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381 POSTER Complicated colorectal cancer in advanced and old age
S114
Poster session: Colorectal and anal cancer
During the period 2002 till the August 2004. we had 57 patients with bilobar hepatic metastases where we performed combined treatment - resection + ablation 30 patients had colon and rectum metastases 27 patients with metastases from other origin Results: There were no intra- and postoperative mortalities 5 patients were febrile on the 4th postoperative day Two patients died in the period of 6 to 8 months after surgery Three patients died year after resection Two patients have died from extra hepatic disease and three from multiple liver recurrence Two patients had recurrent liver disease after one year and were reoperated radically once again and they are still alive Till now all other patients are still alive without recurrence on the liver Conclusion: Surgical treatment of metastases should be applied whenever possible Combined approach allows removal of metastases with preservation of sufficient amount of liver parenchyma Combined approach represents a safe method in the treatment of metastatic liver disease when performed by experienced surgical team. 381
POSTER
Complicated colorectal cancer in advanced and old age N. Jaramov, N. Katev, S. Toshev, K. Angelov. Medical University Sofia, Alexandrovska Hospital, Second Department of Surgery, Sofia, Bulgaria In this retrospective study we analyze 653 patients in advanced and old age with colorectal cancer, operated trough 2000-2005. Complications were diagnosed in 479 (73.4%):bowel obstruction (81.2%); perforation of the tumor itself or diastatic (9.7%); paratumor inflammation (3.6%); rectal bleeding (5.5%). 479 of the patients were staged as: Dukes A-5%, B-65% and C- 30% and as: TNM I-0, II-165(34%), III-177(37%), IV-137(29%). Emergency operations were done in 464(71.1%); radical operation – 434(66.5%) and palliative procedures-219(33.5%). In right colon cancer we performed right hemicolectomy with primary anastomosis. In cases of severe small bowel obstruction the operation ends with terminal ileostomy. In advanced left colon cancer obstruction the Hartmann procedure is a method of choice. Extended surgery – subtotal or total colectomy is another option. Primary anastomosis is indicated when bowel obstruction is not severe or compensated. Localization of obstruction, conditions of bowel wall, level of obstruction, age and concomitant diseases and skill of the surgeon are used to choose the type of operation. Postoperative arterial chemotherapy trough Port a Cath has been performed in 57 cases with multiple hepatic metastases. 5- years postoperative follow-up of 407 patients was performed using tumor markers, ultrasound and computerized tomography. Postoperative mortality for complicated colorectal cancer was 17.6%. The 3- and 5- years survival was 44.7% and 33.3% in the studied group. 382
POSTER
Elevated proteasome activity in blood plasma of patients with advanced stages of colorectal cancer L. Kozlowski 1 , H. Ostrowska 2 , M. Giaro 3 , M. Podlecka 3 , T. Lewandowski 3 , M. Wojtukiewicz 1 . 1 Medical University of Bialystok, Department of Oncology, Bialystok, Poland; 2 Medical University of Bialystok, Department of Biology, Bialystok, Poland; 3 Pro Medica County Hospital, Department of General Surgery, Elk, Poland The ubiquitin-proteasome system (UPS) is a highly conserved intracellular proteolytic pathway for the degradation of many proteins, including those that govern cell division, growth and apoptosis. Therefore, uncontrolled proteolysis by the UPS is thought to be responsible for the development of many human neoplasms. Abnormal high activity of the 20S proteasome has been demonstrated in various tumor cell lines as well as in many solid tumor extracts suggest that proteasome activity could also be elevated in the blood of cancer patients. Recently we have demonstrated that plasma proteasome activity is increased in patients with certain hematologic malignances, such as acute leukemia and myeloma.
The aim of the present study was to compare the 20S proteasome activity in blood plasma of patients with different solid tumors. The plasma was obtain at the time of diagnosis from the blood of patients with colorectal, gastric, renal, prostate, breast, ovarian, lung, skin cancer, and malignant melanoma who had been referred to the Department of Medical Oncology and Internal Medicine, Regional Cancer Center, Bialystok, Poland, and Department of General Surgery, “Pro Medica” County Hospital in Elk, Poland. The plasma of healthy subjects served as control. The 20S proteasome activity in plasma (20gikrogram/mL of total protein) was assayed spectrofluorimetrically using highly selective peptide substrate, SucLeu-Leu-Val-Tyr-AMC (100 mikroM) in a 100mM Tris/HCl buffer, pH 7.5 containing 0.03% SDS, which specifically activates the 20S proteasome. The 20S proteasome activity in plasma of patients with advanced stages of colorectal cancer was about 2-3-fold higher than that in the controls. Among them, the highest proteasome activity was found in the patients with massive metastases to the liver. Plasma 20S proteasome activity did not differ significantly between clinical stages II and III of colorectal cancer. The 20S proteasome activity was only slightly elevated in the plasma of patients with advanced inoperable gastric cancer. The plasma of patients with other cancers (i.e. breast, prostate, lung and malignant melanoma) exhibited the 20S proteasome activity comparable to that in the controls. In conclusion, the 20S proteasome activity is markedly elevated in plasma of patients with advanced colorectal cancer wide it remains within normal range in other solid tumors. The preliminary results suggest that the proteasome may play a role in the patophysiology of colorectal cancer and that determination of plasma proteasome activity in patients with this neoplasm may be of clinical importance. 383
POSTER
Long-term results of preoperative chemoradiation therapy for mid-low locally advanced rectal cancer: a single institution series S. Pucciarelli 1 , P. Toppan 1 , E. Urso 1 , L. Pasetto 2 , M. Friso 3 , M. Briarava 1 , M. Rugge 4 , M. Lise 1 , D. Nitti 1 . 1 Clinica Chirurgica II, Scienze Oncologiche e Chirurgiche, Padova, Italy; 2 Oncologia, IOV, Padova, Italy; 3 Radioterapia, IOV, Padova, Italy; 4 II Servizio di Anatomia Patologica, Anatomia Patologica, Padova, Italy Purpose: To evaluate the long-term outcome of preoperative chemoradiation therapy (pCRT) for rectal cancer Methods: All consecutive patients who underwent surgery after pCRT were considered. Inclusion criteria were: histologically proven primary rectal adenocarcinoma located up to 11 cm from the anal verge (AV); pretreatment TNM stage IIIII (as assessed by pelvic CT and/or TRUS); age 18-80 yrs; minimum follow-up for living patients >48 months; radiotherapy (RT) administered by conventional fractionation (1.8 Gy/day) with total dose >40 Gys, and 5-FU-based chemotherapy administered by bolus or continuous venous infusion (CVI). Survival estimates were calculated using the Kaplan-Meier method. Results: One hundred thirty-four patients were available for analysis (M:F = 85:49; median age: 59 yrs). Median distance of the tumor from the AV was 6 (range 1-11) cm. Pre-treatment TNM stage was II (n=49), and III (n= 85). RT was delivered at a median dose of 50.4 (range 40-60) Gys. 5-FU was administered by CVI in 78 (58%) cases. Radical resection (R0) and sphincter saving procedures were performed in 113 (84%) and 117 (87%) cases, respectively. Pathologic yTNM stage was: 0 (complete response), n= 20 (15%); I, n= 44 (33%), II, n=29 (22%); III, n=25 (19%); IV, n=14 (10%); not evaluable (local excision), n=2 (1%). Median number of lymph nodes evaluated was 7 (range 0-38). Seventy-nine (59%) patients received adjuvant chemotherapy. At a median follow-up of 54 (range 0-141) months, 99 (74%) patients are alive (disease-free, n=95; with disease, n= 4), and 35 (26%) patients have died due to cancer progression (n= 28) or for other causes (n= 7). Recurrences occurred in 15 (13%) patients (local and distant, n=2, distant only, n=13). Twelve (80%) out of 15 recurrences were found within the 3-yearsr follow-up, and none after 5-yearsr follow-up. The 5 and 10-years OS was 74 and 62%, respectively; the 5 and 10-yr DFS was 86 and 86%, respectively. The 5 and 10-years cancer-specific OS was 80 and 72%, respectively. Conclusion: Preoperative RT combined with 5-FU-based chemotherapy was followed by satisfactory long-term OS and DFS. In contrast to some data reported in the literature, in this study most recurrences (80%) were found within three years from surgery, and no relapse was observed after 5-years.
Poster session: Colorectal and anal cancer
During the period 2002 till the August 2004. we had 57 patients with bilobar hepatic metastases where we performed combined treatment - resection + ablation 30 patients had colon and rectum metastases 27 patients with metastases from other origin Results: There were no intra- and postoperative mortalities 5 patients were febrile on the 4th postoperative day Two patients died in the period of 6 to 8 months after surgery Three patients died year after resection Two patients have died from extra hepatic disease and three from multiple liver recurrence Two patients had recurrent liver disease after one year and were reoperated radically once again and they are still alive Till now all other patients are still alive without recurrence on the liver Conclusion: Surgical treatment of metastases should be applied whenever possible Combined approach allows removal of metastases with preservation of sufficient amount of liver parenchyma Combined approach represents a safe method in the treatment of metastatic liver disease when performed by experienced surgical team. 381
POSTER
Complicated colorectal cancer in advanced and old age N. Jaramov, N. Katev, S. Toshev, K. Angelov. Medical University Sofia, Alexandrovska Hospital, Second Department of Surgery, Sofia, Bulgaria In this retrospective study we analyze 653 patients in advanced and old age with colorectal cancer, operated trough 2000-2005. Complications were diagnosed in 479 (73.4%):bowel obstruction (81.2%); perforation of the tumor itself or diastatic (9.7%); paratumor inflammation (3.6%); rectal bleeding (5.5%). 479 of the patients were staged as: Dukes A-5%, B-65% and C- 30% and as: TNM I-0, II-165(34%), III-177(37%), IV-137(29%). Emergency operations were done in 464(71.1%); radical operation – 434(66.5%) and palliative procedures-219(33.5%). In right colon cancer we performed right hemicolectomy with primary anastomosis. In cases of severe small bowel obstruction the operation ends with terminal ileostomy. In advanced left colon cancer obstruction the Hartmann procedure is a method of choice. Extended surgery – subtotal or total colectomy is another option. Primary anastomosis is indicated when bowel obstruction is not severe or compensated. Localization of obstruction, conditions of bowel wall, level of obstruction, age and concomitant diseases and skill of the surgeon are used to choose the type of operation. Postoperative arterial chemotherapy trough Port a Cath has been performed in 57 cases with multiple hepatic metastases. 5- years postoperative follow-up of 407 patients was performed using tumor markers, ultrasound and computerized tomography. Postoperative mortality for complicated colorectal cancer was 17.6%. The 3- and 5- years survival was 44.7% and 33.3% in the studied group. 382
POSTER
Elevated proteasome activity in blood plasma of patients with advanced stages of colorectal cancer L. Kozlowski 1 , H. Ostrowska 2 , M. Giaro 3 , M. Podlecka 3 , T. Lewandowski 3 , M. Wojtukiewicz 1 . 1 Medical University of Bialystok, Department of Oncology, Bialystok, Poland; 2 Medical University of Bialystok, Department of Biology, Bialystok, Poland; 3 Pro Medica County Hospital, Department of General Surgery, Elk, Poland The ubiquitin-proteasome system (UPS) is a highly conserved intracellular proteolytic pathway for the degradation of many proteins, including those that govern cell division, growth and apoptosis. Therefore, uncontrolled proteolysis by the UPS is thought to be responsible for the development of many human neoplasms. Abnormal high activity of the 20S proteasome has been demonstrated in various tumor cell lines as well as in many solid tumor extracts suggest that proteasome activity could also be elevated in the blood of cancer patients. Recently we have demonstrated that plasma proteasome activity is increased in patients with certain hematologic malignances, such as acute leukemia and myeloma.
The aim of the present study was to compare the 20S proteasome activity in blood plasma of patients with different solid tumors. The plasma was obtain at the time of diagnosis from the blood of patients with colorectal, gastric, renal, prostate, breast, ovarian, lung, skin cancer, and malignant melanoma who had been referred to the Department of Medical Oncology and Internal Medicine, Regional Cancer Center, Bialystok, Poland, and Department of General Surgery, “Pro Medica” County Hospital in Elk, Poland. The plasma of healthy subjects served as control. The 20S proteasome activity in plasma (20gikrogram/mL of total protein) was assayed spectrofluorimetrically using highly selective peptide substrate, SucLeu-Leu-Val-Tyr-AMC (100 mikroM) in a 100mM Tris/HCl buffer, pH 7.5 containing 0.03% SDS, which specifically activates the 20S proteasome. The 20S proteasome activity in plasma of patients with advanced stages of colorectal cancer was about 2-3-fold higher than that in the controls. Among them, the highest proteasome activity was found in the patients with massive metastases to the liver. Plasma 20S proteasome activity did not differ significantly between clinical stages II and III of colorectal cancer. The 20S proteasome activity was only slightly elevated in the plasma of patients with advanced inoperable gastric cancer. The plasma of patients with other cancers (i.e. breast, prostate, lung and malignant melanoma) exhibited the 20S proteasome activity comparable to that in the controls. In conclusion, the 20S proteasome activity is markedly elevated in plasma of patients with advanced colorectal cancer wide it remains within normal range in other solid tumors. The preliminary results suggest that the proteasome may play a role in the patophysiology of colorectal cancer and that determination of plasma proteasome activity in patients with this neoplasm may be of clinical importance. 383
POSTER
Long-term results of preoperative chemoradiation therapy for mid-low locally advanced rectal cancer: a single institution series S. Pucciarelli 1 , P. Toppan 1 , E. Urso 1 , L. Pasetto 2 , M. Friso 3 , M. Briarava 1 , M. Rugge 4 , M. Lise 1 , D. Nitti 1 . 1 Clinica Chirurgica II, Scienze Oncologiche e Chirurgiche, Padova, Italy; 2 Oncologia, IOV, Padova, Italy; 3 Radioterapia, IOV, Padova, Italy; 4 II Servizio di Anatomia Patologica, Anatomia Patologica, Padova, Italy Purpose: To evaluate the long-term outcome of preoperative chemoradiation therapy (pCRT) for rectal cancer Methods: All consecutive patients who underwent surgery after pCRT were considered. Inclusion criteria were: histologically proven primary rectal adenocarcinoma located up to 11 cm from the anal verge (AV); pretreatment TNM stage IIIII (as assessed by pelvic CT and/or TRUS); age 18-80 yrs; minimum follow-up for living patients >48 months; radiotherapy (RT) administered by conventional fractionation (1.8 Gy/day) with total dose >40 Gys, and 5-FU-based chemotherapy administered by bolus or continuous venous infusion (CVI). Survival estimates were calculated using the Kaplan-Meier method. Results: One hundred thirty-four patients were available for analysis (M:F = 85:49; median age: 59 yrs). Median distance of the tumor from the AV was 6 (range 1-11) cm. Pre-treatment TNM stage was II (n=49), and III (n= 85). RT was delivered at a median dose of 50.4 (range 40-60) Gys. 5-FU was administered by CVI in 78 (58%) cases. Radical resection (R0) and sphincter saving procedures were performed in 113 (84%) and 117 (87%) cases, respectively. Pathologic yTNM stage was: 0 (complete response), n= 20 (15%); I, n= 44 (33%), II, n=29 (22%); III, n=25 (19%); IV, n=14 (10%); not evaluable (local excision), n=2 (1%). Median number of lymph nodes evaluated was 7 (range 0-38). Seventy-nine (59%) patients received adjuvant chemotherapy. At a median follow-up of 54 (range 0-141) months, 99 (74%) patients are alive (disease-free, n=95; with disease, n= 4), and 35 (26%) patients have died due to cancer progression (n= 28) or for other causes (n= 7). Recurrences occurred in 15 (13%) patients (local and distant, n=2, distant only, n=13). Twelve (80%) out of 15 recurrences were found within the 3-yearsr follow-up, and none after 5-yearsr follow-up. The 5 and 10-years OS was 74 and 62%, respectively; the 5 and 10-yr DFS was 86 and 86%, respectively. The 5 and 10-years cancer-specific OS was 80 and 72%, respectively. Conclusion: Preoperative RT combined with 5-FU-based chemotherapy was followed by satisfactory long-term OS and DFS. In contrast to some data reported in the literature, in this study most recurrences (80%) were found within three years from surgery, and no relapse was observed after 5-years.