A pleiotropy scan to discover new susceptibility loci for pancreatic ductal adenocarcinoma.

Pleiotropic variants (i.e., genetic polymorphisms influencing more than one phenotype) are often associated with cancer risk. A scan of pleiotropic variants was successfully conducted ten years ago in relation to pancreatic ductal adenocarcinoma susceptibility. However, in the last decade, genetic association studies performed on several human traits have greatly increased the number of known pleiotropic variants. Based on the hypothesis that variants already associated with a least one trait have a higher probability of association with other traits, 61,052 variants reported to be associated by at least one genome wide association study (GWAS) with at least one human trait were tested in the present study consisting of two phases (discovery and validation), comprising a total of 16,055 pancreatic ductal adenocarcinoma (PDAC) cases and 212,149 controls. The meta-analysis of the two phases showed two loci (10q21.1-rs4948550 (P=6.52×10-5) and 7q36.3-rs288762 (P=3.03×10-5) potentially associated with PDAC risk. 10q21.1-rs4948550 shows a high degree of pleiotropy and it is also associated with colorectal cancer risk while 7q36.3-rs288762 is situated 28,558 base pairs upstream of the Sonic Hedgehog (SHH) gene, which is involved in the cell differentiation process and PDAC etiopathogenesis. In conclusion, none of the single nucleotide polymorphisms (SNPs) showed a formally statistically significant association after correction for multiple testing. However, given their pleiotropic nature and association with various human traits including colorectal cancer, the two SNPs showing the best associations with PDAC risk merit further investigation through fine mapping and ad hoc functional studies.

Quantitative analysis of detected sentinel lymph nodes and the incidence of micrometastases using two different methods of surgical melanoma treatment--pilot study.

UNLABELLED: The aim of our study was to compare the number of detected sentinel lymph nodes and the incidence of micrometastases between two groups of patients with cutaneous melanoma. METHODS: 100 patients were divided in to two groups: group V and group D. Group V patients (50) with melanoma underwent a single-stage surgery--radical excision of the tumour with sentinel lymph node biopsy (study group "V"). Group D patients (50) with melanoma underwent two-stage surgery; initially primary diagnostic excision of the tumour (0.5 cm from margins of the lesion) followed by a radical re-excision of the post-operative scar and sentinel lymph node biopsy (study group "D"). RESULTS: Study groups "V" and "D" were tested for homogeneity with regard to age, melanoma thickness, location of melanoma, type of melanoma, and ulceration. The groups were found to be homogenous. The average number of removed sentinel lymph nodes in group "D" was 1.0 more than in group "V" (p < 0.05). The averages were 3.7 and 2.7 respectively with a SD of 1.8. The relationship between the SL node staining and type of surgery was (p < 0.05). 49.6% stained radioactive sentinel lymphnodes at the time of surgery was found in group "V", while 33.9% in group "D". CONCLUSIONS: Using two different early-stage cutaneous melanoma management techniques significantly more sentinel lymph nodes (p = 0.006) were detected using the two-stage surgery approach. However, there was no significant difference between the two approaches regarding the number of sentinel lymph nodes with micrometastases that were detected and excised.

Effects of different kinds of meshes on postoperative adhesion formation in the New Zealand White rabbit.

The aim of this study was to compare the effect of different kinds of surgical meshes on postoperative adhesion formation. Forty-two New Zealand White rabbits were studied. The rabbits were grouped into six groups, according to the type of surgical meshes (Prolene, Mersilene, Vypro, polytetraflouroethylene (PTFE), Proceed and control group) implanted into the peritoneum cavity. Thirty days after the operation, the relaparotomies were carried out, and any adhesions observed between the implanted mesh and tissues were evaluated and graded. The mean adhesion degree was 9.2 in the Mersilene mesh group, 9.5 in the Prolene mesh group, 9.7 and in the Vypro mesh group (P > 0.05). The mean adhesion degree was 1 in the control group, 2.75 in the Proceed mesh group and 2.25 in the PTFE mesh group. There was a significant difference in adhesion degree between the control, Proceed and PTFE groups and the Prolene, Mersilene and Vypro mesh groups. The adhesion degree was significantly lower in the Proceed and PTFE mesh groups when comparing them with the Prolene, Mersilene and Vypro meshes.

Morbidity predicting factors of penetrating colon injuries.

THE AIM: To analyze patients suffering from penetrating colon injuries management, clinical outcomes and factors, which predict higher morbidity and complications rate. METHODS: this was a retrospective analysis of prospectively collected data from patients with injured colon from 1995 to 2008. Age, time till operation, systolic blood pressure, part of injured colon, fecal contamination, PATI were registered. Monovariate and multivariate logistic regression was performed to determine higher morbidity predictive factors. RESULTS: 61 patients had penetrating colon injuries. Major fecal contamination of the peritoneal cavity and systolic blood pressure lower than 90 mmHg are independent factors determining the fecal diversion operation. Primary repair group analysis establish that major fecal contamination and systolic blood pressure lower than 90 mmHg OR = 4.2 and 0.96 were significant risk factors, which have contributed to the development of postoperative complications. And systolic blood pressure lower than 90 mmHg and PATI 20 predict OR = 0.05 and 2.61 higher morbidity. CONCLUSIONS: Fecal contamination of the peritoneal cavity and hypotension were determined to be crucial in choice of performing fecal diversion or primary repair. But the same criteria and PATI predict higher rate of postoperative complications and higher morbidity.

[The influence of Barrett's esophagus on the clinical signs and postoperative results of GERD]. / Der Einfluss des Barrett-Osophagus auf die klinische Symptomatik und die postoperativen Ergebnisse nach laparoskopischer Therapie der gastro-ösophagealen Refluxerkrankung.

AIM OF THE STUDY: Was to estimate the influence of the Barrett's esophagus on the clinical signs and post-surgical results of the GERD. PATIENTS AND METHODS: Within 1998-2001 193 patients have been operated upon in our clinic due to GERD, 81 male and 112 female. Mean patient age was 55 years (from 16 to 84 years). All patients had complaints on heartburn and regurgitation. We assessed the severity of heartburn, regurgitation, dysphagia with the help of a special scale ranging from 1 (absence of symptoms) to 5 (most severe symptoms). All patients underwent gastric and esophageal radiological investigation with barium contrast as well as esophago-gastro-duodenoscopy (EGDS) with biopsy. In 190 cases esophageal hernia was found. The reflux-esophagitis was classified according to Savary-Miller after endoscopic examination. Esophagitis of degree I-III was diagnosed presurgically in 176 cases, Barrett's esophagus in 16 (9.1%) cases. In 13 cases we found a short metaplastic segment (< 3 cm), in 3 cases a long segment (> 3 cm). In 15 cases we found metaplasia without dysplasia, in 1 case low-grade dysplasia. In order to assess the presence of BM influence on presurgical clinical signs, the severity of esophagitis, and the regression rate of symptoms after surgery, we divided the patients into two groups and compared them: group I (with Barrett's metaplasia), and group II (without Barrett's metaplasia). All patients underwent laparoscopic Nissen or Toupet fondoplications. For group I patients we performed 14 Nissen and 2 Toupet procedures, in group II 148 Nissen and 29 Toupet interventions. The regression of clinical and endoscopic symptoms was assessed 6 months after surgery by re-questioning the patients and with the help of EGDS. In cases of Barrett's esophagus endoscopic biopsies from all 4 esophageal segments were performed. The patients of group I were followed-up by performing EGDS every 6 months. The mean follow-up period after surgery was 28 months. RESULTS: No statistically significant difference was found when comparing the groups for age (group I--59/SD 11, and group II--54/SD 13.2), gender, disease duration (group I--13.2/SD 13.7 years, group II--8.2/SD 10.5 years), radiologically determined hernial size or preoperative severity of esophagitis. The regression of the severity of heartburn and regurgitation was prominent in both groups with no significant difference between the groups. Dysphagia before and after surgery was comparable in both groups. Esophagitis confirmed by EGDS remained in 3 of 16 cases in group I and in 9 of 164 cases in group II. The metaplastic changes in group I were followed every 6 months for 16-36 months (mean 28 months). In 13 cases the metaplastic segment demonstrated no changes, it became shorter in 3 cases. We didn't observe any complete regression of metaplasia. In the case with preoperative low grade dysplasia, the length of the segment did not change, we observed neither histological progression or regression. CONCLUSIONS: Barrett's metaplasia had no influence on the regression of symptoms of GERD and esophagitis after antireflux surgery. No histological progression of Barrett's metaplasia has been observed after antireflux surgery. The EGDS follow-up should not be very frequent in cases of Barrett's esophagus without dysplasia and good postsurgical regression of symptoms.

[Follow-up results and learning curve in laparoscopic gastrofundoplications]. / Lernkurve und Nachbeobachtungsresultate bei laparoskopischer Gastrofundoplicatio.

AIM OF THE STUDY: To analyze the postoperative results and the learning curve of laparoscopic gastrofundoplications by postoperative clinical monitoring of consequences and self-evaluation of complaints 12 months after surgery. METHODS: One hundred patients (58 female and 42 male) were operated at the Department of Surgery, Hospital of Kaunas University of Medicine, from April 1998 to January 2001 because of hiatal hernias, complicated with gastroesophageal reflux (in 59 cases sliding axial non-fixed, in 38 cases sliding axial fixed, and in 3 cases paraesophageal hernias were found). 89 Nissen and 11 Toupet fundoplications were performed. Patients were distributed into five groups (20 patients in each). Operation time, number of postoperative complications, postoperative hospital stay were analyzed. RESULTS: The mean operation time was 198 min in the 1 st group, 105 min in the 2 nd group, 110 min in the 3 rd group, 124 min in the 4 th group and 120 min in the 5 th group. Conversion to laparotomy was necessary in two cases (the 1 st and the 2 nd groups). The number of postoperative complications decreased from 5 in the 1 st group to 2 in the 2 nd group, and to 1 in the 3 rd and 4 th groups; no complications were noted in the 5 th group. According patient's opinion, successful results were received in 87 %. CONCLUSIONS: Laparoscopy is a good approach for surgical management of hiatal hernias complicated with gastroesophageal reflux, but laparoscopic gastrofundoplication needs advanced skills to be performed safely. The learning curve in terms of operation time covered initial 20 procedures and remained stable afterwards, the number of postoperative complications decreased after initial 20 operations, but dangerous complications occurred until the 60 th procedure. Other conventional elective surgical procedures of medium extent can be successfully performed simultaneously with laparoscopic fundoplication without affecting the outcome. The true learning curve of laparoscopic fundoplication can be drawn by careful follow-up and analysis of long-term postoperative results; this enables to improve operative techniques.

[Venous stasis and deep vein thrombosis prophylaxis during laparoscopic fundoplication]. / Prophylaxe der venösen Stase und tiefen Venenthrombose bei laparoskopischer Fundoplikatio.

AIMS OF THE STUDY: first, to study the effect of a pneumoperitoneum (12 mm Hg) on femoral venous outflow, second, to evaluate the efficacy of mechanical antistasis devices: intermittent pneumatic compression (IPC), intermittent electric calf muscle stimulation (IECS) and graded compression leg bandages (LB) in reducing venous stasis, third, to determinate the incidence of deep venous thrombosis (DVT) after laparoscopic fundoplications using venous occlusion plethysmography method. PATIENTS AND METHODS: 54 patients undergoing elective laparoscopic fundoplications were studied. They were randomized into three groups - 18 patients in each group. The first group received LB, the second group received IECS and the third group IPC during operations. Lower extremity venous blood velocity was evaluated using Doppler ultrasonography during operation. In all 54 patients leg venous outflow was measured 1 day before and 1 day after operation using venous occlusion plethysmography method, in order to detect possible DVT after operation. The blood velocity in the femoral vein without pneumoperitoneum was 20.1 +/- 2.4 cm/s in the IPC group, 20.3 +/- 1.4 cm/s in the IECS group, and 23.9 +/- 1.2 cm/s in the LB group. With the introduction of a pneumoperitoneum (12 mm Hg) and the reverse Trendelenburg position the femoral venous blood velocity was significantly reduced in all groups: 9.3 +/- 0.9 cm/s in IPC group, 9.4 +/- 0.9 cm/s in IECS group, and 9.2 +/- 1.1 cm/s in LB group (p < 0.05). The maximum blood velocity generated by the IPC when a pneumoperitoneum (12 mm Hg) was present was 17.4 +/- 1.9 cm/s, and in the IECS group 14.0 +/- 1.1 cm/s, whereas in the LB group the blood velocity remained the same (9.2 +/- 1.1 cm/s). Calf DVT and pulmonary artery microembolization developed in one patient of the LB group, detected by venous occlusion plethysmography and lung perfusion scintigraphy methods one day after operation. CONCLUSIONS: The femoral vein stasis which appears in laparoscopic fundoplications can be minimized by reducing the intraabdominal pressure during operation, and avoiding reverse Trendelenburg position as much as possible. IPC is more effective than IECS in reducing venous stasis induced by the pneumoperitoneum and the reverse Trendelenburg position. Graded compression by leg bandages is ineffective in patients undergoing laparoscopic gastrofundoplication. With a pneumoperitoneum in place, neither device was able to return the depressed blood flow velocity to the values recorded without a pneumoperitoneum. The incidence of DVT and pulmonary embolism after laparoscopic fundoplications was 1.8 % in our study.

[Introduction of laparoscopic splenectomy for the treatment of immune thrombocytopenic purpura]. / Einführung der laparoskopischen Splenektomie zur Behandlung der immunogenen thrombozytopenischen Purpura.

AIM OF THE STUDY: Was to evaluate retrospectively the outcomes and efficacy of the laparoscopic splenectomies for ITP patients, performed at our institution over a period of 7 years and to compare these results with those after open splenectomies. PATIENTS AND METHODS: We collected and analyzed data of 22 consecutive adult patients with ITP who underwent either laparoscopic (LS gr., n = 9) or open (OS gr., n = 13) splenectomy at Hospital of Kaunas University of Medicine between the years 1996 and 2002. The indications for splenectomy in these patients were unsuccessful treatment with corticosteroids or other medications and/or the requirement of high dosages of steroids for prolonged periods of time to maintain platelet count > 50 G/L before operation. Prior to surgery, all patients were treated with corticosteroids and/or intravenous immunoglobulin to raise the platelet count and to minimize the risk of intraoperative bleeding. The efficacy of the operation was evaluated by counting platelets one day before surgery and on the first and fifth postoperative day. Data chosen for analysis included age, gender, weight, height, American Society of Anaesthesiologists (ASA) score, number of converted patients, estimated blood loss during operation, operating time, postoperative secretion through the drains, morbidity, mortality and postoperative hospital stay. RESULTS: There were no significant differences between LS and OS groups according patients age, weight, height, gender and ASA score. The mean operative time was 138.8 +/- 50.1 min in LS group and was significantly longer than operative time in OS group (102.3 +/- 21.3 min). One patient was converted to open splenectomy because of severe bleeding from splenic hilum. Postoperative complications occurred in one patient from each group. The mean intraoperative blood loss was 460 +/- 125 ml in LS group and 510 +/- 140 ml in OS group (p > 0.05). Postoperative secretion through the drains and postoperative secretion time in LS group was significantly lower and shorter than in OS group. Postoperative hospital stay in LS group (5 +/- 1.1 days) was significantly shorter than in OS group (8 +/- 1.4 days). After splenectomy, there was an immediate increase in the platelet count of all patients in both groups. Between the day before surgery and the first postoperative day, the mean platelet count rose significantly from 75 +/- 57.0 G/L to 117 +/- 84.2 G/L in LS group and from 64 +/- 60.1 G/L to 122 +/- 79.3 G/L in OS group. Between the first postoperative day and the fifth postoperative day, the mean platelet count also rose significantly in both groups: from 117 +/- 84.2 G/L to 259 +/- 151.0 G/L in LS group and from 122 +/- 79.3 G/L to 258 +/- 158.4 G/L in OS group. In the immediate postoperative period (five days after operation), all LS group and OS group patients responded to the splenectomy. CONCLUSIONS: Laparoscopic or open splenectomy are equally efficacious in patients with ITP, with an immediate response rate of 100 % in our study. Our study results show that open splenectomy appears superior to laparoscopic procedure in terms of shorter operative time. Laparoscopic splenectomy appears superior to open procedure in terms of postoperative hospital stay, postoperative drainage time, less postoperative secretion through the drains. These two approaches are similar with regard to blood loss during operations and the rate of postoperative complications.