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Neoadjuvant chemoradiotherapy is not associated with a higher complication rate versus surgery alone in patients undergoing operation for esophageal cancer
postprandial power change; 2) assessment of total symptom scores (TSS) of severity and frequency o[ vomiting, nausea, early satiety, bloating, postprandial fullness and eptgastric pain, each graded using a 5-point scale (0 to 4) at baseline and follow-up; and 3) analysis of a full thickness gastric biopsy taken from the antrum and body during [aparotomy for placement of Emerra device, lmmunohistochemical staining was performed using the Dako Autostainer (Dako,Carpenteria,CA). Monoclonal antibodies were used according to the standard protocol. All slides were examined microscopically and scored for the presence of ICC. The findings were expressed as follows: ( + ) normal number of ICCs; ( +/-) reduced number of 1CCs equivalent to 20-40% of the control; (-) almost complete loss of ICCs, to the point that not more than 5 cells were seen per 10 high power fields (less than 10% of the control). Results: For the purpose of data analysis we combined ( + ) and (+/-) groups (N =9) and compared their findings to (-) group (N = 5). At baseline (-) patients had significantly more tachygastria (slow wave frequency > 4 cpm) than ( + ) and (+/-) patients (54_+36% vs. 11 _+ 13%, P = 0.02). The postprandial EGG power change was substantially lower in (-) patients than the combined group (-1.0 + 5.3 dB vs. 0.6 +-4 7 dB). Patients in (-) group had more seventy in TSS than the combined group at baseline (21.4-+3.6 vs. 18-+5.2). The TSS after 3 months of GES in (-) patients was significantly higher than the combined group (i4.6-+6.0 vs. 6.4_+47, p=0.02). Conclusions: 1) ICCs are absent in approx, one third of patients with diabetic and idiopathic gastroparesis; 2) The absence of ICC is associated with increased abnormalities of gastric slow waves and a more severe symptom status as well as a poorer outcome for GES (Enterra therapy).
most common mihor complications. There were 12 major complications in 7 (21%) CHEMO patients vk 40 in 22 (31%) SURG patients (p=ns). Cardiac, pneumonia and prolonged ilens were the most common major complications. Seven patients required re-operation, 3 CHEMO and 4 SURG (p = ns). Post-operative length of stay was not significantly different between the groups(8 days). Conclusion: CPT-11 based neoadjuvant chemotherapy for gastric cancer can be delivered safely, can result in tumor downstaging, and does not cause increased postoperative morbidity or mortality. Concerns of increased postoperative complications following gastrectomy should not hinder the use of CPT- 11 based neoadjuvant chemotherapy for patterns with locally advanced gastric cancer
499 EFFECT OF SURGICAL TREATMENT ON THE SURVIVAL OF GALLBLADDER CANCER PATIENTS--BENEFIT OF RADICAL CHOLECYSTECTOMY Burcin Taner, David Nagnmey, John Donohue Gallbladder cancer (GBC) is associated with poor survival because of advanced disease stage at presemation. Although the best chance of cure for GBC remains incidental discovery, radical resection of the gallbladder, with adjacem liver, adherent structures, and a regional lymphadenectomy has been purported to improve survival. We retrospectively analyzed all patients with GBC who were treated surgically in our institution between 1984-2000. There were 126 patients (92 women, 34 men) for whom complete survival information was available. Stage distribution was: Stage 0: 1; Stage I: 4; Stage ll: 15; Stage Ill: 39; Stage IVA: 17; Stage IVB: 48; unknnwn: 2. Fifty-seven patients had radical cholecystectomy, 46 patients had a simple cholecystectomy, and 23 patients had other surgical treatments. Forty-seven patients had some form of adjuvant therapy. Patients who underwent a radical cholecystectomy had a significantly longer mean survival (mean = 29.9 mdnths) than those patients who had simple cholecystectomy (mean = 9.3 months, p = 0.0001) or other treatment (mean = 5.4 months, p < 0.0001). The radical cholecystectomy group had significantly longer survivals than simple cholecystectomy group for Stage In (mean = 35 vs. 7.6 months, p=O.O1), Stage IVA (mean = 12.5 vs. 3.2 months, p=O.012), and Stage 1'/8 (mean = 23.5 vs. 5.8 months, p<0.001). Adjuvant therapy significantly improved survival in Stage IVB patients treated with simple cholecystectomy (n=3, mean = 10.1 months) compared to simple cholecystectomy alone (n = 14, mean = 4.9 months, p = 0.03). Although adjuvant chemotherapy appeared to improve survival for other GBC stages or treatment modalities, these effects did not reach statistical significance. Of the different variables tested by muhivanate analysis (age, sex, radical and simple cholecystectomy, stage and grade of tumor), only radical cholecystectomy, and T and N tumor stage were statistically significant predictors for the survival of patients with GBC. We conclude that radical cholecystectomy is associated with improved patient survival and is recommended for patients "~ith locally advanced GBC.
402 Diabetes Correlates with Abnormal Gallbladder Contractility in Leptin-Relatod Murine Obesity Khoi Q Tran, Matthew I. Goldblatt, Deborah A. Swartz-Basile, Carol L. Svatek, Attila Nakeeb, Henry A Pitt Obesity is associated with multiple comorbidities including hyperlipidemia, diabetes and gallstones. However, the interaction among these various modalities remains unclear. We have recently demonstrated that two strains of obese mice with absent (Lep~ and very high (Lepdb) serum [eptin, respectively, have normal (Lep'~) and low (Lepdb) biliary lipids. Both of these leptin-related murine models of obesity have impaired biliary motility and high serum fipids which correlate inversely with gallbladder muscle response. Both leptin-deficient (Lep"~') and leptin-resistant (Lepa~) mice are also diabetic, and diabetes has been recently documented to be a iask factor for gallstone formation Therefore, we tested the hypothesis that serum glucose would correlate with gallbladder comractihty. Thirty-four lean control (C57BL/6J), 10 lean heterozygous [eptin-deficient (Lep~), 18 obese homozygous leptin-deficient (Lep~ and 12 obese homozygons leptin-resistant (Lepdb) mice were fed a nonlithogenic CHOW diet for four weeks. All animals were then fasted overnight and underwent cholecystectomy. In vitro gallbladder responses to cholecystokinin (CCK 10 M), acetylchobne (ACh 105 M) and ne'uropeptide Y (NPY 10 .6 M) were measured. Serum glucose levels (mg/dl) were determined in pooled blood from an additional 221 lean control, 160 lean Lep~, 68 obese kep "band 78 obese Lepab mice. Serum glucose was correlated with normalized gallbladder responses for CCK, ACh and NPY using Pearson's correlation (r). Results are presented in the table. These data suggest that in vitro murine gallbladder responses to cholecystokinin, acetylcholine and neuropeptide Y are inversely correlated with serum glucose. We conclude that hyperglycemia in obese mice with leptin dysfunction is associated with poor gallbladder contractility which, in turn, may contribute to the association between obesity and gallstone formation.
500
Neoadjuvant ChemoradiotherapyIs Not Associated With A Higher Complication Rate Versus Surgery Alone In Patients Undergoing Operation For Esophageal Cancer Scott T. Kelley, Richard C. Karl, Domenico Coppola Introduction: Recent studies cite a higher perioperative complication rate related to the use of neoadjuvam chemomdiothempy in the treatment of esophageal cancer. We tested the hypothesis that nenadjuvam chemoradintherapy has no significant effect on the complication rate at our institution.
Serum Glucose and Gallbladder ReapoNea to Nonrotronsmltters Lean control Lean Lep TM Obese Lep~ Obeae Lep ~
Correlation Signlflconce
Glucose 193 9 9 116
9
428 9 23 498.25
CCK 1.00,0.08
ACh 0.42 ~ 0.03
NPY 0.19 ~ 0.02
0.62 0.10 0.43 ~ 0,06 0.42 ~ 0.11 r = -0,46 p < 0,001
0.33 ~ 0,07 0.18 ~ 0,02 0.16 - 0.05 r = -0.54 p < 0.001
0.13 0.03 0.07 ~ 0.01 0.04,0.01 r = -0.50 p < 0,001
Methods: We identified 170 (148 males-87%; 22 females-13%) patients with esophageal carcinoma who underwent esophagectomy between 1996 and 2002 from our prospective database. This included 73 (43%) patients treated with neoadjuvant chemmadiotherapy (group I) and 97 (57%) who underwent esophagectomy alone (group I1). Neoadjuvant therapy consisted of a preoperative regimen of 2 courses of cisplatinum (day 1 and 28), continuous infusion of 5-FU, and radiation (5040cGy), followed by esophagectomy. IvorLewis esophagectomy was performed in 161 (95%) and transhiatal in 9 (5%) cases. Groups 1 and II were comparable in terms of: age (61.1 _+11 years vs. 64.5 + 11); pathologic diagnosis (adenocarcinoma: 84% vs. 91%, sqnamons: 16% vs. 9%); and pathologic stage (AJCC): (stage I: 39% vs. 35%, Ila: 13%vs. 18%, 2b: 13% vs. 11%, Ill: 29% vs. 32%, and stage IV: 6% vs. 4%). The neoadjuvant group had 24 (33%) complete responses, 22 (30%) partial responses (where tumor size shrunk to at least 50% pre-treatment values via endoscopic ultrasound), and 27 (37%) non-responses
498 Complications of Gastrectomy Following CPT-I I Based Neoadjuvant Chemotherapy for Gastric Cancer Stuart G. Marcus, Daniel Cohen, Ke Lin, Kwok Wong, Scott Thompson, Adina Rothberger, Milan Potmesil, Spiros Hiotis, Elliot Newman
Results: There were 40 (23.5%) postoperative complications for the entire cohort, which included 3 deaths (1.8%) (2 in group [ and 1 in group ll) and 4 anastomotic leaks (2.3%) demonstrated by routine gastrograffin swallow on postoperative day 7 (1 (1.4%) in group I vs. 3 (3.1%) in group I1). Only one leak required reoperation (group I), while all others responded to conservative treatment Group 1 had 14 (192%) complications versus 25 (25.7%) in group [1 (F-test = NS). The groups were comparable (group 1 vs. II) with respect to the rate of pneumonia (4.1% vs. 8.2%), arrhythmia (5.5% vs. 8.2%), and stricture formation (5.5% vs. 7.2%). Within the neoadjuvant group, complete responders were no less likely to have a complication than were nonresponders to preoperative chemoradiation (26% vs. 22%, respectively).
Background: Gastrectomy with complete tumor removal and negative margins (R0 resection) is the most effective treatment for gastric cancer. Potential benefits of neoadjuvant therapy for locally advanced gastric cancer include tumor downstaging and an increased RO resection rate. Potential disadvantages include increased surgical complications. This study was designed to examine the effect of CPT-11 based nenadjuvant chemotherapy on surgical morbidity and mortality. Methods: We reviewed the medical records of 105 patients who underwent gastrectomy for adenocarcinoma of the stomach from October 1998 through July 2002.34 patients with locally advanced gastric cancer (T3 or N + ) were prospectively followed on a Phase 1I neoadjuvant chemotherapy protocol consisting of 2 cycles of CPT11 (75rag/m2) combined w~th Cisplatin (25mg/m2) followed by surgery. Demographic, clinical, morbidity and mortality data were compared by Chi-sqnare analysis for these 34 patients (CHEMO) versus 71 patients undergoing gastrectomy without nenadjuvant chemotherapy during the same time period (SURG). Results: There were no significant differences between the two groups with respect to age, sex, race, tumor location, extent of resection, or AJCC stage. R0 resection rate was 86% in the CHEMO patients with pathologic downstaging demonstrated in 59% as compared to preoperative clinical staging. There were 2 (6%) post-operative deaths in the CHEMO group vs. 3 (4%) in the SURG group (p=ns). Twelve of 34 CHEMO patients (35%) had at least one complication compared to 29 of 71 SURG patients (41%, p = ns). There were 9 minor complications in 6 (18%) CHEMO patients vs. 22 in 16 (23%) SURG patients (p=ns). Wound and urinary tract infections were the
Conclusions: We conclude that the addition of neoadjuvant cbemoradiotherapy in patients with esophageal cancer did not increase perioperative morbidity or mortality rates. In addition, a complete response to preoperative chemoradiotherapy did not affect perioperative complication rate.
A-789
SSAT
Abstracts
most common mihor complications. There were 12 major complications in 7 (21%) CHEMO patients vk 40 in 22 (31%) SURG patients (p=ns). Cardiac, pneumonia and prolonged ilens were the most common major complications. Seven patients required re-operation, 3 CHEMO and 4 SURG (p = ns). Post-operative length of stay was not significantly different between the groups(8 days). Conclusion: CPT-11 based neoadjuvant chemotherapy for gastric cancer can be delivered safely, can result in tumor downstaging, and does not cause increased postoperative morbidity or mortality. Concerns of increased postoperative complications following gastrectomy should not hinder the use of CPT- 11 based neoadjuvant chemotherapy for patterns with locally advanced gastric cancer
499 EFFECT OF SURGICAL TREATMENT ON THE SURVIVAL OF GALLBLADDER CANCER PATIENTS--BENEFIT OF RADICAL CHOLECYSTECTOMY Burcin Taner, David Nagnmey, John Donohue Gallbladder cancer (GBC) is associated with poor survival because of advanced disease stage at presemation. Although the best chance of cure for GBC remains incidental discovery, radical resection of the gallbladder, with adjacem liver, adherent structures, and a regional lymphadenectomy has been purported to improve survival. We retrospectively analyzed all patients with GBC who were treated surgically in our institution between 1984-2000. There were 126 patients (92 women, 34 men) for whom complete survival information was available. Stage distribution was: Stage 0: 1; Stage I: 4; Stage ll: 15; Stage Ill: 39; Stage IVA: 17; Stage IVB: 48; unknnwn: 2. Fifty-seven patients had radical cholecystectomy, 46 patients had a simple cholecystectomy, and 23 patients had other surgical treatments. Forty-seven patients had some form of adjuvant therapy. Patients who underwent a radical cholecystectomy had a significantly longer mean survival (mean = 29.9 mdnths) than those patients who had simple cholecystectomy (mean = 9.3 months, p = 0.0001) or other treatment (mean = 5.4 months, p < 0.0001). The radical cholecystectomy group had significantly longer survivals than simple cholecystectomy group for Stage In (mean = 35 vs. 7.6 months, p=O.O1), Stage IVA (mean = 12.5 vs. 3.2 months, p=O.012), and Stage 1'/8 (mean = 23.5 vs. 5.8 months, p<0.001). Adjuvant therapy significantly improved survival in Stage IVB patients treated with simple cholecystectomy (n=3, mean = 10.1 months) compared to simple cholecystectomy alone (n = 14, mean = 4.9 months, p = 0.03). Although adjuvant chemotherapy appeared to improve survival for other GBC stages or treatment modalities, these effects did not reach statistical significance. Of the different variables tested by muhivanate analysis (age, sex, radical and simple cholecystectomy, stage and grade of tumor), only radical cholecystectomy, and T and N tumor stage were statistically significant predictors for the survival of patients with GBC. We conclude that radical cholecystectomy is associated with improved patient survival and is recommended for patients "~ith locally advanced GBC.
402 Diabetes Correlates with Abnormal Gallbladder Contractility in Leptin-Relatod Murine Obesity Khoi Q Tran, Matthew I. Goldblatt, Deborah A. Swartz-Basile, Carol L. Svatek, Attila Nakeeb, Henry A Pitt Obesity is associated with multiple comorbidities including hyperlipidemia, diabetes and gallstones. However, the interaction among these various modalities remains unclear. We have recently demonstrated that two strains of obese mice with absent (Lep~ and very high (Lepdb) serum [eptin, respectively, have normal (Lep'~) and low (Lepdb) biliary lipids. Both of these leptin-related murine models of obesity have impaired biliary motility and high serum fipids which correlate inversely with gallbladder muscle response. Both leptin-deficient (Lep"~') and leptin-resistant (Lepa~) mice are also diabetic, and diabetes has been recently documented to be a iask factor for gallstone formation Therefore, we tested the hypothesis that serum glucose would correlate with gallbladder comractihty. Thirty-four lean control (C57BL/6J), 10 lean heterozygous [eptin-deficient (Lep~), 18 obese homozygous leptin-deficient (Lep~ and 12 obese homozygons leptin-resistant (Lepdb) mice were fed a nonlithogenic CHOW diet for four weeks. All animals were then fasted overnight and underwent cholecystectomy. In vitro gallbladder responses to cholecystokinin (CCK 10 M), acetylchobne (ACh 105 M) and ne'uropeptide Y (NPY 10 .6 M) were measured. Serum glucose levels (mg/dl) were determined in pooled blood from an additional 221 lean control, 160 lean Lep~, 68 obese kep "band 78 obese Lepab mice. Serum glucose was correlated with normalized gallbladder responses for CCK, ACh and NPY using Pearson's correlation (r). Results are presented in the table. These data suggest that in vitro murine gallbladder responses to cholecystokinin, acetylcholine and neuropeptide Y are inversely correlated with serum glucose. We conclude that hyperglycemia in obese mice with leptin dysfunction is associated with poor gallbladder contractility which, in turn, may contribute to the association between obesity and gallstone formation.
500
Neoadjuvant ChemoradiotherapyIs Not Associated With A Higher Complication Rate Versus Surgery Alone In Patients Undergoing Operation For Esophageal Cancer Scott T. Kelley, Richard C. Karl, Domenico Coppola Introduction: Recent studies cite a higher perioperative complication rate related to the use of neoadjuvam chemomdiothempy in the treatment of esophageal cancer. We tested the hypothesis that nenadjuvam chemoradintherapy has no significant effect on the complication rate at our institution.
Serum Glucose and Gallbladder ReapoNea to Nonrotronsmltters Lean control Lean Lep TM Obese Lep~ Obeae Lep ~
Correlation Signlflconce
Glucose 193 9 9 116
9
428 9 23 498.25
CCK 1.00,0.08
ACh 0.42 ~ 0.03
NPY 0.19 ~ 0.02
0.62 0.10 0.43 ~ 0,06 0.42 ~ 0.11 r = -0,46 p < 0,001
0.33 ~ 0,07 0.18 ~ 0,02 0.16 - 0.05 r = -0.54 p < 0.001
0.13 0.03 0.07 ~ 0.01 0.04,0.01 r = -0.50 p < 0,001
Methods: We identified 170 (148 males-87%; 22 females-13%) patients with esophageal carcinoma who underwent esophagectomy between 1996 and 2002 from our prospective database. This included 73 (43%) patients treated with neoadjuvant chemmadiotherapy (group I) and 97 (57%) who underwent esophagectomy alone (group I1). Neoadjuvant therapy consisted of a preoperative regimen of 2 courses of cisplatinum (day 1 and 28), continuous infusion of 5-FU, and radiation (5040cGy), followed by esophagectomy. IvorLewis esophagectomy was performed in 161 (95%) and transhiatal in 9 (5%) cases. Groups 1 and II were comparable in terms of: age (61.1 _+11 years vs. 64.5 + 11); pathologic diagnosis (adenocarcinoma: 84% vs. 91%, sqnamons: 16% vs. 9%); and pathologic stage (AJCC): (stage I: 39% vs. 35%, Ila: 13%vs. 18%, 2b: 13% vs. 11%, Ill: 29% vs. 32%, and stage IV: 6% vs. 4%). The neoadjuvant group had 24 (33%) complete responses, 22 (30%) partial responses (where tumor size shrunk to at least 50% pre-treatment values via endoscopic ultrasound), and 27 (37%) non-responses
498 Complications of Gastrectomy Following CPT-I I Based Neoadjuvant Chemotherapy for Gastric Cancer Stuart G. Marcus, Daniel Cohen, Ke Lin, Kwok Wong, Scott Thompson, Adina Rothberger, Milan Potmesil, Spiros Hiotis, Elliot Newman
Results: There were 40 (23.5%) postoperative complications for the entire cohort, which included 3 deaths (1.8%) (2 in group [ and 1 in group ll) and 4 anastomotic leaks (2.3%) demonstrated by routine gastrograffin swallow on postoperative day 7 (1 (1.4%) in group I vs. 3 (3.1%) in group I1). Only one leak required reoperation (group I), while all others responded to conservative treatment Group 1 had 14 (192%) complications versus 25 (25.7%) in group [1 (F-test = NS). The groups were comparable (group 1 vs. II) with respect to the rate of pneumonia (4.1% vs. 8.2%), arrhythmia (5.5% vs. 8.2%), and stricture formation (5.5% vs. 7.2%). Within the neoadjuvant group, complete responders were no less likely to have a complication than were nonresponders to preoperative chemoradiation (26% vs. 22%, respectively).
Background: Gastrectomy with complete tumor removal and negative margins (R0 resection) is the most effective treatment for gastric cancer. Potential benefits of neoadjuvant therapy for locally advanced gastric cancer include tumor downstaging and an increased RO resection rate. Potential disadvantages include increased surgical complications. This study was designed to examine the effect of CPT-11 based nenadjuvant chemotherapy on surgical morbidity and mortality. Methods: We reviewed the medical records of 105 patients who underwent gastrectomy for adenocarcinoma of the stomach from October 1998 through July 2002.34 patients with locally advanced gastric cancer (T3 or N + ) were prospectively followed on a Phase 1I neoadjuvant chemotherapy protocol consisting of 2 cycles of CPT11 (75rag/m2) combined w~th Cisplatin (25mg/m2) followed by surgery. Demographic, clinical, morbidity and mortality data were compared by Chi-sqnare analysis for these 34 patients (CHEMO) versus 71 patients undergoing gastrectomy without nenadjuvant chemotherapy during the same time period (SURG). Results: There were no significant differences between the two groups with respect to age, sex, race, tumor location, extent of resection, or AJCC stage. R0 resection rate was 86% in the CHEMO patients with pathologic downstaging demonstrated in 59% as compared to preoperative clinical staging. There were 2 (6%) post-operative deaths in the CHEMO group vs. 3 (4%) in the SURG group (p=ns). Twelve of 34 CHEMO patients (35%) had at least one complication compared to 29 of 71 SURG patients (41%, p = ns). There were 9 minor complications in 6 (18%) CHEMO patients vs. 22 in 16 (23%) SURG patients (p=ns). Wound and urinary tract infections were the
Conclusions: We conclude that the addition of neoadjuvant cbemoradiotherapy in patients with esophageal cancer did not increase perioperative morbidity or mortality rates. In addition, a complete response to preoperative chemoradiotherapy did not affect perioperative complication rate.
A-789
SSAT
Abstracts