Jin Sik Min

Comparative study of transrectal ultrasonography, pelvic computerized tomography, and magnetic resonance imaging in preoperative staging of rectal cancer.

PURPOSE: The preoperative assessment of rectal cancer wall invasion and regional lymph node metastasis is essential for the planning of optimal therapy. This study was done to determine the accuracy and clinical usefulness of transrectal ultrasonography, pelvic computed tomography, and magnetic resonance imaging in preoperative staging. METHODS: A total of 89 patients with rectal cancer were examined with transrectal ultrasonography (n=89), pelvic computed tomography (n=69), and magnetic resonance imaging with endorectal coil (n=73). The results obtained by these diagnostic modalities were compared with the histopathologic staging of specimens. RESULTS: In staging depth of invasion, the overall accuracy was 81.1 percent (72/89) by transrectal ultrasonography, 65.2 percent (45/69) by computed tomography, and 81 percent (59/73) by magnetic resonance imaging. Overstaging was 10 percent (9/89) by transrectal ultrasonography, 17.4 percent (12/69) by computed tomography, and 11 percent (8/73) by magnetic resonance imaging; and understaging was 8 of 89 (8.9 percent) by transrectal ultrasonography, 12 of 69 (17.4 percent) by computed tomography, and 6 of 73 (8 percent) by magnetic resonance imaging. In staging lymph node metastasis, the overall accuracy rate was 54 of 85 (63.5 percent) in transrectal ultrasonography, 39 of 69 (56.5 percent) in computed tomography, and 46 of 73 (63 percent) in magnetic resonance imaging. The sensitivity was 24 of 45 (53.3 percent) in transrectal ultrasonography, 14 of 25 (56 percent) in computed tomography, and 33 of 42 (78.5 percent) in magnetic resonance imaging; and specificity was 30 of 40 (75.0 percent) in transrectal ultrasonography, 25 of 44 (56.8 percent) in computed tomography, and 13 of 31 (41.9 percent) in magnetic resonance imaging. The accuracy in detection of positive lateral pelvic lymph nodes under magnetic resonance imaging (n=8) was 12.5 percent. The accuracy in detection of posterior vaginal wall invasion was 100 percent in transrectal ultrasonography (n=7) and 100 percent in magnetic resonance imaging (n=3), but 28.5 percent in computed tomography (n=7). CONCLUSIONS: Both transrectal ultrasonography and magnetic resonance imaging with endorectal coil exhibited similar accuracy and were superior to conventional computed tomography in preoperative assessment of depth of invasion and adjacent organ invasion. Because transrectal ultrasonography is a safer and more cost-effective modality than magnetic resonance imaging, transrectal ultrasonography is an appropriate method for preoperative staging of rectal cancer. Further efforts will be needed to provide a better staging of lymph node involvement.

Assessment of Sexual and Voiding Function After Total Mesorectal Excision With Pelvic Autonomic Nerve Preservation in Males With Rectal Cancer

AbstractPURPOSE: Total mesorectal excision with pelvic autonomic nerve preservation has been reported to be an optimal surgery for rectal cancer. It minimizes local recurrence and sexual and urinary dysfunction. The aim of this study was to assess the safety of total mesorectal excision with pelvic autonomic nerve preservation in terms of voiding and sexual function in males with rectal cancer. METHODS: We performed urine flowmetry using Urodyn® and a standard questionnaire using the International Index of Erectile Function and the International Prostate Symptom Score before and after surgery in 68 males with rectal cancer. RESULTS: Significant differences in mean maximal urinary flow rate and voided volume were seen before and after surgery (18.9 ± 5.7 vs. 13.7 ± 7.0, 240 ± 91.9 vs. 143 ± 78; P < 0.05, P < 0.05, respectively), but no differences in residual volume before and after surgery were apparent (4.4 ± 2.6 vs. 8.1 ± 4.4; P > 0.05). The total International Prostate Symptom Score was increased after surgery from 6.2 ± 5.8 to 9.8 ± 5.9 (P < 0.05). There were no changes of score for one of each of seven International Prostate Symptom Score items in 49 patients (73.5 percent) to 61 patients (89.7 percent). Five International Index of Erectile Function domain scores (erectile function, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction) were significantly decreased after surgery (18.2 ± 9.3 vs. 13.5 ± 9, 8.4 ± 4.2 vs. 4.4 ± 2.9, 5.8 ± 2.9 vs. 4.4 ± 2.9, 6.1 ± 2.4 vs. 4.8 ± 2, 6.1 ± 2.2 vs. 4.5 ± 2.3, respectively; P < 0.05). Erection was possible in 55 patients (80.9 percent); penetration ability was possible in 51 patients (75 percent). Complete inability for erection and intercourse was observed in three patients (5.5 percent). Retrograde ejaculation was noted in 9 patients (13.2 percent). International Index of Erectile Function domains such as sexual desire and overall satisfaction were greatly decreased in 39 patients (57.4 percent) and 43 patients (63.2 percent), respectively. Multiple regression analysis of factors affecting postoperative sexual dysfunction showed that age older than 60 years (sexual desire, P = 0.019), within six months (erectile function, P = 0.04; intercourse satisfaction, P = 0.011; orgasmic function, P = 0.03), lower rectal cancer (erectile function, P = 0.02; intercourse satisfaction, P = 0.036; orgasmic function, P = 0.027) were significant factors adversely affecting sexual function. CONCLUSION: Total mesorectal excision with pelvic autonomic nerve preservation showed relative safety in preserving sexual and voiding function. The International Prostate Symptom Score and International Index of Erectile Function questionnaires were useful in assessing urinary and sexual function.

Preoperative staging of rectal cancer with MRI: accuracy and clinical usefulness.

AbstractBackground: Preoperative staging is essential for planning of optimal therapy for patients with rectal cancer. Recently, magnetic resonance imaging (MRI) is used frequently because of its benefits of clear pelvic image are better than other diagnostic methods. The purpose of this study was to determine accuracy rates and clinical usefulness of MRI in preoperative staging of rectal cancer. Methods: Between February, 1997, and December, 1999, 217 patients with histologically proven rectal cancer were staged preoperatively and had surgical resections performed. MRI criteria for depth of invasion was determined by the degree of disruption of the rectal wall. Metastatic perirectal lymph nodes were considered to be present if they showed heterogenous texture, irregular margin, and enlargement (.10 mm). Results: The accuracy of the MRI for determining depth of invasion was 176/217 (81%) and regional lymph node invasion was 110/217 (63%). In the T stage, accuracy rate of T1 was 3/4 (75%), T2 was 20/37 (54%), T3 was 141/162 (87%), and T4 was 12/14 (86%), respectively. The specificity of lymph node invasion was 45/110 (41%) and the sensitivity was 91/107 (85%). The accuracy rate of regional lymph node involvement was 136/217 (63%). T1 and T2 were overstaged in 1/4 (25%) and 17/37 (46%), respectively, and T3 was understaged in 15/162 (9.2%). The accuracy rate to detect metastatic lateral pelvic lymph node was 4/14 (29%) after lateral pelvic lymph node dissection was done in 14 patients under MRI. The accuracy rate in assessing levator ani muscle tumor involvement was 8/11 (72%). Conclusions: MRI showed a good, comparable accuracy rate for determining depth of tumor invasion, compared with transrectal ultrasonography, which still has a low accuracy rate for detecting metastatic lymph node. MRI with endorectal coil may increase the accuracy rate of T1 and T2 lesions. In addition, clear sagittal and coronal sectional pelvic images can give a lot of information about adjacent organ invasion or any invasion of levator ani muscle. MRI can be useful for choosing an appropriate extent of lymph node dissection and type of surgery.

Putative chromosomal deletions on 9p, 9q and 22q occur preferentially in malignant gastrointestinal stromal tumors

To characterize the type of genetic alterations in gastrointestinal stromal tumors (GISTs), we performed a comprehensive allelotype study of 14 GISTs (2 benign, 7 borderline and 5 malignant) by polymerase‐chain‐reaction and loss‐of‐heterozygosity (PCR‐LOH) analysis using 102 microsatellite markers, and compared the results with comparative‐genomic‐hybridization (CGH) analysis. Among the 38 evaluated chromosomal arms, 16 (42.1%) showed LOH in at least one patient. Most frequent LOH was observed at chromosome 14p and 14q (9/14, 64%) and this was demonstrated in all types of GISTs (50% in benign, 71% in borderline and 80% in malignant). Additional chromosomal deletions were found in several chromosomal arms. Among them, deletions on chromosomal arms of 22q (3/14, 21.4%), 9p (2/14, 14.3%) and 9q (2/14, 14.3%) were the most frequent, and were detected only in malignant GISTs both by PCR‐LOH and by CGH analysis. Additionally, 2 malignant GISTs with LOH on 9p showed homozygous deletions in the restricted area of 9p by multiplex PCR‐LOH analysis. Thus, several putative chromosomal changes were preferentially present in malignant GISTs but rare in benign and borderline GISTs. These findings suggest that accumulated chromosomal changes may contribute to the progression and/or malignant transformation of GISTs. Int. J. Cancer 85:633–638, 2000.

Prognostic significance of metastatic lymph node ratio in T3 gastric cancer

The fifth International Union Against Cancer tumor node metastasis (UICC TNM) classification, basedon the number of metastatic lymph nodes (LN), has proved to be areliable and objective method for predicting the prognosis of patientswith gastric cancer. However, the prognosis of patients with T3 gastriccancer is still heterogeneous. This study was carried out toinvestigate the validity of metastatic LN ratio as a prognostic factorin T3 gastric cancer. A retrospective analysis was performed on a totalof 833 patients that had either T3N1M0 (n = 504) orT3N2M0 (n = 329) gastric cancer by the fifth UICCclassification. A preliminary analysis revealed the cutoff values forT3N1M0 to be 10% and for T3N2M0 to be 25%. The mean metastatic LNratio was 9.0% for T3N1M0 cancer and 26.9% for T3N2M0 cancer. For theT3N1M0 stage, the patients who showed less than 10% of the metastaticLN ratio were grouped as N1-low with the others grouped as N1-high. Forthe T3N2M0 stage group, those who had less than 25% of the metastaticLN ratio were grouped as N2-low, the remainder as N2-high. Themetastatic LN ratio decreased in proportion to the extent oflymphadenectomy and it increased in relation to the increasing scale ofthe fourth N classification. The rates of recurrence were significantlydifferent according to the metastatic LN ratio in N1 and N2classification of the fifth UICC classification (p < 0.05). The5-year survival rates after gastrectomy decreased significantly byincreasing the metastatic LN ratio in both T3N1M0 cancers (p =0.0026) and T3N2M0 cancers (p = 0.0057). The metastatic LN ratiowas an independent risk factor for recurrence and poor prognosis. Ourdata suggest that the metastatic LN ratio is a significant prognosticfactor for T3 gastric cancer. Furthermore, the application of themetastatic LN ratio can provide information not only about the extentof LN metastasis but also about the extent of lymphadenectomy in T3gastric cancer.

Adverse effects of perioperative transfusion on patients with stage III and IV gastric cancer

AbstractBackground: The degree of immunomodulation by perioperative blood transfusion and its resultant effects on cancer surgery are a subject of controversy. We evaluated the prognostic effects of perioperative blood transfusion on gastric cancer surgery. Methods: A total of 1710 patients who underwent curative gastrectomy for gastric cancer from 1991 to 1995 were retrospectively reviewed. Uni- and multivariate analyses of the incidence, amount, and timing of perioperative blood transfusions and a comparison of the clinicopathological features were performed. Results: A higher incidence of blood transfusions was associated with female sex, large tumors, upper-body location, Borrmann type III or IV lesions, longer operations, total gastrectomies, splenectomies, and D3 or more extended lymphadenectomy. The tumors in the transfused group were more advanced in depth of invasion and nodal classification. More frequent tumor recurrences were found in the transfused group. A dose-response relationship between the amount of transfused blood and prognosis was evident. Subgroup analyses of prognosis according to stage showed significant differences in stages III and IV between the transfused and nontransfused groups. On multivariate analysis, transfusion was shown to be an independent risk factor for recurrence and poor prognosis. Conclusions: These results suggest that perioperative transfusion is an unfavorable prognostic factor. It is thus better to refrain from unnecessary blood transfusion and to give the least amount of blood to patients with gastric cancer when transfusion is inevitable, especially for those with stage III and IV gastric cancers.

Comparison of prognostic significance of nodal staging between old (4th edition) and new (5th edition) UICC TNM classification for gastric carcinoma

Abstract. The description of nodal staging for gastric cancer was changed in the new fifth edition of the International Union Against Cancer (UICC) TNM classification from the anatomic sites of metastatic lymph nodes to the number of metastatic lymph nodes, as pN1 is metastasis in 1 to 6 lymph nodes, pN2 is in 7 to 15 lymph nodes, and pN3 is in 16 or more lymph nodes. The purpose of this study was to investigate the prognostic significance of the new staging system based on the number of metastatic lymph nodes compared to the old staging system by anatomic site. From 1987 to 1994 a total of 2108 patients who underwent potentially curative resections with D2 or D3 lymph node dissection and with 15 or more lymph nodes retrieved were studied retrospectively. Lymph node metastases were found in 1018 patients (48.3%). A mean of 37.9 lymph nodes were retrieved per patient, and a mean of 7.2 lymph nodes were invaded by tumor cells. We found that the new nodal staging based on the number of metastatic lymph nodes closely correlated with the depth of cancer invasion and with the old nodal staging based on the anatomic site of the metastatic nodes, with statistical significance. The 5-year survival rates after gastrectomy decreased significantly by increasing the extent of the pN classification in both nodal staging methods. In a subgroup analysis of survivals between the old and new nodal staging, the new classification showed more homogeneous survival at the same stage than the old one. With a multivariate analysis of prognostic factors, including the old and new nodal staging, the depth of invasion and the new nodal stage were the most significant prognostic factors, followed by the old nodal stage. Our data suggested that the new nodal staging based on the number of metastatic lymph nodes is not only a reliable and objective method for nodal classification, but it is also a significant prognostic determinant for gastric cancer that can be used in practice.

Clinical characteristics of Peutz-Jeghers syndrome in Korean polyposis patients

Abstract Peutz-Jeghers syndrome is an autosomal dominant inherited disorder characterized by hamartomatous polyps in the small bowel and mucocutaneous pigmentation. Patients with Peutz-Jeghers syndrome often present as surgical emergencies with complications of the polyps, such as intussusception, bowel obstruction, and bleeding. Recently an increased risk of malignancies has also been reported. This study was initiated to determine the clinical features of Peutz-Jeghers syndrome in Korean patients, with special attention to the development of malignancies. Thirty patients with Peutz-Jeghers syndrome were investigated; their median age was 23.5 years, and symptoms appeared at a median age of 12.5 years. Family history was positive in one-half of cases, and mucocutaneous pigmentation was observed in almost all patients (93%). The jejunoileum was the most frequent site of the polyps, and there were generally 10–100 polyps. Multiple laparotomies were performed in a substantial portion of the patients, due mainly to polyp-induced bowel obstruction, and the surgical interventions were begun at a relatively young age (average 21.4 years). Four cases of small-bowel cancer and one case of breast cancer were detected in probands, at a relatively young age (mean 36 years). Cancers of the small bowel, stomach, colon, breast and cervix were diagnosed in the first relatives of the probands. Close follow-up from an early age should thus be performed in patients with Peutz-Jeghers syndrome as they are at high risk of surgical emergency and development of malignancy.

P-glycoprotein: The intermediate end point of drug response to induction chemotherapy in locally advanced breast cancer

Expression and clinical relevance of p-glycoprotein (p-gp) were evaluated in 31 cases of locally advanced breast cancer and 9 cases involving inflammatory breast cancer after induction chemotherapy. The de novo p-gp expression rate was 26% and increased up to 58% (p = 0.03) with the FAC (5-fluorouracil, adriamycin, cyclophosphamide) regimen. Although more clinically complete responders were found in the secondary p-gp negative group (p = 0.02), this difference was not found in pathological tumor response. Moreover, as the grade of the secondary p-gp expression increased, the chemotherapeutic effect decreased, suggesting an inverse relationship between p-gp expression and drug effect (p = 0.04). When we subgrouped the patients into 4 groups using these two parameters, p-gp negative patients presenting with a high drug effect showed a low recurrence rate (p = 0.05) and marginal survival benefits (p = 0.09) as opposed to patients with a low drug effect. But in p-gp positive groups, the recurrence rate was the same between the two groups regardless of the drug effect. Thus, in the p-gp negative patient with a high drug effect, adjuvant chemotherapy with the same regimen as induction chemotherapy may induce more prognostically favorable results. Therefore, clinical application of the secondary p-gp detection can be used as an intermediate endpoint in evaluating drug response for an induction regimen.

Sequential production and activation of matrix-metalloproteinase-9 (MMP-9) with breast cancer progression

The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical pointin tumor invasion and metastasis. We measured theactivity of MMP-9 from 28 normal, 12 benignand 126 breast cancer tissues using gelatin zymographywith an image analysis system. ProMMP-9 was expressedin 17.5% of the cancer patients compared to2.5% in 40 non-cancerous tissues (p=0.014).The mature form of MMP-9 (82 kD) wasexpressed only in T2–T4 stages. During the earlyphase of breast cancer (DCIS and T1 stage)progression, only production of proMMP-9 increased. However, asthe cancer grew or invaded skin (T2–T4), orwith lymphovascular permeation, both production and activation ofMMP-9 increased. In conclusion, proMMP-9 production was themain cause of increased MMP-9 activity during theearly phase, while both production and activation increasedin the late phase of breast cancer.