This is the first in a series of practice guidelines commissioned by the Infectious Diseases Society of America through its Practice Guidelines Committee. The purpose of these guidelines is to provide assistance to clinicians when making decisions on treating the conditions specified in each guideline. The targeted providers are internists, pediatricians, and family practitioners. The targeted patients and setting for the fever and neutropenia guideline are hospitalized individuals with neutropenia secondary to cancer chemotherapy. Panel members represented experts in adult and pediatric infectious diseases and oncology. The guidelines are evidence-based. A standard ranking system was used for the strength of the recommendations and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council. An executive summary, algorithms, and tables highlight the major recommendations. The guideline will be listed on the IDSA home page at http://www.idsociety.org.

/pdf/1997-guidelines-for-the-use-of-antimicrobial-agents-in-1wxhwgdaus.pdf

1997 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Unexplained Fever

Background
This is the second updated version of the original Cochrane review published in the Cochrane Library 2009, Issue 3.

Most women with early cervical cancer (stages I to IIA) are cured with surgery or radiotherapy, or both. We performed this review originally because it was unclear whether cisplatin-based chemotherapy after surgery, radiotherapy or both, in women with early stage disease with risk factors for recurrence, was associated with additional survival benefits or risks.

Objectives
To evaluate the effectiveness and safety of adjuvant platinum-based chemotherapy after radical hysterectomy, radiotherapy, or both in the treatment of early stage cervical cancer.

Search methods
For the original 2009 review, we searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library 2009, Issue 1), MEDLINE, Embase, LILACS, BIOLOGICAL ABSTRACTS and CancerLit, the National Research Register and Clinical Trials register, with no language restriction. We handsearched abstracts of scientific meetings and other relevant publications. We extended the database searches to November 2011 for the first update and to September 2016 for the second update.

Selection criteria
Randomised controlled trials (RCTs) comparing adjuvant cisplatin-based chemotherapy (after radical surgery, radiotherapy or both) with no adjuvant chemotherapy, in women with early stage cervical cancer (stage IA2-IIA) with at least one risk factor for recurrence.

Data collection and analysis
Two review authors extracted data independently. Meta-analysis was performed using a random-effects model, with death and disease progression as outcomes.

Main results
For this second updated version we identified only one small trial reporting grade 4 toxicity results, without disease-free or overall survival data with a median follow-up of 16 months.

From the first updated version, we identified three trials that were ongoing, and remain so in 2016.

Four trials including 401 women with evaluable results with early cervical cancer were included in the meta-analyses. The median follow-up period in these trials ranged from 29 to 42 months. All women had undergone surgery first. Three trials compared chemotherapy combined with radiotherapy versus radiotherapy alone; and one trial compared chemotherapy followed by radiotherapy versus radiotherapy alone. It was not possible to perform subgroup analyses by stage or tumour size.

Compared with adjuvant radiotherapy, chemotherapy combined with radiotherapy significantly reduced the risk of death (two trials, 297 women; hazard ratio (HR) = 0.56, 95% confidence interval (CI): 0.36 to 0.87) and disease progression (two trials, 297 women; HR = 0.47, 95% CI 0.30 to 0.74), with no heterogeneity between trials (I² = 0% for both meta-analyses). Acute grade 4 toxicity occurred significantly more frequently in the chemotherapy plus radiotherapy group than in the radiotherapy group (three trials, 321 women; risk ratio (RR) 6.26, 95% CI 2.50 to 15.67). We considered the evidence for all three outcomes to be of a moderate quality, using the GRADE approach due to small numbers and limited follow-up in the included studies. In addition, it was not possible to separate data for bulky early stage disease.

In the one small trial that compared adjuvant chemotherapy followed by radiotherapy with adjuvant radiotherapy alone there was no difference in disease recurrence between the groups (one trial, 71 women; HR = 1.34; 95% CI 0.24 to 7.66) and overall survival was not reported. We considered this evidence to be of a low quality.

No trials compared adjuvant platinum-based chemotherapy with no adjuvant chemotherapy after surgery for early cervical cancer with risk factors for recurrence.

Authors' conclusions
The addition of platinum-based chemotherapy to adjuvant radiotherapy (chemoradiation) may improve survival in women with early stage cervical cancer (IA2-IIA) and risk factors for recurrence. Adjuvant chemoradiation is associated with an increased risk of severe acute toxicity, although it is not clear whether this toxicity is significant in the long term due to a lack of long-term data. This evidence is limited by the small numbers and low to moderate methodological quality of the included studies. We await the results of three ongoing trials, which are likely to have an important impact on our confidence in this evidence.

Adjuvant platinum-based chemotherapy for early stage cervical cancer.

Reduction of chemotherapy-induced febrile leucopenia by prophylactic use of ciprofloxacin and roxithromycin in small-cell lung cancer patients: An EORTC double-blind placebo-controlled phase III study

Ovarian cancer is characterized by dysbiosis, referred to as oncobiosis in neoplastic diseases. In ovarian cancer, oncobiosis was identified in numerous compartments, including the tumor tissue itself, the upper and lower female genital tract, serum, peritoneum, and the intestines. Colonization was linked to Gram-negative bacteria with high inflammatory potential. Local inflammation probably participates in the initiation and continuation of carcinogenesis. Furthermore, local bacterial colonies in the peritoneum may facilitate metastasis formation in ovarian cancer. Vaginal infections (e.g. Neisseria gonorrhoeae or Chlamydia trachomatis) increase the risk of developing ovarian cancer. Bacterial metabolites, produced by the healthy eubiome or the oncobiome, may exert autocrine, paracrine, and hormone-like effects, as was evidenced in breast cancer or pancreas adenocarcinoma. We discuss the possible involvement of lipopolysaccharides, lysophosphatides and tryptophan metabolites, as well as, short-chain fatty acids, secondary bile acids and polyamines in the carcinogenesis of ovarian cancer. We discuss the applicability of nutrients, antibiotics, and probiotics to harness the microbiome and support ovarian cancer therapy. The oncobiome and the most likely bacterial metabolites play vital roles in mediating the effectiveness of chemotherapy. Finally, we discuss the potential of oncobiotic changes as biomarkers for the diagnosis of ovarian cancer and microbial metabolites as possible adjuvant agents in therapy.

/pdf/the-role-of-the-microbiome-in-ovarian-cancer-mechanistic-4gkgt1v79p.pdf

The role of the microbiome in ovarian cancer: mechanistic insights into oncobiosis and to bacterial metabolite signaling.

Cancer of the neovagina.

Chemoprophylaxis with oral ciprofloxacin in ovarian cancer patients receiving taxol.

The aim of this study was to investigate gray scale and color flow characteristics of a group of patients with a suspected uterine pathologic condition. One hundred and twenty-two consecutive patients at the Women's Cancer Center, University of Minnesota, undergoing transvaginal sonography and color flow Doppler imaging for suspected uterine corpus abnormality made up the study group. After gray scale morphologic assessment, color flow Doppler imaging of the tumor and uterus was performed, including the ipsilateral uterine artery. Malignant tumors were confirmed pathologically in all 35 patients who had them. In comparing patients with benign versus malignant tumors, gray scale morphologic assessment confirmed that malignant uterine tumors (31 endometrial cancers and four sarcomas) were more likely to have a thickened echoic endometrium (P = < 0.0001), be enlarged (P = 0.004), to be retroverted (P = 0.02), and to lack a subendometrial halo (P < 0.0001). Patients with four benign and 13 malignant tumors demonstrated increased flow when assessed by CFD. The calculated sensitivity of increased color flow in predicting malignancy was 39%, with a specificity of 92%, a positive predictive value of 77%, and a negative predictive value of 71%. No difference existed between the benign and malignant groups for the systolic, diastolic, and mean velocities and for the calculated pulsatility index and resistive index in both sampled uterine and intramyometrial or tumor vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Gray scale and color flow Doppler characterization of uterine tumors

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer

Recurrent squamous cell carcinoma in a rectus abdominis neovagina.

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Chemoprophylaxis with oral ciprofloxacin in ovarian cancer patients receiving taxol.

Gray scale and color flow Doppler characterization of uterine tumors

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer

Recurrent squamous cell carcinoma in a rectus abdominis neovagina.