CD40 Agonists Alter the Pancreatic Cancer Microenvironment by Shifting the Macrophage Phenotype toward M1 and Suppress Human Pancreatic Cancer in Organotypic Slice Cultures

Background/Aims@#CD40 agonists are thought to generate antitumor effects on pancreatic cancer via macrophages and T cells. We aimed to investigate the role of CD40 agonists in the differentiation of macrophages and treatment of human pancreatic adenocarcinoma. @*Methods@#Immunohistochemistry was performed on paraffin-embedded surgical blocks from patients with pancreatic cancers to evaluate macrophage phenotypes and their relationship with survival. The effects of CD40 agonists on macrophage phenotypes and human pancreatic cancer were evaluated utilizing cell cocultures and organotypic slice cultures. @*Results@#CD163 + (predominant in M2 macrophages) and FOXP3 + (predominant in regulatory T cells) expression levels in the tumors were significantly lower in patients with stage IB pancreatic cancer than in those with stage II or III disease (p=0.002 and p=0.003, respectively). Patients with high CD163 + expression had shorter overall survival than those with low CD163 + expression (p=0.002). In vitro treatment of THP-1 macrophages with a CD40 agonist led to an increase in HLA-DR + (predominant in M1 macrophages) and a decrease in CD163 + expression in THP-1 cells. Cell cocultures showed that CD40 agonists facilitate the suppression of PANC-1 human pancreatic cancer cells by THP-1 macrophages. Organotypic slice cultures showed that CD40 agonists alter the pancreatic cancer microenvironment by shifting the macrophage phenotype toward M1 (increase HLA-DR + and decrease CD163 + expression), decreasing the abundance of regulatory T cells, and increasing tumor cell apoptosis. @*Conclusions@#CD163 is related to advanced human pancreatic cancer stages and shorter overall survival. CD40 agonists alter macrophage phenotype polarization to favor the M1 phenotype and suppress human pancreatic cancer.

Development and External Validation of Survival Prediction Model for Pancreatic Cancer Using Two Nationwide Databases: Surveillance, Epidemiology and End Results (SEER) and Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP)

Background/Aims@#Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. @*Methods@#Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. @*Results@#Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. @*Conclusions@#The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

Treatment Methods for Functional Recovery after Total Knee Arthroplasty / 대한정형외과학회잡지

Total knee arthroplasty is performed widely in degenerative arthritis of the knee joint, and the frequency of use is increasing. Efforts should be made to achieve functional recovery, such as returning to daily life, and the recovery of strength and range of motion after surgery. The procedure should be approached from a range of perspectives, such as patient factors, surgical technique and rehabilitation. The patient’s age, degree of obesity, sex, and strength of the quadriceps muscle can affect the functional recovery after surgery. In addition, the patient’s mental state, such as expectation value and satisfaction, can also have an effect. For functional recovery, patient education, pain control, and strengthening of the quadriceps muscle can be performed prior to surgery. Postoperative physiotherapy, such as icing and compression, transcutaneous electrical nerve stimulation therapy, neuromuscular electrical stimulation therapy, low frequency low intensity magnetic field therapy, strengthening of quadriceps muscle, and range of motion exercise can also be applied. In recent years, hydrotherapy, which restores the strength and balance of the leg, is being performed increasingly. These treatments are not only performed shortly after surgery, but are also performed continuously. In addition, the surgeon should apply it appropriately considering the patient’s condition, compliance, and social and psychological conditions.

The Optimal Suture Site for the Repair of Posterior Horn Root Tears: Biomechanical Evaluation of Pullout Strength in Porcine Menisci

PURPOSE: There are few studies on biomechanical evaluation of suture points in repair of root tears. The purpose of this study was to determine the point of greatest pullout strength for root tear repair. MATERIALS AND METHODS: A total of 120 fresh porcine medial menisci were obtained. The red-red and red-white zones of the meniscus were divided by two lines designated as lines A and B (groups A and B). Groups A and B were further divided into three groups each by dividing lines A and B into three points: 3, 5, and 7 mm from the meniscal ligament root insertion. Vertical meniscal repair was performed on each point. The pullout failure strength was tested using a biaxial servohydraulic testing machine. RESULTS: The average maximal load at failure was significantly greater in group A than group B (87.65 vs. 62.93; p<0.001) The average length at maximal load failure was greater in group A than group B (4.35 vs. 3.2; p<0.001). Among the subgroups of 3, 5, and 7 mm in both groups A and B, 7 mm showed the greatest maximal load (p<0.001). CONCLUSIONS: The pullout strength was statistically significantly greater in group A than group B and in the 7 mm subgroup than the 3 and 5 mm subgroups. Thus, the 7 mm subgroup in group A showed the greatest pullout strength.

Clinical Features of Male Breast Cancer: Experiences from Seven Institutions Over 20 Years / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. MATERIALS AND METHODS: Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. RESULTS: Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor–positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti–HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. CONCLUSION: Anti–HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.

Usefulness of Ultrasound-Guided Lower Extremity Nerve Blockade in Surgery for Patellar Fracture

PURPOSE: To evaluate the usefulness of ultrasound-guided nerve blockade in patellar fracture surgery. MATERIALS AND METHODS: Twenty-three patients who underwent metal fixation under ultrasound-guided lower extremity blockade after diagnosis of patellar fracture from July 2011 to June 2012 were enrolled in this study. Under ultrasound guidance, femoral nerve, lateral femoral cutaneous nerve, obturator nerve, and sciatic nerve blockades were performed. For evaluation of anesthesia, interference with overall surgery, such as intraoperative knee pain and tourniquet pain, was checked. Individual anesthetic complications, satisfaction with nerve blocks, and choice of future anesthesia method were investigated. RESULTS: Nineteen patients underwent surgery without any pain and 4 patients with mild pain. Satisfaction was excellent in 17 patients, good in 5, and unsatisfactory in 1. No complications such as infection or nerve injury occurred. In terms of selection of future anesthesia, 22 patients chose a nerve blockade of the lower extremity under ultrasound guidance, and one chose general anesthesia. CONCLUSIONS: Overall, ultrasound-guided nerve block of the lower extremity for patellar fracture surgery showed satisfactory results. Therefore, it could be a useful method to prevent complications associated with general or spinal anesthesia.

Suction Drain Tip Culture after Spine Surgery: Can It Predict a Surgical Site Infection?

STUDY DESIGN: Retrospective clinical study. PURPOSE: To assess the diagnostic value of suction drain tip culture in patients undergoing primary posterior spine surgery. OVERVIEW OF LITERATURE: To date, the diagnostic value of suction drain tip culture for predicting surgical site infection (SSI) has not been firmly established in orthopedic or spinal surgery. METHODS: In total, 133 patients who underwent primary posterior spine surgery from January 2013 to April 2015 were included in this retrospective study. Patients diagnosed with infective disease or condition was excluded. The suction drain tip was cut off approximately 5 cm from its far end. The sample was sent to the microbiological laboratory of the hospital for culture analysis. Any signs of infection, such as wound discharge or dehiscence, fever, chills, or chronic pain, were recorded. The culture outcome, identification of bacteria, and postoperative transition of the serum C-reactive protein level were also recorded in all patients. The wounds were followed up for a minimum of 3 months. RESULTS: A positive drain tip culture was found in 48 patients (36.1%), of whom, 6 developed SSI. The sensitivity of drain tip culture for SSI after primary posterior spine surgery was 60.0%, and the specificity was 65.9%. The association between the incidence of positive suction tip culture and SSI was not statistically significant. Among the 48 positive drain tip cultures, there was no significant association between the occurrence of SSI and virulence of isolated bacteria. There was no significant association between drain tip culture positivity and the duration of drainage, or between the rate of SSI and duration of drainage. CONCLUSIONS: Suction drain tip culture analysis is a poor predictor of SSI after primary posterior spine surgery. Routine use of a drain tip culture is not supported by the results of this study.

Metastatic Brain Neuroendocrine Tumor Originating from the Liver

A 67-year-old male presented with left temporal hemianopsia and left hemiparesis. A contrast-enhanced magnetic resonance image revealed a 4.5x3.5x5.0 cm rim-enhancing mass with central necrosis and associated edema located in the left occipital lobe. Of positron emission tomography and abdominal computed tomography, a 9-cm mass with poor enhancement was found in the right hepatic lobe. Craniotomy and right hemihepatectomy was performed. The resected specimen showed histological features and immunochemical staining consistent with a metastatic neuroendocrine tumor (NET). Four months later, the tumors recurred in the brain, liverand spinal cord. Palliative chemotherapy with etoposide and cisplatin led to complete remission of recurred lesions, but the patient died for pneumonia. This is the first case of a metastatic brain NET originating from the liver. If the metastatic NET of brain is suspicious, investigation for primary lesion should be considered including liver.

Recurrence of Multiple Focal Nodular Hyperplasia in a Young Male Patient / 대한소화기학회지

Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor that is usually found in women. Diagnosis of FNH mainly depends on imaging studies such as color Doppler flow imaging, computed tomography, and magnetic resonance imaging. It is characterized by the presence of stellate central scar and is nowadays incidentally diagnosed with increasing frequency due to advances in radiologic imaging technique. FNH typically presents as a single lesion in 70% of cases and generally does not progress to malignancy or recur after resection. Herein, we report a case of a young male patient with recurrent multiple FNH who underwent surgical resection for presumed hepatic adenoma on computed tomography.

MicroRNA expression profiling of diagnostic needle aspirates from surgical pancreatic cancer specimens

PURPOSE: MicroRNAs (miRNAs) have been widely investigated as potential biomarkers for several malignancies. To establish the feasibility of miRNA expression profiling of small biopsy samples of pancreatic cancers, we assessed expression profiles in freshly collected aspirates obtained immediately after surgical resection of the pancreas. METHODS: We used separate fine needles (20-23 gauge) to aspirate the pancreatic cancer and adjacent normal pancreatic tissue. miRNAs that were differentially expressed in pancreatic cancers and matched paraneoplastic normal pancreatic tissues were identified using an miRNA microarray. RESULTS: We identified 158 aberrantly expressed miRNAs in pancreatic cancers; 51 were overexpressed and 107 underexpressed compared with normal pancreatic tissue. To confirm the microarray findings, quantitative RT-PCR was performed on individual samples. We chose eight miRNAs for further analysis; of which five were overexpressed (miR-21, miR-27a, miR-146a, miR-200a, and miR-196a) and three underexpressed (miR-217, miR-20a, and miR-96) in pancreatic cancer samples compared to benign pancreatic tissue. Expression of miR-21, miR-27a, miR-146a, miR-200a, and miR-196a was significantly increased in cancer fine-needle aspirates relative to matched controls in all samples. Expression of miR-217, miR-20a, and miR-96 was significantly downregulated in almost all pancreatic cancer tissues. CONCLUSION: We demonstrate the feasibility of performing miRNA profiling on very small specimens obtained using fine-needle aspiration of pancreatic cancers.

Use of video-assisted thoracoscopic surgery to retrieve a broken guidewire / 대한외과학회지

Subclavian venous catheterization was once widely used for volume resuscitation, emergency venous access, chemotherapy, parenteral nutrition, and hemodialysis. However, its use has drastically reduced recently because of life-threatening complications such as hemothorax, pneumothorax. In this case, a patient admitted for a scheduled operation underwent right subclavian venous catheterization for preoperative, intraoperative, and postoperative volume resuscitation and parenteral nutrition. The procedure was performed by an experienced senior resident. Despite detecting slight resistance during the guidewire insertion, the resident continued the procedure to the point of being unable to advance or remove it, then attempted to forcefully remove the guidewire, but it broke and became entrapped within the thorax. We tried to remove the guidewire through infraclavicular skin incision but failed. So video-assisted thoracoscopic surgery was used to remove the broken guidewire. This incident demonstrates the risks of subclavian venous catheterization and the importance of using a proper and gentle technique.

Pinch-off syndrome / 대한외과학회지

Subclavian venous catheterization was previously frequently performed, but because of life-threatening complications such as hemothorax, pneumothorax, mediastinal hematoma, and myocardial injury, its use has become less common. However, this practice has some advantages in patient mobility, secured dressing, and rapidity and adequacy of vascular access. In some situations where patient comfort is an especially important consideration, such as with totally implantable venous port insertion for chemotherapy, the subclavian route can be a good choice if an experienced and well-trained faculty is available. The authors have had recent experience with pinch-off syndrome-in other words, spontaneous catheter fracture-in 3 patients who had undergone venous port implantation through the right subclavian route. Through these cases, we intend to review the dangers of subclavian venous catheterization, the causes of pinch-off syndrome, and its clinical presentation, progress, treatments, and prevention.

Role of Experimental Research as a Hepatobiliary Surgeon / 한양의대학술지

In the 1970s, surgeons performed a variety of experimental procedures on animals. Experimental surgery has scientific merit and allows surgeons to carry out many studies to understand pathophysiology in several fields of medicine. However, the strong opposition to animal research and the surgeon's increasing demand of clinical activities has threatened the opportunities of performing experimental studies. Although large animals are not permitted, small animals are available to use. The rat is a frequently used species, since it is economical and easy to breed and anesthetize. As a hepatobiliary surgeon, I studied liver resection and liver transplantation in rats. The technique of transplantation is not easy to obtain since it requires skillful microsurgical techniques. However, these techniques help to undergo experimental research and can be used as practice operations before it is actually performed on humans. As the experimental research continues to be an important part of surgery, every possible method should be considered in order to increase support and opportunities for research. The first step will be training young surgeons to enhance research. The second step is redirecting priorities among surgeons. The scientific productivity should be set as first priority for surgeons. Final strategy is to collaborate with basic scientists such as immunologist, biochemist and so on. There is no doubt that major advancement in the field of medicine in the 21st century will continue to arise from research in surgery. Surgeons should seek for more opportunities in good research training, and provide some time for experimental research.

Hepatogenic differentiation of human mesenchymal stem cells from peritoneal adipose tissue

BACKGROUNDS/AIMS: It has been reported that functional hepatogenic differentiation has the possibility to occur in subcutaneous adipose tissue-derived stem cells. However, no studies have investigated whether the adipose tissue-driven stem cells present in various body parts differ according to hepatogenic differentiations. In this study, stem cells were separated from body visceral fat and abdominal subcutaneous adipose tissue, and cultured, and then hepatogenic differentiation was induced. We aim to investigate the possibilities and aspects of hepatogenic differentiations within the two types of fat cells. METHODS: Omental fat tissues were obtained as visceral fat and abdominal subcutaneous adipose tissues were obtained from patients who had suction-assisted lipectomy. Stem cells were separated from the obtained fat tissues, and then, hepatogenic differentiation was carried out by utilizing 2-step differentiation protocols. RESULTS: After the differentiation, two types of cultured cells that showed the similar neuron-like shapes were changed to cuboidal shapes and included several binucleated cells which could be characteristics of mature hepatocytes. We confirmed that hepatocyte specific genes and proteins such as albumin and CYP3A4 were being expressed. By utilizing the ELISA test, we were able to observe that the albumin was secreted into the culture fluids in both cells. After completing the differentiation, we observed the presence of the hepatocyte specific properties by confirming glycogen storage within the cells and the ICG reagent uptake. CONCLUSIONS: We confirmed that hepatogenic differentiation was possible to occur in the omental fat as well as subcutaneous adipose tissue.

Managements of simple liver cysts: ablation therapy versus cyst unroofing

BACKGROUNDS/AIMS: Simple liver cysts were easily recognizable with the advanced imaging procedures, such as ultrasound and computed tomography scan. A large cyst or significant symptoms were indications for the treatments. Ablation therapy with sclerotic agents was effective, but there were several complications including severe pain. With the surgical cyst unroofing method introduced, we compared the cyst unroofing method and ablation therapy. METHODS: Between March 1997 and May 2011, we performed treatments of simple liver cysts in 27 patients. There were 23 women and 4 men (age range: 42-84 years; mean age: 64 years). The cyst unroofing was undergone with laparoscopic (n=13) and open technique (n=1). The ablation therapy was performed with ethanol (n=13) and acetic acid (n=1). RESULTS: The usual symptoms of the liver cysts were abdominal mass (n=7), indigestion (n=4), abdominal discomfort (n=3), and the increasing size of the cysts (n=4). The mean diameter of the cysts was 10.9 cm. The cyst unroofing method was performed effectively in 14 patients. One patient had bleeding during operation, and was converted to the open technique. One patient had a bile leak from the cyst, but it was successfully closed with the laparoscopic technique. Among the 14 cases with the ablation therapy, there were 4 complications: hematoma (n=1); cyst leaking during aspiration (n=2); acute renal failure (n=1); and death due to acetic acid intoxication (n=1). CONCLUSIONS: Laparoscopic cyst unroofing was more effective and safer in management than the ablation therapy in simple liver cysts.

Clinical Analysis of Endoscopic Thyroidectomy by the Axillary Approach for Papillary Thyroid Microcarcinoma / 대한내시경복강경외과학회지

PURPOSE: The aim of this study is to evaluate the feasibility and surgical outcomes of endoscopic thyroidectomy by the axillary approach for treating papillary thyroid microcarcinoma (PTMC). METHODS: We analyzed 56 patients who underwent endoscopic thyroidectomy by the axillary approach for treating PTMC between May 2002 and October 2008 at Bucheon ST hospital. We evaluated the operation type, the tumor size, the operative time, the hospital days, the number of retrieved lymph nodes and the complications. RESULTS: All the patients except one were women. The mean age was 40.5+/-8.7 years. All the procedure was performed by one surgeon and endoscopic thyroidectomy was done by the axillary approach. There was no conversion to open surgery. The type of operation was classified according to the extent of the surgery. The mean operative time for lobectomy and isthmectomy with CLND (24 cases) and total thyroidectomy with CLND (5 cases) was 142.5+/-40 minutes and 270+/-84.3 minutes, respectively. The mean tumor size was 0.66+/-0.46 cm. The mean number of retrieved lymph nodes was 3.7+/-2.4. The mean number of hospital days was 3.7+/-1.4 days. There were no serious complications. There were no tumor recurrence and the mean follow-up was 50.7 months. All the patients were satisfied with the cosmetic results. CONCLUSION: Endoscopic thyroidectomy by the axillary approach for PTMC is feasible and safe. Although a larger series and longer follow up are necessary, endoscopic thyroidectomy can be a alternative treatment method for selected patients with PTMC.

Composite Large Cell Neuroendocrine Carcinoma and Adenocarcinoma of the Ampulla of Vater

Large Cell Neuroendocrine Tumors (LCNEC) in the ampulla of Vater are extremely rare. This report addresses a case of concurrent LCNEC and adenocarcinoma in the ampulla of Vater. A 60-year-old male patient experienced fever, body chills and jaundice. He had a periampullary ulcerative lesion and underwent radical pancreaticoduodenectomy. Histopathologically, the tumor consisted of an LCNEC component and an adenocarcinoma component. Simultaneous LCNEC and adenocarcinoma has been reported in a few cases. Our patient had a coexisting LCNEC and an adenocarcinoma of the ampulla of Vater. We also present a review of the literature

Pancreatic Cyst in von Hippel-Lindau Disease

The von Hippel-Lindau (VHL) disease is an autosomal dominant disorder by germline mutation of VHL tumor suppressor gene. The affected patients mainly develop cancers of the central nervous system, renal cell carcinoma, pheochromocytoma, and pancreatic cysts. Pancreatic involvement was observed 12~77% in VHL patients and included true cysts, serous cystadenomas, and neuroendocrine tumors. We experienced two cases of pancreatic cyst of the von Hippel-Lindau disease and reviewed associated literatures.

Synchronous Carcinoma Showing Thymus-like Elements (CASTLE) of the Thyroid Combined with Rectal Carcinoma: Report of a Case and Review of the Literature / 대한내분비외과학회지

Carcinoma showing thymus-like elements (CASTLE) is a rare neoplasm arising from the thyroid gland. This tumor is thought to originate from ectopic thymic tissue or remnants related to thymic development in or adjacent to the thyroid gland and usually located in the lower two-thirds of the thyroid gland. The patient was a 66-year-old man admitted to our hospital with rectal carcinoma for surgery. He had undergone a right upper lobectomy of the lung for the pulmonary tuberculosis 35 years previously. He underwent a chest computed tomography (CT) pre-operatively, and an incidental nodule of the thyroid gland was detected. Based on aspiration cytology of the nodule, the lesion was suspected to be an anaplastic carcinoma. He underwent a low anterior resection and thyroid lobectomy for a double primary neoplasm. On the final pathologic examination, the thyroid lesion was shown to be CASTLE. Therefore, completion thyroidectomy with lymph node dissection of the central compartment and radiotherapy were performed, and there was no evidence of recurrence 15 months postoperatively.

Laparoscopic Cystogastrostomy for the Patient of Pancreatic Pseudocyst with Intra-abdominal Adhesion

A large symptomatic and unresolved pancreatic pseudocyst is treated surgically by internal drainage to a neighboring adherent viscus. Recently the various minimal invasive approaches have been used to treat this condition. A 30- year-old man who had been in clinical follow-up for a chronic pancreatitis. For the necrotizing pancreatitis, the patient had undergone surgical debridement and external drainage 5 years, and 3 years ago, respectively. Abdominal ultrasonography and computed tomography revealed 8.2x7.7 cm sized pseudocyst in the body of pancreas. Endoscopic internal fistula formation was tried, but it was failed due to bleeding. We underwent adhesiotomy and cystogastrostomy totally with laparoscopic techniques. The patient started a diet on the 5th postoperative day and discharged on the 11th postoperative day. There was no postoperative complicationand no recurrence during 6 months. Laparoscopic cystogastrostomy is safe and feasible method in the pancreatic pseudocyst even in case of severe abdominal adhesion.