Gastrointestinal Stromal Tumor of the Small Intestine: A Clinicopathologic Study of 70 Cases in the Postimatinib Era

Background  The small intestine, after the stomach, is the second most common primary site for gastrointestinal stromal tumors (GISTs). This study aimed to identify clinicopathologic prognostic factors of tumor recurrence and survival and to analyze the influence of imatinib and sunitinib for small-intestine GISTs. Methods  We reviewed the surgical experience of patients with small-intestine GISTs at National Taiwan University Hospital from January 1995 to March 2007. We analyzed the perioperative clinicopathologic data and treatment course. Results  Seventy patients were included. The tumor was local in 43 patients, advanced in 21 patients, and 6 had metastasis. The median size of the tumor was 6.5 cm. Forty-four patients had a mitotic rate of less than 5/50 high-power field. The 1-year and 5-year disease-free survival rates were 85 and 66.7%, respectively, while the 1-year and 5-year overall survival rates were 98.5 and 86.6%, respectively. There were 19 patients with recurrent disease and 6 patients died of intestinal GISTs. The response rate of imatinib and sunitinib were 73.3 and 60%, respectively. According to multivariate analysis for disease recurrence, only invasion status, tumor size, and mitotic rate are significant (P = 0.007, 0.035, 0.007 respectively). They are also associated with poor survival (P ≤ 0.001, 0.006, 0.002, respectively). Conclusions  The invasion status, size, and mitotic rate of tumor involve higher risk of recurrence and poor survival in small-intestine GISTs. The patients with recurrent small-intestine GISTs may have a lower mortality rate after using imatinib and sunitinib.     

Risk Criteria and Prognostic Factors for Predicting Recurrences After Resection of Primary Gastrointestinal Stromal Tumor

Background The introduction of adjuvant imatinib in gastrointestinal stromal tumors (GISTs) raised debate over the accuracy of National Institutes of Health risk criteria and the significance of other prognostic factors in GIST. Methods Tumor aggressiveness and other clinicopathological factors influencing disease-free survival (DFS) were assessed in 335 patients with primary resectable CD117-immunopositive GISTs (median follow-up, 31 months after primary tumor resection) from a prospectively collected tumor registry. Results Overall median DFS was 37 months, and estimated 5-year DFS was 37.8 %. In univariate analysis, high or intermediate risk group (P < .000001), mitotic index >5/50 high-power field (P < .00001), primary tumor size >5 cm (P < .00001), nongastric primary location (P = .0001), male sex (P = .01), R1 resection/tumor rupture (P = .0003), and epithelioid cell or mixed cell pathological subtype (P = .05) negatively affected DFS. In multivariate analysis, statistically significant factors negatively influencing DFS for model 1 were mitotic index >5/50 high-power field (P = .004), primary tumor size >5 cm (P = .001), male sex (P = .003), R1 resection/tumor rupture (P = .04), and nongastric primary tumor location (P = .02), and for model 2 were high/intermediate risk primary tumor (P < .0001 and P = .008, respectively), male sex (P = .007), resection R1/tumor rupture (P = .01), and nongastric primary tumor location (P = .02). Five-year DFS for high, intermediate, and low/very low risk group was 20%, 54%, and 96%, respectively. Conclusions The risk criteria for assessing the natural course of primary GISTs were validated, but additional independent prognostic factors—primary tumor location and sex—were also identified.     

Outcome following surgical therapy for gastrointestinal stromal tumors

We have pursued an approach of complete resection for patients with gastrointestinal stromal tumors (GISTs), including multivisceral resection, for patients with disease involving adjacent organs. We have also extended the limits of resection to include patients with metastatic disease who were treated with imatinib mesylate. The aim of this study is to report the outcomes and prognostic factors associated with this clinical approach. Study subjects were identified using the pathology database at our institution; for inclusion in the study group, patients must have undergone surgical resection for a KIT-positive gastrointestinal stromal tumor between January 1992 and March 2004. We calculated survival by using the Kaplan-Meier method. Univariate and multivariate analysis was performed using log-rank analysis and the Cox proportional hazards model. Thirty-four patients met the study criteria. Fifty-nine percent of patients had GISTs of gastric origin, 20.6% had duodenal GISTs, and the remainder was comprised of a variety of other sites. Twenty-two (64.7%) patients underwent single-organ resection, and 12 patients (35.3%) underwent multivisceral resection. Estimated actuarial survival at 5 years was 65.2%. Seven patients (five patients with metastases, one patient with locally advanced disease, and one patient with organ-confined disease) received imatinib mesylate. Independent predictors of poor survival included incomplete resection, metastatic disease at presentation, and high mitotic index. Mitotic index and the presence of metastases remain the primary predictors of postoperative survival. Complete surgical resection, even if multivisceral resection is required, is associated with improved survival. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–19, 2005 (poster presentation).     

Prognosis and Results After Resection of Very Large (≥10 cm) Hepatocellular Carcinoma

Introduction Few potentially curative treatment options exist besides resection for patients with very large (≥10 cm) hepatocellular carcinoma (HCC). We sought to examine the outcomes and risk factors for recurrence after resection of ≥10 cm HCC. Methods Perioperative and long-term outcomes were examined for 189 consecutive patients from 1993 to 2004 who underwent potentially curative resection of HCC ≥10 cm (n = 24; 13%) vs. those with HCC <10 cm (n = 165; 87%). Disease-free survival (DFS) and overall survival (OS) were determined by Kaplan–Meier analysis and patient, tumor, and treatment characteristics were compared using univariate and multivariate analysis. Results Median follow-up was 34 months. Tumors ≥10 cm were more likely to be symptomatic, of poorer grade, and have vascular invasion (p < 0.05). Twelve patients (50%) underwent an extended resection of more than four hepatic segments or resection of adjacent organs for oncologic clearance (diaphragm-2, inferior vena cava (IVC)-2, median sternotomy-1). Postoperative complications were more common after resection of >10 cm HCC (12/24, 50% vs. 35/165, 21%; p = 0.04). Median DFS was significantly shorter in patients with large HCC (≥10 cm) group compared to patients with smaller HCC (8.4 vs. 38 months; p = 0.001), but overall survival was not different between the two groups (5-year survival 54% vs. 53%; p = 0.43). Seventeen patients (71%) with very large HCC developed recurrences (12 intrahepatic, five systemic); eight of these patients (47%) underwent additional therapy (resection-4, TACE-3, RFA-1). Pathological positive margins and vascular invasion were significant determinants of DFS in tumors ≥10 cm (p < 0.05), but only vascular invasion was an independent risk factor for recurrence after multivariate analysis (HR 0.17; 95% CI: 0.04–0.8). Median OS after recurrence was 24 months. Conclusion Surgical resection is the optimal therapy for very large (≥10 cm) HCC. Although recurrences are common after resection of these tumors, overall survival was not significantly different from patients after resection of smaller HCC in this series. Presented at the 2006 American Hepato-Pancreatico-Biliary Congress, Miami, FL, March 9–12, 2006.     

Surgical Therapy for Gastrointestinal Stromal Tumours of the Upper Gastrointestinal Tract

Aim  This study aimed to examine clinicopathological features and outcomes after primary resection of gastrointestinal stromal tumours (GIST) of the upper gastrointestinal tract Method  Fifty consecutive patients were identified as having a mesenchymal tumour of the upper gastrointestinal tract resected at our institution, of which 47 were GISTs. The influence of clinicopathological variables on disease-free survival was evaluated using Kaplan–Meier estimates and Cox hazard model. Results  The median age was 62.8 (21.3–94.7). The commonest presenting symptoms were anaemia (43%) and pain (34%). Tumours were located in the stomach (64%), small bowel (34%) and oesophagus (2%). Median follow-up was 20.4 (2–106) months. Fletcher low/intermediate-risk tumours had a significantly better (p = 0.0008) 2- and 5-year actuarial survival of 100% compared with 88% and 58% for high-risk group. Recurrence-free survival at 2 and 5 years was 100% for low/intermediate-risk group compared with 68% and 45% for the high-risk group (p = 0.0008). Univariate analysis of predictors of recurrence identified male sex, high mitotic rate and tumour size as significant. Multivariate analysis showed high mitotic rate as the only poor prognosticator (Hazard ratio = 16.7, p = 0.02). Conclusion  Surgical excision of low- and intermediate-grade GIST has an excellent prognosis. Surgery remains the mainstay of treatments, and high-grade tumours carry a significantly worse prognosis. High mitotic rates are an independent poor prognosticator. Presentation: This work has not been presentedDisclaimers: The authors indicated no potential conflicts of interest Grant Support: None Note all graphs produced using StatView statistical software and further edited with Adobe Photoshop.     

Neoadjuvant Imatinib in Locally Advanced Gastrointestinal Stromal Tumors (GIST): The EORTC STBSG Experience

Background

Preoperative imatinib therapy of locally advanced GIST may facilitate resection and decrease morbidity of the procedure.

Methods

We have pooled databases from 10 EORTC STBSG sarcoma centers and analyzed disease-free survival (DFS) and disease-specific survival (DSS) in 161 patients with locally advanced, nonmetastatic GISTs who received neoadjuvant imatinib. OS was calculated from start of imatinib therapy for locally advanced disease until death or last follow-up (FU) after resection of the GIST. DFS was calculated from date of resection to date of disease recurrence or last FU. Median FU time was 46 months.

Results

The primary tumor was located in the stomach (55 %), followed by rectum (20 %), duodenum (10 %), ileum/jejunum/other (11 %), and esophagus (3 %). The tumor resection after preoperative imatinib (median time on therapy, 40 weeks) was R0 in 83 %. Only two patients have demonstrated disease progression during neoadjuvant therapy. Five-year DSS/DFS rates were 95/65 %, respectively, median OS was 104 months, and median DFS was not reached. There were 56 % of patients who continued imatinib after resection. Thirty-seven GIST recurrences were diagnosed (only 5 local relapses). The most common mutations affected exon 11 KIT (65 %). Poorer DFS was related to primary tumor location in small bowel and lack of postoperative therapy with imatinib.

Conclusions

Our analysis comprising the largest group of GIST patients treated with neoadjuvant imatinib in routine practice indicates excellent long-term results of combined therapy in locally advanced GISTs.     

Predicting the Antitumor Effects of STI571 by Analysis of c-kit Gene Mutations in Gastrointestinal Stromal Tumors of the Stomach: Report of a Case

We report a case of a large gastrointestinal stromal tumor (GIST), greater than 5 cm in diameter, in the stomach. Microscopically, high levels of mitosis were observed, indicative of a high-grade malignancy. We analyzed the c-kit gene mutations by a replication competent retrovirus assay and DNA sequencing, which revealed a c-kit mutation in exon 11. Liver metastases were detected 7 months after surgery. Patients with an exon 11 mutation of the c-kit gene are reported to have a high response to STI571 (imatinib mesylate, Glivec). Accordingly, a 1-month course of STI571 treatment clearly changed the characterization of the metastatic tumors radiographically. Thus, it may be important to analyze c-kit gene mutations in patients presenting with GISTs to predict the effectiveness of STI571 in suppressing GISTs, especially tumors thought to have malignant potential.     

Does Microvascular Invasion Affect Outcomes After Liver Transplantation for HCC? A Histopathological Analysis of 155 Consecutive Explants

Macroscopic vascular invasion (macroVI) is associated with poor outcomes after liver transplantation (LT) for hepatocellular carcinoma (HCC). Whether microvascular invasion (microVI) is associated with the same adverse prognosis is unclear. One hundred and fifty-five consecutive patients with confirmed HCC after LT from March 1991 to 2004 at our institution were reviewed. Patients had to satisfy Milan criteria to be accepted for LT. They were followed with surveillance images every 3 months while on the waiting list. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan–Meier analysis. Demographic, tumor, and histopathologic characteristics were tested for their prognostic significance. Median follow-up after LT was 30 months. Overall graft survival rates were 87, 74, and 65% at 1, 3, and 5 years, respectively. All recurrences (22/155, 14%) developed within 4 years after LT with an overall 5-year DFS of 79%. Vascular invasion, either microVI or macroVI, was more likely in patients with multicentric HCC (n ≥ 3, p < 0.001) and larger tumor size >4 cm (p = 0.04). Tumor size >5 cm (p = 0.04), advanced pathological TMN stage (p = 0.007), microVI (p = 0.001), and macroVI (p < 0.001) predicted poor tumor-free survival on univariate analysis, but only macroVI was significant in multivariate analysis (hazard ratio 54.2, 95% confidence interval 11, 266). Furthermore, only macroVI was a significant predictor of mortality after LT (p = 0.01). Macrovascular invasion is strongly associated with high rates of recurrence and diminished survival after LT whereas microVI is not an independent risk factor. Presented at the 2005 American Transplant Congress, Seattle, WA, May 20–23, 2005.     

Prognostic Factors and Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy for Pancreatic Adenocarcinoma

Background  The aim of this study was to determine prognostic factors for survival after resection of pancreatic adenocarcinoma (PC) and to compare outcomes after surgery alone versus surgery plus adjuvant therapy. Methods  We performed a retrospective review of 219 patients who underwent pancreaticoduodenectomy for PC with curative intent between 1995 and 2007. Data were collected prospectively. Postoperative adjuvant chemoradiation therapy (CRT) consisted of fluorouracil or gemcitabine-based chemotherapy; the median radiation dose was 45 Gy. Results  The 3- and 5-year overall survival (OS) rates were 24.3% and 14.2%, respectively. Median OS was 14.0 months [95% confidence interval (CI), 12–16 months]. Patients with metastatic lymph nodes experienced improved median survival (16 vs 10 months; P < 0.001) and 3-year OS (3-year OS 28% vs 8%) after adjuvant CRT compared with those who had no CRT. Patients who underwent non-curative resection had the same effect (median OS, 13 vs 8 months; P = 0.037). Lymph node metastasis and non-curative resection showed no significance on multivariate analysis. Poor differentiation [risk ratio (RR) = 2.10; P < 0.001] and tumor size >3 cm (RR = 1.57; P = 0.018) were found to be adverse prognostic factors; adjuvant CRT had borderline significance (RR = 0.70; P = 0.087). Conclusions  Adjuvant CRT benefited a subset of patients with resected PC, particularly those with lymph node metastasis and those undergoing non-curative resection. Multivariate analysis demonstrated that patients with tumors larger than 3 cm and poor differentiation had poor prognosis.     

A Single-Institution Experience with Eight CD117-Positive Primary Extragastrointestinal Stromal Tumors: Critical Appraisal and a Comparison with Their Gastrointestinal Counterparts

Introduction  Gastrointestinal stromal tumors (GISTs) arising from outside the gut wall also termed extragastrointestinal stromal tumors (EGISTs) are reported to be rare. Presently, their pathogenesis remains controversial, and recently, it has been proposed that EGISTs may be the result of extensive extramural growth of GISTs which lose contact with the gut wall. This study presents a single-institution experience with eight EGISTs and compares their clinicopathological features with mural GISTs in order to determine further insight to their possible origin. Methods  Between 1997 and 2008, 156 patients with pathologically proven CD117-positive primary GISTs were retrospectively reviewed. Eight tumors were identified as EGISTs, 104 were gastric GISTs, and 44 were small-bowel GISTs. Mural GISTs were classified as extramural or intra/transmural according to their gross pattern of growth. Results  There were five male and three female patients with a median age of 58 years (range, 42–81 years). All patients were symptomatic, and the tumors were located in the greater omentum (n = 2), lesser sac (n = 2), lesser omentum, retroperitoneum, small-bowel mesentery, and pancreas. The median tumor size was 140 mm (range, 55 to 220 mm). Seven of eight EGISTs were found to be in close association to the adjacent gut wall. Pathological examination demonstrated that two tumors demonstrated focal involvement of the muscularis propria of the adjacent gut wall. Four tumors demonstrated tumor abutting or adherent to the serosa but no muscle involvement and one tumor was separated from the serosa. Comparison between the clinicopathological features of EGISTs with extramural GISTs and intra/transmural GISTs demonstrated that EGISTs were significantly larger [140 range (55–220) mm vs 80 (5–260) mm vs 50 (15–190) mm, P = 0.049, P < 0.001 respectively]. Conclusion  The occurrence of true EGISTs is rare. Most cases demonstrate some form of communication or contact with the gut wall, and EGISTs are significantly larger than extramural or intra/transmural GIST. These observations suggest that most, if not all, cases of EGISTs are likely to represent mural GISTs with extensive extramural growth with eventual loss of contact with the muscle layer of the gut.     

Surgical Resection Versus Radiofrequency Ablation in the Treatment of Small Unifocal Hepatocellular Carcinoma

Background  Hepatocellular carcinoma (HCC) has a high worldwide prevalence and mortality. While surgical resection and transplantation offers curative potential, donor availability and patient liver status and comorbidities may disallow either. Interventional radiological techniques such as radiofrequency ablation (RFA) may offer acceptable overall and disease-free survival rates. Materials and Methods  Sixty-eight cirrhotic patients matched for age, sex, tumor size, and Child–Pugh grade with small (1–5 cm) unifocal HCC were studied retrospectively to find determinants of overall and disease-free survival in those treated with surgical resection and RFA between 1991 and 2003. Results  Multivariate analysis using Cox proportional regression modeling showed that overall survival was related to tumor recurrence (p = 0.010), tumor diameter (p = 0.002), and treatment modality (p = 0.014); overall p = 0.008. Recurrence was independently related to the use of RFA over surgery (p = 0.023) on multivariate analysis; overall p = 0.034. Conclusion  Surgical resection offers longer disease-free survival and potentially longer overall survival than RFA in patients with small unifocal HCC.     

Imatinib mesylate inhibits osteoclastogenesis and joint destruction in rats with collagen-induced arthritis (CIA)

Macrophage colony-stimulating factor (M-CSF) is a key factor for osteoclastogenesis at the bone–pannus interface in patients with rheumatoid arthritis as well as a receptor activator of NF-κB ligand (RANKL). Imatinib mesylate inhibits the phosphorylation of c-fms, a receptor for M-CSF. The present study investigates the effect of imatinib mesylate on joint destruction in rats with collagen-induced arthritis (CIA) and on osteoclastogenesis in vitro. Imatinib mesylate (50 or 150 mg/kg), dexamethasone, or vehicle was administered daily to CIA rats for 4 weeks from the onset of arthritis. Hind-paw swelling and body weight were measured weekly. At weeks 2 and 4, the metatarsophalangeal (MTP) joints and the ankle and subtalar joints were radiographically and histologically assessed. The effect of imatinib mesylate on osteoclast formation from rat bone marrow cells with M-CSF and soluble RANKL (sRANKL) in vitro was also examined. Radiographic assessment showed that 150 mg/kg imatinib mesylate suppressed the destruction of the MTP and the ankle and subtalar joints at week 2, and MTP joint destruction at week 4 in CIA rats, although hind-paw swelling was not suppressed. The number of TRAP-positive cells at the bone–pannus interface was significantly reduced in the group administered with 150 mg/kg imatinib mesylate compared with that given vehicle at week 4. Imatinib mesylate dose-dependently inhibited the proliferation of M-CSF-dependent osteoclast precursor cells in vitro as well as osteoclast formation induced by M-CSF and sRANKL. These findings suggest that imatinib mesylate could prevent joint destruction in patients with rheumatoid arthritis.     

围手术期伊马替尼治疗在可切除原发中高危胃肠间质瘤患者中的应用

目的探讨围手术期应用伊马替尼对可切除原发中高危胃肠间质瘤（GIST）患者凡切除率及预后的影响。方法回顾性分析2001年12月至2012年2月在北京大学肿瘤医院诊断为可切除中高危GIST、并进行手术切除加围手术期伊马替尼治疗的48例患者的临床资料．根据伊马替尼治疗方式分为新辅助治疗组（术前加术后伊马替尼治疗,15例）及辅助治疗组（术后伊马替尼治疗,33例）。比较两组患者R。切除率、术后并发症发生率、无病生存率及总体生存率。结果新辅助治疗组的肿瘤最大径（11．2cm）和平均径（9．1em）均明显大于辅助治疗组（7．7cm和6．2cm,P．0．005和P=0．014）。新辅助治疗组术前治疗疾病控制率为93．3％（14／15）。新辅助治疗组和辅助治疗组患者R0切除率分别为86．7％（13／15）和84．8％（28／33）（P=1．000）。手术并发症发生率分别为13．3％（2／15）和9．1％（3／33）（P=-0．642）。两组患者术后3年无病生存率分别为55％和41％,5年总体生存率分别为83％和75％,差异均无统计学意义（P=0．935,P=0．766）。结论对于可切除的原发中高危GIST,围手术期应用伊马替尼的治疗模式具有潜在优势。     

Surgery for Gastrointestinal Stromal Tumors of the Stomach

Background  Gastrointestinal stromal tumors (GISTs) are the main mesenchymal neoplasms in the gastrointestinal tract. Tumor size, mitotic rate, and location correlate with potential malignancy and recurrence rate. Results of surgical treatment of gastric GIST are analyzed with emphasis on recurrence of disease after intermediate follow-up. Methods  From 1998 to 2006, a total of 63 patients (median age 62.1 ± 14.1) underwent gastric resection for GIST. Fifty-five patients (93.6%) returned for follow-up investigations, which included computed tomography in 45, gastroscopy in 32, and endosonography in 29. Positron emission tomography was done in five patients. Results  Mean tumor size was 5.3 ± 3.8 cm. Open atypical gastric resection was done in 32, distal gastric resection in five, and remnant gastrectomy in four patients. Laparoscopic gastric resection was initiated in 22 patients; the conversion rate was four of 22 (18.2%). Overall, R0 resection was reached in 61/63 patients (96.8%). According to the Fletcher criteria, 33 tumors (52.4%) were classified as intermediate or high risk GIST. Six patients (9.5%) died of unrelated causes before follow-up. After a median follow-up of 2.5 years, overall recurrence rate was 7.0% after R0 resection. Conclusion  Histologically proven complete resection is an effective treatment for gastric GIST. Laparoscopic procedures were carried out successfully in selected patients. Preliminary data were presented at the annual meeting of the European Association of Endoscopic Surgeons, Berlin 2006. No research grants funded this study.     

Resection Versus Laparoscopic Radiofrequency Thermal Ablation Of Solitary Colorectal Liver Metastasis

Purpose  There is scant data in the literature regarding radiofrequency thermal ablation (RFA) versus resection of colorectal liver metastases. The aim of this study is to compare the clinical profile and survival of patients with solitary colorectal liver metastasis undergoing resection versus laparoscopic RFA. Methods  Between 1996 and 2007, 158 patients underwent RFA (n = 68) and open liver resection (n = 90) of solitary liver metastasis from colorectal cancer. Patients were evaluated in a multidisciplinary fashion and allocated to a treatment type. Data were collected prospectively for the RFA patients and retrospectively for the resection patients. Results  Although the groups were matched for age, gender, chemotherapy exposure and tumor size, RFA patients tended to have a higher ASA score and presence of extra-hepatic disease (EHD) at the time of treatment. The main indication for referral to RFA included technical reasons (n = 25), patient comorbidities (n = 24), extra-hepatic disease (n = 10) and patient decision (n = 9). There were no peri-operative mortalities in either group. The complication rate was 2.9% (n = 2) for RFA and 31.1% (n = 28) for resection. The overall Kaplan–Meier median actuarial survival from the date of surgery was 24 months for RFA patients with EHD, 34 months for RFA patients without EHD and 57 months for resection patients (p < 0.0001). The 5-year actual survival was 30% for RFA patients and 40% for resection patients (p = 0.35). Conclusions  This study shows that, although patients in both groups had a solitary liver metastasis, other factors including medical comorbidities, technically challenging tumor locations and extra-hepatic disease were different, prompting selection of therapy. With a simultaneous ablation program, higher risk patients have been channeled to RFA, leaving a highly selected group of patients for resection with a very favorable survival. RFA still achieved long-term survival in patients who were otherwise not candidates for resection.     

Nodal Microinvolvement in Patients with Carcinoma of the Papilla of Vater Receiving No Adjuvant Chemotherapy

Background  To assess the prognostic significance of nodal microinvolvement in patients with carcinoma of the papilla of Vater. Methods  From 1993 to 2003 at the University Clinic Hamburg, 777 patients were operated upon pancreatic and periampullary carcinomas. The vast majority of patients were operated upon pancreatic ductal adenocarcinoma (n = 566, 73%), followed by carcinomas of the papilla of Vater (n = 112, 14%), pancreatic neuroendocrine carcinomas (n = 39, 5%), intraductal papillary mucinous neoplasms (n = 33, 4%), and distal bile duct carcinomas (n = 27, 3%). Fresh-frozen tissue sections from 169 lymph nodes (LNs) classified as tumor free by routine histopathology from 57 patients with R0 resected carcinoma of the papilla of Vater who had been spared from adjuvant chemotherapy were immunohistochemically (IHC) examined, using a sensitive IHC assay with the anti-epithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathology, 39 (63%) of the patients were staged as pT1/pT2, 21 (37%) as pT3/pT4, 30 (53%) as pN0, while 38 (67%) as G1/G2. Results  Of the 169 “tumor-free” LNs, 91 LNs (53.8%) contained Ber-EP4-positive tumor cells. These 91 LNs were from 40 (70%) patients. The mean overall survival in patients without nodal microinvolvement of 35.8 months (median—not yet reached) was significantly longer than that in patients with nodal microinvolvement (mean 16.6; median 13; p = 0.019). Multivariate Cox regression analysis for overall survival revealed that grading was the most significant independent prognostic factor (p = 0.001), followed by nodal microinvolvement (p = 0.013). Conclusions  The influence of occult tumor cell dissemination in LNs of patients with histologically proven carcinoma of the papilla of Vater supports the need for further tumor staging through immunohistochemistry.     

Borrmann Type IV: An Independent Prognostic Factor for Survival in Gastric Cancer

Background  Borrmann type IV gastric cancer has a poorer prognosis than other gastric carcinomas. This study compared the clinicopathological features of Borrmann type IV gastric cancer with those of other types of cancer and examined the significance of a Borrmann type IV carcinoma as a prognostic factor after gastrectomy. Methods  The clinicopathological features, tumor–node–metastasis (TNM) stage, and survival rates of 4,191 advanced gastric cancer patients, who had undergone a gastrectomy at the Samsung Medical Center between 1995 and 2005, were reviewed. Results  Borrmann type IV gastric cancer was found to be associated with more advanced and unfavorable clinicopathological features at diagnosis than the other cancers. The 5-year survival rate of the patients with Borrmann type IV cancer was 27.6%. In contrast, the 5-year survival rate of patients with the other types of cancer was 61.2%. The 5-year survival rate for each stage of Borrmann type IV gastric cancer and the other type gastric cancer was 61.0% and 88.8% for stage Ib (P < 0.001), 49.8% and 76.1% for stage II (P < 0.001), 36.4% and 55.1% for stage IIIa (P < 0.001), 15.2% and 38.5% for stage IIIb (P = 0.001), and 10.2% and 20.1% for stage IV (P = 0.008), respectively. Multivariate analyses revealed a Borrmann type IV carcinoma, the surgical extent, curability, tumor stage, including T, N, and M status, and adjuvant therapy to be independent prognostic factors for survival. Conclusion  A Borrmann type IV carcinoma has unique clinicopathological features compared with other types of gastric carcinomas and is an important independent prognostic factor.     

Pancreatic Adenocarcinoma: The Actual 5-Year Survivors

Background Most reports of patients undergoing resection for pancreatic adenocarcinoma report estimated (actuarial) 5-year survival rates. Actual 5-year survival is rarely described, and factors associated with long-term survival are not well described. Methods Review of a prospectively maintained database identified 618 patients who underwent resection for pancreatic adenocarcinoma between 1/1983–1/2001. Patient, tumor, and treatment-related variables were assessed for their association with 5-year survival. Results There were 75 patients who survived >5 years after resection (75 out of 618, 12%), and 18 patients who survived >10 years (18 out of 352, 5%). Patient age, gender, and tumor location were not associated with 5-year survival, whereas early American Joint Committee on Cancer (AJCC) stage (p < 0.001) and negative margins (p = 0.001) were associated with 5-year survival. Patients with stage IA disease had an actual 5 year survival of 26%. Median follow-up was 108 months. Recurrent disease developed in 38 patients (51%) and all died from disease. Adjuvant therapy was received by 21% (16 out of 75), and tumors were moderately differentiated in 58% (42 out of 75) and had a median size of 2.8 cm (0.8–13 cm). Conclusions Actual 5-year survival after resection of pancreatic adenocarcinoma was 12%. AJCC stage and negative margins were the only significant predictors of long-term survival. Early detection and intervention for patients with pancreatic cancer is crucial. Oral presentation at AHPBA 2007 Las Vegas.     

Gastrointestinal Stromal Tumor of the Rectum: An Analysis of Seven Cases

Purpose Gastrointestinal stromal tumors (GISTs) rarely originate in the rectum. We investigated the clinicopathologic characteristics of rectal GISTs. Methods We analyzed the medical records of seven patients who underwent surgery for GIST of the rectum between 1998 and 2003. Results There were two men and five women with a median age of 55 years (range, 41–72 years) at the time of diagnosis. The median follow-up period was 23 months (range, 7–75 months). The chief symptoms were hematochezia, constipation, and anal pain. All patients underwent curative resection; in the form of abdominoperineal resection in five patients, transanal excision in one, and Hartmann's operation with prostatectomy in one. The median tumor size was 6.6 cm (range, 1–12 cm). Four patients received adjuvant radiation therapy. Local recurrence developed in two patients; 54 months and 23 months after surgery, respectively. Conclusion The common symptoms of rectal GIST were the same as those of other rectal tumors. Curative surgical resection should be done, but further studies are necessary to investigate better adjuvant treatment strategies for patients with rectal GISTs     

Chordomas of the skull base and cervical spine: clinical outcomes associated with a multimodal surgical resection combined with proton-beam radiation in 40 patients

Previous studies of chordoma have focused on either surgery, radiotherapy, or particular tumor locations. This paper reviewed the outcomes of surgery and proton radiotherapy with various tumor locations. Between 2001 and 2008, 40 patients with chordomas of the skull base and cervical spine had surgery at our hospital. Most patients received proton therapy. Their clinical course was reviewed. Age, sex, tumor location, timing of surgery, extent of resection, and chondroid appearance were evaluated in regard to the progression-free survival (PFS) and overall survival (OS). The primary surgery (PS) group was analyzed independently. The extensive resection rate was 42.5%. Permanent neurological morbidity was seen in 3.8%. Radiotherapy was performed in 75% and the mean dose was 68.9 cobalt gray equivalents. The median follow-up was 56.5 months. The 5-year PFS and OS rates were 70% and 83.4%, respectively. Metastasis was seen in 12.5%. The tumor location at the cranio-cervical junction (CCJ) was associated with a lower PFS (P = 0.007). In the PS group, a younger age and the CCJ location were related to a lower PFS (P = 0.008 and P < 0.001, respectively). The CCJ location was also related to a lower OS (P = 0.043) and it was more common in young patients (P = 0.002). Among the survivors, the median of the last Karnofsky Performance Scale score was 80 with 25.7% of patients experiencing an increase and 11.4% experiencing a decrease. Multimodal surgery and proton therapy thus improved the chordoma treatment. The CCJ location and a younger age are risks for disease progression.