bluuebunny/crossref_metadata_2025 huggingface dataset:
Nipple-sparing mastectomy and immediate breast reconstruction: Critical appraisal of five-year, single-center outcomes.
Authors: Westbroek D. , Mann K. , Ho M. , Gukas I. , Karat I. , Daoud R. , Laidlaw I. J.
Published: February 2017

99

Background: Approximately 5,000 patients undergo breast reconstruction annually in the United Kingdom (2:1 ratio of immediate versus delayed respectively). Preservation of the breast envelope, i.e., skin and nipple areola complex (NAC) improves cosmesis. While skin-sparing mastectomy is an accepted modality for local control in appropriately selected patients, nipple-sparing mastectomy (NSM) remains controversial. In over 1,800 published NSM cases, the local event rate attributable to NAC preservation following NSM (therapeutic and prophylactic) is 0.16% with no evidence of deleterious impact on disease-free survival. In our cohort, patient selection criteria included: preoperative lesion characterisation; 5-mm margin acceptance; submission of separate nipple core specimens for paraffin block histological assessment and re-excision of all involved margins. This study is intended to evaluate the efficacy of loco-regional control in a consecutive cohort of patients, under uniform conditions undergoing nipple-sparing mastectomy and immediate breast reconstruction. We highlight the surgical technique used and propose in/exclusion criteria for appropriate patient selection.

Methods: 84 consecutive patients underwent NSM and IBR at Frimley Park Hospital, Surrey, UK (IJL, RD) between January 2004 and December 2008. Data was accrued retrospectively from the institution’s clinical coding, electronic records, and WinPath database. Endpoints recorded include: the incidence of (occult) malignancy at the nipple margins; NAC subcutaneous tissue loss; local (NAC) recurrence rates and disease free survival.

Results: The mean age was 51.1 years and follow-up 4.9 years. There was one case of local recurrence in a patient who declined re-excision of close/involved margins. The immediate peri-operative complication rate was within the national mastectomy breast reconstruction audit outcome guidelines.

Conclusions: In appropriately selected patients, our findings support nipple preservation at the time of mastectomy and immediate reconstruction as this enhances the cosmetic outcome without compromising oncologic safety.
Availability of sentinel node as predictive index of lymph node metastases to early-stage gastric cancer surgery.
Authors: Kamiya S. , Takeuchi H. , Niihara M. , Kaburagi T. , Nakamura R. , Oyama T. , Takahashi T. , Wada N. , Saikawa Y. , Kitagawa Y.
Published: February 2017

10

Background: Recently, the less invasive surgery for the early gastric cancer attract considerable attention, in particular, sentinel node navigation surgery (SNNS) is expected to be a new strategy. We analyzed the feasibility of sentinel node (SN) biopsy and its accuracy in predicting the lymph node status in patients with early gastric cancer.

Methods: Between 1999 and 2009, we have performed the gastrectomy with SN biopsy during an operation in over 500 cases. We focused attention on 115 patients with cT1N0, less or equal 40 mm in size, and isolated gastric cancer and they had undergone the individualized minimizing gastrectomy. Proximal, pylorus-preserving gastrectomy and wedge resections were performed in 51, 54 and 10 patients, respectively. We used a dual procedure with dye- and gamma probe-guided techniques for SN mapping and resected SN and non-SN as was conventionally done for the safety.

Results: Subjects were 85 males and 30 females with a mean age of 63.4 years. 53 patients had undergone laparoscopy-assisted gastrectomy. The mean number of SNs was 4.3/case. Of the four patients were SN positive and false-negative was found in one case. The sensitivity of detecting metastases was 80.0% (4/5) and the accuracy was 99.1% (114/115). One case had a recurrence in the liver and no cases without SN metastasis were confirmed any recurrences and metastases.

Conclusions: This study showed the diagnostic accuracy of metastasis based on SN was very high, and the minimized resection and lymphadenectomy could be performed safely.

No significant financial relationships to disclose.
Prognostic significance of positive lymph node ratio in resected esophageal cancer.
Authors: Thota R. , Tashi T. , Gonsalves W. , Sama A. R. , Silberstein P. T. , Townley P. , Subbiah S.
Published: February 2017

100

Background: Nodal involvement in esophageal cancer is associated with poor survival. We aim to determine whether the ratio of metastatic to examined lymph nodes (the lymph node ratio [LNR]) is a better predictor of survival as compared to the number of positive lymph nodes in resected esophageal cancer.

Methods: 1,149 patients with resected esophageal cancer from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. The patients were further characterized to 3 lymph node quartiles based on LNR and their median survivals were calculated using the Kaplan-Meier method.

Results: Out of 1149 patients 26.4% patients (303) had squamous cell carcinoma and 73.6% (846) were of adenocarcinoma histology. Median age of diagnosis is 63 years. 353 (31%) are stage 1, 384 (33%) are stage 2, and 412 (36%) are stage 3. Majority of them 71% arise in lower third of esophagus followed by 13% in middle third, 4% in upper third and 12 % had unknown site of origin. The group was subdivided into 3 quartiles with 62.7% in LNR1 (0.0-0.1), 25.6% in LNR2 (0.1-0.5) and 11.7% in LNR3 (0.5-1.0). 13.7% had less than 2 nodes removed, 29.3% had 3-6 nodes and 57% had >7 nodes examined. 28% of them had tumor invading sub mucosa, 23.5% had tumor invading muscularis mucosa, 43.2% had involvement of adventitia and 5.3% had penetrating tumor at the time of diagnosis The 5 year survivals based on number of lymph nodes examined, number of positive lymph nodes and positive lymph node ratio are listed in the table. The median overall survival for resected esophageal cancer based on LNR quartiles was 37 vs 14 vs 11.5 months (p<0.0001).

Conclusions: Number of positive lymph nodes and positive lymph node ratio correlated with survival outcomes but number of lymph nodes retrieved did not predict any survival differences. However LNR was a better predictor of survival when compared to number of positive nodes. Further validation of this observation needs to done in large multicenter studies.

[Table: see text]

No significant financial relationships to disclose.
Phase II study of docetaxel (DTX) and S-1 as neoadjuvant chemotherapy for potentially R0 advanced gastric cancer.
Authors: Watanabe M. , Emi Y. , Kakeji Y. , Oki E. , Sakaguchi Y. , Yoshida K. , Hirabayashi N. , Yamanaka T. , Baba H. , Maehara Y.
Published: February 2017

106

Background: This trial sought to evaluate the efficacy and safety of preoperative chemotherapy with DTX plus S-1 for advanced gastric cancer with poor prognosis even after R0 curative resection.

Methods: Preoperative staging was confirmed by laparoscopy. Eligibility criteria included 1) negative peritoneal cytology, H0, P0 and M0, 2) possible curative resection, and 3) ECOG PS 0-1. Patients received DTX (35 mg/m2) on days 1 and 15, and daily oral administration of S-1 (80 mg/m2/day) for days 1–14 every 4 weeks of 2 courses, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was pathological response rate (pRR), which was defined as degeneration occupying more than one-third of the cross-sectional surface area of the tumor. A sample size of 45 was planned for the expected pRR of 40% and threshold value of 20%, with one-sided alpha of 0.05 and beta of approximately 0.1. This study was registered in the UMIN clinical trial registry (UMIN000000875).

Results: A total of 47 patients were centrally registered between November 2007 and November 2009 from 14 centers. All patients were eligible for analysis. The median age was 63 (range 37–79); male/female: 36/11; PS0/1:41/6; and clinical stage IIIA/IIIB: 31/16. The target pRR was 47% (90% CI, 34–60%; p < 0.0001). Forty six patients (98%) underwent surgery, in whom curative resection was performed in 44 patients, and 37 patients completed the protocol treatment. The response to preoperative chemotherapy was PR/SD/PD/NE in 16/24/2/5 with a response rate of 34%. The most common toxicities of neoadjuvant chemotherapy were grade 3/4 neutropenia (42%), febrile neutropenia (4%), grade 2 anorexia (21%), and fatigue (15%). Seven did not complete the neoadjuvant therapy due to 2 allergic reaction, 1 grade 3 anorexia, 2 grade 2 nausea and anorexia, 2 PD (all 7 had gastrectomy). Major operative morbidity included pancreatic fistula (9%), abdominal abscess (11%), pneumonia (2%), and anastomotic leakage (0%). No patients died due to surgical complications.

Conclusions: The combination of DTX and S-1 was well tolerated and promising as a preoperative chemotherapy regimen for patients with potentially resectable advanced gastric cancer.

[Table: see text]
Surgical lymph node clearance and pathologic evaluation in gastric cancer.
Authors: Khattak A. G. , Sachdev J. C. , Evangelist M. C. , Denbo J. , Orr W. S. , Ul-Haq M. , Farooq A. , Thompson A. C. , Dilawari R. A. , Osarogiagbon R. U.
Published: February 2017

131

Background: Lymph node (LN) metastasis is common in gastric cancer, with survival implications. The number of LN with metastasis determines pathologic nodal stage; optimal staging requires examination of >14 LN. This requires adequate surgical LN clearance and careful pathology evaluation. Sub-optimal LN examination may be due to surgical or pathology laboratory quality problems, affecting the rational implementation of corrective measures. We evaluated LN examination practice in our community.

Methods: Review of all gastric resections at two hospital systems in Memphis, TN from 1999 to 2008, excluding patients with pre-operative chemo/radiation therapy. Two surgeons separately reviewed all operation reports for details of LN station clearance. We tested concordance between surgeons by the kappa statistic (k) and correlated surgeon reports of LN clearance to the number of examined LN in the pathology report.

Results: 51% of 116 operative reports did not state LN stations resected. The concordance rate between the two surgeons was high (k score per station ranging from 0.66 [very good] to 1.0 [perfect]). The median number of LN stations cleared was similar after proximal (PG) and distal gastrectomy (DG), but significantly more after total gastrectomy (TG) (p<0.0001). Only 39% of patients had >14 LN examined, 6% had none. The number of LN examined was lowest for PG, intermediate for DG and highest for TG patients (Table). There was no correlation between number of surgically cleared LN stations and number of examined LNs (Spearman correlation coefficient 0.23).

Conclusions: Operating surgeons frequently did not identify a LN dissection procedure. Fewer LN were retrieved by pathologists during examination of PG specimens although the surgeon-reported LN clearance was similar between PG and DG. The lack of correlation between LN stations cleared and number of LN examined suggests inadequate pathological examination of LNs submitted in surgical specimens.

[Table: see text]

No significant financial relationships to disclose.
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis arising from gastric cancer.
Authors: Piso P. , Glockzin G. , Schlitt H. J.
Published: February 2017

132

Background: Peritoneal carcinomatosis is a common sign of advanced tumor stage or disease recurrence in patients with gastric cancer. The prognosis of these patients is poor. There is some evidence that CRS and HIPEC may improve the oncological outcome of a highly selected part of patients with peritoneal carcinomatosis arising from gastric cancer. Nevertheless, the use of CRS and HIPEC as an additional therapeutic option is still controversial.

Methods: Between 01/2005 and 09/2009 16 out of 256 patients underwent CRS and HIPEC for peritoneal carcinomatosis arising from gastric cancer at the University of Regensburg Medical Center. The mean age of patients at the time of surgery was 52 years (range 32-69). Four patients were female (25%). The mean follow-up time was 16.3 months.

Results: Thirteen patients (81.25%) underwent complete macroscopic cytoreduction (CC-0/1). HIPEC was performed in all patients. The median hospital stay was 19.5 days (range 8-44) and the median stay on ICU 1 day (range 0-14), respectively. The median operating time was 342 minutes (range 49- 510). The perioperative grade 3/4 morbidity rate was 37.5%. Postoperative complications were pneumonia (2), pancreatitis (2), pneumothorax (2), intraabdominal abscess (2), renal insufficiency (1), urine bladder dysfunction (1) and wound infection (1). There was no operative mortality in our series. The 1-year survival rate was 68.7%. The mean survival of the ten patients that died during follow-up was 14.1 months (range 3.4-44.8).

Conclusions: In highly selected patients with gastric cancer and peritoneal carcinomatosis CRS and HIPEC may lead to prolonged survival rates. However, the therapy should be integrated in an interdisciplinary multimodality treatment concept. Further prospective randomized trials are required to determine the role of CRS and HIPEC in the treatment of patients with gastric cancer.

No significant financial relationships to disclose.
Phase II multicenter study of erlotinib with radiation therapy (RT) for elderly patients (pts) with esophageal carcinoma (EC): Final report.
Authors: Iyer R. V. , Yang G. , Schefter T. E. , Tan W. , Nava H. R. , Levea C. , Litwin A. , Robins M. , Khushalani N. I.
Published: February 2017

135

Background: Elderly pts with comorbidities have limited Rx options for localized EC. High EGFR expression correlates with poor response to RT. We examined the safety and efficacy of erlotinib, an oral EGFR tyrosine kinase inhibitor with RT in these pts.

Methods: Pts older than 65 yrs ineligible for platinum based Rx with carcinoma of the thoracic esophagus or gastroesophageal junction received erlotinib 150mg PO QD for one year starting D1 of RT [50.4 Gy D1-28 (M-F) at 1.8 Gy per fraction]. Assessments- mucosal response by EGD 4-8 wks post RT; RECIST response by CT q3mo. Endpoints: Primary- overall survival (OS), secondary- quality of life (QOL) using the FACT-E QOL tool, progression free survival (PFS) and toxicity; correlative- pre-treatment tumor EGFR and pEGFR expression by immunohistochemistry (IHC).

Results: The study was closed after 17 of planned 35 pts were included due to poor accrual. Baseline characteristics: median age 78 yrs (66-91); gender M/F: 11/6; ECOG PS 0/1/2=2/12/3; stage I-1, II=5, III=7 and IVa= 4; histology: adenocarcinoma 16, squamous cell 1; dysphagia at baseline 13/17 (76%). Median OS was 7.3 months (95% CI: 4.5-22.3) with 12 pts dead (5 alive, 3 still on treatment). Reason for coming off study (n=14): disease progression (n=6), toxicity (n=5), withdrew consent, completed one year of treatment, death from unrelated cause (n=1 each). There were 2 mucosal CRs and one residual carcinoma in situ, 3 partial endoscopic responses of the 9 pts who had post RT endoscopy. Estimated PFS is 5.3 months (95% CI: 2.4-11). Sites of progression- distant 3, locoregional 6, unknown 5 and too early 3. Estimated one year survival is 26 %, 3 pts lived >12 months. Smoking status- current/past/never 3/12/2. Treatment related toxicities (any grade n=or>5) were, rash (16), fatigue (16), diarrhea (11), lymphopenia (10), anorexia (7) and dehydration (6) and 21 grade 3/4 toxicities occurred. IHC results- EGFR, neg: 1/16; pos: 15/16 and pEGFR, neg: 2/16; pos:14/16.

Conclusions: For elderly pts with localized EC and no chemotherapy options, erlotinib monotherapy with RT is a tolerable therapy with modest activity. Further studies are needed to define the role of EGFR inhibition with RT in EC.

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

14

Background: Gastric cancer is the fourth most prevalent malignancy and second leading cause of cancer death worldwide. For all stages, gastric cancer is rapidly fatal with a 5-year survival rate of 25%. Of those patients who survive, very little is known about their demographic and tumor characteristics.

Methods: Cases of gastric and gastroesophageal junction (GEJ) adenocarcinoma diagnosed between 1998 and 2005 were identified within the California Cancer Registry, a SEER registry. Univariate and multivariate logistic regression models were constructed predicting the outcome of survival to 3, 5 and 8 years based on demographic, disease and treatment variables.

Results: Of the 47,049 patients with gastric or GEJ cancer, 38,380 (82%) died within 3 years of diagnosis, 8,669 (18%) survived at least 3 years, 5,336 (11%) survived at least 5 years, and 3,002 (6%) survived at least 8 years. The 5-year survivors had a median age at diagnosis of 67 years with a male predominance (64%). The majority were non-Hispanic whites (64%), followed by Asian/Pacific Islanders (23%), and Hispanics (18%). Most had localized (48%) or regional (41%) disease. In the multivariate model, odds of surviving to 5 years were highest with localized stage (odds datio=27), surgery (7.8), regional stage (5.9), fundus/body/antrum site (1.7), Asian/Pacific Islander race (1.5), intestinal histology (1.5), high SES (1.4), and well/moderately differentiated tumors (1.4). Kaplan-Meier curves for cause-specific death were examined by anatomic site and histology. Persons with tumors originating in the fundus/body/antrum had longer median OS compared to patients with tumors originating in the esophagus/cardia (15 vs. 12 months). Intestinal histology had longer median OS (30 months) compared to other or diffuse (both approx 12 months).

Conclusions: Long-term survivors of gastric and GEJ cancer have distinct demographic patterns when compared to patients who died within three years. The multivariate analyses demonstrated that earlier stage, surgery, anatomic site (fundus/body), Asian race, intestinal histology, high SES, well/moderately differentiated tumors, and radiation were the strongest independent predictors of survival.

No significant financial relationships to disclose.
S-1 and intraperitoneal and intravenous paclitaxel as neoadjuvant chemotherapy for gastric cancer with positive peritoneal cytology.
Authors: Peng Y. , Imano M. , Imamoto H. , Nishiki K. , Nakamori Y. , Shiraishi O. , Yasuda A. , Shinkai M. , Yasuda T. , Shiozaki H.
Published: February 2017

142

Background: The prognosis of gastric cancer with positive peritoneal cytology is dismal. Standard treatments for these patients have not been established. The purpose of this study was to evaluate the safety and response of the regimen.

Methods: Patients who were diagnosed with advanced gastric cancer between 2007 and 2010 underwent staging laparoscopy and received intraperitoneal paclitaxel when peritoneal cytology were positive and sequential systemic chemotherapy, S-1 combined with intravenous paclitaxel within 14 days after staging laparoscopy. Paclitaxel was administered intraperitoneally at 80 mg/m2. S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Paclitaxel was administered intravenously at 50 mg/m2 on day 1 and day 8. After 2 courses of S-1 combined with paclitaxel were administered, clinical response was assessed by gastroendoscopy and computed tomography. Additional 2 or 3 courses were administered unless progression of disease was proved. Patients who achieved complete response (CR) or partial response (PR) and patients with stable disease (SD) underwent second-look laparoscopy following gastrectomy when peritoneal cytology turned negative.

Results: 8 (7 male, 1 female) patients were enrolled: median age was 64 years (range 40-75). Of 8 patients, 1 patient achieved CR, and 5 PR. 2 patients showed progressive disease (PD). Grade 3 neutropenia occurred in 1 patient. 6 patients underwent second-look laparoscopy and peritoneal cytology turned negative in all 6 patients. Total or distal gastrectomy with lymphnode dissection was performed consecutively in 3 or 3 patients, respectively. Median follow-up duration was 775 days (range 187-1,028). No recurrence has not been observed, while the 1-year and 2-year survival rates of 14 patients with peritoneal cytology positive gastric cancer who have not received neoadjuvant chemotherapy were 58.3% and 33.3%, respectively.

Conclusions: S-1, intraperitoneal and intravenous paclitaxel as neoadjuvant chemotherapy seems to be a effective strategy against gastric cancer with positive peritoneal cytology.

No significant financial relationships to disclose.
A comparison of IMRT and 3DCRT in the treatment planning of patients with distal esophageal cancer.
Authors: Patil S.
Published: February 2017

143

Background: There is limited data comparing intensity modulated radiation therapy (IMRT) and 3D conformal radiation therapy (3DCRT) in node-negative patients with cancer of the distal esophagus.

Methods: Eight patients with node-negative cancer of the distal esophagus measuring 1-5 cm tumors were selected for this study. Target volumes were generated for all patients based on standard current practice; 3DCRT and IMRT plans optimized to obtain minimum dose to the heart were then created using the using the Eclipse Treatment Planning. Conformality index (CI, the amount of target volume covered by the prescription dose) and conformation number (CN, the amount of normal tissue receiving prescription dose) were calculated. Dose volume histograms also were generated and clinically relevant parameters were extracted and compared for each planning modality using paired T-tests. Each patient served as his or her own control.

Results: The difference in CI ranged from 0-0.01, indicating equivalent target coverage for each patient. IMRT produced superior CN (mean CN = 0.74) vs. the 3DCRT plans (mean CN = 0.45). Heart V40 and the maximum dose to spinal cord were lower for IMRT (mean difference in heart V40 = 34.5%, p=0.0006 and mean difference in the maximum dose to the spinal cord = 18.1 Gy, p=0.0005) but lung V5 and V20 were lower for 3DCRT (mean difference in lung V5 = -21.3%, p=0.0026 and mean difference in lung V20 = -5.2%, p=0.0014).

Conclusions: When optimized to minimize dose to the heart, IMRT plans were substantially more conformal to the target structures with less dose to the heart as compared to 3DCRT plans; however this occurred at the expense of increased dose delivered to the lung.

No significant financial relationships to disclose.
Spray cryotherapy for palliation of locally advanced adenocarcinoma in Barrett's esophagus.
Authors: Lin C. , Kerstetter D. , Habr F.
Published: February 2017

152

Background: Up to 60% of patients with esophageal cancer are deemed inoperable at the time of diagnosis due to either advanced stage or significant co-morbidities. Currently, endoscopic palliative measures include stenting and photodynamic therapy. Although spray cryotherapy has been successfully used in ablating Barrett's esophagus, and different grades of dysplasia, there has been only one published case describing complete remission of squamous cell carcinoma following cryoablation. We present the first case of the use of the CryoSpray Ablation System (CSA Medical, Baltimore, MD) for palliative treatment of an esophageal T3 adenocarcinoma in an elderly woman with dysphagia and weight loss.

Methods: An upper endoscopy was performed with standard monitored anesthesia. A special dual lumen Cryo decompression tube is introduced over an endoscopically placed savary guidewire in the gastric antrum and connected to suction. This tube is used to decompress the stomach when the liquid nitrogen is sprayed. Cryoablation is performed using the CryoSpray Ablation System that uses liquid nitrogen is delivered via a 7 Fr catheter at low pressures (2-3 PSI) at -196°C.The lesion was treated with four freeze cycles of 10-20 seconds each with 60 second interim thaws. Freezing and thawing techniques were monitored by direct visualization. The procedure is repeated every 4-6 weeks. The patient received a total of 7 treatments over 10 months.

Results: The patient did not experience any adverse effects after treatment. After 3 treatments (week 20), complete endoscopic resolution of the lesion was noted, with regression of the Barrett's mucosa and major improvement of her dysphagia. At week 28, a recurrent mass was seen on EGD in the mid-esophagus. This was treated with 3 sessions of spray cryotherapy at 4 week intervals with improvement of dysphagia after each application. 11 months after her initial cryotherapy, the patient opted to have an esophageal stent due to tumor progression.

Conclusions: Spray cryotherapy is a safe and effective endoscopic modality for the ablation of Barrett's esophagus and superficial esophageal cancer, it is a promising new modality for the palliation of advanced esophageal cancer.

No significant financial relationships to disclose.
IV-HCC: Clinical and prognostic implications of plasma IGF-1 and VEGF in patients with hepatocellular carcinoma.
Authors: Kaseb A. O. , Morris J. , Hassan M. , Lin E. , Xiao L. , Abdalla E. K. , Vauthey J. , Abbruzzese J. L.
Published: February 2017

155

Background: Hepatocellular carcinoma (HCC) is a vascular tumor, derived mainly by vascular endothelial growth factor (VEGF)-mediated angiogenesis. It is always associated with chronic liver disease (CLD) and cirrhosis, which directly affect survival of HCC patients. Insulin-like growth factor-1 (IGF-1) is produced predominantly in the liver, and therefore, CLD is associated with low levels of IGF-1.

Methods: 288 new consecutive patients with HCC were eligible for the study between 2001 and 2008 at M. D. Anderson Cancer Center. Baseline clinicopathologic features, CLIP and BCLC staging, plasma IGF-1 and VEGF levels were available and multivariate Cox regression models and median survival were calculated. Kaplan-Meier curves were used to estimate overall survival and the log-rank test was used to compare survival probabilities in patients with different IGF-1 and VEGF levels. Recursive partitioning was used to determine the optimal cut point for IGF-1 and VEGF, using repeated training/validation samples, each using 2/3 of the data to determine the best cut point and the remaining 1/3 to validate it. Prognostic ability of different molecular staging systems was compared using C-index.

Results: Lower plasma IGF-1 and higher plasma VEGF levels significantly correlated with advanced clinicopathologic parameters and poor overall survival, with an optimal cut point of 26 pg/mL and 450 pg/mL respectively. The combination of low IGF-1 and high VEGF predicts median OS of 2.7 months compared with 19 month for patients with high IGF-1 and low VEGF (p-value=<0.0001), and further refines the prognostic ability of BCLC and CLIP HCC staging systems (p<0.0001).

Conclusions: Molecular classification of HCC using baseline plasma IGF-1 and VEGF significantly correlated with clinical features and survival of HCC patients. Furthermore, integrating IGF-1 and VEGF into HCC staging systems, CLIP and BCLC, significantly enhanced their ability to predict prognosis. It may prove to be useful in designing strategies to personalize treatment approaches to these patients.

No significant financial relationships to disclose.
Clinical benefit of peretinoin for the suppression of hepatocellular carcinoma (HCC) recurrence in patients with Child-Pugh grade A (CP-A) and small tumor: A subgroup analysis in a phase II/III randomized, placebo-controlled trial.
Authors: Okusaka T. , Makuuchi M. , Matsui O. , Kumada H. , Tanaka K. , Kaneko S. , Moriwaki H. , Izumi N. , Ohashi Y. , Okita K. ,   Peretinoin Study Group, Japan
Published: February 2017

165

Background: HCC has a high recurrence rate and poor prognosis; however, no effective treatment has been established for preventing recurrence after resection or ablation. Peretinoin, an acyclic retinoid, of 600 mg/day reduced HCC recurrence and a strong effect after two years suggested that it mainly suppressed de novo carcinogenesis (ASCO2010). Liver impairment causes non- HCC-related deaths or adverse events, and can potentially mask drug efficacy. The size of the main HCC nodule associates vascular invasion and intrametastasis. To evaluate peretinoin efficacy and assess its mechanism of action, we performed subgroup analysis in CP-A patients who had undergone curative therapy for a small tumor.

Methods: Eligibility criteria included HCV positive, CP-A or B, and prior curative resection or ablation for conventional HCC. The patients were randomized into groups to receive peretinoin 600 mg/day (high dose, H), peretinoin 300 mg/day (low dose, L), or placebo (P). The patients were grouped according to the CP grade and the size of the major tumor <20mm at the time of diagnosis. Cumulative recurrence-free survival rates were calculated. Hazard ratio (HR) was calculated using Cox regression analysis.

Results: Of the 401 patients, 310 showed CP-A, and 144 showed CP-A and tumor size <20 mm. In the CP-A subgroup, the HR of H group (100) vs. P group (106) was 0.603 (95% CI, 0.408-0.891); in the CP-A and tumor size <20 mm subgroup, the HR of H group (49) vs. P group (49) was 0.376 (95% CI, 0.200-0.705). The common treatment-related adverse events in the CP-A subgroup were albuminuria, hypertension, and headache, which were tolerated.

Conclusions: Subgroup analysis with CP-A reinforced the peretinoin efficacy in preventing HCC recurrence. In addition, the CP-A and tumor size <20mm subgroup results strongly suggested that peretinoin inhibited de novo carcinogenesis. The subgroup analyses results of our phase II/II study supported the efficacy and safety of peretinoin and showed that it has early benefits for patients with well-preserved liver function and undergone curative therapy for a small tumor.

[Table: see text]
The correlation between the decrease of intratumoral arterial enhancement and time-to-tumor progression in patients with hepatocellular carcinoma treated with sorafenib.
Authors: Kojima Y. , Mitsunaga S. , Ikeda M. , Takahashi H. , Shimizu S. , Ohno I. , Nakachi K. , Imoto A. , Okusaka T. , Ochiai A.
Published: February 2017

167

Background: In the diagnostic work-up of hepatocellular carcinoma (HCC), intratumoral enhancement in the arterial phase (IE) of dynamic computed tomography (CT) or magnetic resonance imaging (MRI) represents tumor viability. Although such IE has been known to disappear during the course of sorafenib therapy, the precise impact of decreased IE has not yet been elucidated. Therefore, we focused on the impact of decreased IE on the time-to-tumor progression (TTP) in HCC patients (pts) treated with sorafenib.

Methods: The change in IEduring the course of sorafenib therapy was reviewed in 52advanced HCC patients treated between January 2004 and April 2010. decreased IE was defined as the disappearance of arterial enhancement to a level equal to or less than that of the surrounding cancer-free hepatic parenchyma on dynamic CT or MRI. Even if one of the HCC tumors in a patient showed decreased IE, that patient was regarded as showing decreased IE. The impact of the pretreatment variables, decreased IE, and adverse events on the TTP were evaluated by the log-rank test. The Cox proportional hazard model was used to determine the most significant variables related to TTP.

Results: Of the 52 pts, 48 were males and 4 females, and the median age was 70.5 years. The Child-Pugh classification was A in 28 pts and B in 24 pts. HCV Ab positivity, HBs Ag positivity, and seronegativity for both were observed in 39 pts, 7 pts and 6 pts, respectively. Decreased IE was found in 23 patients. The median TTP was 114 days in all patients, 165 days in patients showing decreased IE, and 89 days in patients who did not show decreased IE. The median time to decreased IE was 41 days. In the univariate analysis, decreased IE, female, prothrombin time, and serum PIVKA II were identified as being significantly associated with the TTP. Multivariate analysis using the Cox proportional hazards model revealed decreased IE (p=0.04) and prothrombin time (p=0.04) to be independently associated with a favorable TTP.

Conclusions: Decreased IE is correlated with a favorable time-to-tumor progression in HCC pts treated with sorafenib.

No significant financial relationships to disclose.
Fluorescence in situ hybridization biomarkers of gastric cancer risk in intestinalized Helicobacter pylori pangastritis.
Authors: Kim B. , Bronner M. P.
Published: February 2017

17

Background: H. pylori (HP) intestinalized pangastritis predisposes to gastric adenocarcinoma. Biomarkers to identify the less than 10% subset of chronic gastritis patients who will develop gastric cancer are greatly needed to focus surveillance efforts onto those patients most likely to benefit. Investigations in ulcerative colitis and Barrett's esophagus reveal that chromosomal alterations in far distant and nondysplastic mucosa are powerful cancer biomarkers. We hypothesized a similar situation in gastric tumorigenesis.

Methods: The full morphologic spectrum of gastric neoplasia was examined using flow-sorted gastric epithelial cells from 10 gastric cancer resections versus 20 normal gastric control patients. Then we addressed whether we could distinguish the subset of HP intestinalized pangastritis patients who develop cancer (progressors), from those who remain neoplasia-free (nonprogressors). A single nondysplastic intestinalized gastric antral biopsy collected using chromoendoscopy on each of 41 Korean progressors with gastric cancer and 30 nonprogressors without dysplasia. Interphase FISH on whole epithelial cell preparations using 4q32-q33, 10q22.1, 18q21.2 and 19p11-q11 chromosomal arm probes was performed.

Results: Increasing chromosomal alterations occurred throughout the morphologic spectrum of gastric neoplasia. Significantly increased FISH alterations for chromosomes 4q32-q33 (p = 0.016) and 10q22.1 (p = 0.028) occurred as early in the neoplastic spectrum as nondysplastic distant intestinal metaplasia. Subsequent nondysplastic antral biopsy testing of progressors versus nonprogressors revealed parallel FISH results for 4q32-q33 (p = 0.039) and 10q22.1 (p = 0.023), and 19p11-q11 (p = 0.019). Receiver operator characteristic analysis for these 3 combined probes demonstrated a sensitivity of 0.53 and specificity of 0.92 with optimal choice of thresholds.

Conclusions: Interphase FISH for 4q32-q33, 10q22.1, and 19p11-q11 chromosomal probes on nondysplastic intestinalized antral mucosa shows promise as a biomarker of gastric cancer in multifocal HP intestinalized pangastritis.

No significant financial relationships to disclose.
A matched analysis comparing the epidemiology of intraductal papillary mucinous neoplasms to standard pancreatic adenocarcinoma and healthy controls.
Authors: Ludwig E. , Olson S. H. , Kurtz R. C. , Simon J. , Brennan M. F. , Jarnagin W. R. , Allen P. J.
Published: February 2017

173

Background: The epidemiology of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas is poorly defined.

Methods: An epidemiologic questionnaire was administered to patients (pts) with IPMN (n=79), pancreatic adenocarcinoma (PC) (n=689) and healthy controls (n=307). Results were adjusted for age, gender and BMI. IPMN was defined either by surgical pathology (n=62) or characteristic endoscopic ultrasound appearance and cyst fluid CEA>200 ng/ml (n=17).

Results: In unadjusted analysis IPMN pts were more likely to be ≥ 70 years of age (OR 5.40 [2.88, 10.46]) when compared with PC pts (OR 2.82) and controls. After adjustment for age, gender and BMI, current tobacco smoking was associated with PC (OR 3.06 [1.78, 5.23]) but not IPMN. Pts with IPMN more often had diabetes mellitus for >3 years compared with controls (OR 3.25 [1.45, 7.00], while pts with PC (OR 1.52 (0.86, 2.67]) did not. IPMN pts were more likely to have a history of hypercholesterolemia compared with controls (OR 1.77 [1.05-2.98]); this was not seen for PC pts (OR 1.16 [0.87-1.55]). A first degree relative with PC was not associated with increased risk for IPMN (OR 0.84 [0.27, 2.62]) or PC (OR 1.48 [0.82, 2.67]). Compared to PC, pts with IPMN were more likely to have a history of an unrelated cancer (OR 1.84 [1.08, 3.14]).

Conclusions: Risk factors for IPMN and PC may differ. Compared to PC and control pts, IPMN patients were older; more often had diabetes mellitus and hypercholesterolemia; and did not currently smoke. IPMN was more often associated with a prior history of cancer than PC.

No significant financial relationships to disclose.
Prognostic relevance of a novel AJCC staging classification for neuroendocrine tumors of the pancreas.
Authors: Strosberg J. R. , Cheema A. , Weber J. , Kvols L. K.
Published: February 2017

177

Background: The AJCC Cancer Staging Manual (7th edition, 2010) has introduced a novel TNM staging classification for pancreatic neuroendocrine tumors that is derived from the staging system for exocrine pancreatic adenocarcinomas. This classification has not yet been validated.

Methods: Patients with pancreatic neuroendocrine tumors treated at the H. Lee Moffitt Cancer Center between 1999 and 2010 were assigned a stage (I-IV) based on the new AJCC classification. Overall survival from time of initial diagnosis was measured and statistical significance calculated using the log-rank test. The prognostic relevance of the AJCC staging classification was compared to the relevance of a staging classification proposed recently by the European Neuroendocrine Tumor Society (ENETS).

Results: 425 patients with histologically proven pancreatic neuroendocrine tumors were identified. Both the novel AJCC classification and the ENETS classification were highly prognostic for survival (p<0.00001; Table).

Conclusions: The novel AJCC 7th edition TNM classification for pancreatic neuroendocrine tumors is highly prognostic for overall survival and should be adopted in clinical practice.

[Table: see text]

No significant financial relationships to disclose.
Association of interleukin-6 levels and neutropenia during gemcitabine monotherapy for advanced pancreatic cancer.
Authors: Okuyama H. , Mitsunaga S. , Nakachi K. , Ohno I. , Shimizu S. , Takahashi H. , Okusaka T. , Ueno H. , Ochiai A. , Ikeda M.
Published: February 2017

178

Background: Neutropenia is an important dose-limiting toxicity of gemcitabine (GEM) in patients with advanced pancreatic cancer (PC). Serum haptoglobin, regulated by pro-inflammatory cytokines, is a predictor of neutropenia in PC patients under treatment with GEM. We conducted this study with the aim of identifying the association between serum levels of haptoglobin and cytokines and the risk of development of neutropenia in advanced PC patients receiving GEM therapy.

Methods: Serum levels of haptoglobin and pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1β, IL-2β, IL-6, IL-8, IL-10, IL-12, TNF-α) were measured in 55 patients with advanced PC. All patients (median age: 67 years, male/female: 26/29, ECOG performance status: 0/1/2: 32/21/2,) received GEM monotherapy as the initial treatment for PC. The severity of neutropenia within the first 90 days of the GEM treatment was graded according to the NCI Common Terminology Criteria for Adverse Events, version 3.0. Categorical or and noncategorical data were compared using Student's t test. Multivariate regression analysis was performed using logistic regression modeling. The significance level was set at p<0.05.

Results: Grade 0 to 2 (G0/1/2) and grade 3 to 4 (G3/4) neutropenia were observed in 32 patients (58.2%) and 23 patients (41.8%), respectively. The G3/4 neutropenia group showed low serum levels of haptoglobin (mean 144.4 mg/dl vs. 186.7 mg/dl, p=0.097), IL-1β (mean 0.07 pg/ml vs. 0.24 pg/ml, p=0.044), IL-6 (mean 1.13 pg/ml vs. 6.43 pg/ml, p=0.002), IL-8 (mean 18.4 pg/ml vs. 44.8 pg/ml, p=0.015), and TNF-α (mean 6.28 pg/ml vs. 8.86 pg/ml, p=0.017) as compared to the G0/1/2 neutropenia group. Multivariate analysis revealed that only low serum IL-6 was significantly associated with the development of G3/4 neutropenia (OR=0.081, p=0.0011).

Conclusions: Low serum IL-6 level was associated with severe neutropenia. Thus, circulating IL- 6 levels may be a predictor of the development of severe neutropenia in advanced PC patients receiving GEM therapy.

No significant financial relationships to disclose.
Regenerative nodular hyperplasia (RNH) induced by oxaliplatin-based chemotherapy for colorectal liver metastases (CRLM): A contraindication for major liver resection?
Authors: Aussilhou B. , Ragot E. , Dokmak S. , Faivre S. J. , Paradis V. , Belghiti J.
Published: February 2017

179

Background: Oxaliplatin is recognized to induce vascular lesions in the nontumoral liver parenchyma. Regenerative nodular hyperplasia (RNH), the ultimate state of the vascular lesions, is very rare. In some reported cases, RNH was associated with severe lethal postoperative complications after hepatic resection. This study aimed to compare the postoperative course after major hepatectomy, in patients with colorectal liver metastases treated with oxaliplatin-based chemotherapy, with or without RNH in the resected specimen.

Methods: Between 2001 and 2009, among 420 patients who underwent liver resection for CRLM, 17 (4%) patients had RNH lesions (RNH+ group) on the resected specimen after right hepatectomy. These 17 patients were compared to another group of 20 patients with similar clinicopathologic data but without RNH (RNH- group) who underwent right hepatectomy. The mean age of the RNH + and RNH- groups was 57 years (range: 37-71 years) and 60 years (range: 43-73 years), respectively. Preoperatively the patients were treated with a mean number of 7 cycles of oxaliplatin (range: 3-12 cycles). The peroperative blood loss (560 vs. 830 ml) and blood transfusion (18% vs. 20%) were similar in the two groups.

Results: The mortality in the RNH+ group and the RNH- group (6% vs. 5%, respectively) were similar (p>0.005). The postoperative morbidity was 53% in the RNH+ group and 35% in RNH– group (p>0.005). The most frequent complications were biliary fistula (3 in the RNH+ group and 2 in the RNH- group) and pulmonary complications (6 in the RNH+ group and 5 in the RNH- group). However, the post operative ascites was significantly encountered in the RNH+ group with 70% of patients compared with 40% in the RNH- group. The number of patients who had a bilirubin level at day 5 superior to 50 was significantly higher in the RNH+ group (35%) compared with 15% in the RNH-group.

Conclusions: RNH lesions allow major hepatectomy without increased mortality but with increased postoperative ascites and jaundice justifying preoperative liver biopsy to detect this lesion with subsequent portal embolisation or sparing liver resection in order to avoid major resections.

No significant financial relationships to disclose.
Predictors of hepatitis B screening among patients with cancer.
Authors: Hwang J. , Fisch M. , Zhang H. , Kallen M. A. , Routbort M. , Lal L. , Vierling J. , Suarez-Almazor M.
Published: February 2017

180

Background: Patients with hepatitis B virus (HBV) infection are at risk of reactivation after chemotherapy. It is unclear whether all patients or only those with certain risk factors should be screened for HBV before chemotherapy. The purpose of our study was to determine the clinical predictors of HBV screening in a single institution.

Methods: In this retrospective, cross-sectional study, we evaluated new patients who received chemotherapy between 1/1/04 and 9/30/07. We collected data on patients' demographics, types of cancer and chemotherapy, and HBV risk factors such as a previous ICD-9 code for hepatitis C or other liver conditions. We searched for HBV screening as defined by an HBsAg or anti-HBc test ordered prior to chemotherapy. In univariate analyses, we examined the association between each of the patient-related variables and HBV screening. We then determined predictors of HBV screening in a multivariable logistic regression model.

Results: We found 10,729 patients who had chemotherapy during the study period. Overall, 16.7% had HBV screening. All of the following predictors in the univariate analysis were significant for HBV screening at the p<0.01 level: age, gender, ethnicity, U.S. residence, cancer type, chemotherapy type, and having a HBV risk factor. In multivariable logistic regression examining predictors for screening using HBsAg, we found that Asian ethnicity (OR 1.75; 1.16-2.66), hematologic malignancies (OR 22.65; 19.3-26.31), and the receipt of rituxamab (OR 3.71; 3.03-4.48) were significant predictors at the p<0.01 level. Women were less likely to be screened than men (OR 0.68; 0.59-0.78). We repeated the analyses using the anti-HBc screening test, and the results were similar. Overall, 1.5% of the screened patients had a positive HBV test.

Conclusions: We found that ethnicity, cancer types, and chemotherapy drugs predict physician-driven HBV screening. Future research is needed to study the predictors of a positive HBV screening test and reactivation of HBV after chemotherapy.

[Table: see text]
Survival analyses of pancreatic neuroendocrine tumors: Contrasting institutional databases with population-based studies.
Authors: Strosberg J. R. , Halfdanarson T. R.
Published: February 2017

186

Background: Prognostic data in pancreatic neuroendocrine tumors derives from population-based studies as well as from institutional databases.

Methods: The stage-stratified rates of 5-year survival derived from two institutional databases were contrasted with rates of 5-year survival derived from two national population-based studies (SEER 1973-2000 and National Cancer Data Base 1985-2004).

Results: The 5-year survival rates derived from the two separate institutional databases were concordant with each other, but markedly higher than the 5-year survival rates derived from the population databases (Table). 5-year survival rates among stage IV patients were 55% and 57% in the institutional databases versus 15% and 19% in the population databases.

Conclusions: Survival rates derived from institutional databases are substantially higher than survival rates derived from national population databases. The causes of these differences have yet to be clarified.

[Table: see text]

No significant financial relationships to disclose.