Musa Akoglu

Yüksek İhtisas Hastanesi, Ankara, Engüri, Ankara, Turkey

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Publications (77)108.18 Total impact

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    ABSTRACT: Background: Radiation therapy is an essential therapeutic modality in the management of a wide variety of tumors. We aimed to investigate the short-term effects of pelvic irradiation on the healing of colon anastomoses and to determine the potential protective effects of β-glucan in this situation. Material and Methods: Sixty Wistar albino rats were randomized into three experimental groups: a control group (n = 20), an irradiation (IR) group (n = 20), and an irradiation+β-glucan (IR+β-glucan) group (n = 20). Only segmental colonic resection and anastomosis were performed on the control group. The IR group underwent the same surgical procedure as the control group 5 days after pelvic irradiation. In the IR+β-glucan group, the same procedure was applied as in the IR group after β-glucan administration. The groups were subdivided into subgroups according to the date of euthanasia (third [n = 10] or seventh [n = 10] postoperative [PO] day), and anastomotic colonic segments were resected to evaluate bursting pressures and biochemical and histopathological parameters. Results: Bursting pressure values were significantly lower in the IR group (p p p Conclusions: The results of this study indicate that irradiation has negative effects on the early healing of colon anastomoses. The administration of β-glucan ameliorates these unfavorable effects by altering bursting pressures and biochemical parameters.
    Journal of Investigative Surgery 01/2014; 27(3). · 1.32 Impact Factor
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    ABSTRACT: This paper consists of an experimental animal study. The aim of the study is to investigate the early effects of irradiation on anastomotic rat colon segment and efficacy of Pycnogenol(®) administration.
    International Journal of Surgery (London, England) 06/2013; · 1.44 Impact Factor
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    ABSTRACT: A 58-year-old male patient presented with an anorectal verrucous carcinoma, also known as Buschke–Lowenstein tumor. Clinically, the lesion of the patient best resembled giant condyloma acuminatum with a cauliflower-like appearance. The diagnosis was confirmed with biopsy and an abdominoperineal resection was performed. The perineal defect was reconstructed with bilateral gluteal musculocutaneous V-Y advancement flap. Both functional and cosmetic results 6 years after the operation were excellent. To date, no recurrence has been noted. As long as one is aware of its existence and of its characteristic appearances, the Buschke–Lowenstein tumor is fairly easily diagnosed. The treatment of choice remains surgical resection, and adequate follow-up is essential.
    Indian Journal of Surgery 06/2013; 75(1). · 0.09 Impact Factor
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    ABSTRACT: The differentiation of gallbladder adenomyomatosis from gallbladder carcinoma is important as both conditions may present with thickening of the gallbladder wall or as a focal mass. Identification of Rokitansky-Aschoff sinuses is the key feature in making an accurate diagnosis of gallbladder adenomyomatosis on imaging studies. The diagnosis of gallbladder adenomyomatosis can be made with accurately by multidetector computed tomography when the presence of Rokitansky-Aschoff sinuses (small cystic spaces within the thickened gallbladder wall) are noted. Herein we present multidetector computed tomography findings of a 27-year-old patient with gallbladder adenomyomatosis.
    The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 06/2013; 24(3):286-9. · 0.48 Impact Factor
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    ABSTRACT: :Background/Aims: A single-center, prospective observational study was performed to evaluate outcomes in patients undergoing D2 or D3 lymphadenectomy for gastric cancer. Methodology: Lymphadenectomies were performed according to the classification published by the Japanese Gastric Cancer Association. Results: Of 468 consecutive patients, 370 underwent D2 and 98 underwent D3 lymphadenectomy. Postoperative complications were significantly less common in the D2 group than in the D3 group (19.2% vs. 35.7%, p=0.001). Postoperative mortality in the two groups was similar, being 3.8% in the D2 group and 5.1% in the D3 group (p>0.05). Median postoperative survival times were also similar, in the D2 group being 37.8 months (95% CI: 23-52.5), and in the D3 group 30.2 months (95% CI: 13-47.3, p>0.05). Conclusions: In patients who underwent gastrectomy with curative intent, lymphadenectomy that was more extensive than D2 did not provide a survival benefit compared to D2 dissection.
    Hepato-gastroenterology 05/2013; 60(123). · 0.77 Impact Factor
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    ABSTRACT: Primary anorectal malignant melanoma is an exceptionally rare neoplasm associated with poor prognosis. Anorectal malignant melanoma has been very rarely described with coexisting primary tumors of the colorectum. A 56-year-old female patient was admitted with a history of rectal bleeding. She had experienced increasing constipation and a sense of obstruction in the rectum for 6 months. Flexible rectosigmoidoscopy showed a large, pedinculated polypoid lesion extending from the anal canal to the rectum. She underwent a transanal local excision and was diagnosed with a melanoma of the anorectum with positive margins. Therefore, a formal abdominoperineal resection was performed. In addition to multiple synchronous anorectal malignant melanoma, we incidentally found another primary tumor in the proximal surgical margin of the resected specimen. Histopathologically, the lesion was an intramucosal adenocarcinoma of the sigmoid colon. Postoperatively, the patient received adjuvant chemotherapy of six cycles duration. At present, the patient has completed 18 months of follow-up.
    Indian Journal of Surgery 04/2013; 75(2). · 0.09 Impact Factor
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    ABSTRACT: Introduction. Gastric cancer is the second cause of cancer-related deaths worldwide. Delayed diagnosis leads to high mortality rates. Eotaxin-1 was originally discovered as an eosinophil-selective chemoattractant and may play a role in a number of chronic inflammatory diseases, cancer, and other gastrointestinal disorders. The aim of this study was to analyse diagnostic and prognostic significance of serum eotaxin-1 (s-eotaxin-1) levels in gastric cancer. Methods. Sixty gastric cancer patients and 69 healthy subjects were included into the study. S-eotaxin-1 levels were compared with clinicopathological features and outcomes in gastric cancer. Results. Serum levels of eotaxin-1 in gastric cancer patients were significantly higher than controls (74.51 ± 16.65 pg/mL versus 16.79 ± 5.52 pg/mL, respectively (P < 0.001)). The s-eotaxin-1 levels did not differ significantly with histopathological grade, tumor-node-metastasis (TNM) stage, tumor localization, lymph node metastases, positive lymph node ratio, size, perineural and perivascular invasion. So there is no relationship found between s-eotaxin-1 level and prognosis. Conclusion. S-eotaxin-1 levels may be used as an easily available biomarker for gastric cancer risk and may alert physicians for early diagnosis. Due to the limited number of patients included in this study, larger cohort studies are warranted to validate the diagnostic value of s-eotaxin-1 level in gastric cancer.
    Disease markers 01/2013; 35(5):363-7. · 2.14 Impact Factor
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    ABSTRACT: The aim of this study was to determine whether intraoperative Ankaferd blood stopper (ABS) application into the pancreatic channel and to the pancreatic remnant surface following distal pancreatectomy can or cannot prevent postoperative pancreatic fistula formation. Three pigs underwent distal pancreatectomy under general anesthesia. In two of the pigs, 0.5 ml of ABS was applied to the stump surface area after adding 0.5 ml of ABS into the pancreatic channel. The remaining one animal served as the control. The pigs were sacrificed on the seventh postoperative day for autopsy. The pancreatic remnants from the animals were then taken for histopathological analyses. It was observed that the oral intake had been broken and abdominal distention had developed in the control pig following on the third postoperative day. However, no significant clinical changes were observed in the ABS-applied pigs. In the autopsy, it was found that the control pig had generalized peritonitis with pancreatic necrosis. On the other hand, the ABS-applied pigs had either macroscopically and microscopically normal pancreatic tissue architecture with an occluded Wirsung duct at the pancreatic stump. It was concluded that application of ABS on the transected surface and into the pancreatic channel could prevent pancreatic fistula formation and improve wound healing in the residual pancreatic tissue following distal pancreatectomy.
    Indian Journal of Surgery 01/2013; · 0.09 Impact Factor
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    ABSTRACT: Background: Gastric cancer is the second commonest cause of cancer-associated deaths in the world. Its molecular markers can be useful not only for the diagnostic pursuit but also for prognostic purposes. Endoglin was proposed as a marker of neovascularization in solid malignancies. A circulating form of endoglin is referred to as soluble endoglin (sol-end).The purpose of this study was to investigate the clinical importance of serum level of soluble form of sol-end in gastric cancer patients.Materials and methods: Serum levels of sol-end were measured in 69 healthy controls and in 60 gastric adenocarcinoma patients with ELISA and serum levels of sol-end were compared with clinicopathological features and outcomes in gastric cancer patients.Results: Serum levels of sol-end in gastric adenocancer patients were significantly higher than in control patients (p<0.001). The serum levels of sol-end did not differ relative to clinical and pathologic criteria.Conclusion: Presented data suggest that serum levels of sol-end do not seem to be a valuable tool in the assessment of gastric cancer prognosis (Tab. 1, Ref. 11). Keywords: endoglin, gastric cancer, prognosis.
    Bratislavske lekarske listy 01/2013; 114(10):566-8. · 0.47 Impact Factor
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    ABSTRACT: ABSTRACT Objective: The objective of this study was to evaluate the serum and bile concentrations of cefazolin and ceftriaxone at the third and sixth hours in an experimental obstructive jaundice model and to identify the rate of excretion of these antibiotics into the bile. Material and methods: Thirty-two Wistar albino rats were used in this study. The bile and serum levels of cefazolin were measured at the third hour in the A1 group and at the sixth hour in the A2 group, with cefazolin administered as 5 mg/rat; while the bile and serum levels of ceftriaxone were studied at the third hour in the B1 group and at the sixth hour in the B2 group, with ceftriaxone administered as 5 mg/rat. Results: After 3 hr of cefazolin administration, the serum concentration in the A1 group reached a mean of 1.8 μg/ml, while the bile concentration was 90% of the serum concentration, with a mean of 1.6 μg/ml; whereas in the B1 group, the third-hour serum concentration of ceftriaxone was 18.6 μg/ml, while the bile concentration was found to be as high as 330% of this level, i.e., 56 μg/ml. The serum value of cefazolin decreased to 1.4 μg/ml in the A2 group and ceftriaxone decreased to 3.7 μg/ml in the B2 group at the sixth hour. Conclusions: Although the excretory level of cefazolin and ceftriaxone into the bile reaches therapeutic doses, the duration for which these levels are above those required for bactericidal activity is short. Ceftriaxone is better concentrated in the serum and bile than cefazolin.
    Journal of Investigative Surgery 12/2012; · 1.32 Impact Factor
  • ANZ Journal of Surgery 12/2012; 82(12):948. · 1.50 Impact Factor
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    ABSTRACT: ABSTRACT Purpose: We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on intestinal mucosal injury induced by superior mesenteric occlusion. Methods: This experimental study was conducted on 48 male Wistar-albino rats. The animals were randomly allocated into four groups: (i) Sham-operated group, laparotomy without intestinal ischemia/reperfusion (IR) injury (n = 12); (ii) Sham + CAPE group, identical to group 1 except for CAPE treatment (10 μmol/kg, intravenously) (n = 12); (iii) Intestinal IR group, 60 min of superior mesenteric ischemia followed by 3 hr of reperfusion (n = 12); and (iv) (IR + CAPE)-treated group, 10 μmol/kg injection of CAPE intravenously 30 min before the reperfusion period (n = 12). We evaluated the degree of intestinal mucosal injury on a grading scale, histopathologically, and by measuring oxidative stress markers and antioxidant parameters, biochemically. Intestinal edema was estimated by using wet/dry weight ratios. The plasma proinflammatory cytokine levels were measured. Animal survival was observed up to one week. Results: Intestinal mucosal injury scores were significantly decreased with CAPE administration (p < .05). CAPE treatment significantly reduced oxidative stress markers in the intestinal tissues (p < .05) and the plasma proinflammatory cytokine levels (p < .05), and significantly increased antioxidant parameters in the intestinal tissues (p < .05). Intestinal edema was significantly alleviated by CAPE treatment (p < .05). The survival rates of CAPE-treated IR animals were significantly higher than IR-subjected rats (p < .05). Conclusion: This study clearly showed that CAPE treatment significantly alleviated the intestinal mucosal injury caused by superior mesenteric ischemia/reperfusion. Further clinical studies are required to clarify whether CAPE has a useful role in reperfusion injury during particular surgeries in which IR-induced organ injury occurs.
    Journal of Investigative Surgery 12/2012; 25(6):354-365. · 1.32 Impact Factor
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    ABSTRACT: Background/aims: The aim of this study was to investigate the effects of the H2 receptor antagonists famotidine and ranitidine on lower esophageal sphincter pressure in the rat isolated lower esophageal sphincter preparation contracted with carbachol. Materials and Methods: Lower esophageal sphincter tissues of eight rats for each group were placed in a standard organ bath. After contraction with carbachol, freshly prepared famotidine and ranitidine were added directly to the tissue bath in cumulatively increasing concentrations. Activities were recorded on an online computer using the software BSL PRO v 3.7, which also analyzed the data. Results: Ranitidine caused a small statistically insignificant relaxation in the contracted lower esophageal sphincter at the two applied concentrations. Although 1.5x10-5 M famotidine did not cause a significant relaxation in lower esophageal sphincter tone, this value for 4.5x10-5 M famotidine was 9.33%, and the relaxation was significant when compared with controls (p<0.05). Conclusions: Neither famotidine nor ranitidine caused any direct significant change in lower esophageal sphincter tone in the therapeutic dose range applied to the organ bath. However, the higher dose of famotidine caused a significant relaxation in the lower esophageal sphincter tone. Further in vivo human studies may affect the usage of these drugs during gastroesophageal reflux disease treatment.
    The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 10/2012; 23(5):438-43. · 0.48 Impact Factor
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    ABSTRACT: ABSTRACT Purpose: We aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on wound healing in left colonic anastomoses in the presence of intraperitoneal sepsis induced by cecal ligation and puncture (CLP) in a rodent model. Methods: This experimental study was conducted on 48 male Wistar albino rats. The animals were randomly allocated into four groups and a left colonic anastomosis was performed on the day following sham operation or CLP in all rats: (i) sham-operated control group, laparatomy plus cecal mobilization (n = 12) (Group 1), (ii) sham + CAPE group, identical to Group 1 except for CAPE treatment (10 μmol/kg, intraperitoneally, 30 min before construction of the colonic anastomosis) (n = 12) (Group 2), (iii) CLP group, cecal ligation and puncture (n = 12) (Group 3), and (iv) CLP + CAPE-treated group, 10 μmol/kg, intraperitoneally, 30 min before the construction of colonic anastomosis (n = 12) (Group 4). On the postoperative day 7, the animals were subjected to relaparotomy for in-vivo measurement of the colonic anastomotic bursting pressure. A colonic segment including the anastomotic site was resected for histopathological evaluation and biochemical analyses of hydroxyproline (Hyp) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA) levels, reduced glutathione (GSH) levels, and superoxide dismutase (SOD) activity. Body weight changes were examined. Results: CAPE treatment significantly increased colonic anastomotic bursting pressures (p < .05), colonic anastomotic tissue Hyp contents, and enzymatic and nonenzymatic antioxidant markers (p < .05), and significantly decreased oxidative stress parameters in colonic anastomotic tissues (p < .05). Histopathological scores were significantly better by CAPE administration (p < .05). Conclusion: This study clearly showed that CAPE treatment prevented the detrimental effects of intraperitoneal sepsis on colonic anastomotic wound healing. Further clinical studies are required to determine whether CAPE has a useful role in the enhancement of gastrointestinal anastomotic wound healing during particular surgeries in which sepsis-induced organ injury occurs.
    Journal of Investigative Surgery 10/2012; 25(5):301-10. · 1.32 Impact Factor
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    ABSTRACT: BACKGROUND: Laparoscopic cholecystectomy (LC) still leads to significant postoperative nausea and vomiting (PONV) and pain. Our aim was to evaluate the efficacy of dexamethasone or pheniramine hydrogen maleate, either alone or combined, in reducing the stress response and symptoms after LC. METHODS: Patients were randomly assigned to 1 of 4 groups, each consisting of 20 patients: control, dexamethasone (8 mg/2 mL), pheniramine hydrogen maleate (45.5 mg/2 mL), and the combined group. The drugs were given before anesthesia induction. RESULTS: C-reactive protein levels (CRP) and visual analog scale (VAS) scores were significantly less in the dexamethasone (P = .003) and combined groups (P < .001). Both dexamethasone (P < .001) and pheniramine hydrogen maleate (P = .005) significantly reduced PONV. CONCLUSIONS: Dexamethasone significantly reduced postoperative pain and the systemic acute-phase response, whereas these effects were only partially attained with pheniramine hydrogen maleate. Both dexamethasone and pheniramine hydrogen maleate significantly reduced PONV. An additive effect seemed to occur if these drugs were used in combination.
    American journal of surgery 08/2012; · 2.36 Impact Factor
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    ABSTRACT: The regeneration process causes the liver to achieve an adequate volume and function after major hepatectomy or living donor liver transplantation. Sildenafil, a selective phosphodiesterase-5 inhibitor used for erectile dysfunction, impacts the liver by enhancing the effects of nitric oxide. The aim of this study was to investigate the influence of sildenafil on liver regeneration in rats after partial hepatectomy. Sixty young female Wistar Albino rats were randomly divided into three equal groups before 70% hepatectomy. Thereafter, we administered intraperitoneal saline to the control group (G1); 10 μg/kg sildenafil to the low-dose group (G2) and 100 μg/kg to the high-dose sildenafil group (G3). Half of the rats per group were sacrificed on the first and the other half on the fifth postoperative day after partial hepatectomy. Regeneration was assessed using three methods: (1) the formula described by Kwon et al formula, (2) the average number of mitotic figures in 10 microscopic fields, and (3) the average of Ki-67-positive nuclei in 1000 cells using immunohistochemistry. Although, the hepatic regeneration and mitosis rates were similar in all three groups, Ki-67 levels were significantly higher in both G2 and G3 than the control group on the first postoperative day. Hepatic regeneration was significantly greater in G2 and G3 than the control group as was the mitosis rate in the G2 group versus the two groups. By the 5th postoperative day Ki-67 levels were similar in the three groups. Sildenafil treatment accelerated hepatic regeneration after partial hepatectomy in rats.
    Transplantation Proceedings 07/2012; 44(6):1747-50. · 0.95 Impact Factor
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    ABSTRACT: ABSTRACT Purpose: We aimed to investigate whether caffeic acid phenethyl ester (CAPE) prevents detrimental systemic effects of intestinal ischemia-reperfusion (IR) injury on colonic anastomotic wound healing. Methods: This experimental study was conducted on 48 male Wistar albino rats. The rats were randomly allocated into four groups and a left colonic anastomosis was performed in all rats: (i) sham-operated group (n = 12), laparatomy without intestinal IR injury; (ii) sham + CAPE group (n = 12), identical to Group 1 except for CAPE treatment (10 μmol/kg, intravenously); (iii) intestinal IR group (n = 12), 60 min of superior mesenteric ischemia followed by reperfusion; and (iv) IR + CAPE-treated group (n = 12) (10 μmol/kg, intravenously, 30 min before the construction of colonic anastomosis). On the postoperative day 7, the rats were subjected to relaparotomy for in vivo measurement of the colonic anastomotic bursting pressure. A colonic segment including the anastomotic site was resected for histopathological evaluation and biochemical analyses. The plasma proinflammatory cytokine levels were measured. Body weight changes were examined. Results: CAPE treatment significantly increased colonic anastomotic bursting pressures, and colonic anastomotic tissue hydroxyproline contents and antioxidant parameters (p < .05), and significantly decreased oxidative stress markers in colonic anastomotic tissues and plasma proinflammatory cytokine levels (p < .05). Histopathological scores were significantly better due to CAPE administration (p < .05). Conclusions: This study clearly showed that CAPE treatment prevented the delaying effects of remote IR injury on colonic anastomotic wound healing. Further clinical studies are required to determine whether CAPE has a useful role in the enhancement of gastrointestinal anastomotic wound healing during particular surgeries in which IR-induced organ injury occurs.
    Journal of Investigative Surgery 05/2012; · 1.32 Impact Factor
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    ABSTRACT: The most important criterion in the management of endoscopic retrograde cholangiopancreatography (ERCP)-related perforations is the delineation of the injury pattern. The aim of the present study was to evaluate in a retrospective manner the patients who undergo surgery due to ERCP-related perforations. Between January 2006 and December 2010, a total of 9209 ERCPs were performed at Turkiye Yuksek Ihtisas Teaching and Research Hospital, Ankara, Turkey. From these, perforation was diagnosed in 52 patients (0.56%). Twenty-four patients (46.2%) underwent surgery. Patients were evaluated according to age, gender, ERCP indication, comorbid disease, the time between diagnosis and perforation, the time between ERCP and surgical intervention, radiological and clinical signs, localization of the perforation, surgical procedure, hospitalization period, and postoperative outcome. Twenty-four patients underwent surgery. Thirteen patients (54.1%) had lateral duodenal wall perforation, 4 patients (16.7%) had perforation in the afferent loop (these patients had Billroth-II gastroenterostomy at ERCP admission), 2 patients (8.3%) had bile duct perforation, and 1 patient (4.1%) had esophageal perforation. In 4 patients (16.7%), the localization of the perforation could not be found. Nine patients (37.5%) died in the postoperative period. Six patients had lateral duodenal wall perforation, 2 patients had afferent loop perforation, and one patient had esophagus perforation. Three patients died of nonsurgical reasons (myocardial infarction, serebrovascular occlusion, and cardiac dysrhythmia). Duodenal wall perforations have a serious fatal outcome even if early surgical intervention is performed. In contrast to duodenal wall injuries, perivaterian and choledochal injuries have a better outcome.
    Journal of Laparoendoscopic & Advanced Surgical Techniques 01/2012; 22(4):371-7. · 1.07 Impact Factor
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    ABSTRACT: Background: Hepatic artery aneurysm (HAA) is a rare clinical entity that can lead to potentially life threatening complications. We reported our personal experience of 4 cases, in which we used different procedures.Methods: The first case had a pseudo-aneurysm involving the right hepatic artery. The second case had a pseudo-aneurysm, which was localized distal to the accidentally ligated right hepatic artery from the previous cholecystectomy operation. The third case had multiple aneurysms with accompanying dissecting abdominal aortic aneurysm. The fourth case had a pseudo-aneurysm originating from the proper hepatic artery. A covered stent was successfully placed in the case 1. In the second case, the right hepatic artery was ligated distal to the aneurysm. In the third case, vascular structures were not appropriate for vascular reconstruction, and a covered stent placement and embolization were unsuccessful. In the fourth case, ligation of the proper hepatic artery and cholecystectomy was performed.Results: The third case with multiple aneurysms died from multi-organ failure due to sepsis. The remaining cases (case 1, 2, and 4) are disease free and alive.Conclusion: HAAs are more commonly observed clinical entities, and their treatment should be handled for each patient separately. Computerized tomography-Angiography and intraoperative Doppler ultrasound are useful radio-diagnostics for determination of aneurysm and planning the operative procedure (Fig. 5, Ref. 15). Keywords: pseudo-aneurysm, covered stent, embolization, angiography.
    Bratislavske lekarske listy 01/2012; 113(11):676-9. · 0.47 Impact Factor
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    ABSTRACT: Benign anastomotic stricture after hepaticojejunostomy is one of the serious complications of biliary surgery. If left untreated, jaundice, cholangitis, or cirrhosis may develop. A 58-year-old male patient was admitted with benign hepaticojejunostomy stricture. The patient initially underwent an endoscopic retrograde cholangiography using double-balloon enteroscope, which was unsuccessful due to the sharp angle between the jejunal limb and the biliary tree. It was decided to perform surgery. During the operation, we performed Heineke-Mikulicz strictureplasty to the narrowed anastomosis. Patient's postoperative course was uneventful. At the end of followup, for 18 months, his liver enzymes were within normal ranges, and the ultrasound examination showed a patent hepaticojejunostomy anastomosis. The simplicity of the technique and the promising result support the applicability of the Heineke-Mikulicz principle in suitable cases as an alternative treatment approach for hepaticojejunostomy strictures.
    Case reports in surgery. 01/2012; 2012:454975.

Publication Stats

326 Citations
108.18 Total Impact Points

Institutions

  • 1998–2013
    • Yüksek İhtisas Hastanesi, Ankara
      Engüri, Ankara, Turkey
  • 2002
    • Inonu University
      • Department of General Surgery
      Malatia, Malatya, Turkey
  • 2000
    • University of Pittsburgh
      • Thomas E. Starzl Transplantation Institute
      Pittsburgh, Pennsylvania, United States