Tumescent local anesthetic technique for inguinal hernia repairs

PURPOSE: We evaluated the adequacy and feasibility of a tumescent solution containing lidocaine and bupivacaine for inguinal hernia repairs. METHODS: The medical records of 146 consecutive inguinal hernia patients with 157 hernia repairs using the tumescent local anesthesia technique performed by a single surgeon between September 2009 and December 2013 were retrospectively reviewed. RESULTS: The mean operation time (+/-standard deviation) and hospital stay were 64.5 +/- 17.6 minutes and 2.7 +/- 1.5 days. The postoperative complication rate was 17.8%. There were four cases of recurrences (2.5%) at a mean follow-up of 24 +/- 14 months. CONCLUSION: Our results suggest that local anesthesia with the tumescent technique is an effective and safe modality for inguinal hernia repairs.

Circulating cell-free DNA as a promising biomarker in patients with gastric cancer: diagnostic validity and significant reduction of cfDNA after surgical resection

PURPOSE: The aim of this study is to determine whether levels of circulating free DNA (cfDNA) increase according to cancer progression, whether they are restored after surgical resection, and to evaluate cfDNA in gastric cancer patients as a useful biomarker. METHODS: A case-control study design was used. Thirty gastric cancer patients and 34 healthy subjects were enrolled from two hospitals in South Korea. The plasma cfDNA of patients with gastric cancer were obtained before surgery and 24 hours after surgery, and then analyzed by a quantitative, real-time polymerase chain reaction. Plasma samples were also obtained from the control group. RESULTS: The mean levels of cfDNA in the healthy control group, patients with early gastric cancer, and with advanced gastric cancer were 79.78 +/- 8.12 ng/mL, 106.88 +/- 12.40 ng/mL, and 120.23 +/- 10.08 ng/mL, respectively (P < 0.01). Sensitivity was 96.67% and specificity was 94.11% when the cutoff value was 90 ng/mL. Variables representing the tumor burden such as tumor size, T stage, TNM stage, and curative resection are also associated with the levels of cfDNA. The levels of cfDNA in the 24-hour-after-surgery group decreased significantly (112.17 +/- 13.42 ng/mL vs. 77.93 +/- 5.94 ng/mL, P < 0.001) compared to the levels of cfDNA in the preoperation group. CONCLUSION: The changes in the levels of cfDNA can act as reliable biomarkers to detect cancer early, to predict tumor burden, estimate curative resection and even prognosis.

Differences in the Survival of Gastric Cancer Patients after Gastrectomy according to the Medical Insurance Status

PURPOSE: In Korea, the entire population must enroll in the national health insurance system, and those who are classified as having a lower socioeconomic status are supported by the medical aid system. The aim of this study was to evaluate the association of the medical insurance status of gastric cancer patients with their survival after gastrectomy. MATERIALS AND METHODS: A total of 247 patients who underwent surgical treatment for gastric cancer between January 1999 and December 2010 at the Seoul Medical Center were evaluated. Based on their medical insurance status, the patients were classified into two groups: the national health insurance registered group (n=183), and the medical aid covered group (n=64). The survival rates were calculated using the Kaplan-Meier method. RESULTS: The median postoperative duration of hospitalization was longer in the medical aid covered group and postoperative morbidity and mortality were higher in the medical aid group than in the national health insurance registered group (P<0.05). The overall 5-year survival rate was 43.9% in the medical aid covered group and 64.3% in the national health insurance registered group (P=0.001). CONCLUSIONS: The medical insurance status reflects the socioeconomic status of a patient and can influence the overall survival of gastric cancer patients. A more sophisticated analysis of the difference in the survival time between gastric cancer patients based on their socioeconomic status is necessary.

Adrenal Mass as Initial Presentation of Metastatic Hepatocellular Carcinoma: A Case Report

Metastases from hepatocellular carcinoma (HCC) can be found in the multiple organs including adrenal gland. But adrenal metastasis of HCC without obvious hepatic lesion is very rare. We report CT and MR findings of a patient who presented with adrenal metastasis as the first clinical manifestation of HCC. Signal intensity and enhancement pattern of adrenal metastastic mass of HCC were similar to those of HCC on MRI.

A Peterson's hernia and subsequent small bowel volvulus: surgical reconstruction utilizing transverse colon as a new Roux-en-Y limb - 1 case / 대한외과학회지

Peterson's hernia is an internal hernia that can occur after Roux-en-Y anastomosis. It often accompanies small bowel volvulus and is prone to strangulation. Reconstruction of intestinal continuity after massive small bowel resection in a patient who undergoes near total gastrectomy and Roux-en-Y anastomosis can be difficult. A 74-year-old man who had undergone a near total gastrectomy and Roux-en-Y gastrojejunostomy for stomach cancer presented with abdominal pain. The preoperative computed tomography showed strangulated small bowel volvulus. During the emergent laparotomy, we found a strangulated Peterson's hernia with small bowel volvulus. After resection of the necrotized intestine, we made a new Roux-en-Y anastomosis connecting the remnant stomach and the jejunum with a transverse colon segment. We were safely able to connect the remnant stomach and the jejunum by making a new Roux-en-Y anastomosis utilizing a transverse colon segment as a new Roux-limb by two stage operation.

Urachal cyst presenting with huge abscess formation in adults / 대한외과학회지

Urachal disease, a disorder where embryonic remnant of the cloaca and the allantois present after birth as a midline fibrous cord, is usually detected in infancy and childhood. But urachal disease in adults is rare. We report a case of a huge abscess derived from a urachal cyst in an adult. A 52-year-old man presented with peri-umbilical distension and abdominal pain for 2 weeks. Ultrasonography and abdominal computed tomography scan demonstrated a huge abscess derived from the abdominal wall. After prompt incision and drainage, the remaining abscess cavity was removed completely under general anesthesia. Pathologic report was consistent with urachal duct cyst, and the patient was discharged in a week without complication.

Clinical Correlation between Gastric Cancer Type and Serum Selenium and Zinc Levels

PURPOSE: We conducted this study to study the clinical correlation between the characteristics of gastric cancer and serum selenium and zinc levels. MATERIALS AND METHODS: The following data were measured in the baseline serum selenium and zinc levels of 74 patients with curative gastrectomy subsequent to confirmed gastric cancer, from March 2005 to August 2012. RESULTS: Among the 74 gastric cancer patients, 53 patients were male. Mean serum selenium and zinc levels were 118.7+/-33.1 ug/L and 72.2+/-24.3 ug/dl, respectively. Seven patients (9.5%) showed lower selenium level, and 33 patients (44.6%) showed lower zinc level. Serum Selenium level was 99.1+/-31.8 ug/L in cardia cancer group (10 cases) and 121.8+/-32.4 ug/L in non-cardia cancer group (64 cases)(P=0.044). According to tumor gross type, zinc level was 78.7+/-29.6 ug/dl in early gastric cancer (33) and 66.9+/-17.8 ug/dl in advanced gastric cancer (41) (P=0.064). CONCLUSIONS: The serum selenium level was highly correlated with the location of gastric cancer. The serum zinc level was lower in advanced gastric cancer.

Clinical Correlation between Gastric Cancer Type and Serum Selenium and Zinc Levels

PURPOSE: We conducted this study to study the clinical correlation between the characteristics of gastric cancer and serum selenium and zinc levels. MATERIALS AND METHODS: The following data were measured in the baseline serum selenium and zinc levels of 74 patients with curative gastrectomy subsequent to confirmed gastric cancer, from March 2005 to August 2012. RESULTS: Among the 74 gastric cancer patients, 53 patients were male. Mean serum selenium and zinc levels were 118.7+/-33.1 ug/L and 72.2+/-24.3 ug/dl, respectively. Seven patients (9.5%) showed lower selenium level, and 33 patients (44.6%) showed lower zinc level. Serum Selenium level was 99.1+/-31.8 ug/L in cardia cancer group (10 cases) and 121.8+/-32.4 ug/L in non-cardia cancer group (64 cases)(P=0.044). According to tumor gross type, zinc level was 78.7+/-29.6 ug/dl in early gastric cancer (33) and 66.9+/-17.8 ug/dl in advanced gastric cancer (41) (P=0.064). CONCLUSIONS: The serum selenium level was highly correlated with the location of gastric cancer. The serum zinc level was lower in advanced gastric cancer.

Synchronous Multiple Colorectal Cancer Occurring in Polyposis

The frequencies of multiple synchronous carcinomas of the colon and the rectum have been reported to range from 2.1 to 6.3%. Currently, the frequency is higher in colorectal cancer patients, and the diagnosis is better due to the many diagnostic tools that have been developed. There are a few reported cases of five cancers in a patient at the same time. We report here on the case of five synchronous cancers arising from the colon and the rectum in a patient without a familial history of colon cancer or of genetic predisposing factor. The patient was a 62-yr-old woman who presented with frequently loose stool for six months and intermittent abdominal pain for two months. Colonoscopic examination revealed two adenocarcinomas, one each at the sigmoid colon and the rectum; the cancer in the sigmoid colon was obstructed at nearly 40 cm above the anal verge. Computed tomographic colonoscopy revealed many other polyps and masses in the colon and a metastatic mass at segment 8 in the liver. A total proctocolectomy and ileostomy were performed. Histologic evaluation revealed the five lesions to be adenocarcinomas invading the pericolic fat; 1 out of 30 lymph nodes was invaded by the cancer cells.

Clinical Experiences of Fitz-Hugh-Curtis Syndrome

PURPOSE: Fitz-Hugh-Curtis (FHC) syndrome has been described as perihepatitis associated with pelvic inflammatory disease during surgery. Recently, on computerized tomography a linear enhancement of the liver capsule was detected in a patient with FHC syndrome. We studied to evaluate the clinical course of the disease. METHODS: Sixteen patients diagnosed with FHC syndrome from CT findings were retrospectively studied from April, 2006 to June, 2008. RESULTS: The mean age of the patients was 25.9 (19~35) years and mean duration of abdominal pain was 3.9 (1~14) days. The most common complaint was right upper quadrant area pain (11 cases, 68.8%). 12 patients showed leukocytosis and all the patients had elevated serum C-reative protein levels. All the patients had normal liver function. Among the 9 patients which had polymerase chain reaction test for sexually transmitted disease (Chlamydia trachomatis, Ureaplasma urealyticum, Neisseria gonorrheae, Mycoplasma hominis), all showed more than one positive results (Chlamydia trachomatis 6 cases, Ureaplasma urealyticum 6 cases, Mycoplasma hominis 2 cases). On simple abdomen X-ray, 7 cases (43.8%) showed paralytic ileus. 14 cases received only antibiotic treatment, but 1 case had to take operation (laparoscopic-assisted adhesiolysis) due to constant abdominal pain and prolonged ileus. CONCLUSION: It is important to rule out FHC syndrome by using CT findings, especially young women with right upper abdominal pain and PID. Usually, FHC syndrome can be treated easily with proper antibiotics.

Conventional Angiogram versus Multi-detector Row Helical Computed Tomography Angiogram for Preoperative Diagnostic Imaging in Low Extremity Arterial Surgery

PURPOSE: We performed this study to assess the suitability of conventional angiography (CA) vs. multi-detector row helical CT angiogram (MD-CTA) as a method of preoperative diagnostic imaging for low extremity arterial surgery. METHODS: From February 2004 to September 2006, 23 patients (4 claudicants, 19 limb-threatening ischemia) were studied with CA and MD-CTA preoperatively. The site and degree of stenotic or occlusive lesions in arterial segments from the renal artery to the dorsalis pedis artery were compared with both methods. We also compared the surgical inflow and outflow site changes in preoperative planning based on CA and MD-CTA and the final outcome. Additional diagnostic value and test-related complications were also analyzed. RESULTS: The median age of patients was 68 years old (range: 43~89 years), with a male to female ratio of 1.3:1. Twenty-three patients had CA after an MD-CTA scan. One hundred fifty lesions were detected in these patients. The total ratio of consistency for occlusion in CA vs. MD-CTA was 69.6%. Three patients received amputation treatment and eleven patients received a bypass operation. The agreement between the preoperative plan based on MD-CTA and the final operation was 100%, even in critical limb ischemia. There were no serious complications related to the tests. CONCLUSION: These findings suggest that MD-CTA is an adequate preoperative imaging study of infrainguinal arterial surgery and may be substituted for conventional angiography without any serious complications.

The Effects of Mistletoe Extract and Anti-cancer Drugs on the Apoptosis of Gastric Cancer Cells

PURPOSE: Mistletoe extract was widely used for cancer treatment as complementary or alternative therapy in European area from early twenty century. It is currently used as alternative anti-cancer remedy by piecemeal in domestic medical group, however, the anti-cancer mechanism of mistletoe extract was not known precisely until now. In this study the effect of mistletoe extract on gastric cancer was studied vis cell line experiments. MATERIALS AND METHODS: The SNU719 gastric cancer cell line was used, and ABNOBAviscum-Q and ABNOBAviscum-F were treated to cells as mistletoe extract, or 5-FU and cisplatin were used with mistletoe extract. The cell viability and cell death rate were estimated by CCK-8 assay kit and lactate dehydrogenase (LDH) assay kit in each. Caspase 3 assay kit was used to measure caspase 3 activity. The protein expression amounts of Bcl2, p53, and PTEN were estimated through Western blot analysis. RESULTS: The co-treatments of mistletoe extract Q/F and 5-FU/cisplatin decreased lesser cell viability than only mistletoe treat. Caspase 3 activity was increased 4~6 times in co-treatment of mistletoe extracts and 5-FU than control. Bcl2 protein expression was reduced by mistletoe extracts or anti-cancer drugs, further more, the co-treatment of mistletoe extracts and 5-FU/cisplatin diminished more the expression than only mistletoe treatment. Mistletoe extracts did not affect the protein expressions of p53 and PTEN. CONCLUSION: It was concluded that the anti-cancer mechanism of mistletoe extracts was made by caspase 3 activation and lowered Bcl2 expression, and this apoptosis inducing mechanism was independent to p53.

The Immunological Effect of Mistletoe Extract on Gastric Cancer Patients

PURPOSE: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. MATERIALS AND METHODS: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum Q(R) was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-1beta, IL-2, IL-6, IFN-gamma, TNF-alpha) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. RESULTS: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. CONCLUSION: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.

Expression of RUNX3 in Human Gastric Cancer

PURPOSE: RUNX3, a novel tumor suppressor, is frequently inactivated in gastric cancer. In the present study, we examined the pattern of RUNX3 expression in gastric cancer cells from gastric cancer specimens and the impact of its alteration on clinical outcome. MATERIALS AND METHODS: A total of 124 samples of both gastric cancer and normal tissue were obtained from 124 patients who underwent curative gastrectomy at the Seoul Medical Center from January 2001 to December 2005. RUNX3 expression was determined by immunohistochemical staining, and the results were analyzed. Statistical analysis wabased on clinicopathological findings and differences in survival rates. RESULTS: The mean age of the patients was 61 years, and the male:female ratio was 1.9:1. The expression rate of RUNX3 was 59.7% (74/124). The expression rate was higher in differentiated gastric cancers (nucleus: 9.1%, cytoplasm: 57.6%) than in the undifferentiated types (nucleus: 5.2%, cytoplasm: 46.6%) (P=0.133). The 5-year survival rates according to RUNX3 expression determined from cancer tissue were 88.9% for the nucleus +/- cytoplasm(+) group of patients, 76.1% for the cytoplasm only (+) group of patients, and 65.3% for the RUNX3 negative expression group of patients (P=0.626). Only UICC TNM staging showed statistical significance related to the survival rate, as determined by multivariate analysis. CONCLUSION: The RUNX3 expression rate was higher in differentiated gastric cancer than in the undifferentiated types without significance. Although RUNX3 expression predicted better survival, based on multivariate analysis, the finding was not statistically significant. More cases should be further evaluated.

Expression of the Peroxisome-proliferator-activated Receptor-gamma in Human Gastric Cancer

PURPOSE: Recently, interest in peroxisome-proliferator-activated receptors (PPAR) has increased, although clinical studies of the effect of PPAR-gamma expression on gastric cancer have not been reported yet. In this study, we investigated the role of PPAR-gamma expression in gastric cancer patients. MATERIALS AND METHODS: One hundred twenty-eight (128) samples of both gastric cancer and normal tissues were obtained from 128 patients who had undergone at a curative gastrectomy at Seoul Medical Center from Jan. 2001 to Dec. 2005. PPAR-gamma expression was determined by using immunohistochemical staining, and the results were analyzed. The statistical analysis was based on clinicopathological findings and the differences in survival rates. RESULTS: The mean age of the patients was 61, and the male:female ratio was 1.9:1. PPAR-gamma expression was significantly higher in cancer tissues than in normal tissue (81.3% vs. 57.0%, P<0.001). There was insignificant difference between well and moderately differentiated types and poorly differentiated types in terms of the expression of PPAR-gamma (87.0% vs. 74.6%, P=0.074). In the univariate analysis the survival rate was significantly increased when PPAR-gamma was expressed in normal tissue (P=0.003). In the multivariate analysis, only the UICC TNM staging had significance related to the survival rate. CONCLUSION: The rate of PPAR-gamma expression was higher in cancer tissue than it was in normal tissue from gastric cancer patients. In the univariate analysis, PPAR-gamma expression in normal tissue had significance with respect to survival, but the multivariate analysis showed no such significance. Thus, we should further evaluate more cases to determine whether or not such a significance exists.

Predictive Factors for Conversion of Laparoscopic to Open Cholecystectomy

PURPOSE: Laparoscopic cholecystectomy (LC) has replaced open cholecystectomy (OC) for the treatment of gallbladder disease. However certain cases still require conversion to open procedures. Identifying these patients at the risk of conversion remains difficult. This study evaluated risk factors that may predict conversion from a laparoscopic to an open procedure. METHODS: From January 1994 to December 2004, a total of 582 laparoscopic cholecystectomies were performed at Seoul Medical Center. A retrospective analyses of clinical parameters including patient demographics, clinical histories, laboratory data, ultrasound results, intraoperative details and postoperative pathologic findings were performed. RESULTS: A total of 30 patients (5.2%) had their cholecystectomies converted to an open procedure. Causes for conversion were inability to correctly identify the anatomy of surgical field due to adhesion and inflammation (56.7%), bile duct injury (13.3%), bleeding (13.3%) and others (16.7%). Univariate analysis showed that ASA (the classification of American Society of Anesthesiologists, p = 0.034), previous abdominal operation history (p = 0.008), RUQ tenderness(right upper quadrant tenderness, p = 0.002), acute cholecystitis (p < 0.001) and time elapsing between diagnosis and operation (p = 0.013) to be risk factors. Multivariate analysis revealed that acute cholecystitis (4.2 greater odds ratio [OR] of conversion, p = 0.002) and previous abdominal operation history (3.6 greater odds ratio [OR] of conversion, p = 0.003) were positive independent predictive factors for conversion to open cholecystectomy. CONCLUSION: Although laparoscopic cholecystectomy is a safe and beneficial procedure in the management of patients with gallbladder disease, there are still many chances of conversion of laparoscopic to open cholecystectomy. In this study, patients with acute cholecystitis and previous abdominal operation histories were more likely to require conversion to an open procedure. These two positive independent predictive factors can help operators to make early decision and to counsel patients undergoing laparoscopic cholecystectomy with regards to the posibility of conversion to an open procedure.

The Significance of Metastatic Lymph Node Ratio in the Survival Rate of pT2 Gastric Cancer

PURPOSE: The number of resected lymph nodes can influence the current N staging. This study examined the significance of the metastatic lymph node ratio on the survival of patients with pT2 gastric cancer. METHODS: The records of 176 patients who had undergone curative gastrectomy and diagnosed with pT2 gastric cancer by pathology, between February 1990 and October 2002 were retrospectively reviewed. Those patients with other organ metastases or those who had undergone a dissection of less than 15 lymph nodes were excluded. The clinicopathologic prognostic variables were evaluated using the SPSS statistical program. RESULTS: There were 115 men and 61 women with a mean age of 59 years. The median survival period was 93 months (2~184 months). Metastatic lymph nodes were found in 100 cases (56.8%), a mean of 34.6 lymph nodes were dissected, a mean of 3.2 lymph nodes metastasized, and a mean metastatic lymph node ratio of 0.09 was found. According to the UICC TNM classification, the number of stage IB (N0) cases was 76 (43.2%), stage II (N1) was 74 (42.0%), stage IIIA (N2) was 18 (10.2%), and stage IV (N3) was 8 (4.5%). The overall 5-year survival rate was 75.2%. According to the UICC TNM classification, the 5-year survival rate was stage IB, II, IIIA, and IV was 88.6%, 74.3%, 39.5%, and 33.3%, respectively. The metastatic lymph node ratio (nR) was divided into 4 categories; nR0 (76) = 0, 0

Benign Solitary Cecal Ulcer Accompanied by Massive Lower Gastrointestinal Tract Hemorrhage

A benign cecal ulcer is an uncommon lesion. The etiology remains unknown, and there are no pathognomonic lesions or symptoms. Lower gastrointestinal tract hemorrhage secondary to benign cecal ulcer is the most common complication. Herein, the case of a 24-year-old man with a benign cecal ulcer presenting with a massive lower gastrointestinal tract hemorrhage requiring transfusion until a exploratory laparotomy and right hemicolectomy, is reported with a review of the literature. Surgical intervention is warranted if malignancy is suspected or if the patient has signs of uncontrollable hemorrhage, perforation, or peritonitis.

Primary Melanoma of the Stomach at Cardia

Melanoma is a malignant neoplasm of melanocytes most frequently arising from the skin, but primary melanoma can also arise from the mucosa of the gastrointestinal tract. Gastrointestinal melanomas are most commonly metastases from a cutaneous melanoma. Primary melanoma of the stomach is rare and carries a poor prognosis. Reported here is the case of a 75-year-old man with a primary gastric melanoma who presented with a melena, abdominal pain, and weight loss. Most cases of melanoma are treated by excision of the primary tumor. Patients with melanoma have been treated with adjuvant chemotherapy, radiation therapy, and immunotherapy. None of these modalities has been demonstrated to prolong the survival rate. To improve long-term disease-free survival, early diagnosis and surgical intervention are very important.

Expression of E-cadherin and CD44H in Borrmann Type IV Gastric Cancer

PURPOSE: E-cadherin and CD44H have been shown to play a role in the progression and the metastasis of tumors. This study evaluated the clinical correlations between expression of E-cadherin and CD44H and various clinicopathologic factors and the value of expressions of E-cadherin and CD44H as prognostic factors in Borrmann type IV gastric cancer. MATERIALS AND METHODS: In 122 patients with Borrmann type IV gastric cancer, we performed the immunohistochemical stainings for E-cadherin and CD44H. We analyzed the correlation between the expressions of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, stage, and peritoneal dissemination, and survival. RESULTS: There were no correlations between reduced expression of E-cadherin and CD44H and lymphatic invasion, venous invasion, perineural invasion, histologic type, lymph node metastasis, depth of invasion, and stage. However, there was a significant correlation between lymph node metastasis and the lymphatic invasion (P=0.022). There was also a significant correlation between the peritoneal dissemination and CD44H expression (P=0.005). The 5-year survival rate was correlated with CD44H expression (P=0.026), peritoneal dissemination (P<0.01), depth of invasion (P<0.01), lymph node metastasis (P<0.01), stage of tumor (P<0.01), and lymphatic invasion (P<0.01). There was no correlation between expression of E-cadherin and survival rate. CONCLUSION: The expression of CD44H and peritoneal dissemination was correlated. The expression of CD44H was an independent prognostic factor in Borrmann type IV gastric cancer. Further prospective studies with a large number of cases are required.