bluuebunny/crossref_metadata_2025 huggingface dataset:
Lobular neoplasia on core biopsy: Is excision always indicated?
Authors: Makarewich C. A. , Rosenkranz K. M.
Published: February 2017

75

Background: Lobular neoplasia (LN) is a continuum of rare, noninvasive lesions of the breast including lobular carcinoma in situ and atypical lobular hyperplasia. Current management is controversial and often includes excisional biopsy in women diagnosed with LN on percutaneous core biopsy (PCB) to exclude an occult malignancy. This strategy is based on retrospective data in women undergoing selective excisions. We performed routine excision of all lesions diagnosed as LN in our institution in order to ascertain a more accurate assessment of pathologic upgrade.

Methods: Retrospective review of all prospectively collected cases of LN treated in a single institution from 2007-2010. Excisional biopsies were performed in all cases of LN excepting one (patient declined). Histologic findings of excisional biopsies were reviewed to assess the rate of pathologic upgrade.

Results: Of the 2,289 PCBs performed during the study period, LN was found in 23 cases (1.0%). Twenty two (0.96%) cases proceeded to excisional biopsy. On final pathology, malignancy was found in 4 patients (18%). Two of 22 (9%) women were upgraded to ductal carcinoma in situ (DCIS) (both intermediate grade with foci of <1mm and 4mm) and 2/22 (9%) women were diagnosed with invasive lobular carcinoma.

Conclusions: While 18% of women in our series had upgraded pathology at the time of excisional biopsy, we support selective rather than routine excisional biopsy. One of the invasive diagnoses was an incidental finding unrelated to the microcalcifications for which biopsy was initially performed. In the second case of invasive disease, the upgraded lesion was a mass identified on MRI performed for surgical planning in a woman already diagnosed with breast cancer. In both cases of DCIS, the area of malignancy was small (<1mm and 4mm) and of uncertain clinical significance. Based on these findings, we do not recommend routine excision of all LN identified on PCB. Cases in which the lesion is associated with a radiographic mass and/or is identified in a breast with a synchronous malignancy do warrant excisional biopsy. Patients without these high risk features can be counseled on the risks of malignancy and given the option of observation with close follow up.
Serum calcitonin gene-related neuropeptide (CGRP) in patients with benign and malignant breast lesions: Correlation with mammographic breast density.
Authors: Papantoniou V. , Valsamaki P. , Fothiadaki A. , Archontaki A. , Skalistis V. , Marinopoulos S. , Liotsou T. , Karianos T. , Tsakmakli A. , Tsaroucha A. , Stipsanelli A. , Antsaklis A.
Published: February 2017

78

Background: The aim of this study was to assess the variation of the serum neo-angiogenic neuropeptide CGRP in patients with benign and malignant breast lesions and to evaluate its possible correlation with mammographic findings.

Methods: Our study included forty eight women with histologically confirmed breast lesions: mild epithelial hyperplasia (MEH): n=12, florid epithelial hyperplasia (FEH): n=5, atypical hyperplasia (AH): n=4, ductal carcinoma in situ (DCIS): n=5, mixed in situ with invasive ductal carcinoma (DCIS+IDC): n=9 and pure IDC: n=13. Serum CGRP levels were measured by RIA methods and compared among the various groups by Mann-Whitney test. Mammographic breasy density (BD%) was calculated using computer-assisted methods and was correlated with serum CGRP concentration by applying linear regression analysis.

Results: Serum CGRP concentration (mean±SD: pg/mL) in the various groups, was: MEH: 96.8±22.5, FEH: 135.5±33.5, AH: 139±44.4, DCIS: 131.4±37.5, DCIS+IDC: 1167.5±927.5, pure IDC: 198±82. DCIS+IDC lesions presented statistically significantly higher serum CGRP levels (versus: MEH p<0.001, FEH p<0.001, AH p<0.001, DCIS p<0.001 and IDC p<0.001). Serum CGRP concentration presented statistically significant correlation with BD% (r=0.947, p<0.0001).

Conclusions: Statistically increased serum CGRP concentration was determined in women with DCIS+IDC lesions. The significant correlation between serum CGRP levels and BD, enhances the suggestion that DCIS+IDC represents a distinct pathological entity, associated with an interactive mechanism between BD and serum CGRP expression. Therefore, serum CGRP levels could constitute a future useful preoperative index of the nature or type of suspicious mammographic lesions, in order to schedule the appropriate therapeutic treatment, and potentially propounds the perspective of adjunctive therapeutic administration of anti-CGRP peptides.
The ideal screening age for breast cancer in developing countries.
Authors: Al Ratroot H. , Wadaani H. , AbdelHadi M. S. A.
Published: February 2017

79

Background: Due to the lack of structured breast cancer screening programs in developing countries early detection is generally based on international western criteria. This principle is not valid in many instances since women withdraw from voluntary involvement in such activities. In addition breast cancer in developing countries is characterized by younger age and advanced disease at the initial presentation. This review aims to identify the suitable screening age for women in developing countries in order to develop a reliable national structured screening programs.

Methods: This retrospective study was undertaken at King Fahd Hospital of the University, eastern province of Saudi Arabia between 1984-2010. Medical records of patients diagnosed with from the outpatient department and hospital admission records was reviewed. It mainly focused on demographic data and the time of presentation. Radiological and histo-pathological records were also reviewed.

Results: The total number of patients reviewed was 483. The majority of patients were within the reproductive age group. Considering the standard screening age is 40 years, patients are divided into two groups, group I included those below the age of 40 years accounting for 193 patients (40%), while group II above the age of 40 years accounting for 290 patients (60%). Patients in group I were mostly reassured and were mainly diagnosed initially using ultrasonography, while in group II mammography aided in diagnosis.

Conclusions: Despite the undisputable concept that breast cancer has higher predilection for women above the age of 40 years, yet in developing countries, a substantial subset of affected younger women contradicts this concept. The need for breast cancer screening cannot be overemphasized, yet, international screening guidelines for breast cancer cannot be fully implemented in developing countries. Therefore, it is mandatory that screening programs should be tailored according to individual communities. Dropping the screening age by a decade may possibly increase the capture of early breast cancer and improve the outcome.
Use of a novel device to reduce positive margins for ductal carcinoma in situ.
Authors: Boolbol S. K. , Cocilovo C. , Tafra L.
Published: February 2017

87

Background: The ability to obtain negative margins with a single surgical procedure remains a challenge, particularly in patients with ductal carcinoma in situ (DCIS). A novel device (MarginProbe, Dune Medical Devices, Inc.) is intended to provide surgeons with real-time, intraoperative detection of cancerous tissues at the margins of excised specimens. A study was performed to determine if there was a device-associated improvement in complete surgical resection (CSR) and therefore a decreased re-excision rate in patients with a DCIS component.

Methods: 596 patients who were undergoing breast conservation using needle localization were randomized in a prospective, international, multicenter (n=21) study. Randomization occurred in the operating room, following standard of care lumpectomy, including palpation followed by indicated additional cavity resections. Device positive readings required additional resections of the cavity. Pathologists were blinded to study arm. A primary endpoint of this study was CSR, defined as the correct intraoperative identification and resection (if not skin or fascia) of all positive margins on the main lumpectomy specimen. Positive lumpectomy specimens were those having at least one margin having cancer ≤1mm from the surface. Successful CSR results in reduced positive margin rate after lumpectomy.

Results: The improvement in CSR was significant for each diagnosis (p<0.0001). The decrease in candidates for reexcision due to failed CSR was significant for all pathology involving DCIS (p<0.0001). Overall results are presented in the table.

Conclusions: Device use delivered significant improvement in CSR and therefore a significant decrease in reexcision rates for patients with DCIS. Further studies need to be conducted evaluating the use of the device on additional margins that the surgeon may resect or in the actual cavity.

[Table: see text]
Surgical margins and the risk of local-regional recurrence (LRR) following mastectomy for early-stage breast cancer.
Authors: Childs S. K. , Chen Y. , Pochebit S. , Golshan M. , Duggan M. M. , Wong J. S. , Harris J. R. , Bellon J. R.
Published: February 2017

95

Background: We sought to clarify the influence of a positive or close superficial or deep mastectomy margin on the risk of LRR.

Methods: We reviewed the charts of 561 consecutive women who underwent mastectomy without radiation for newly diagnosed in situ or invasive breast cancer between 1998 and 2005. The study cohort consists of 167 of these women who had a positive or close (≤2 mm) superficial or deep surgical margin. LRR as the site of first recurrence (+/− simultaneous distant disease) and distant metastasis (DM) rates were calculated using the Kaplan-Meier method. The median age was 50 years. Forty-five (27%) had ductal carcinoma in situ (DCIS) only. Of the 122 women with invasive disease, 79% had T1, 18% T2, and 3% T3 tumors, and 25% had positive axillary nodes (range, 1-4; 68% 1 positive node). Twenty-nine (24%) of those with invasive disease had lymphovascular invasion. The superficial margin was positive in 61 (37%) and close in 69 (41%). The deep margin was positive in 28 (17%) and close in 51 (31%).

Results: The median follow-up was 6.3 years (range, 1-12.4). The 5-year LRR rate was 5% (95% CI 2-10%) and the DM rate was 3% (95% CI 1-8%). Twelve patients had a LRR; this included the chest wall in 9 and the axilla in 4. Five of the 12 had positive nodes. Four of 92 (4%) with close margins had a LRR vs. 8/75 (11%) with positive margins (log-rank p=0.15). Of the 45 with pure DCIS, 1 (2%) had a LRR. Of those with invasive disease, LRR occurred in 1/28 (4%) who had invasive disease at (positive) or near (close) the superficial margin, 3/38 (8%) with DCIS at or near the superficial margin, 0/12 with invasive disease at or near the deep margin, and 1/12 (8%) with DCIS at or near the deep margin. Both margins were positive or close in 32/122 patients with invasive disease; 6 of these (19%) had a LRR.

Conclusions: The risk of LRR in patients with a positive or close surgical margin after mastectomy is generally low. The benefit of post-mastectomy radiation in this population with otherwise favorable features is likely to be small. While there may be a higher risk of LRR in patients with disease at or close to both margins (likely representing extent of disease), numbers in these categories are small and these results should be interpreted with caution.
Navigation of sentinel node biopsy and selective axillary dissection using 3D-CT mammary lymphography with the arm lymph flow enhancement.
Authors: Yamashita K. , Shimizu K. , Haga S.
Published: February 2017

98

Background: In early breast cancer, the presence of metastasis in axillary lymph nodes (AN) is an important factor in prognosis and further treatment. However, AN dissection causes many complications such as contracture of shoulder joint, lymph edema, and paralysis of upper extremities. Sentinel node (SN) biopsy provides us a valuable information about no need to dissect AN for node-negative patients. However, on node-positive patients, the conventional AN dissection has been performed. 3D-CT lymphography (LG) can show the precise individual lymphatic flow not only from the breast tumor to SN but also from SN to venous angle, which means breast lymphatic channel. We applied 3D-CT LG to distinguish them from the arm channel to avoid any arm complications.

Methods: 3D-CT LG was performed before surgery to mark SN on the skin. Above the tumor and near the areola and the arm pit, 2 ml of iopamidol 300 was injected subcutaneously. Images of CT scan were taken at 1, 3, and 10 min after injection. They were reconstructed to produce a 3D image of lymph ducts and lymph nodes by the volume rendering software. The axillary node groups were classified to 5 groups as described before. The arm lymph channel was classified to 4 regions. SN biopsy and AN sampling were performed by dye-staining method using endoscopy.

Results: We have performed 3D-CT LG on 200 patients and evaluated the arm lymph flow on 50 patients. The average age was 55.1 years old. The average tumor size was 2.4 cm. The average sampled number of SN was 2.3. The arm lymph channels were observed at 10 minutes after injection. They were divided into four directions: around and above the axillary vein (64%), the axilla (12%), the supraclavicule (8%), and the lateral chest (16%). The connection between the breast and the arm channel was observed in each five groups of axillary nodes shown by 3D-CT LG. We could detect their position on the axillary lymphatic mapping by 3D-CT LG during surgery. The selective axillary dissection can be performed by avoiding the arm lymph channel.

Conclusions: The arm lymph channel can be observed by 3D-CT LG with the arm enhancement, which will help the selective axillary dissection to prevent the arm lymph edema.
The prognostic significance of apoptosis-related biological markers in Chinese gastric cancer patients.
Authors: Liu X. , Xu Y. , Long Z. , Zhu H. , Wang Y.
Published: February 2017

108

Background: The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as P21, P27, P53, Bcl-2, Bax, and c-myc, and clinicopathological features and their prognostic value.

Methods: From January 1996 to December 2007, 4,426 patients had undergone gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of P21, P27, P53, Bcl-2, Bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated.

Results: There were 339 males and 162 females (2.09:1) with a mean age of 57. The percentages of positive expression of P21, P27, P53, Bcl-2, Bax, and c-myc were 73%, 25%, 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between P21, P53, Bax, and c-myc expression (p = 0.00). There was significant association between P27, Bcl-2, and Bax expression (p < 0.05). The P21 expression correlated with male (p = 0.00), histological grade (p = 0.00), Borrmann type (p = 0.02), tumor location (p = 0.01); the P53 expression with histological grade (p = 0.01); Bcl-2 expression with pathological stage (p = 0.01); Bax expression with male (p = 0.02), histological grade (p = 0.01), Borrmann type (p = 0.01), tumor location (p = 0.00), lymph node metastasis (p = 0.03), pathological stage (p = 0.01); c-myc expression with Borrmann type (p = 0.00). Bcl-2 expression was related with good survival in univariate analysis (p = 0.01). Multivariate analysis showed that Bcl-2 expression and pathological stage were defined as independent prognostic factors for gastric cancers. There was significant differences of overall 5-year survival rates according to Bcl-2 expression or not in stage III (p = 0.00).

Conclusions: The expressionof Bcl-2 was an independent prognostic factor for Chinese patients with gastric cancer; it might be a candidate for the gastric cancer staging system.

No significant financial relationships to disclose.
Conditional survival nomogram after an R0 resection for gastric cancer.
Authors: Dikken J. L. , Van De Velde C. J. , Verheij M. , Baser R. , Gonen M. , Kattan M. W. , Shah M. A. , Brennan M. F. , Coit D. G.
Published: February 2017

11

Background: The risk of dying of cancer is highest in the first two years after a curative resection for gastric cancer. Therefore, the prognosis of patients who did not recur in the first two years is improved because they survived this critical period, a phenomenon called conditional survival. The US-derived gastric cancer nomogram predicts disease-specific survival (DSS) based on pathological variables. However, a disease-free interval after surgery, which improves the prognosis, is not captured by the nomogram. Therefore, it has only been used directly after surgery and not in the follow-up setting. The purposes of this study were to develop a conditional survival nomogram for 1, 2 and 3-year survivors (step 1) and to test if the introduction of follow-up variables would improve predictive accuracy of the nomogram in the follow-up setting (step 2).

Methods: In a combined US-Dutch population of 1642 patients who underwent an R0 resection for gastric cancer and for whom the old nomogram variables were available, a conditional survival nomogram based on the original variables was developed for one (N=1147), two (N=879) and three (N=721) year survivors (step 1). To improve predictive accuracy in the follow-up setting, weight loss, performance status (PS), hemoglobin (HGB), and albumin (ALB) at one year after resection were retrospectively collected and added to the baseline variables in a new nomogram (step 2).

Results: The conditional survival nomograms for 1, 2 and 3-year survivors (step 1) showed a high predictive accuracy in the calibration plots. Surviving one, two and three years shows a median improvement of 5-year DSS of 4%, 9% and 14% respectively. The introduction of weight loss, PS, HGB, and ALB at one year after surgery (step 2) did not improve this nomogram, but availability of these variables was limited.

Conclusions: A strongly predictive conditional survival nomogram was developed, giving an improved prognosis for 1, 2 and 3-year survivors of gastric cancer. Introduction of variables available at one year after resection did not further improve this nomogram. This might be caused by the limited availability of follow-up data, as well as the strong predictive accuracy of the original variables.

No significant financial relationships to disclose.
Outcomes and efficiency of National Cancer Screening Program for gastric cancer in Korea.
Authors: Kim B. , Cheon W. , Kim J. , Park J. , Kim S.
Published: February 2017

13

Background: Gastric Cancer is a major cause of death and a substantial socioeconomic burden in Korea. The National Cancer Screening Program for Medicaid recipients was initiated in 1999 and has contributed to reduction of cancer-related mortality in Korea. Endoscopy may be cost-effective screening tool in Korea, where the cost of endoscopy and UGIS are similar and the gastric cancer incidence is high. Most of Japanese studies on the efficiency of mass screening for gastric cancer have dealt with photoflurography as a screening tool. Although biennial gastric cancer screening by endoscopy has been increasing in Korea as part of the National Cancer Screening Program, few studies have evaluated its efficiency. Therefore, we analyzed the outcomes and efficiency of the National Cancer Screening Program for gastric cancer using endoscopy in Korea.

Methods: We reviewed results from the National Cancer Screening Program for gastric cancer at Chung-Ang University Yongsan Hospital in Korea from March 2003 to March 2008. The study population was comprised of Medicaid recipients ≥ 40 years of age who were taken from the National Health Insurance Corporation.

Results: A total of 7,278 asymptomatic subjects underwent endoscopy for gastric cancer screening. The mean age of the screened subjects was 51.3 years for men and 48.9 years for women. The male to female ratio of the screened subjects was 1.2:1. Gastric cancer was diagnosed in 32 (0.44%) of 7,278 subjects (22 men and 10 women). Their mean age was 54.4 years. Of these, 21 subjects (0.29%) were diagnosed as early gastric cancer and 11 subjects (0.15%) were advanced gastric cancer. The proportion of EGCs among total gastric cancers was 65.6%. The compliance with this program was low (59% for men and 49% for women).

Conclusions: Despite accomplishments of the National Cancer Screening Program for gastric cancer in Korea, its effectiveness remains an issue. Efficiency and cost-effectiveness analysis will be needed for successful progression.

No significant financial relationships to disclose.
Locally advanced gastric cancer treated with neoadjuvant chemotherapy: Epirubicin, oxaliplatin, and capecitabine (EOX).
Authors: Pluschnig U. , Zacherl J. , Schoppmann S. , Raderer M. , Prager G. , Bartsch R. , Ba-Ssalamah A. , Lamm W. , Zielinski C. , Hejna M.
Published: February 2017

136

Background: Gastric cancer is a worldwide common malignant disease with a high mortality rate. Adjuvant chemotherapy did not result in a survival advantage in Caucasian populations. Therapeutic chemotherapy options consist of either monotherapy or of polychemotherapy and have been applied as neoadjuvant chemotherapy with combinations of epirubicin, cyclophosphamide and 5-fluorouracil or capecitabine as well as cisplatin or oxaliplatin. The aim of this retrospective analysis was to investigate the use of the EOX regimen in the neoadjuvant setting which had shown activity in advanced gastric cancer.

Methods: 23 patients (pts) (median age: 70, range 36-85, years; 16 pts >65 years) with locally advanced adenocarcinoma of the upper GI-tract received 3 courses of preoperative chemotherapy with epirubicin 50 mg/m2, day1, oxaliplatin 130 mg/m2, day 1, and capecitabine 2,000 mg/m2, days 1-14, of a 3-week cycle. Toxicity was assessed by CTC (Common Toxicity Criteria) after every cycle. Progression free survival (PFS) was defined as time from surgery to disease progression assessed by PET-CT which was performed at diagnosis and after 3 cycles chemotherapy.

Results: 20 pts completed all three planned cycles of preoperative chemotherapy, 2 pts received only 1 cycle because of rapid tumor progression and 1 pt. is currently still on treatment. 16 pts. underwent surgery with curative resection with 2 pCRs on pathological review. 6 pts. remained inoperable despite chemotherapy and 1 pt is currently scheduled for surgery. After surgery, 2 pts. died after a median of 9 months (8-10). 4 pts. died without surgery due to disease progression. After a median follow-up of eight months (range 5-26), median PFS and overall survival was not reached yet. In 2 pts., grade 3-4 toxicities including nausea, diarrhea and hand-foot syndrome and one non-life-threatening pulmonary embolism occurred.

Conclusions: In summary, EOX is a well tolerated, safe, and efficacious neoadjuvant treatment in also elderly patients with locally advanced adenocarcinoma of the upper GI-tract. However, more studies with a larger population are needed to corroborate the current results of this promising treatment schedule.

[Table: see text]
Role of chemoradiotherapy alone in the management of unfit patients with nonmetastatic locally advanced squamous cell carcinoma of the esophagus.
Authors: Pisa A. , Moya I. , Pericay C. , Dotor E. , Alfaro J. , Alvarado A. , Navarro S. , Orellana R. , Pampols M. , Saigí E.
Published: February 2017

138

Background: Surgery is considered the best treatment for patients (pts) with non-metastatic locally advanced squamous cell carcinoma of the esophagus who have responded to neoadjuvant chemoradiotherapy (CRT) in terms of locoregional control. However, in these pts PFS and OS have not been proved superior to those achieved by CRT alone. Besides, the addition of surgery to CRT increases treatment-related morbidity and mortality. Unfit pts are usually declined for surgical procedures and included in definitive CRT programs. The aim of this study was to define the role of non-surgical strategies (CRT, CT or RT) in unfit pts considered non-optimal for surgical procedures.

Methods: We retrospectively reviewed 90 pts with squamous cell carcinoma of the esophagus who had been diagnosed and treated at our institution from January 2004 to December 2009. Fifty-one pts were non-metastatic among which 19 underwent surgery and 32 a non-surgical procedure (CRT, CT, RT or BSC). Our aim was to identify OS, PFS, RR, data on comorbidity and toxicity in these 32 pts.

Results: Thirty out of the 32 pts were men with a median age of 62 years (range 41-90). Comorbidity was detected in 17 pts (53%) as means of respiratory disorders (21.9%), cardiopathy (12.5%), hepatopathy (21.9%), synchronic tumors (25%) and metachronic tumors (25%). Seventeen pts received CRT, 7 received CT, 1 received RT and 7 received BSC alone (53%, 22%, 3% and 22% respectively). Grade 3 and 4 toxicities were observed in 15 pts (46.9%) as means of mucositis (18.8%), oesophagitis (15.6%), diarrhoea (12.5%) and neutropaenia (12.5%). One patient in the CRT group died of toxicity. RR was 43.8% (70.6% for CRT, 14.3% for CT alone). Median follow-up was 17.2 months. Median PFS was 11.3 ± 6.12 months (17.9 for CRT, 5.1 for CT alone). Median OS was 15.6 ± 7.6 months (6.9 for CT alone).

Conclusions: Our experience with CRT alone in unfit pts with locally advanced squamous cell carcinoma of the oesophagus supports its use with a median PFS of 17.9 months and controllable toxicity. Data on median OS are lacking due to pending long-term follow-up.

No significant financial relationships to disclose.
Phase I study of biweekly intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel for gastric cancer with peritoneal metastasis.
Authors: Ishigami H. , Kitayama J. , Kaisaki S. , Yamaguchi H. , Yamashita H. , Emoto S. , Nagawa H.
Published: February 2017

139

Background: Intraperitoneal (IP) chemotherapy is promising for the treatment of gastric cancer with peritoneal metastasis. We previously verified the safety and efficacy of IP paclitaxel (PTX) combined with S-1 and intravenous (IV) PTX in phase I and phase II studies (Oncology. 2009; Ann Oncol. 2010). Secondly, we developed a new IP-containing chemotherapy regimen, IV PTX plus IP cisplatin (CDDP) and PTX, for patients who have failed S-1-based chemotherapy. We performed a phase I study to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients.

Methods: A total of 9 gastric cancer patients were enrolled who had shown progression of peritoneal metastasis after S-1-based chemotherapy. PTX was administered intravenously at a dose of 100 mg/m2 and intraperitoneally over 1 hour with an initial dose of 20 mg/m2 (level 1), stepped up to 30 or 40 mg/m2 depending on observed toxicity. CDDP was subsequently administered intraperitoneally at a dose of 30 mg/m2 over 24 hours after PTX infusion. PTX and CDDP were administered on days 1 and 15 in 4-week cycles.

Results: At dose level 1, dose-limiting toxicities (DLTs) were observed in 2 of 3 patients. One patient experienced grade 4 leukopenia, and the other grade 3 vomiting. Because of higher toxicities than anticipated, the initial dose-escalation schedule was abandoned, and the doses of IV PTX and IP CDDP were reduced to 80 mg/m2 and 25 mg/m2, respectively, while keeping the dose of IP PTX at 20 mg/m2 (level 0). At dose level 0, one of the first 3 patients experienced grade 3 nausea, and an additional 3 patients experienced no DLTs. Consequently, the MTD and RD were determined to be dose level 1 and dose level 0, respectively. No patients experienced complications related to the peritoneal access device or IP infusion.

Conclusions: Combination chemotherapy of IV PTX plus IP CDDP and PTX was shown to be a safe regimen that should be further explored in clinical trials.

No significant financial relationships to disclose.
Laparoscopic distal gastrectomy for gastric cancer: Institutional experience with 38 consecutive patients and oncologic outcomes.
Authors: Ho J. , Kachikwu E. L. , Nelson R. A. , Ellenhorn J. D.
Published: February 2017

145

Background: The application of laparoscopy in the surgical treatment of gastric cancer has become more popular in recent years. Most of the published series are from Asia and few report on survival. Our objective was to elucidate the safety, efficacy, and oncologic outcomes of laparoscopic distal gastrectomy in patients with gastric cancer.

Methods: The medical records of all patients who underwent laparoscopic distal gastrectomy at City of Hope National Medical Center between 6/2005 and 8/2010 were retrospectively reviewed. Relevant data analyzed included patient demographics, operative parameters, complications, recurrence, and survival.

Results: A total of 38 consecutive patients were identified. Thirty-four of the 38 patients had a diagnosis of gastric adenocarcinoma. Median age was 70 years (35-96). Median operative time was 379 min (228-583). Median EBL was 200 ml (10-900). Seventeen of the 38 laparoscopic distal gastrectomy cases employed robotic assistance in lymph node dissection. The median number of lymph node retrieval was 23.5. Twenty-two cases included D2 lymph node dissections, 14 cases were D1 dissections, and 2 cases involved D0 dissections. All intended D2 dissections had greater than 15 nodes retrieved. Median hospital stay was 6 days (3-39). Morbidity and mortality rates were 11% and 0%, respectively. Of the 34 patients with gastric adenocarcinoma, histological staging revealed 1 patient had stage 0 disease, 25 had stage I, 7 had stage II, and 2 had stage III. Median follow-up was 12 months (0.5 to 58). Cancer recurrence occurred in 2 patients (6%). The 3 year overall survival is 69% and disease specific survival is 90%. The median survival has not been reached.

Conclusions: Laparoscopic distal gastrectomy is feasible and safe and can be performed in patients with gastric cancer with excellent surgical and oncologic outcomes.

No significant financial relationships to disclose.
Palliative resection for stage IV gastric cancer.
Authors: Muto O. , Kotanagi H.
Published: February 2017

148

Background: Metastatic gastric adenocarcinoma is an incurable condition and little progress has been made in its treatment. The role of palliative surgical resection is still debatable.

Methods: We retrospectively evaluated the efficacy of palliative gastrectomy for treating incurable gastric cancer. In our institution 51 cases were found to have incurable tumors at laparotomy and received palliative gastrectomy from 2003 through 2009. In the analysis, particular attention was paid to the prognostic factors of age, tissue type (diffuse type and intestinal type), metastatic site (liver, peritoneal and lymph node) and postoperative chemotherapy.

Results: One-year survival rate of all patients was 58% and the median survival time was 23.5 months. The median survival time was significantly greater in patients undergoing chemotherapy group than in those not undergoing chemotherapy (24.0 versus 9.4 months; p=0.016).

Conclusions: Long-term survival for patients with stage IV gastric cancer who are managed with surgical resection and chemotherapy is achievable. Further study with a larger number of patients is warranted.

No significant financial relationships to disclose.
Effect of six months neoadjuvant imatinib on resectability potential of gastric stromal tumors in Egyptian patients.
Authors: Saied G. M. , Kensarah A. M.
Published: February 2017

151

Background: Though recurrence is high, local excision is the preferred approach for dealing with gastric stromal tumors. Achieving negative margins is mandatory, sometimes requiring subtotal gastrectomy. Adjuvant imatinib is essential for advanced cases and prolonging survival; however, there is not enough data to recommend its use before surgery to increase resectability. The current study aims at investigating this concept in Egyptian patients.

Methods: The study included 16 patients (13 males, 3 females, mean age 60 years) presenting with gastrointestinal stromal tumors (GISTs) who were candidates for emergency (n = 3) or elective (n = 13) surgery. Investigations included endoscopy (+ biopsy), sonography, and computed tomography (CT). Patients were enrolled in two groups: A (n = 6: projected to planned surgery) and B (n = 7: harboring c-kit+ tumors). Each B patient received imatinib (400 mg/day) for 6 months before surgery. Clinical and radiological evaluation was at day 100. The Chi-square test was used to check size changes, and p = <0.02535 was considered significant.

Results: All patients had abdominal discomfort, while 62.5% had epigastric pain, and 12.5% had hematemesis. Tumor sizes ranged from 8.4 to 20 cm; 2/3 were located in the upper stomach. Five patients (31.3%) harbored lesions with low risk malignancy, eight (50%) with moderate risk and three (18.8%) with high risk. Wedge gastrectomy was the most common operation performed (81.25%) while partial gastrectomy was carried out in the rest, reporting no recurrence for 6 months. Not determined in group A patients, c-kit status was strongly positive in all members of group B; in two of them treatment was suspended due to poor response.

Conclusions: Imatinib has an acceptable safety profile and can be considered as a neoadjuvant therapy in GISTs. Until clear guidelines have been developed, we report that a 6-month intake may noticeably increase their resectability potential and improve prognosis.

No significant financial relationships to disclose.
Effect of helicobacter pylori on prognosis of curatively resected gastric cancers in a population with high prevalence: Short-term results of a prospective study.
Authors: Hur H. , Kim J. Y. , Kim Y. B. , Lim Y. A. , Cho Y. K. , Han S. U.
Published: February 2017

152b

Background: Although two prospective studies reported that negative H pylori is associated with good prognosis in Western countries, these results are not generally acceptable due to regional differences in H pylori virulence and incidence of gastric cancer. Here, we prospectively assessed the correlation between H pylori status of patients who underwent curative resection for treatment of gastric adenocarcinoma and their prognosis in Korea, where H pylori is highly prevalent in the population.

Methods: Between 2006 and 2007, 192 patients who had undergone curative resection for treatment of gastric adenocarcinoma were prospectively enrolled. Of these patients, 18 patients were excluded due to inexact evaluation of H pylori status, and 174 patients were finally analyzed. Serologic testing for H pylori was assessed using an enzyme-linked immunosorbent assay kit for IgG, and histological presence was identified using Giemsa stain.

Results: Of 174 patients, 111 patients (63.8%) who showed both serologically and histologically positive results were confirmed as having positive H pylori infection. H pylori status was not correlated with overall or disease-free survival. In term of patients who were diagnosed with AJCC stage III or IV, disease-free survival of patients with positive H pylori status was a significant predicting factor for recurrence longer than that of negative patients (p = 0.019). Negative H pylori status became a predicting factor for recurrence in multivariable analysis (RR = 2.724, 95% C.I.: 1.192-6.228).

Conclusions: H pylori status did not show correlation with clinicopathologic factors of gastric adenocarcinoma in Korea. However, negative H pylori may be a predictive factor for recurrence in patients diagnosed with gastric adenocarcinoma of advanced status. Therefore, in H pylori endemic areas, patients diagnosed with locally advanced gastric cancer accompanied by negative H pylori status should be considered for an aggressive treatment strategy and close follow-up. In addition, correlation in an early stage should be confirmative through the results of longer follow-up.

No significant financial relationships to disclose.
Association of RecQ1 A159C polymorphism with overall survival of patients with resected pancreatic cancer: A replication study in RTOG 9704.
Authors: Li D. , Moughan J. , Crane C. H. , Hoffman J. P. , Regine W. , Abrams R. A. , Safran H. , Freedman G. M. , Guha C. , Abbruzzese J. L.
Published: February 2017

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Background: To confirm whether a previously observed association between a DNA repair gene and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population.

Methods: We evaluated the RecQ1 A159C variant (rs13035) in patients with resected pancreatic cancer who were enrolled on the RTOG 9704 trial of 5FU-based chemoradiation preceded and followed by 5-FU or gemcitabine. DNA was extracted from paraffin-embedded tissue sections and genotype was determined using the Taqman method. A multivariate Cox proportional hazards model was used to determine if there is a correlation between genotype and overall survival (OS). Models were built using the stepwise selection procedure. The following variables were included in the model: genotype, treatment arm, age, gender, race, nodal involvement, tumor diameter, and surgical margin status.

Results: A total of 154 out of 451 eligible patients were evaluated for the RecQ1genotype. There was no significant difference in baseline characteristics and overall survival time between patients who were and were not evaluated for the RecQ1genotype. In the 154 evaluated patients, the genotype distribution followed the Hardy-Weinberg Equilibrium, i.e. 37% had genotype AA, 43% AC, and 20% CC. The RecQ1 variant AC/CC genotype carriers were more likely to be node positive compared to the AA carrier (p=0.03). The median survival times (95% C.I.) for AA, AC, and CC carriers were 1.72 (1.36, 2.17), 1.57 (1.18, 1.80), and 1.18 (0.86, 1.75) years, respectively. On multivariate analysis, patients with the AC/CC genotypes were more likely to die than patients with AA genotype (HR=1.54, 95% C.I. = [1.07, 2.23], p=0.022). This effect is more definitive for patients on the 5-FU arm (n=82) (HR=1.64, 95% C.I. = [0.99, 2.70], p=0.055) than for patients on the gemcitabine arm (n=72, HR=1.46, 95% C.I. = [0.81, 2.63], p=0.21).

Conclusions: Results of this study suggest that the RecQ1 A159C genotype is a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant chemoradiation.

No significant financial relationships to disclose.
Use of gene expression analysis of periampullary carcinomas to identify biliary-like and intestinal-like subgroups of ampullary and duodenal carcinomas.
Authors: Overman M. J. , Zhang J. , Varadhachary G. R. , Hwang R. F. , Kapoor M. , Abbruzzese J. L. , Wolff R. A. , Wang H. , Broom B.
Published: February 2017

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Background: Though adenocarcinomas of the ampulla of Vater are classified as biliary cancers, the epithelium of origin and treatment approach for these rare tumors remains controversial. We compared the gene expression profiles of ampullary carcinomas with that of known periampullary carcinomas.

Methods: We analyzed 32 fresh-frozen resected untreated periampullary carcinomas (8 pancreatic, 2 extrahepatic biliary, 8 non-ampullary duodenal, and 14 ampullary) with verified histology and >70% tumor tissue using the Affymetrix U133 Plus 2.0 genome array. Hierarchical clustering of all samples based upon pancreatic and duodenal differentially expressed genes and unsupervised hierarchical clustering was done. Ampullary and duodenal samples were analyzed for histologic subtype (pancreaticobiliary, intestinal, mixed), MSI by PCR, CDX-2 by IHC and KRAS and PI3K mutations by mass spectroscopy-based sequencing (Sequenom).

Results: We identified 3 subgroups: pancreatic (8 pancreatic, 1 duodenal), biliary-like (4 duodenal, 7 ampullary, 2 biliary) and intestinal-like (3 duodenal, 7 ampullary). The intestinal-like subgroup had a significantly improved RFS (p=0.03) and OS (p =0.04) compared to the biliary-like subgroup, after stratification by grade and stage. Unsupervised clustering of only ampullary and duodenal samples identified very similar good prognostic (4 duodenal, 5 ampullary) and bad prognostic groups (3 duodenal, 9 ampullary) with 3-year RFS 75% vs. 31%, p =0.05 and 3-year OS 100% vs. 27%, p =0.01. These 2 groups showed no statistically significant differences in adenoma (56% vs 25%), poor differentiation (11% vs 42%), T4 (33% vs 25%), N1 (67% vs 100%), MSI-high (22% vs 0%), KRAS mutations (33% vs 17%), or PI3K mutations (0% vs 17%). CDX-2 expression (100% vs 50%, p=.04) and intestinal histologic subtype (100% vs 0%, p <0.01) were more common in the good prognostic group.

Conclusions: Gene expression analysis classifies ampullary carcinomas with duodenal carcinomas and identifies a good prognosis intestinal-like group and a poor prognosis biliary-like group. These findings have therapeutic implications.

[Table: see text]
Correlation of DPC4 status with outcomes in pancreatic adenocarcinoma patients receiving adjuvant chemoradiation.
Authors: Herman J. M. , Hsu C. C. , Fishman E. K. , Hruban R. H. , Lin S. H. , Hacker-Prietz A. , Cameron J. L. , Laheru D. , Wolfgang C. L. , Iacobuzio-Donahue C. A.
Published: February 2017

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Background: In an autopsy series of patients with advanced pancreatic cancer (PCA), loss of DPC4 was highly correlated with disseminated metastasis. The purpose of this study was to determine if DPC4 gene status predicts for survival and patterns of recurrence following adjuvant (adj) chemoradiation (CRT).

Methods: 101 patients who underwent surgery followed by adjuvant 5-FU or gemcitabine-based CRT were studied. Imaging studies were reviewed to assess patterns of recurrence and tumor tissue obtained to determine DPC4 immunolabeling status. DPC4 status was graded as intact or lost/mutated. Kaplan-Meier estimates were used to compute survival and Cox proportional hazards were used to compare risk factors.

Results: Median overall (mOS) and progression-free survival (PFS) was 22.6 mos (95% CI 18.8 to 31.6) and 14.0 mos (95% CI 11.5 to 18.4). The mOS and 1-yr OS for patients with DPC4 intact vs. lost status was 21.9 mos (95% CI 16.8-32.4) and 78.4% vs. 22.6 mos (95% CI 18.4-32.6) and 78.2%, respectively (HR: 1.05, p=0.82). After adjusting for node, margin status, tumor grade, tumor size, and age, DPC4 status did not predict for mOS (RR 1.04, 95% CI: 0.62-1.74, p=0.89). Time to first progression at any site for PCA with DPC4 intact vs. lost status was 13.8 vs. 14.0 mos (p=0.79). Local recurrence was more common in PCA with DPC4 loss than with intact status (34.4% vs. 13.7%, p=0.012). There was no difference in the rates of distant recurrence in PCA with intact vs. loss of DPC4 expression (62.8% vs. 55.7%, p=0.45); however, DPC4 loss was more commonly associated with liver recurrence (27.9% vs. 19.6%, p=0.31).

Conclusions: In pancreatic cancer patients receiving adj CRT, loss of DPC4 labeling in their resected PCA indicates a greater likelihood of developing local recurrence despite having received adj CRT. Efforts to improve loco-regional control are therefore needed for these patients following surgery and adj CRT.

No significant financial relationships to disclose.
Long-term survivorship in pancreatic adenocarcinoma.
Authors: Gubens M. A. , Kunz P. L. , Fisher G. A. , Ford J. M. , Lichtensztajn D. , Clarke C. A.
Published: February 2017

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Background: Pancreatic cancer is one of the most lethal malignancies, with an estimated 5-year survival rate of 6%, often due to advanced stage at diagnosis. However, there is a small population of patients, even with metastatic disease, who survive 3 years and beyond.

Methods: Cases of pancreatic adenocarcinoma diagnosed from 1998 to 2005 were identified in the California Cancer Registry. A multivariate logistic regression model was constructed to predict the outcome of 3+ year survival according to demographic, disease and treatment variables defined a priori: age, gender, race/ethnicity, socioeconomic status (SES), histology, stage, treatment within 4 months of diagnosis (surgery, chemotherapy, and/or radiation), prior cancer history, and treatment at an academic hospital.

Results: Among 54,475 cases of pancreatic cancer with ≥3 years of follow-up data available, median survival was 3.5 months. 2,855 patients (5.2%) survived at least 3 years, of whom 19% had remote stage disease at diagnosis. On multivariate analysis, advanced age was associated with decreased odds of long-term survival (p<0.01). By race, Asian/Pacific Islanders (odds ratio (OR) 1.76, p<0.01), Hispanics (OR 1.29, p=0.01) and non-Hispanic blacks (OR 1.24, p=0.14) were more likely to be long-term survivors than non-Hispanic whites. There was a gradient toward increased long- term survival for patients with higher SES (OR 1.49 for highest vs. lowest quintile, p<0.01). Mucinous tumors were associated with higher long-term survival than other adenocarcinomas (OR 2.21, p<0.01). Localized (OR 6.82) and regional stage disease (OR 2.61) showed more long-term survival than remote stage disease, both p<0.01. Surgery (OR 8.20, p<0.01), chemotherapy (OR 1.44, p<0.01), and radiation therapy (OR 1.25, p=0.02) increased the odds of long-term survival, as did treatment at an academic hospital (OR 1.54, p<0.01).

Conclusions: In a well- characterized population-based registry with rigorous follow-up, we were able to identify a cohort of long-term survivors of pancreatic adenocarcinoma as well as factors associated with their exceptional survival. Planned future work with this cohort includes case-control studies making use of tumor and germline specimens, as well as survivorship research.

No significant financial relationships to disclose.
The association between diabetes mellitus and HCC: Noise or real? A meta-analysis of epidemiologic evidence.
Authors: Janarthanan S. , Ditah I. C. , Tageja N. , Kutait A.
Published: February 2017

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Background: Diabetes mellitus (DM) has been linked to an increase in the incidence of hepatocellular carcinoma (HCC). However, these studies have yielded controversial findings. This study evaluates the association between DM and risk of HCC in a meta-analysis.

Methods: Two investigators independently conducted a search of studies on the association between DM and HCC from January 1970 through August 2010 on Medline. Identified articles were manually reviewed for additional references. Only full articles that provided risk estimates for the association were selected. The most adjusted risk estimates were abstracted and synthesized using the random-effects model. A stratified analysis by study design and study region has also been done. All studies were evaluated for publication bias before analysis.

Results: A total of 35 studies, 20 case-control and 15cohort studies, were eligible for analysis. The overall summary risk ratio for HCC in DM was 1.60 (95% CI 1.49, 1.70; p<0.001). Among the case-control and cohort studies, the pooled risk estimate was 1.33 (95% CI 1.21, 1.46; p<0.001) and 2.24 (2.05, 2.44; p<0.001) respectively. By geographic location, the association remained significant among the European (15) and U.S. (10) based studies with risk ratios of 2.7 (95% CI 2.37, 3.05; p<0.001) and 1.58 (95% CI 1.45, 1.7) respectively. However, among the Japanese (10) based studies there was a nonsignificant 3% reduction in the risk of HCC (RR 0.97; 95% CI 0.71, 1.24; p>0.05). There was no evidence of publication bias among the studies included.

Conclusions: The evidence in support of DM as an independent risk factor for HCC remains unclear. Though not significant, the finding among the Japanese based populations raises concerns over the potential role of environmental and/or genetic factors in the observed association. Further studies with great attention to potential confounders are warranted to definitively define the association between DM and HCC.

No significant financial relationships to disclose.