Yong Hee Kim

Surgical resection of esophageal gastrointestinal stromal tumors.

BACKGROUNDnDue to the rarity of esophageal gastrointestinal stromal tumors (GISTs), their clinical course and treatment are poorly understood. We have assessed our experience in the diagnosis and management of esophageal GISTs.nnnMETHODSnWe performed a retrospective chart review of patients diagnosed with esophageal GISTs who underwent surgical resection.nnnRESULTSnWe identified 7 patients (6 males and 1 female) who underwent surgical procedures due to esophageal GISTs between 2001 and 2003; their median age was 46 years (range, 39 to 68 years). Four patients presented with dysphagia. Two patients were diagnosed with GIST by endoscopic biopsy before surgery. Five patients underwent enucleation, and two underwent esophagectomy. All tumors were resected completely and no patient received perioperative imatinib therapy. Median postoperative follow-up was 4.4 years (range, 2.2 to 7.0 years), during which two patients were diagnosed with recurrences.nnnCONCLUSIONSnEsophageal GIST is a rare disease, and complete surgical resection is the standard treatment. Regular follow-up is needed even if resection is complete and negative margins are achieved.

Salvage Esophagectomy for Locoregional Failure After Chemoradiotherapy in Patients With Advanced Esophageal Cancer

BACKGROUNDnDefinitive chemoradiotherapy is associated with high local treatment failure rates, and surgical resection may be an appropriate salvage therapy. However, the efficacy and safety of salvage esophagectomy have not been elucidated fully. The clinical outcomes of salvage esophagectomy for locoregional failure after chemoradiotherapy were assessed.nnnMETHODSnTwelve patients who underwent salvage esophagectomy after chemoradiotherapy between January 2003 and November 2010 were included in this retrospective analysis. Baseline demographics and survivals of these patients were compared with 21 patients who did not receive salvage esophagectomy for locoregional failure only after chemoradiotherapy, identified from our own previous prospective trials.nnnRESULTSnThe median age was 62.5 years (range 50 to 69) and all patients had squamous cell carcinoma. The median radiation dose was 54.0 Gy (range 41.4 to 66.0) and the median interval between completion of chemoradiation and surgery was 8.0 months (range 2.0 to 32.9). There were no in-hospital deaths. Pulmonary complication was the most common postoperative morbidity (42%), and anastomotic leakage occurred in 1 patient (8%). With a median follow-up period of 29.3 months (range 5.8 to 73.0), the overall 3-year survival rate was 58%. Patients with early pathologic stage disease (T1/2 and N0) showed significantly prolonged survival (p=0.03) compared with those with advanced pathologic stage (T3/T4 or N1). Patients with salvage esophagectomy had prolonged event-free survival and overall survival compared with those patients with locoregional failure who received primary chemotherapy or boost radiotherapy (p<0.001).nnnCONCLUSIONSnWhile salvage esophagectomy for locoregional failure after chemoradiotherapy should be employed with great caution, it appears to be a feasible and effective therapeutic option for highly selected patients, especially with early pathologic stage disease. Salvage esophagectomy can be recommended as the only current curative treatment option for patients with locoregional failure after chemoradiotherapy.

TREATMENT OUTCOME AND RECURSIVE PARTITIONING ANALYSIS-BASED PROGNOSTIC FACTORS IN PATIENTS WITH ESOPHAGEAL SQUAMOUS CELL CARCINOMA RECEIVING PREOPERATIVE CHEMORADIOTHERAPY

PURPOSEnTo analyze the clinical outcomes and devise a prognostic model for patients with operable esophageal carcinoma who underwent preoperative chemoradiotherapy (CRT).nnnMETHODS AND MATERIALSnA total of 269 patients were enrolled into three clinical trials assessing preoperative CRT at our institution. We assessed the significance of the pretreatment and treatment factors with regard to tumor recurrence and long-term survival and used recursive partitioning analysis to create a decision tree.nnnRESULTSnAt a median follow-up of 31 months for the surviving patients, the median overall survival of all 180 patients in this study was 31.8 months, and the 5-year overall survival rate was 33.9%. The median event-free survival was 24.1 months, and the 5-year event-free survival rate was 29.3%. Of the 180 patients, 129 (71.7%) also underwent esophagectomy, and the perioperative mortality rate was 7.8%. A pathologic complete response was achieved by 58 patients (45%). The 5-year overall survival rate was 57.1% for patients who attained a pathologic complete response and 22.4% for those with gross residual disease (p = 0.0008). Recursive partitioning analysis showed that female patients who achieved a clinical response and underwent esophagectomy had the most favorable prognosis (p <0.0001). Among the patients who underwent esophagectomy, the group with good performance status, clinical Stage II, and a major pathologic response to CRT had the most favorable prognosis (p = 0.0002).nnnCONCLUSIONnAlthough preoperative CRT was generally effective and well-tolerated, an individualized approach is necessary to improve outcomes. Strategies to increase the response and reduce treatment failure should be investigated.

INITIAL STAGE AFFECTS SURVIVAL EVEN AFTER COMPLETE PATHOLOGIC REMISSION IS ACHIEVED IN LOCALLY ADVANCED ESOPHAGEAL CANCER: ANALYSIS OF 70 PATIENTS WITH PATHOLOGIC MAJOR RESPONSE AFTER PREOPERATIVE CHEMORADIOTHERAPY

PURPOSEnTo analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT).nnnMATERIALS AND METHODSnOutcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT.nnnRESULTSnAt a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008).nnnCONCLUSIONSnEven though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

Randomized Phase 2 Trial of S1 and Oxaliplatin-Based Chemoradiotherapy With or Without Induction Chemotherapy for Esophageal Cancer

PURPOSEnTo assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer.nnnPATIENTS AND METHODSnPatients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate.nnnRESULTSnA total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery.nnnCONCLUSIONSnCombination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.

Risk factor analysis for postoperative acute respiratory distress syndrome and early mortality after pneumonectomy: The predictive value of preoperative lung perfusion distribution

OBJECTIVESnThis study aims to establish the preoperative risk factors in the development of acute respiratory distress syndrome (ARDS) and early mortality after pneumonectomy for lung cancer and to examine the influence of reduced pulmonary perfusion on outcomes.nnnMETHODSnBetween 1994 and 2009, of 425 patients who underwent simple pneumonectomy for primary lung cancer, 164 who were preoperatively evaluated with lung perfusion scanning formed the population of this study.nnnRESULTSnOf 30 (18.3%) patients who had major pulmonary complications, 17 (10.4%) progressed to ARDS, 15 of whom subsequently died. On multivariable logistic regression analyses, lower predicted postoperative forced expiratory volume in 1 second (ppo-FEV(1); relative risk of 0.93 [P = .020] for ARDS and 0.94 [P = .027] for mortality) and greater perfusion fraction of resected lung (relative risk of 1.10 [P = .003] for ARDS and 1.09 [P = .002] for mortality) were found to be independent factors associated with ARDS and early mortality. With a cut-off value of 35% for perfusion fraction of resected lung, patients with a perfusion fraction of greater than 35% had a greater incidence of ARDS (17.3% vs 3.3%, P = .005) and early mortality (19.8% vs 6.0%, P = .010) than those with a perfusion fraction of 35% or less.nnnCONCLUSIONSnPatients with a low ppo-FEV(1), a high perfusion fraction of resected lung, or both had a higher incidence of ARDS and early mortality after pneumonectomy. Therefore, although the ppo-FEV(1) appears to be within an acceptable limit for pneumonectomy, much attention should be given to patients with a high perfusion fraction of resected lung.

Surgical Outcomes in Small Cell Lung Cancer

Background The experience of a single-institution regarding surgery for small cell lung cancer (SCLC) was reviewed to evaluate the surgical outcomes and prognoses. Materials and Methods From July 1990 to December 2009, thirty-four patients (28 male) underwent major pulmonary resection and lymph node dissection for SCLC. Lobectomy was performed in 24 patients, pneumonectomy in eight, bilobectomy in one, and segmentectomy in one. Surgical complications, mortality, the disease-free survival (DFS) rate, and the overall survival rate were analyzed retrospectively. Results The median follow-up period was 26 months (range, 4 to 241 months), and there was one surgical mortality (2.9%). Six patients (17.6%) experienced recurrence, all of which were systemic. Eight patients died during follow-up; four died of disease progression and the other four died of pneumonia or of another non-cancerous cause. The three-year DFS rate was 79.2±2.6% and the overall survival rate was 66.4±10.5%. Recurrence or death was significantly prevalent in the patients with lymph node metastasis (p=0.001) as well as in those who did not undergo adjuvant chemotherapy (p=0.008). The three-year survival rate was significantly greater in the patients with pathologic stage I/II cancer than in those with stage III cancer (84% vs. 13%, p=0.001). Conclusion Major pulmonary resection for small cell lung cancer is feasible in selected patients. Patients with pathologic stage I or II disease showed an excellent survival rate after surgery and adjuvant treatment. Prospective randomized studies will be needed to define the role of surgery in early-stage small cell lung cancer.

18 F-FDG PET/CT is Useful for Pretreatment Assessment of the Histopathologic Type of Thymic Epithelial Tumors

PurposeThis study was performed to assess the usefulness of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) or PET/computed tomography (CT) for distinguishing thymic epithelial tumors according to World Health Organization (WHO) classifications.MethodsWe analyzed a total of 45 patients (range, 29–75xa0years of age; mean, 55xa0years) with pathologically confirmed thymic epithelial tumors who underwent pretreatment 18F-FDG PET or PET/CT between November 2003 and October 2009. The size, visual grading of uptake value, peak standardized uptake value (SUVpeak), uptake pattern, and contour of each tumor, and associated findings on PET or PET/CT, were analyzed relative to the three simplified WHO subgroups: less-invasive thymomas (types A and AB), more-invasive thymomas (types B1, B2, and B3) and thymic carcinomas. We statistically assessed the relationship of 18F-FDG PET or PET/CT findings with these simplified subgroups.ResultsOf the 45 patients, ten had less-invasive thymomas, 23 had more-invasive thymomas, and 12 had thymic carcinomas. The SUVpeak of the less- and more-invasive thymomas were significantly lower than those of thymic carcinomas (pu2009<u20090.000), but there was no difference in SUVpeak between less- and more-invasive thymomas. The visual grading scale (pu2009<u20090.000), uptake pattern (pu2009=u20090.001), and contour (pu2009<u20090.000) of the tumors differed significantly among the three simplified subgroups.ConclusionThe image findings of 18F-FDG PET or PET/CT differed significantly by histologic subgroups. Pre-treatment evaluation with 18F-FDG PET or PET/CT might be helpful in differentiating subgroups of thymic epithelial tumors.

The Feasibility of 18 F-Fluorothymidine PET for Prediction of Tumor Response after Induction Chemotherapy Followed by Chemoradiotherapy with S-1/Oxaliplatin in Patients with Resectable Esophageal Cancer

PurposeThe aim of this study was to determine whether 18F-fluorothymidine (FLT) PET is feasible for the early prediction of tumor response to induction chemotherapy followed by concurrent chemoradiotherapy in patients with esophageal cancer.MethodsThis study was prospectively performed as a collateral study of “randomized phase II study of preoperative concurrent chemoradiotherapy with or without induction chemotherapy with S-1/oxaliplatin in patients with resectable esophageal cancer”. 18F-FLT positron emission tomography (PET) images were obtained before and after two cycles of induction chemotherapy, and the percent change of maximum standardized uptake value (SUVmax) was calculated. All patients underwent esophagography, gastrofiberoscopy, endoscopic ultrasonography (EUS), computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) PET at baseline and 3–4xa0weeks after completion of concurrent chemoradiotherapy. Final tumor response was determined by both clinical and pathologic tumor responses after surgery.ResultsThe 13 patients for induction chemotherapy group were enrolled until interim analysis. In a primary tumor visual analysis, the tumor detection rates of baseline 18F-FLT and 18F-FDG PET were 85% and 100%, respectively. The tumor uptakes on 18F-FLT PET were lower than those of 18F-FDG PET. Among nine patients who completed second 18F-FLT PET, eight patients were responders and one patient was a non-responder in the assessment of final tumor response. The percent change of SUVmax in responders ranged from 41.2% to 79.2% (median 57.1%), whereas it was 10.2% in one non-responder.ConclusionThe percent change of tumor uptake in 18F-FLT PET after induction chemotherapy might be feasible for early prediction of tumor response after induction chemotherapy and concurrent chemoradiotherapy in patients with esophageal cancer.

Temporary stent placement with concurrent chemoradiation therapy in patients with unresectable oesophageal carcinoma: is there an optimal time for stent removal?

AbstractObjectiveTo investigate the influence of the timing of stent removal on the outcome of temporary stent placement with concurrent chemoradiation therapy in patients with unresectable oesophageal carcinoma.MethodsRetrospective analysis was performed on 52 patients undergoing temporary stent placement. Stents were electively removed within 4xa0weeks in 15 patients (group A), 4–6xa0weeks in 17 patients (group B) and after 6xa0weeks in 20 patients (group C). Recurrent symptoms after stent removal, dysphagia score and overall survival periods were compared among the groups.ResultsStent placement and removal were technically successful in all patients. The dysphagia score was significantly improved in all groups (Pu2009<u20090.001). In 19 patients (36xa0%), recurrent symptoms occurred 15–441xa0days after stent removal. In group A, recurrent obstruction was significantly higher than in groups B (Pu2009=u20090.049) and C (Pu2009=u20090.019). Incidence of oesophago-respiratory fistulas in group C was significantly higher than in group A (Pu2009=u20090.027). There was no significant difference in survival periods.ConclusionThe ideal time for stent removal likely falls between 4 and 6xa0weeks following the start of palliative CCRT allowing the temporary stents to relieve dysphagia effectively in patients with unresectable oesophageal carcinoma.Key Points• Stents are usually required for unresectable oesophageal carcinoman • Optimal timing of stent removal is 4–6xa0weeks after starting palliative CCRT.n • Early stent removal (<4xa0weeks) is associated with higher recurrence rates.n • Delayed stent removal (>6xa0weeks) is associated with greater oesophago-respiratory fistula development.