Differential Perspectives by Specialty on Oligometastatic Colorectal Cancer: A Korean Oligometastasis Working Group’s Comparative Survey Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Despite numerous studies on the optimal treatments for oligometastatic disease (OMD), there is no established interdisciplinary consensus on its diagnosis or classification. This survey-based study aimed to analyze the differential opinions of colorectal surgeons and radiation oncologists regarding the definition and treatment of OMD from the colorectal primary. @*Materials and Methods@#A total of 141 participants were included in this study, consisting of 63 radiation oncologists (44.7%) and 78 colorectal surgeons (55.3%). The survey consisted of 19 questions related to OMD, and the responses were analyzed using the chi-square test to determine statistical differences between the specialties. @*Results@#The radiation oncologists chose “bone” more frequently compared to the colorectal surgeons (19.2% vs. 36.5%, p=0.022), while colorectal surgeons favored “peritoneal seeding” (26.9% vs. 9.5%, p=0.009). Regarding the number of metastatic tumors, 48.3% of colorectal surgeons responded that “irrelevant, if all metastatic lesions are amendable to local therapy”, while only 21.8% of radiation oncologist chose same answer. When asked about molecular diagnosis, most surgeons (74.8%) said it was important, but only 35.8% of radiation oncologists agreed. @*Conclusion@#This study demonstrates that although radiation oncologists and colorectal surgeons agreed on a majority of aspects such as diagnostic imaging, biomarker, systemic therapy, and optimal timing of OMD, they also had quite different perspectives on several aspects of OMD. Understanding these differences is crucial to achieving multidisciplinary consensus on the definition and optimal management of OMD.

Metastasis-Directed Local Therapy of Hepatic Oligometastasis from Colorectal Cancer and Future Perspective in Radiation Therapy / Journal of the Korean Cancer Association, 대한암학회지

Introduction of the concept for oligometastasis led to wide application of metastasis-directed local ablative therapies for metastatic colorectal cancer (CRC). By application of the metastasis-directed local ablative therapies including surgical resection, radiofrequency ablation (RFA), and stereotactic ablative body radiotherapy (SABR), the survival outcomes of patients with metastatic CRC have improved. The liver is the most common distant metastatic site in CRC patients, and recently various metastasis-directed local therapies for hepatic oligometastasis from CRC (HOCRC) are widely used. Surgical resection is the first line of metastatic-directed local therapy for HOCRC, but its eligibility is very limited. Alternatively, RFA can be applied to patients who are ineligible for surgical resection of liver metastasis. However, there are some limitations such as inferior local control (LC) compared with surgical resection and technical feasibility based on location, size, and visibility on ultrasonography of the liver metastasis. Recent advances in radiation therapy technology have led to an increase in the use of SABR for liver tumors. SABR is considered complementary to RFA for patients with HOCRC who are ineligible for RFA. Furthermore, SABR can potentially result in better LC for liver metastases > 2-3 cm compared with RFA. In this article, the previous studies regarding curative metastasis-directed local therapies for HOCRC based on the radiation oncologist’s and surgeon’s perspective are reviewed and discussed. In addition, future perspectives regarding SABR in the treatment of HOCRC are suggested.

Clinical outcomes of surgical management for recurrent rectal prolapse: a multicenter retrospective study

Purpose@#There are few reports on outcomes following surgical repair of recurrent rectal prolapse. The purpose of this study was to examine surgical outcomes for recurrent rectal prolapse. @*Methods@#We conducted a multicenter retrospective study of patients who underwent surgery for recurrent rectal prolapse. This study used data collected by the Korean Anorectal Physiology and Pelvic Floor Disorder Study Group. @*Results@#A total of 166 patients who underwent surgery for recurrent rectal prolapse were registered retrospectively between 2011 and 2016 in 8 referral hospitals. Among them, 153 patients were finally enrolled, excluding 13 patients who were not followed up postoperatively. Median follow-up duration was 40 months (range, 0.2–129.3 months). Methods of surgical repair for recurrent rectal prolapse included perineal approach (n = 96) and abdominal approach (n = 57). Postoperative complications occurred in 16 patients (10.5%). There was no significant difference in complication rate between perineal and abdominal approach groups. While patients who underwent the perineal approach were older and more fragile, patients who underwent the abdominal approach had longer operation time and admission days (P < 0.05). Overall, 29 patients (19.0%) showed re-recurrence after surgery. Among variables, none affected the re-recurrence. @*Conclusion@#For the recurrent rectal prolapse, the perineal approach is used for the old and fragile patients. The postoperative complications and re-recurrence rate between perineal and abdominal approach were not different significantly. No factor including surgical method affected re-recurrence for recurrent rectal prolapse.

Laparoscopic surgery: an effective and safe surgical method of pediatric inguinal hernia repair

Purpose@#Inguinal hernia (IH) repair is very commonly performed in children. While open repair (OR) is the standard approach, laparoscopic repair is increasingly used. This study was aimed to investigate safety and feasibility of laparoscopic repair of pediatric IH compared to OR. @*Methods@#We retrospectively enrolled 105 pediatric patients with IH repair between January 2011 and October 2019. The laparoscopic procedures performed were laparoscopic percutaneous extraperitoneal closure (LPEC), and three-port mini-laparoscopic repair (TLR). The OR was performed as per usual technique. @*Results@#Thirty-nine patients underwent OR, 16 LPEC, and 50 TLR. The preoperative laterality of IH was 45 patients (42.9%) on the right side, 50 (47.6%) on the left side, and 10 (9.5%) on both sides. It was, however, diagnosed postoperatively in 27 patients (25.7%) on the right side, 38 (36.2%) on the left side, and 40 (38.1%) on both sides. Of the 63 patients who presented with unilateral IH in the laparoscopic groups, 32 (50.8%) had synchronous contralateral patent process vaginalis (PPV) which were simultaneously repaired. This was significantly more common in children under 3 years of age. Operative time in unilateral or bilateral repair was significantly shorter in the laparoscopic repair groups (p < 0.001). Ipsilateral recurrence was not observed in any group. Metachronous contralateral IH occurrence was not significantly different between groups. @*Conclusion@#Laparoscopic IH repair may have benefit in terms of shorter operation time and diagnosis of unpredicted contralateral PPV compared to OR.

Korean physicians' policies for postoperative surveillance of colorectal cancer

BACKGROUND/AIMS: We explored Korean physicians’ policies for surveillance of colorectal cancer (CRC) after curative surgery. METHODS: Web-based self-report questionnaires were developed. Invitations to participate were emailed to physicians who diagnosed and treated CRC from October 1 to November 15, 2015. The questionnaire consisted of the role doctors played in the surveillance, examination of surveillance, and duration of postoperative surveillance according to CRC stage or primary site of the cancer. RESULTS: Ninety-one physicians participated in the online survey, and 78 completed the survey. Sixty-seven participants (13%) answered “up to 5 years” for stage I surveillance duration; and 11 (13%) responded with a duration of > 5 years for stage I. A total of 61 (75%) responded with a surveillance duration of up to 5 years for stage II; and 19 (24%) responded with a duration of > 5 years for stage II. Sixty-seven (97%) and 61 (91%) physicians monitored patients with stage II/III every 3 or 6 months by laboratory examination and by abdominopelvic computed tomography scan for the first year, respectively. A total of 43 (53%) responded with a surveillance duration of up to 5 years for stage IV; and 46 (46%) responded with a duration of > 5 years for stage IV after curative resection. CONCLUSIONS: Korean physicians mostly followed up CRC using intensive postoperative surveillance. In preference to monitoring over a comparatively shorter period of time, the physicians tended to prefer monitoring patients post-operatively over a > 5 year period, particularly in cases of advanced-stage CRC.

The outcomes of intensified 5-fluorouracil plus leucovorin chemotherapy for preoperative chemoradiation in rectal cancers

PURPOSE: The clinical benefit of intensified neoadjuvant chemoradiotherapy (CRT) in rectal cancer has not been proved. We investigated clinical outcomes of intensified 5-fluorouracil plus leucovorin (5-FU/LV) chemotherapy.METHODS: We retrospectively analyzed 45 patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant CRT between 2010 and 2015. Intensified group took additional 1 cycle of 5-FU/LV chemotherapy after radiation completion (resting period) before surgery, compared to conventional group.RESULTS: Eighteen patients were in conventional group and 27 were in intensified group. Median follow-up duration was 33.7 months (range, 7.8–75.6 months). Complete response rate was 11.4% (5/45). Twelve patients in conventional group and 16 patients in intensified group achieved downstaging (P=0.435). In aspect of toxicity, anemia and thrombocytopenia tended to be more frequent in intensified group without statistical difference. There was also no difference in survival between two groups.CONCLUSION: The intensified CRT with additional 1 cycle of 5-FU/LV in rectal cancer revealed no clinical benefit compared to conventional regimen. Considering that the adverse event was minimal and generally acceptable, further research with additional cycles of 5-FU/LV is needed to prove a real benefit of intensified CRT.

Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for stage II–III resectable rectal cancer: a meta-analysis of randomized controlled trials

PURPOSE: Whether preoperative chemoradiotherapy (CRT) is better than postoperative CRT in oncologic outcome and toxicity is contentious in prospective randomized clinical trials. We systematically analyze and compare the treatment result, toxicity, and sphincter preservation rate between preoperative CRT and postoperative CRT in stage II–III rectal cancer. MATERIALS AND METHODS: We searched Medline, Embase, and Cochrane Library from 1990 to 2014 for relevant trials. Only phase III randomized studies performing CRT and curative surgery were selected and the data were extracted. Meta-analysis was used to pool oncologic outcome and toxicity data across studies. RESULTS: Three randomized phase III trials were finally identified. The meta-analysis results showed significantly lower 5-year locoregional recurrence rate in the preoperative-CRT group than in the postoperative-CRT group (hazard ratio, 0.59; 95% confidence interval, 0.41–0.84; p = 0.004). The 5-year distant recurrence rate (p = 0.55), relapse-free survival (p = 0.14), and overall survival (p = 0.22) showed no significant difference between two groups. Acute toxicity was significantly lower in the preoperativeCRT group than in the postoperative-CRT group (p < 0.001). However, there was no significant difference between two groups in perioperative and chronic complications (p = 0.53). The sphincter-saving rate was not significantly different between two groups (p = 0.24). The conversion rate from abdominoperineal resection to low anterior resection in low rectal cancer was significantly higher in the preoperative-CRT group than in the postoperative-CRT group (p < 0.001). CONCLUSIONS: As compared to postoperative CRT, preoperative CRT improves only locoregional control, not distant control and survival, with similar chronic toxicity and sphincter preservation rate in rectal cancer patients.

Preoperative chemoradiotherapy versus postoperative chemoradiotherapy for stage II–III resectable rectal cancer: a meta-analysis of randomized controlled trials

PURPOSE: Whether preoperative chemoradiotherapy (CRT) is better than postoperative CRT in oncologic outcome and toxicity is contentious in prospective randomized clinical trials. We systematically analyze and compare the treatment result, toxicity, and sphincter preservation rate between preoperative CRT and postoperative CRT in stage II–III rectal cancer. MATERIALS AND METHODS: We searched Medline, Embase, and Cochrane Library from 1990 to 2014 for relevant trials. Only phase III randomized studies performing CRT and curative surgery were selected and the data were extracted. Meta-analysis was used to pool oncologic outcome and toxicity data across studies. RESULTS: Three randomized phase III trials were finally identified. The meta-analysis results showed significantly lower 5-year locoregional recurrence rate in the preoperative-CRT group than in the postoperative-CRT group (hazard ratio, 0.59; 95% confidence interval, 0.41–0.84; p = 0.004). The 5-year distant recurrence rate (p = 0.55), relapse-free survival (p = 0.14), and overall survival (p = 0.22) showed no significant difference between two groups. Acute toxicity was significantly lower in the preoperativeCRT group than in the postoperative-CRT group (p < 0.001). However, there was no significant difference between two groups in perioperative and chronic complications (p = 0.53). The sphincter-saving rate was not significantly different between two groups (p = 0.24). The conversion rate from abdominoperineal resection to low anterior resection in low rectal cancer was significantly higher in the preoperative-CRT group than in the postoperative-CRT group (p < 0.001). CONCLUSIONS: As compared to postoperative CRT, preoperative CRT improves only locoregional control, not distant control and survival, with similar chronic toxicity and sphincter preservation rate in rectal cancer patients.

The Korean guideline for colorectal cancer screening

Colorectal cancer is the third most common cancer in Korea; it is the second most common cancer in men and the third most common in women. The incidence rate in Korea has continuously increased since 1999 when the National Cancer Registry statistics began. Currently; there are several screening modalities; that have been recommended by expert societies, including fecal occult blood test, colonoscopy, computed tomographic colonography The annual fecal immunochemical test (FIT) has been used in adults aged 50 and older as part of the National Cancer Screening Program in Korea since 2004. Although several study results from regional or national colorectal cancer screening programs in other countries have been reported, the National Cancer Screening Program in Korea has not yet been evaluated with evidence-based methods. Herein report the consensus statements on the National Screening Guideline for colorectal cancer developed by a multi-society expert committee in Korea, as follows: 1) We recommend annual or biennial FIT for screening for colorectal cancer in asymptomatic adults, beginning at 45 years of age and continuing until 80 years (recommendation B). 2) There is no evidence for the risks or benefits of FIT in adults older than 80 years (recommendation I). 3) Selective use of colonoscopy for colorectal cancer screening is recommended, taking into consideration individual preference and the risk of colorectal cancer (recommendation C). 4) There is no evidence for the risks or benefits of double-contrast barium enema for colorectal cancer screening in asymptomatic adults (recommendation I). 5) There is no evidence for the risks or benefits of computed tomographic colonography for colorectal cancer screening in asymptomatic adults (recommendation I).

Voiding Dysfunction after Total Mesorectal Excision in Rectal Cancer / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to assess the voiding dysfunction after rectal cancer surgery with total mesorectal excision (TME). METHODS: This was part of a prospective study done in the rectal cancer patients who underwent surgery with TME between November 2006 and June 2008. Consecutive uroflowmetry, post-voided residual volume, and a voiding questionnaire were performed at preoperatively and postoperatively. RESULTS: A total of 50 patients were recruited in this study, including 28 male and 22 female. In the comparison of the preoperative data with the postoperative 3-month data, a significant decrease in mean maximal flow rate, voided volume, and post-voided residual volume were found. In the comparison with the postoperative 6-month data, however only the maximal flow rate was decreased with statistical significance (P=0.02). In the comparison between surgical methods, abdominoperineal resection patients showed delayed recovery of maximal flow rate, voided volume, and post-voided residual volume. There was no significant difference in uroflowmetry parameters with advances in rectal cancer stage. CONCLUSIONS: Voiding dysfunction is common after rectal cancer surgery but can be recovered in 6 months after surgery or earlier. Abdominoperineal resection was shown to be an unfavorable factor for postoperative voiding. Larger prospective study is needed to determine the long-term effect of rectal cancer surgery in relation to male and female baseline voiding condition.

Small Bowel Carcinoma in Young Patient Detected by Double-balloon Enteroscopy / 대한소화기학회지

A 17-year old female presented with a chief complaint of melena and epigastric pain. She had a family history of colon cancer, her mother having been diagnosed with hereditary nonpolyposis colorectal carcinoma (HNPCC). After close examination including double-balloon enteroscopy, the patient was diagnosed with small bowel carcinoma, in spite of her young age. Here we report this rare case of small bowel carcinoma in a young patient with a family history of HNPCC.

Update for Indeterminate Colitis

The distinctive diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) is based on a combination of clinical, histologic, endoscopic, and radiologic data. Both UC and CD show characteristic, but non-specific, pathological features that may overlap and result in a diagnosis of indeterminate colitis (IC), which was proposed by pathologists for colectomy specimens in 1978, usually from patients operated on for severe colitis, especially in cases of acute fulminant disease of the colorectum. The subgroup of patients with an uncertain diagnosis has been classified as IC. Later, the same terminology was used for patients showing no clear clinical, endoscopic, histologic, or other features allowing a diagnosis of either UC or CD. More recently, the term IC has been applied to biopsy material when it is not been possible to differentiate between UC and CD. However, this term IC has suffered varying definitions, which in addition to numerous difficulties in diagnosing inflammatory bowel disease, has led to much confusion. In resected specimens, the term colitis of uncertain type or etiology is preferred. Over time, the majority of patients remain with a diagnosis of IC or show symptoms similar to UC. Ileal pouch anal anastomosis can be performed in such patients, with outcomes of pouch failure and with functional outcomes that are similar to those in patients with UC, but with increased risk of postoperative pouch complications. This review addresses the definition of indeterminate colitis, its pathology, its natural history, and the outcomes of restorative proctocolectomy.

Antimicrobial Prophylaxis Using a 2nd Generation Cephalosporin after Laparoscopic Colorectal Resection: A Randomized Trial of 1-day vs. 3-day

PURPOSE: We performed this study to compare 1-day group using a 2nd generation cephalsporin with 3-day group for evaluating hospital acquired infection. METHODS: The patients underwent laparoscopic colorectal surgery at Korea University Medical Center Anam Hospital, from August, 2007 to June, 2008. They were randomly allocated to 2 groups: 1-day or 3-day group. A 2nd generation cephalosporin was administered within 1 hour before surgery with 12-hour intervals. In cases of suspected infection, further studies were done to identify infection. RESULTS: The study included 154 patients (1-day group - 78, vs. 3-day group - 76). No differences were noted between the 2 groups in age, body mass index, smoking, diabetes mellitus, corticosteroid-use were noted. Gender (P=0.011) and mean operative time (P=0.047) between the 2 groups were different. The preventive rates of infection were 87.18% in the 1-day group compared with 82.89% in the 3-day group (P=0.456). CONCLUSION: Our prospective randomized control study concluded that there were no differences between the 1-day and 3-day group in hospital acquired infection. We could come to the conclusion that 1-day antimicrobial agent in laparoscopic colorectal surgery would be adequate in preventing infection.

Acquired Omental Cystic Lymphangioma after Subtotal Gastrectomy: A Case Report

We herein describe a case of cystic lymphangioma in the greater omentum of the remnant stomach, which is thought it to be related with subtotal gastrectomy 10 yr ago for early gastric cancer. A 76-yr-old man was admitted to our department with postprandial abdominal discomfort and bowel habit change. Intraabdominal multilocular cystic mass was detected by ultrasonography and computed tomography. We performed a complete En-bloc tumor resection including spleen and distal pancreas, and histological examination confirmed cystic lymphangioma originated from the greater omentum of the remnant stomach. Although the etiology of omental lymphangioma remains largely unclear, these findings suggested strongly that obstruction of the lymphatic vessels after gastric resection for gastric carcinoma might be the most plausible cause. The surgical extirpation with resection of organs involved appears to be a treatment of choice for such unusual case.

The Prognostic Significance of ErbB1 (EGFR) Expressions in Patients with Curative Resection for Colorectal Cancers

PURPOSE: The ErbB family is associated with cell growth, differentiation, cell survival, apoptosis, cell cycle progression, angiogenesis. In this study, the expressions of ErbB family of colorectal cancer specimen were investigated to determined correlations between the clinicopathologic characteristics and the expression of ErbB family in the curative resection for colorectal cancers, including cancer specific survival. METHODS: Patients who underwent the curative surgery for colorectal cancers from January 1997 to December 2000 at Ansan Medical Center, Korea University College of Medicine were enrolled in this study, and one hundred ninety six of colorectal cancer. The clinical relationship between the expression of ErbB family for colon adenocarcinoma and clinicopathologic characteristic factors including survival were analyzed. RESULTS: There was no clinical relationship of the expression of ErbB family with clinicopatholologic characteristics. However, survival analysis demonstrated that 5 year survival rates (5YSR) of patients with the positive expression of ErbB1 (EGFR) was lower than those of the negative expression of ErbB1 (P<0.05) in colorectal cancer patients. Moreover 5YSR of the positive expression of ErbB1 was lower than that of negative expression of ErbB1 in well differentiation subgroup, node negative subgroup, node positive subgroup, and also stage T3 subgroup (P<0.05). CONCLUSIONS: The positive ErbB1 expression of colorectal cancer was one of poor prognostic factors in patients with colorectal cancer in this study. We need the further study to prove the real relation between target therapy for the positive expression of ErbB1 (EGFR) in colorectal cancer and the improvement of survival rate.

Primitive Neuroectodermal Tumor on the Buttock

Primitive neuroectodermal tumors (PNET) usually arise in the brain and central nervous system, but rarely occur outside of the brain, such as in the limbs, pelvis, paravertebral region or chest wall. Herein, a case of PNET on the buttocks is reported. A 24-year-old female was admitted for evaluation of a mass on her left buttock. An incisional biopsy revealed a primitive neuroectodermal tumor, with focal neural differentiation histologically. Preoperative MRI demonstrated the tumor was located in the subcutaneous layer of the left perineum, and extended to the ischiorectal fossa. The lesion showed an irregular, but well defined border; however, the differentiation from the left posterior wall of anus was focally obliterated. On operation, the tumor was not adhered to the surrounding structure, except for the external anal sphincter. The mass was completely resected. The tumor was about 8 x 9 x 5.8 cm in size, and the pathological evaluation confirmed a PNET, with a free anal sphincter margin. Therefore, chemoradiation therapy was planned, but the tumor recurred two months later. It was recommended the patient undergo a re-resection, but was lost before the procedure could be undertaken.

Granular Cell Tumors of the Abdominal Wall

Granular cell tumors (GCT) are found in virtually any body site, including the tongue, skin, subcutaneous tissue, breast, rectum and vulva. However, they are rarely seen in the abdominal wall. We report here on a rare case of GCT in the rectus muscle of the abdominal wall. A 44-year-old woman presented with a non-tender, hard mass in the right lower abdominal wall. Upon microscopic examination, the tumor was found to comprise of large polygonal cells with an abundant eosinophilic granular cytoplasm and round to oval nuclei. Upon immunohistochemical staining, the large cells showed S-100 and CD68 positive granular aggregates in the cytoplasm. Many lysosomes of variable size were observed in the cytoplasm.

Granular Cell Tumors of the Abdominal Wall

Granular cell tumors (GCT) are found in virtually any body site, including the tongue, skin, subcutaneous tissue, breast, rectum and vulva. However, they are rarely seen in the abdominal wall. We report here on a rare case of GCT in the rectus muscle of the abdominal wall. A 44-year-old woman presented with a non-tender, hard mass in the right lower abdominal wall. Upon microscopic examination, the tumor was found to comprise of large polygonal cells with an abundant eosinophilic granular cytoplasm and round to oval nuclei. Upon immunohistochemical staining, the large cells showed S-100 and CD68 positive granular aggregates in the cytoplasm. Many lysosomes of variable size were observed in the cytoplasm.

Prognostic Factors of Resected Stage IV Gastric Cancer Patients

PURPOSE: The prognosis of stage IV gastric cancer is poor with the 5-year survival rate still being about 10%. We investigated the prognostic factors of stage IV gastric cancer patients who underwent resection. MATERIALS AND METHODS: A retrospective study of 383 patients with stage IV gastric cancer who underwent surgery in our department between September 1983 to December 2000 was conducted. We classified the 383 patients into two groups: patients surviving 2 years or more (n=77) and those surviving less than 2 years (n=306). Clinicopathologic differences were analyzed between the two groups. We also performed univariate and multivariate analyses of various clinicopathologic factors concerning survival. RESULTS: Statistically significant clinicopathologic differences between the two groups were observed in regard to macroscopic type, distant metastasis, lymph node dissection, curability, and histology. Curability and histology were significant survival factors in 2-year survival. The 5-year survival rate was 5.4% in stage IV gastric cancer. Significant differences in survival among macroscopic type, distant metastasis, lymph node dissection, curability and histology were observed in the univariate analysis. In the Multivariate analysis, Curability, lymph node dissection, and histology were significantly beneficial factors for survival. CONCLUSION: Lymph node dissection, curability, and histology were independent prognostic factors in stage IV gastric cancer, and radical treatment is recommended to improve survival.

15-Deoxy-delta12,14-PGJ2inhibits IL-6-induced Stat3 phosphorylation in lymphocytes

15-deoxy-delta12,14-PGJ2(15d-PGJ2) is a natural ligand that activates the peroxisome proliferators-activated receptor (PPAR) gamma, a member of nuclear receptor family implicated in regulation of lipid metabolism and adipocyte differentiation. Recent studies have shown that 15d-PGJ2 is the potent anti-inflammatory agent functioning via PPARgamma-dependent and -independent mechanisms. Most postulated mechanisms for anti-inflammatory action of PPARgamma agonists are involved in inhibiting NF-kappaB signaling pathway. We examined the possibility that IL-6 signaling via the Jak-Stat pathway is modulated by 15d-PGJ2 in lymphocytes and also examined whether the inhibition of IL-6 signaling is dependent of PPARgamma. 15d-PGJ2 blocked IL-6 induced Stat1 and Stat3 activation in primary human lymphocytes, Jurkat cells and immortalized rheumatoid arthritis B cells. Inhibition of IL-6 signaling was induced rapidly within 15 min after treatment of 15d-PGJ2. Other PPARgamma-agonists, such as troglitazone and ciglitazone, did not inhibit IL-6 signaling, indicating that 15d-PGJ2 affect the IL-6-induced Jak-Stat signaling pathway via PPARgamma-independent mechanism. Although cycloheximide reversed 15d-PGJ2-mediated inhibition of Stat3 activation, actinomycin D had no effect on 15d-PGJ2-mediated inhibition of IL-6 signaling, indicating that inhibition of IL-6 signaling occur independent of de novo gene expression. These results show that 15d-PGJ2 specifically inhibit Jak-Stat signaling pathway in lymphocytes, and suggest that 15d-PGJ2 may regulate inflammatory reactions through the modulation of different signaling pathway other than NF-kappaB in lymphocytes.