Reviewing the review: a qualitative assessment of the peer review process in surgical journals.

BACKGROUND: Despite rapid growth of the scientific literature, no consensus guidelines have emerged to define the optimal criteria for editors to grade submitted manuscripts. The purpose of this project was to assess the peer reviewer metrics currently used in the surgical literature to evaluate original manuscript submissions. METHODS: Manuscript grading forms for 14 of the highest circulation general surgery-related journals were evaluated for content, including the type and number of quantitative and qualitative questions asked of peer reviewers. Reviewer grading forms for the seven surgical journals with the higher impact factors were compared to the seven surgical journals with lower impact factors using Fisher's exact tests. RESULTS: Impact factors of the studied journals ranged from 1.73 to 8.57, with a median impact factor of 4.26 in the higher group and 2.81 in the lower group. The content of the grading forms was found to vary considerably. Relatively few journals asked reviewers to grade specific components of a manuscript. Higher impact factor journal manuscript grading forms more frequently addressed statistical analysis, ethical considerations, and conflict of interest. In contrast, lower impact factor journals more commonly requested reviewers to make qualitative assessments of novelty/originality, scientific validity, and scientific importance. CONCLUSION: Substantial variation exists in the grading criteria used to evaluate original manuscripts submitted to the surgical literature for peer review, with differential emphasis placed on certain criteria correlated to journal impact factors.

Steps to Getting Your Manuscript Published in a High-Quality Medical Journal.

Publication of your research represents the culmination of your scientific activities. The key to getting manuscripts accepted is to make them understandable and informative so that your colleagues will read and benefit from them. We describe key criteria for acceptance of manuscripts and outline a multi-step process for writing the manuscript. The likelihood that a manuscript will be accepted by a major journal is significantly increased if the manuscript is written in polished and fluent scientific English. Although scientific quality is the most important consideration, clear and concise writing often makes the difference between acceptance and rejection. As with any skill, efficient writing of high-quality manuscripts comes with experience and repetition. It is very uncommon for a manuscript to be accepted as submitted to a journal. Thoughtful and respectful responses to the journal reviewers' comments are critical. Success in scientific writing, as in surgery, is dependent on effort, repetition, and commitment. The transfer of knowledge through a well-written publication in a high-quality medical journal will have an impact not only in your own institution and country, but also throughout the world.

Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial.

BACKGROUND: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. METHODS: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. RESULTS: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. CONCLUSIONS: Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity.

Constituents of the leaves of Verbascum blattaria.

Phytochemical investigation of the dried leaves of Verbascum blattaria L. (Scrophulariaceae) led to the isolation and identification of five known compounds, E-harpagoside, laterioside, kaempferol 3-O-ß-D-glucopyranoside, bis(2-ethylhexyl)phthalate, and (2S)-liquiritigenin. The structures of these compounds were determined by physical and spectroscopic data analysis. All compounds were isolated from V blattaria for the first time.

Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04.

PURPOSE: The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. PATIENTS AND METHODS: Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). RESULTS: From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). CONCLUSION: Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.

The coat protein of Alternanthera mosaic virus is the elicitor of a temperature-sensitive systemic necrosis in Nicotiana benthamiana, and interacts with a host boron transporter protein.

Different isolates of Alternanthera mosaic virus (AltMV; Potexvirus), including four infectious clones derived from AltMV-SP, induce distinct systemic symptoms in Nicotiana benthamiana. Virus accumulation was enhanced at 15 °C compared to 25 °C; severe clone AltMV 3-7 induced systemic necrosis (SN) and plant death at 15 °C. No interaction with potexvirus resistance gene Rx was detected, although SN was ablated by silencing of SGT1, as for other cases of potexvirus-induced necrosis. Substitution of AltMV 3-7 coat protein (CPSP) with that from AltMV-Po (CP(Po)) eliminated SN at 15 °C, and ameliorated symptoms in Alternanthera dentata and soybean. Substitution of only two residues from CP(Po) [either MN(13,14)ID or LA(76,77)IS] efficiently ablated SN in N. benthamiana. CPSP but not CP(Po) interacted with Arabidopsis boron transporter protein AtBOR1 by yeast two-hybrid assay; N. benthamiana homolog NbBOR1 interacted more strongly with CPSP than CP(Po) in bimolecular fluorescence complementation, and may affect recognition of CP as an elicitor of SN.

Alternating systemic and hepatic artery infusion therapy for resected liver metastases from colorectal cancer: a North Central Cancer Treatment Group (NCCTG)/ National Surgical Adjuvant Breast and Bowel Project (NSABP) phase II intergroup trial, N9945/CI-66.

PURPOSE Prior trials have shown that surgery followed by hepatic artery infusion (HAI) of floxuridine (FUDR) alternating with systemic fluorouracil improves survival rates. Oxaliplatin combined with capecitabine has demonstrated activity in advanced colorectal cancer. Based on this observation a trial was conducted to assess the potential benefit of systemic oxaliplatin and capecitabine alternating with HAI of FUDR. The primary end point was 2-year survival. PATIENTS AND METHODS Patients with liver-only metastases from colorectal cancer amenable to resection or cryoablation were eligible. HAI and systemic therapy was initiated after metastasectomy. Alternating courses of HAI consisted of 0.2 mg/m(2)/d FUDR and dexamethasone, day 1 through 14 weeks 1 and 2. Systemic therapy included oxaliplatin 130 mg/m(2) day 1 with capecitabine at 1,000 mg/m(2) twice daily, days 1 through 14, weeks 4 and 5. Two additional 3-week courses of systemic therapy were given. Capecitabine was reduced to 850 mg/m(2) twice daily after interim review of toxicity. Results Fifty-five of 76 eligible patients were able to initiate protocol-directed therapy and completed median of six cycles (range, one to six). Three postoperative or treatment-related deaths were reported. Overall, 88% of evaluable patients were alive at 2 years. With a median follow-up of 4.8 years, a total of 30 patients have had disease recurrence, 11 involving the liver. Median disease-free survival was 32.7 months. CONCLUSION Alternating HAI of FUDR and systemic capecitabine and oxaliplatin met the prespecified end point of higher than 85% survival at 2 years and was clinically tolerable. However, the merits of this approach need to be established with a phase III trial.

Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03.

PURPOSE: Although chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma. PATIENTS AND METHODS: Patients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: From August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P = .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence. CONCLUSION: Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.