Current trends of major arterial diseases in Korea: based on data from the Health Insurance Review and Assessment Service

PURPOSE: This study aims to figure out the changes of the prevalence and management of carotid arterial occlusive diseases (CAOD), abdominal aortic diseases (AAA), and arterial diseases of the lower extremities (LAOD) in Korea over the past 5 years. METHODS: Data were extracted from the Health Insurance Review and Assessment Service during the period from 2008 to 2012. RESULTS: The number of patients with CAOD increased by about 30% every year. From the year 2008, the number of open surgeries (OS) and endovascular treatments (ET) increased by more than 20% during each of the first 2 years and by 10% every year for 3 years thereafter for CAOD. ET was preferred to OS and occupied 77%-79% of the total number of procedures. The number of patients with AAA increased by 11%-17% every year. ET for AAA occupied 52% of the total number of procedures in 2008 and gradually increased to 70% in 2012. The number of patients who were diagnosed with LAOD fluctuated over the five years. The total number of procedures to treat LAOD increased each year by 20%-25%. ET for LAOD constantly increased by 18%-24% each year and occupied 80%-95% of the total number of procedures. CONCLUSION: It is evident that the incidence of vascular diseases will be increasing as our society ages, not to mention its care costs. The need for long-range plans and guidelines are urgent.

Comparison between operative versus non-operative management of traumatic liver injury

BACKGROUNDS/AIMS: The aim of this study was to compare operative versus non-operative management of patients with liver injury and to ascertain the differences of the clinical features. METHODS: From April 2000 to July 2012, 191 patients were admitted to Seoul St. Mary's Hospital and St. Vincent's Hospital for liver injuries. Of these, 148 patients were included in this study. All patients were diagnosed using computed tomography (CT). The liver injury was graded in accordance with the American Association for the Surgery of Trauma liver injury scoring scale. Patients were divided into two groups: those who underwent surgery and those treated with non-operative management (NOM). There was a comparison between these two groups concerning the clinical characteristics, grade of liver injury, hemodynamic stability, laboratory findings, and mortality. RESULTS: According to the 148 patient records evaluated, 108 (72.9%) patients were treated with NOM, and 40 (27.1%) underwent surgery. Patients treated with NOM had significantly fewer severe injuries as rated using the Revised Traumatic Injury Scale, Injury Severity Score, and Glasgow Coma Scale. Grade of liver injury and number of patients with extravasation of contrast dye on CT and hemoperitoneum were higher in the operative group than in the NOM group. There were significant differences between the two groups for: heart rate, respiratory rate, systolic blood pressure, and mean hemoglobin levels at admission and after 4 hours. The operative group experienced a significantly higher mortality than the NOM group. CONCLUSIONS: The results of our study suggest that hemodynamic stability and the following should be considered for deciding the treatment for liver injuries: grade of liver injury, amount of blood loss, and injury scales scores.

Occurrence and Prognosis of Symptomatic Venous Thromboembolism in Colorectal Cancer Surgery Patients

PURPOSE: Colorectal cancer (CRC) has a high risk for postoperative thromboembolic complications such as venous thromboembolism (VTE) compared to other surgical diseases, but the relationship between VTE and CRC in Asian patients remains poorly understood. The present study examined the incidence of symptomatic VTE in Korean patients who underwent surgery for CRC. We also identified risk factors, incidence and survival rate for VTE in these patients. MATERIALS AND METHODS: The patients were identified from the CRC database treated from January 2011 to December 2012 in a single institution. These patients were classified into VTE and non-VTE groups, their demographic features were compared, and the factors which had significant effects on VTE and mortality between the two groups were analyzed. RESULTS: We analyzed retrospectively a total of 840 patients and the incidence of VTE was 3.7% (31 patients) during the follow-up period (mean, 17.2 months). Histologic subtype (mucinous adenocarcinoma) and previous history of VTE affected the incidence of VTE on multivariate analysis. There was a statistically significant difference in survival rate between the VTE and non-VTE group, but VTE wasn't the factor affecting survival rate on multivariate analysis. Comparing differences in survival rate for each pathologic stage, there was only a significant difference in stage II patients. CONCLUSION: Among CRC patients after surgery, the incidence of VTE was approximately 3% within 1 year and development of VTE wasn't a significant risk factor for death in our study but these findings are not conclusive due to our small sample size.

Anterior Tibial Artery Angioplasty and Stenting by Retrograde Pedal Artery Approach in Diabetic Patient with Critical Limb Ischemia: A Case Report / 대한혈관외과학회지

Endovascular therapy of critical limb ischemia is indicated in high risk patients, especially the diabetics. The ipsilateral antegrade femoral approach is the most common access site. When this approach fails, the retrograde pedal artery percutaneous approach can be considered. A 51-year-old diabetic male patient was presented with severe rest pain and gangrene on his right 4th toe. Computed tomography angiography showed multilevel calcific arterial occlusive disease, involving the popliteal and proximal anterior tibial arteries. Below knee angioplasty and stenting of the right leg was done through ipsilateral antegrade femoral approach and retrograde pedal artery approach. The C-arm guided retrograde pedal approach for calcific artery was useful for recanalization of the occluded anterior tibial artery when antegrade approach failed.

A Clinical Consideration of Abdominal Aortic Aneurysm Rupture / 대한혈관외과학회지

PURPOSE: With current advances in surgical technique, the prognosis for elective open repair of abdominal aortic aneurysm (AAA) has improved, but the mortality rate for ruptured AAA remains high. The aim of this study was to define the risk factors of AAA rupture. METHODS: We performed a retrospective analysis of 169 AAA patients who underwent open surgical repair between March 2000 and October 2010. According to the rupture, the patients were divided into 2 groups: 'ruptured' (n=41), 'non-ruptured' (n=128). To define the risk factor of ruptured AAA, we compared following variables between the 2 groups: clinical co-morbidities (hypertension, diabetes mellitus, ischemic heart disease, malignancies), diameter (maximal diameter of AAA), location of rupture, gender, and previous abdominal surgery history. RESULTS: Mean patient-age was 68.4+/-4.4 years (range: 32 to 86 years); the majority of patients were males, 135 (79.8%). Mean diameter of AAA was 6.67+/-2.0 cm (range: 4 to 15 cm); 'non-ruptured': 6.3+/-1.6 cm, 'ruptured': 7.8+/-2.6 cm. The risk of AAA rupture was statistically significantly increased with increased diameter of the AAA (P=0.007). On multivariateanalysis, the only statistically significant risk factor for AAA rupture was diameter of AAA (P=0.004). CONCLUSION: The only significant risk factor for AAA rupture found in this study is the diameter of AAA. To minimize the rupture rate of the AAA patients, we will have to closely monitor the size of AAA diameter.

Significance of CD133 as a cancer stem cell markers focusing on the tumorigenicity of pancreatic cancer cell lines / 대한외과학회지

PURPOSE: The cancer stem cell hypothesis states that the capacity of a cancer to grow and propagate is dependent on a small subset of cells. To determine the significances of the cancer stem cell markers CD133, CD44, and CD24 using a comparative analysis with a focus on tumorigenicity. METHODS: Four pancreatic cancer cell lines, Capan-1, Mia-PACA-2, Panc-1, and SNU-410 were analyzed for the expressions of CD133, CD44, and CD24 by flow cytometry. The tumorigenicity was compared using tumor volumes and numbers of tumors formed/numbers of injection in nonobese diabetic severe combined deficiency mice. Fluorescence-activated cell sorting (FACS) analysis was used to confirm that xenograft explants originated from human pancreatic cancer cells. RESULTS: CD133 was positive in only Capan-1, CD44 positive in all, CD24 partially positive in Panc-1. After injecting 2 x 10(6) cells, all mice administered Capan-1 or Mia-Paca-2 developed tumors, 3 of 5 administered Panc-1 developed tumors, but no mouse administered SNU-410 developed any tumors. The volumes of Capan-1 tumors were seven times larger than those of Mia-Paca-2 tumors. When 2 x 10(5) or 2 x 10(4) of Capan-1 or Mia-Paca-2 was injected, tumors developed in all Capan-1 treated mice, but not in Mia-Paca-2 treated mice. Furthermore, xenograft explants of Capan-1 expressed CD133+CD44+ and Capan-1 injected mice developed lung metastasis. FACS analysis showed that xenograft explants originated from human pancreatic cancer cell lines. CONCLUSION: CD133 positive cells have higher tumorigenic and metastatic potential than CD44 and CD24 positive cells, which suggests that CD133 might be a meaningful cell surface marker of pancreatic cancer stem cells.

Solid pseudopapillary tumor with hepatic metastasis / 대한외과학회지

Solid pseudopapillary tumor of the pancreas is a rare tumor that affects young females with low malignant potential and good prognosis with more than 90% survival at 5 years. Metastasis is very rare. We report the case of a 74-year-old female who had pancreatic solid-pseudopapillary tumor and synchronous hepatic metastasis.

A Case of Perforated Acute Cholecystitis in CAPD Patient who Returned to CAPD after Laparoscopic Cholecystectomy / 대한신장학회지

We experienced a 59 year-old female diabetic CAPD patient with severe peritonitis due to perforated acute cholecystitis. Because of heart failure due to old myocardial infarction and cerebral infarction she had been treated with CAPD for 5 years in bed-ridden state. Initial presentation was dark brown colored peritoneal dialysate effluent (changed greenish bile color later) and septic shock. We diagnosed perforated acute cholecystitis by computerized tomography three days after improvement of sepsis. She was received laparoscopic cholecystectomy and continuous venovenous hemodiafiltration for two weeks and returned to peritoneal dialysis without complication. Secondary CAPD peritonitis with cholecystitis or bowel disease should be carefully considered in patients with specific dialysate color, which could be cured with laparoscopic surgery, and then patients can be returned to CAPD again without complication.

Carotid-axillary Bypass for Subclavian Atery Occlusion with Gaining Access through the Axillary Fossa: Report of One Case

Some representative operative techniques have been introduced for treating subclavian artery stenosis or occlusion: carotid-subclavian bypass, carotid-subclavian interposition and axillo-axillary bypass. But the cases of carotid-axillary bypass are rare and moreover, carotid-axillary bypass with gaining access through the axillary fossa are rare in the medical literature. A 77-year-old man who had left upper arm claudication that was aggravated when he performed some hand movements like buttoning-up or undoing buttons visited our hospital. The upper extremity computed tomography angiography showed a 4-centemeter-long occlusion of the left subclavian artery, which began at the point passed by the bulb of the vertebral artery. We performed carotid-axillary bypass between the left axillary artery at the axillary fossa and the left common carotid artery at the left neck at the anterior aspect of the sternocleidomastoid muscle. This operation could be a feasible alternative modality for a patient with occlusion of a long distal segment of the subclavian artery.

A Case of Adrenocortical Oncocytoma Misrecognized for Fibrolamellar Hepatocellular Carcinoma

Adrenocortical oncocytoma is a very rare disease which has been reported in 40 cases. A 27-years-old female patient was admitted for a suspicious hepatocellular mass on ultrasonogram. On CT scan, sono-guided needle biopsy and 18F-FDG PET scan, all results were unsatisfactory. During laparotomy, the mass was originated from Rt. adrenal gland and liver was pushed sideward by the mass. On pathology report, an adrenocortical oncocytoma was diagnosed. Adrenocortical oncocytoma has pathological characteristics comprised of oncocytes with granular, eosinophilic cytoplasm, and sufficient mitochondria in their cytoplasm. There were no established criteria for differential diagnose between benign and malignant adrenocortical oncocytoma. There are no sufficient data for the long-term outcome of adrenocortical oncocytoma in the medical literature. Thus we report a case of adrenocortical oncocytoma with review of the related literature.

Palma-Dale Operation for Chronic Ilio-femoral Vein Thrombosis

PURPOSE: Deep vein thrombosis is usually managed conservatively or with radiologic intervention. Yet deep vein reconstruction is of value as one of the treatments for a small group of patients who present with significant chronic venous insufficiency due to hypoplastic, absent or occluded deep venous outflow such as occurs because of chronic ilio-femoral vein thrombosis. Therefore, we evaluate the improvement of symptoms and graft patency after a Palma-Dale operation as a treatment modality for chronic ilio-femoral vein thrombosis. METHODS: From January 2001 to August 2008, a retrospective study was performed on 15 patients with chronic ilio-femoral vein thrombosis that was treated with a Palma-Dale operation. RESULTS: The mean age of the patients was 51.1+/-15.9 years. The ratio of males to females was 8 to 7. All the patients had lower limb swelling. A Palma-Dale operation was performed on all the patients. Simultaneous thrombectomy was done for 1 patient and arteriovenous fistulas were used to improve graft patency in four patients. The mean follow-up period was 36.3+/-24.0 months. Postoperatively, there was improvement of symptoms in all the patients. However, there was recurrence of symptoms in three patients after two or three months. The rate of graft patency was 84.1% at one year after surgery. CONCLUSION: The Palma-Dale operation has the possibility of recurrence of deep vein thrombosis and postoperative complications. Yet in patients with significant chronic venous insufficiency due to chronic ilio-femoral vein thrombosis, this type of surgery is obviously of value with respect to improvement of symptoms and an acceptable graft patency rate.

Prognostic Significance of HER2 Gene Amplification According to Stage of Breast Cancer

It is well known that the amplification of the HER2 gene is closely associated with poor prognosis of breast cancer. However, there is controversy about the clinical significance of HER2 according to lymph node status in breast cancer. The aim of this study was to identify the differences in the prognostic significance of HER2 gene amplification according to the stages of breast cancer. We prepared a tissue array for fluorescence in situ hybridization (FISH) with breast cancer specimens from the surgery in 1994 to 1999. Total 338 cases of breast cancer were enrolled and the median follow-up period was 6.3 yr. The detection rates of HER2 gene amplification were as follows: 10.3% in stage I, 22.3% in stage II, and 43.8% in stage III. On survival analyses HER2-positive groups showed worse prognosis in stage III of breast cancer, but not in stage I or II. Multivariate analyses with a Cox-regression model also revealed that HER2 amplification was an independent prognostic factor only in stage III breast cancer. Regarding HER2 gene amplification as a prognostic factor of breast cancer, the clinical significance of the gene was found to be confined to advanced breast cancer.

Fenestration of the Common Femoral Artery in Patients with Acute Aortic Dissection Combined with Lower Limb Ischemia

Acute aortic dissection is a catastrophic event. Nowadays, the management of aortic dissection can be challenging with performing procedures such as aortic fenestration, stenting and endovascular treatment. While most cases of acute Stanford type A dissection are managed surgically, many cases of acute Stanford type B dissection are treated medically, although open surgery or stent-graft placement is sometimes performed. Patients with Stanford type B dissection may develop vascular complications such as mesenteric or peripheral ischemia, which cannot be managed medically. Fenestration is a procedure for decompressing the hypertensive false lumen by creating a hole in the distal part of the dissection flap and this allows outflow from the false lumen, it relieves branch vessel obstruction, it restores the flow to the ischemic organ and it reduces the risk of extension or rupture of the dissection. Urgent revascularization is required to correct mesenteric and renal ischemia and to restore distal perfusion if there is rest pain and ischemia signs at the lower extremity. We report here on a case of successful surgical fenestration of an acute aortic dissection for relief of lower limb ischemia, and we utilized a transfemoral artery to puncture the obstructed intimal flap.

Inhibition of EGFR and HER2 in Tamoxifen-resistant T47D:A18/4-OHT Breast Cancer Cells

PURPOSE: Tamoxifen has been prescribed as a very effective hormonal agent not only for the treatment of breast cancer, but also for the prevention of the disease. The development of resistance to tamoxifen is one of the most important obstacles to hormonal therapy of breast cancer. HER2 or EGFR expression has been reported to be associated with the development of tamoxifen resistance. This study was performed to evaluate the effect of HER2 and EGFR inhibition on tamoxifen resistance using tamoxifen-resistant breast cancer cells (T47D:A18/4-OHT cells). METHODS: Tamoxifen-resistant T47D:A18/4-OHT cells were established by long-term treatment of 1micrometer 4-hydroxytamoxifen on T47D:A18 human breast cancer cells. The effect of HER2 and EGFR inhibition was investigated by the use of a cell proliferation assay with treatment of trastuzumab, a monoclonal antibody to the extracellular domain of the human HER2 receptor, and ZD1839, an ERFR tyrosine kinase inhibitor. RESULTS: In contrast to T47D:A18 cells, T47D:A18/4-OHT cells showed estrogen-independent proliferation and partial regulation by treatment with tamoxifen. With a single treatment of trastuzumab or ZD1839, T47D:A18/4-OHT cell growth was reduced to 77.8% (P=0.15) or 74.4% (P=0.034) respectively, as compared to untreated cells. Combinational treatment with 1 nM estradiol resulted in a further reduction of T47D:A17 cell proliferation by 83.6% (P=0.002) for trastuzumab and 77.7% (P=0.047) for ZD1839, as compared to the single treatments. CONCLUSION: Tamoxifen resistance could be partially regulated by inhibition of HER2 or EGFR in T47D:A18/4-OHT cells, especially in combination with a low dose of estradiol. This effect may provide an important clue to overcome tamoxifen resistance in the treatment of breast cancer.

Carcinoid Tumor of the Extrahepatic Bile Duct: A Case Report and Review of the Literature / 대한소화기내시경학회지

A carcinoid tumor of the bile duct represents between 0.2 and 2% of all gastrointestinal carcinoids, most of which are located in the gallbladder or in the ampulla of Vater. A carcinoid tumor of the extrahepatic bile duct is extremely rare. A 43-year-old man presented with epigastric discomfort for several months. An abdominal ultrasound revealed a mass of the common bile duct. An endoscopic retrograde cholangiopancreatographic (ERCP) examination showed a 1.5 cm sized filling defect in the distal common bile duct and marked dilatation of the common bile duct and intrahepatic bile ducts. A 7 F endoprosthesis was put in place during the examination. The histological finding following an intralesional biopsy was a carcinoid tumor. We performed a pylorus preserving pancreaticoduodenectomy. The final pathological diagnosis was a well-differentiated carcinoid tumor of a malignant nature.

Aorta and Peripheral Arterial Diseases in Renal Transplant Patients / 대한이식학회지

BACKGROUND: In the era of surgical advancement of transplantation, renal transplant patients with risks of atherosclerosis have improved its survival rate. And these renal transplant patients with aortic or peripheral arterial diseases required surgical treatment. Herein, we discussed the prevalence and treatment options for the atherosclerotic disease in renal transplant patients. METHODS: We retrospectively reviewed 1,163 patients who underwent renal transplant surgery from Jan. 1990 to May. 2007. Among them, we found 10 patients with atherosclerotic disease of aorta and peripheral arteries. Four patients had abdominal aortic aneurysm (AAA), five patients had atherosclerosis obliterans in the lower extremities, and one had renal artery stenosis in transplanted kidney. RESULTS: Four patients with AAA had aorto-biiliac bypass surgery with bifurcated grafts. Two of them had transplanted kidney protection during surgery, the others did not. Five patients with atherosclerosis obliterans in lower extremities had arterial bypass surgery. One patient with renal artery stenosis had patch angioplasty with great saphenous vein graft. CONCLUSIONS: Renal transplant patients also have possibilities to have severe atherosclerotic disease. Furthermore, transplanted kidney could be damaged during operation. Therefore, we have to do our best to prevent development and aggravation of atherosclerotic condition and try to minimize the ischemic injury of transplanted kidney during vascular operation in renal transplant patients.

The Anatomical Relationship of the Aortic Bifurcation and the Iliocaval Junction to the Lumbar Vertebrae in a Korean Population

PURPOSE: The objective of this study was to determine the anatomic significance and the level of the abdominal aortic bifurcation and the iliocaval junction in relation to the lumbar spine. METHOD: We conducted a retrospective study of 79 patients who underwent prosthetic replacement of an intervertebral disc by the anterior approach. The location of the aortic bifurcation and iliocaval junction and the size of the aorta and IVC were evaluated using CT angiography. The levels of the aortic bifurcation and iliocaval junction were recorded in relation to the upper or lower half of the adjacent vertebral body or intervertebral disc. RESULT: The aorta was bifurcated at the lower half of the L4 vertebral body in 35.4% of the cases. The iliocaval junction was between L4 and L5, and it was most often at the upper half of L5 (43.0%). CONCLUSION: The variability of the aortic bifurcation and iliocaval junction is high and an accurate description may be useful for using the various retroperitoneal approaches for not only aortic and venacaval surgery, but also for the anterior approach for spinal surgery.

Surgical Treatments for Takayasu's Arteritis

PURPOSE: Takayasu's arteritis (TA) is a chronic inflammatory, stenotic or aneurysmal disease of an unknown etiology. TA occurs worldwide, but it disproportionately affects young females of Asian descent. TA is known to affect a variety of vessels, but the subclavian artery, axillary artery, carotid arteries and infraabdominal aorta are most frequently affected. In this article, we evaluated surgical treatment as a modality for the management for TA. METHOD: We retrospectively reviewed 20 patients with TA and who were operated on from January 1994 to December 2007. RESULT: The ages of patients were ranged from 12 to 56 years. The ratio of males to females was 1 to 19. The main affected vessels were the subclavian artery (n=10), the common carotid artery (n=10), the abdominal aorta (n=4) and the renal artery (n=4). 20 patients with TA were operated on. 17 of them underwent arterioarterial bypass, and 5 patients received angioplasty. There were 8 cases of reoperation due to the effect on other arteries, or due the stenosis or occlusion of the previous bypass graft. Angioplasty and stenting can be used in the treatment of shorter stenoses such as those encountered in the renal arteries. CONCLUSION: Symptomatic patients who have Takayasu's arteritis can be operated on. Our surgical experiences have showed low mortality and the surgical procedures relieved the symptoms. Surgical therapy for Takayasu's arteritis was safe and it showed good results.

The Difference of Akt Phosphorylation with Different Strengths of Hemodynamic Forces on the Endothelial Cell

PURPOSE: Mechanical forces including shear stress (SS) and cyclic strain (CS) trigger signal transducing events and modulate gene expression in vascular endothelial cells (ECs). However, differences in intracellular events and gene expression depend on the intensity of the forces, which remain unknown. We attempted to clarify the effect of different strengths of SS and CS by determination of the Akt phosphorylation of ECs. METHOD: ECs were exposed to the arterial level of orbital SS with an orbital shaker (210 rpm) or laminar SS (14 dyne/cm2) with a parallel plate or CS (10%) at a frequency of 60 cycles/min. Akt phosphorylation was assessed by immunocytochemical staining and Western blotting with specific antibodies against the phosphorylated Akt. RESULT: Akt demonstrated a time-dependent stimulation of Akt phosphorylation by mechanical forces with a maximal increase up to 2.5-fold after 30 minutes of orbital SS exposure, 3-fold after 2 minutes of laminar SS exposure and 2.3-fold after 30 minutes of CS exposure. Akt phosphorylation in the periphery of the membrane was significantly increased, compared to at the center of the membrane. It was up to 1.4-fold after 30 minutes of orbital SS and up to 2.4-fold after 30 minutes of CS (P<0.05). CONCLUSION: Our results demonstrate that all types of hemodynamic forces phosphorylated Akt in a time-dependent manner and different types of SS may have different effects on the ECs. In addition, the phosphorylation of Akt is dependent on the intensity of the mechanical forces on ECs.

Relation of the E-cadherin Expression and the Lauren Classification in Stomach Cancer according to the Tumor Location

PURPOSE: E-cadherin (ECD) plays a pivotal role in integrating the normal tissue architecture and the suppression of cancer invasion, including stomach cancer. The epidemiology of stomach cancers is noticeably different according to the site of the index tumor, even though the stomach cancers all have similar gross shapes. In this study, the relation between the expression of ECD, along with the clinicopathologic parameters and recurrence or survival, were investigated for patients with gastric adenocarcinoma according to the tumor location. METHODS: We examined formalin-fixed, paraffin-embedded archival tissues from 50 surgically resectable gastric adenocarcinomas, which were grouped by the index tumor site as follows: distal (antrum) versus proximal (mid and upper body). To elucidate the correlation between the ECD expression and the site of the stomach cancer with the other clinicopathologic factors, we examined the ECD tissue status via performing immunohistochemistry. To compare the rates of recurrence and survival among subgroups, the patients were followed up for an average of 42 months. RESULTS: Among the 50 tumors examined, 28 (56%) tumors showed various degrees of a ECD expression. The gender, age, size, depth of invasion, lymph node metastasis, stage, lymphatic invasion and vascular invasion were not related with the ECD expression. The Lauren classification was cor-related with the ECD expression in the mid and upper body stomach cancer, but not in the antral stomach cancer (P=0.042). The expression of ECD was not related with the survival rate (P=0.223). There was no significant difference in the recurrence rate between the subgroups with and without an abnormal expression of ECD (P=0.588). CONCLUSION: For the mid and upper body stomach cancer, the expression of E-cadherin correlated with the diffuse type of cancer, according to the Lauren classification, but not with the survival rate.