Sven Richter

Hepatic arteriolo‐portal venular shunting guarantees maintenance of nutritional microvascular supply in hepatic arterial buffer response of rat livers

1 To elucidate the hepatic microvascular response upon the hepatic arterial buffer response (HABR), we analysed blood flow (ultrasonic flowprobes) of the hepatic artery (HA) and portal vein (PV), microcirculation (intravital microscopy), and tissue oxygenation (polarography) in anaesthetized Sprague‐Dawley rats and re‐evaluated the role of adenosine in mediating the HABR by using 8‐phenyltheophylline as a competitive antagonist. 2 Upon restriction of PV blood flow to 11 ± 3 % of baseline values, HA blood flow increased by a factor of 1.77 (P < 0.05), thus confirming HABR. Strikingly, red blood cell velocity and volumetric blood flow in terminal hepatic arterioles (THAs) did not increase but were even found to be slightly decreased, by 8 and 13 %, respectively. In contrast, red blood cell velocity and volumetric blood flow in terminal portal venules (TPVs) decreased to only 66 % (P < 0.05), indicating upstream hepatic arteriolo‐portal venular shunting. As a consequence, red blood cell velocity and volumetric blood flow in sinusoids were found to be reduced to only 66‐68 % compared with baseline (P < 0.05). Diameters of neither of those microvessels changed, thus excluding THA‐, TPV‐, and sinusoid‐associated mechanisms of vasomotor control in HABR. 3 Tissue PO2 and hepatocellular NADH fluorescence remained unchanged, indicating HABR‐mediated maintenance of adequate oxygen delivery, despite the marked reduction of total liver blood flow. Further, hepatic arteriolo‐portal venular shunting guaranteed homogeneity of nutritive blood flow upon HABR, as given by an unchanged intra‐acinar coefficient of variance of sinusoidal perfusion. 4 Pretreatment of animals with the adenosine antagonist 8‐phenyltheophylline completely blocked the hepatic arterial buffer response with the consequence of decreased tissue oxygenation and increased heterogeneity of sinusoidal perfusion. 5 In conclusion, hepatic microhaemodynamics, in particular unchanged diameters of THAs, TPVs and sinusoids, during HABR indicate that reduction in resistance to HA flow is located upstream and functions via hepatic arteriolo‐portal venular shunts resulting in equal distribution of microvascular blood flow and oxygen delivery under conditions of restricted PV blood supply.

One-stage sigmoid colon resection for perforated sigmoid diverticulitis (Hinchey stages III and IV).

IntroductionGuidelines for the treatment of complicated sigmoid diverticulitis recommend Hartmann’s procedure or anastomosis with protective colostomy for Hinchey stage III diverticulitis and Hartmann’s procedure only for Hinchey stage IV diverticulitis. We evaluated the outcome of patients with perforated sigmoid diverticulitis Hinchey III/IV undergoing one-stage colon resection and primary anastomosis without protective colostomy.MethodsAfter implementation of a protocol to treat Hinchey III/IV diverticulitis with primary anastomosis without protective ileocolostomy, the patients’ data were recorded prospectively between August 2001 and August 2003 and analyzed retrospectively from a computer-related database.ResultsOf 41 patients, 34 (81%%) underwent one-stage sigmoid resection and primary anastomosis, 3 of 41 patients (7%%) underwent primary anatomosis with protective ileostomy, and 5 of 41 patients (12%%) had a Hartmann’s procedure. The mortality was 11%% in patients undergoing primary anastomosis and 60%% in patients with Hartmann’s procedure. The relative risk of co-morbidity factors for lethal outcome after sigmoid resection was 6.94 for preceding operations, 3.75 for renal failure or renal transplantation, and 3.25 for immunosuppression.ConclusionsOne-stage sigmoid resection and primary anastomosis can be performed safely in nearly 90%% of all patients with perforated sigmoid diverticulitis (Hinchey III/IV) by surgeons of different training levels. Patients with immunosuppression, chronic renal failure, liver cirrhosis, or previous organ transplantation or complex cardiovascular reconstructive procedures have a significantly increased risk of dying after sigmoid resection for perforated diverticulitis.

Loss of physiologic hepatic blood flow control ("hepatic arterial buffer response") during CO2-pneumoperitoneum in the rat.

We analyzed whether a compensatory increase of hepatic arterial (HA) flow, known as the “hepatic arterial buffer response” (HABR), may serve for maintenance of liver blood supply during laparoscopy-associated portal venous (PV) flow reduction. We assessed HA and PV flow, as well as hepatic tissue oxygenation (Po2) during CO2-pneumoperitoneum in anesthetized and mechanically ventilated Sprague-Dawley rats (n = 7). Control animals (n = 7) without pneumoperitoneum, but tourniquet-induced PV flow reduction served to demonstrate physiologic HABR. Although stepwise tourniquet-induced reduction of PV flow to 20% of baseline values led to a significant (P < 0.05) increase of HA flow from 4.3 ± 0.7 mL/min to 9.9 ± 1.7 mL/min, stepwise intraabdominal pressure-induced decrease of PV flow was paralleled by a linear reduction of HA flow from 2.4 ± 0.3 mL/min to 1.2 ± 0.5 mL/min at 18 mm Hg intraabdominal pressure. This loss of HABR was sustained during a subsequent 2 h-period of CO2- pneumoperitoneum contrasting the 2 h of maintenance of HABR in controls. Hepatic tissue Po2 decreased during the 2 h-period of pressure- and tourniquet-induced PV flow reduction by 35% to 51%, respectively. On tourniquet release, all variables regained baseline values, whereas evacuation of the pneumoperitoneum allowed all variables except hepatic Po2 to return to baseline, indicating prolonged tissue hypoxia despite restored total liver blood flow in the Laparoscopic group. Concomitantly, increased liver enzyme activities reflected moderate tissue damage after 2 h of pneumoperitoneum. In conclusion, intraabdominal CO2- insufflation-induced hemodynamic alterations may impair tissue oxygenation and enzyme release, indicating the potential risk for hepatic tissue damage after prolonged periods of laparoscopic interventions.

Boerhaave's syndrome: primary repair vs. esophageal resection—case reports and meta-analysis of the literature

Boerhaave’s syndrome is a life-threatening disease with a high mortality. With regard to the heterogeneity of treatment strategies, no comparative studies exist and recommendations remain controversial. Seventeen cases of Boerhaave’s syndrome operated on between 1989 and 2000 at our hospital were reviewed retrospectively to compare the time period between perforation and diagnosis, and the morbidity and mortality among the different treatment options. In addition, we conducted a meta-analysis of the literature including all series containing five or more patients and compared the findings with our own data. Our patients with a perforation history of less than 12 hours showed significantly fewer signs of sepsis compared to patients with a history of more than 12 hours. In a comparison of patients with primary repair vs. patients treated with esophageal resection or an exclusion operation, no differences were found. In the literature, patients with a long period of perforation (more than 24 hours) were treated more often with an esophageal resection than patients with primary repair. In cases of Boerhaave’s syndrome, primary suturing of the esophageal perforation should be reserved only for those patients presenting within 12 hours after perforation. In all other cases, depending on the extent of the tissue damage, a two-stage esophageal resection with cervical esophagostomy and gastrostomy is recommended as the safest treatment.

Preparation and investigation of tumor affinity, uptake kinetic and transport mechanism of iodine-123-labelled amino acid derivatives in human pancreatic carcinoma and glioblastoma cells

In developing radioiodinated agents for pancreatic and brain tumor imaging by single photon emission tomography (SPET), we prepared p-amino-3-[123I]iodo-l-phenylalanine (IAPA), p-[123I]iodo-l-phenylalanine (IPA), L-8-[123I]iodo-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (ITIC) and L-3-[123I]iodo-alpha-methyl-tyrosine (IMT) in radiochemical yields up to 95%, and we investigated their uptake in human pancreatic carcinoma and glioblastoma cells as well as the mechanisms promoting the tumor uptake. The radiopharmaceutical uptake into tumor cells was rapid (t(1/2) < or = 5 min) and temperature- and pH-dependent. The radioactivity concentration in tumor cells varied from 10 to 33% of the total activity (105-310 cpm/1000 cells) following a 30-min incubation at 37 degrees C (pH 7.4). In comparison, accumulation of the radiopharmaceuticals into normal brain and pancreatic tissue remained relatively low. Depolarizing the plasma membrane potential in high K+ buffer significantly altered the radioactivity concentration in the tumor cells, suggesting that membrane potential plays a certain role in the cellular uptake. Competitive inhibition experiments with specific amino acid transport inhibitors indicated that the uptake of IAPA, IPA and IMT into human pancreatic carcinoma and glioblastoma cells is predominantly mediated by the L and ASC transport systems, while no substantial involvement of the transport system A in their tumor uptake could be demonstrated. In contrast, results of the present investigation indicated that ITIC is not taken up into tumor cells via the common neutral amino acid carrier systems, including the A, L and ASC system. Furthermore, preloading with naturally occurring L-amino acids failed to stimulate the cellular uptake of the radiopharmaceuticals. These data indicate that the investigated radiopharmaceuticals exhibit interesting characteristics with promise for in vivo tumor investigations to ascertain their potential as radioligands for glioma and pancreatic carcinoma imaging by SPET.

Impact of postoperative pancreatic fistula on surgical outcome--the need for a classification-driven risk management.

BackgroundThe International Study Group of Pancreatic Fistula (ISGPF) classification allows comparison of incidence and severity of postoperative pancreatic fistula (POPF). Its post hoc character, however, does not provide a guideline for the treatment of POPF in individual patient. We therefore studied the association of POPF type A-C on secondary surgical morbidity and mortality in patients undergoing pancreatic resection.Patients and methodsBetween 3/2001-12/2007, 483 patients underwent pancreatic resections. POPF were classified according to the ISGPF classification. All patient data were entered in a clinical data management system prospectively.ResultsPatients who developed POPF had significantly more vascular but not other surgical complications than patients without POPF. Patients with POPF A had no vascular or surgical complications. Twenty one of the 29 patients with POPF C had surgical complications (17 vascular complications). Mortality attributed to surgical complications after POPF C was 5/29. A soft pancreatic consistency (OR 8.5; p < 0.008) and a high drain lipase activity on postoperative day 3 (OR 4.4; p = 0,065) were predictors for the development of POPF C.DiscussionPOPF C is associated with vascular complications like erosion bleeding and other surgical complications like delayed gastric emptying or pleural effusions. A soft pancreatic consistency and a high drain lipase activity on postoperative day 3 are early predictors for the development of POPF C.

Parenchyma-preserving hepatic resection for colorectal liver metastases

BackgroundHepatic resection of colorectal liver metastases is the only curative treatment option. As clinical and experimental data indicate that the extent of liver resection correlates with growth of residual metastases, the present study analyzes the potential benefit of a parenchyma-preserving liver surgery approach.MethodsData from a prospectively maintained database of patients undergoing liver resection for colorectal metastases were reviewed. Evaluation of outcome was performed using the Kaplan–Meier method. Correlations were calculated between clinical–pathological variables.ResultsOne hundred sixty-three patients underwent 198 liver resections for colorectal metastases: 26 major hepatectomies, 65 minor anatomical resections, 78 non-anatomical resections, as well as 29 combinations of minor anatomical and non-anatomical procedures. Overall 1-, 3-, and 5-year survival was 93%, 62%, and 40%, respectively. Patients with repeated liver resections had a 5-year survival of 27%. Interestingly, large dissection areas were associated with a significant reduction of the 5-year survival rate (33%). Five-year survival after major hepatectomy was not significantly reduced.ConclusionFor colorectal liver metastases, minor resections offer a prolonged survival compared to major hepatectomies. As patients with stage IV colorectal disease are candidates for repeat resections, preservation of hepatic parenchyma is of increasing importance in the setting of multi-modal and repeated therapy approaches.

Triclosan-coated sutures reduce wound infections after hepatobiliary surgery—a prospective non-randomized clinical pathway driven study

ObjectivesWound infections after abdominal surgery are still frequent types of nosocomial infections. Suture materials might serve as a vehicle for mechanical transport of bacteria into the surgical wound. To reduce bacterial adherence to surgical sutures, triclosan-coated polyglactin 910 suture materials with antiseptic activity (Vicryl plus®) were developed. The aim of this prospective non-randomized clinical pathway driven study was to ascertain if the use of Vicryl plus® reduced the number of wound infections after transverse laparotomy.Patients and methodsBetween October 2003 and October 2007, 839 operations were performed using a transverse abdominal incision. In the first time period, a PDSII® loop suture was used for abdominal wall closure. In the second time period, we used Vicryl plus®. Risk factors were collected prospectively to compare the two groups.ResultsUsing a PDSII® loop suture for abdominal wall closure in the first time period, 9.2% of the patients developed wound infections. In the second time period, using Vicryl plus®, the number of wound infections decreased to 4.3% (p < 0,005). Both groups were comparable regarding risk factors despite no other changes in protocols of patient care.ConclusionAntiseptic-coated loop Vicryl suture for abdominal wall closure can be superior to PDSII sutures in respect to the development of wound infections after a two-layered closure of transverse laparotomy.

Surgery of Liver Metastasis in Gynecological Cancer – Indication and Results

Background: Liver surgery for patients with liver metastases from gynecological malignancies, an indicator of advanced cancer disease, has remained unclear in the literature. We therefore analyzed the potential survival benefit of patients with surgically resectable compared to unresectable liver metastases. Patients and Methods: 43 patients who underwent surgery for liver metastases from gynecological cancers were included in our retrospective observational analysis. Overall survival was estimated according to the Kaplan-Meier method and compared with the log-rank test. Results: Primary gynecological tumors were breast (n = 27), ovarian (n = 8), and uterine (n = 8) cancers. Solely exploratory laparotomy was performed in 13 patients who served as controls. Whereas the perioperative mortality was 0%, minor complications occurred in 18.7%. The overall survival of all patients undergoing liver resection was significantly higher (p < 0.05) than that of patients with unresectable metastases. Subgroup analyses showed that particularly patients with respectable liver metastases from breast cancer had a significantly higher (50%) 5-year survival compared to patients with only an exploratory laparotomy. Conclusion: In selected patients, liver resection of metastases from gynecological cancers can achieve a survival benefit similar to that of patients with colorectal cancer metastases.

Improvement of microvascular graft equilibration and preservation in non-heart-beating donors by warm preflush with streptokinase.

Using in situ fluorescence microscopy with Sprague Dawley rats, we studied the hypothesis of compromised microvascular kidney perfusion on organ harvest in non-heart-beating donors (NHBDs), and we evaluated the potential benefit of an additional preflush with saline solution containing streptokinase. Aortal flush of NHBD kidneys solely with University of Wisconsin solution resulted in a significantly (P <0.05) reduced functional capillary density (FCD) with increased perfusion heterogeneity compared with kidneys of heart-beating controls. This was associated with an increased lactate dehydrogenase (LDH) release on 24 hr postpreservation rinse of the grafts (76.7±18.9 U/L). Warm preflush with low-viscosity Ringer’s lactate (RL) solution alone did not influence the decreased renal FCD and the postpreservation LDH release (76.2±29.1 U/L). In contrast, the addition of streptokinase to the RL preflush solution resulted in a significant (P <0.05) improvement of FCD with values not statistically different from those of heart-beating controls. This was associated with an attenuation of perfusion heterogeneity and a significantly lowered postpreservation LDH release (17.0±2.5 U/L). Furthermore, in transplanted and reperfused NHBD kidney grafts, the use of streptokinase-supplemented RL for preflush during organ harvest significantly (P <0.05) reduced early manifestation of tubular necrosis (29%±8%) when compared with kidneys preflushed exclusively with University of Wisconsin solution (56%±4%). Thus, we conclude that kidney harvest from NHBDs is prone to severe microvascular perfusion deficits, which are likely to preclude successful preservation of organ integrity during cold storage. Temporary fibrinolytic preflush with streptokinase may represent a feasible tool to improve microvascular graft equilibration, which effectively protects the renal integrity during both cold storage and posttransplant reperfusion.