis is to our knowledge the first systematic randomized evaluation in patients undergoing laparotomy in visceral surgery to clarify whether widely used subcutaneous drains (Redon) affect wound infection as the primary outcome measure.ResultsIn 200 patients, we were unable to show a statistically significant impact on the postoperative healing process in patients with the full variety of abdominal surgical interventions. Overall, we observed surgical site infection in 9.5% of all patients (n = 19), of these n = 9 (47.4%) were in the control group without a drain, and 10 (52.6%) were in the experimental group with a Redon drain (not significant).ConclusionAs this study could not demonstrate a reduction of SSI by the use of Redon drains, there is no indication for prophylactic subcutaneous suction drains after laparotomy.

Expression of Connexin26 in Islets of Langerhans Is Associated With Impaired Glucose Tolerance in Patients With Pancreatic Adenocarcinoma

Objectives: Impairment of glucose tolerance is one of the leading clinical presentations in patients with pancreatic carcinoma. The mechanism of disturbed glucose metabolism, however, is still under debate. Using microarray technology, key mechanisms of deregulated molecular functions of cancer cell–specific mRNAs and tumor-induced mRNAs in peritumorous tissue should be identified in pancreatic ductal adenocarcinoma (PDAC) by comparison to chronic pancreatitis and normal pancreas. Methods: Forty-three mRNAs were abundant in tissue specimens of patients operated due to pancreatic carcinoma but absent or of low abundance in chronic pancreatitis and normal pancreas. One of these mRNAs encodes the gap junction protein connexin26, known as a tumor suppressor, which was 10.8- and 6.9-fold more abundant in pancreatic carcinoma than in normal pancreas and chronic pancreatitis, respectively. Quantitative RT-PCR was performed for connexin26, with mRNA being expressed 26.7- and 2.9-fold more than in normal pancreas (n = 6), in pancreatic carcinoma (n = 7), and chronic pancreatitis (n = 8), respectively. Results: By immunohistochemistry, connexin26 was predominantly localized to the islets in the vicinity of the pancreatic carcinoma tissue. Control sections of tissue with chronic pancreatitis and normal pancreas show connexin26 expression in the islets as well. Interestingly, the level of mRNA abundance (fold over normal pancreas) in RT-PCR correlates (r = 0.62) with the 2h value of the pre-operative oral glucose tolerance test of these patients. Conclusion: Whether overexpressed connexin26 in pancreatic cancer is a cause of impaired glucose tolerance remains to be elucidated in further experimental studies.

Complete pancreatic encasement of the portal vein—surgical implications of an extremely rare anomaly

BackgroundDue to the complex embryologic development, pancreatic anatomy can be very variable.DiscussionThe authors present the second ever reported case in the literature of a complete pancreatic encasement of the portal vein which forced us to alter the standard operative procedure of pancreatic head resection, thus enabling possible dangerous complications.

Pankreasleckage nach Pankreasresektion Eine Analyse von 345 operierten Patienten

AbstractIntroduction. Complications after pancreatic resections remain frequent despite a decreasing mortality. Pancreatic leakages represent a relevant part of those complications but data on risk factors for their occurrence are rare. We analyzed our experience with incidence, clinical course, and risk factors of pancreatic leakage in a large patient group. Methods. We analyzed the prospectively documented perioperative data of 345 patients with pancreatic resections carried out between 1994 and 2001. Main indications for surgery were chronic pancreatitis (57%) and malignant tumors (37%). The following operations were performed: Whipples operation 15%, pylorus-preserving pancreaticoduodenectomy 53%, duodenum-preserving pancreatic head resection 19%, and distal pancreatic resection 13%. Risk factors were analyzed using uni- and multivariate methods. Results. Postoperative mortality and complication rate were 2.9% and 41%, respectively. A pancreatic leakage occurred in 9.9%. In the majority of patients, pancreatic leakage was asymptomatic and controlled by prolonged drainage. However, one fourth of the patients with pancreatic leakage required reoperation. The mortality of pancreatic leakage was 12%. No patient with chronic pancreatitis died as a consequence of pancreatic leakage. Impaired preoperative renal function was the only risk factor for the occurrence of postoperative pancreatic leakage. Conclusions. Although easily managed in the majority of cases, pancreatic leakage still represents a relevant postoperative complication after pancreatic resection, especially in patients with malignant disease. Because of an increased risk of developing pancreatic leakage, an impaired renal function should be considered specifically in the perioperative management of the patients.ZusammenfassungEinleitung. Trotz einer zunehmend sinkenden Letalität bleiben Komplikationen nach Pankreasresektion häufig. Pankreasleckagen stellen einen relevanten Anteil an den postoperativen Komplikationen dar, aber Daten zu Risikofaktoren sind rar. Anhand eines umfangreichen Patientenkollektives analysierten wir in vorliegender Arbeit Inzidenz, Verlauf und Risikofaktoren der postoperativen Pankreasleckage. Methoden. Die prospektiv erhobenen perioperativen Daten von 345 zwischen 1994 und 2001 durchgeführten Pankreasresektionen wurden ausgewertet. Indikationen zur Operation waren hauptsächlich eine chronische Pankreatitis (57%) und maligne Tumoren (36%). Folgende Operationsverfahren wurden durchgeführt: klassische Whipple-Operation (15%), pyloruserhaltende Pankreaskopfresektion (53%), duodenumerhaltende Kopfresektion (19%) und distale Resektion (13%). Die Analyse von Risikofaktoren wurde univariat und multivariat durchgeführt. Ergebnisse. Die Letalität betrug 2,9%, die Morbidität 41%. Eine Pankreasleckage trat bei 9,9% der Patienten auf, war aber in der Mehrzahl asymptomatisch und konnte durch Drainagenbelassung beherrscht werden. Ein Viertel der Patienten mit einer Pankreasleckage musste reoperiert werden. Die Letalität der Komplikation betrug 12%, aber kein Patient mit chronischer Pankreatitis verstarb wegen einer Pankreasleckage. Einzig signifikanter Risikofaktor für eine Pankreasleckage war ein präoperativ erhöhter Kreatininwert. Schlussfolgerungen. Obwohl in der Mehrzahl problemlos, stellen Pankreasleckagen nach Pankreasresektion vor allem bei Tumorpatienten weiterhin klinisch relevante Komplikationen dar. Da Patienten mit präoperativ eingeschränkter Nierenfunktion ein erhöhtes Risiko dieser Komplikation aufwiesen, sollte dieser Tatsache perioperativ besonderes Augenmerk geschenkt werden.

The penetration of ciprofloxacin into human pancreatic and peripancreatic necroses in acute necrotizing pancreatitis

AbstractBackground: Antibiotic prophylaxis in necrotizing pancreatitis has recently gained acceptance. Published studies, however, used different antibiotic regimes and some antibiotics penetrated pancreatic tissue or pancreatic necroses only poorly. The aim of this study was to assess the penetration of ciprofloxacin (CIP) into necrotic pancreatic and peripancreatic tissue. Patients and Methods: Serum, pancreatic necroses, peripancreatic fat tissue necroses and infected omental fluid levels of CIP were measured after 51 operations in 14 patients. Results: The median penetration ratio of CIP was 137.5% (range 11–196%) in infected omental bursa fluid, 59.6% (3–214%) in pancreatic necroses and 67.1% (1–250%) in peripancreatic necroses. Chemotherapeutical ratios of CIP as a marker for antimicrobial potency were high against most relevant pathogens in necrotizing pancreatitis. Conclusion: Due to its antimicrobial spectrum and the good penetration into the relevant compartments, CIP may be useful in preventing local infection in necrotizing pancreatitis.