Port-site hernia recurrence at previous 5-mm laparoscopic access: case report and review of literature.

Port-site hernia (PSH) of less than 10 mm is an exceptionally rare complication of minimally invasive surgery (MIS). To date, there have been no cases in the literature reporting recurrence of PSH from a 5 mm incision. We present the first case of PSH recurrence in a woman who underwent surgery for benign gynaecological pathology via a MIS approach. Her post-operative course was complicated by an episode of symptomatic hernia arising from a 5 mm accessory trocar which was surgically managed. A few months later she re-presented with the same symptoms and had a PSH recurrence of the same port-site. Two corrective surgeries employing different techniques were performed. The first episode was managed laparoscopically using interrupted stitches. On the other hand, the PSH recurrence was managed by placement of a mesh. Ultrasound played a crucial role in diagnostics, especially in the recurrent setting. Due to the complete absence of similar cases in the literature, the decision making around the management of a PSH recurrence from a 5 mm trocar site proved to be challenging. As MIS is the current standard of care, more cases are likely to occur, however despite the increasing number of surgical procedures performed via MIS, no established guidelines for managing such complications have been proposed. Trying to bridge this gap, we present the case report of the first case of PSH recurrence from a 5 mm accessory port and a review of the most significant literature available to date. We finally summarise the reported cases of PSH and the types of surgical repair conducted to highlight the absence of a standard of care.

Oxygen-ozone therapy as support and palliative therapy in 50 cancer patients with fatigue - A short report.

OBJECTIVE: Fatigue may be cause by all cancer treatments, maybe because the tissue damage or the build-up of dead cells derived products. PATIENTS AND METHODS: At the Mede Clinic in Sacile, Pordenone, Italy, from February 2016 to May 2018 we studied 50 patients with cancer and fatigue (15 with breast cancer, 12 with lung cancer, 11 with colon cancer, 5 with renal cancer, 3 with prostate cancer, 2 with melanoma and 2 hepatocellular carcinoma). Patients were treated with Auto Hemotransfusion (GAE) according to the SIOOT (Scientific Society of Oxygen Ozone Therapy) protocols, two times a week for one month and then twice monthly as maintenance therapy. RESULTS: Nineteen of them were undergoing neoplastic treatment, 10 had already ended the cancer therapy and 21 were in a palliative setting. The Fatigue Severity Scale was used to assess the extent of fatigue in patients, in order to estimate the severity of the symptom with a score from 1 to 7. No side effects were found, and 35 patients (70%) achieved a significant improvement (> 50%) of the symptoms. CONCLUSIONS: Our preliminary data demonstrate that ozone therapy is a valid supportive therapy for fatigue in cancer patients, both during cancer therapy and in a palliative setting with no significant side effects.

Risk of cancer after assisted reproduction: a review of the available evidences and guidance to fertility counselors.

OBJECTIVE: Infertile women requiring ovarian stimulation and assisted reproduction techniques (ART) are faced with difficult issues. The fear that using hormones could increase their risk of cancer is the most significant. One of the main challenges for assessing cancer risk after ART is the difficulty to separate it from the underlying condition of infertility per se. The delay or the inability to achieve a pregnancy is an important risk factor for breast, endometrial and ovarian cancer. We analyzed the current literature on the topic. MATERIALS AND METHODS: The published literature in Medline and Cochrane was screened using the following keywords: ovulation induction, reproductive techniques, clomiphene, in vitro fertilization, fertility agents, female/adverse effects, female/toxicity gonadotropins/ adverse effects or gonadotropins/toxicity and "neoplasms or cancer". RESULTS: A total of 95 articles were evaluated. Limited evidence suggests that high doses or many cycles of clomiphene citrate could increase the risk of endometrial cancer, although the confounding factors of polycystic ovarian disease and overweight are not always considered. In some studies, ART modestly increased the risk of borderline ovarian cancer. Fertility treatments do not increase the risk of breast, cervical, endometrial and ovarian cancers, thyroid, melanoma and colon cancer. CONCLUSIONS: Women can be reassured that fertility drugs do not appear to significantly increase the risk of invasive ovarian, endometrial, breast or other cancers, while achieving a pregnancy at an earlier age is a significant protective factor.

Is ovulation induction with letrozole in breast cancer patients still safe even if it could increase progesterone levels?

Very high progesterone levels (mean 186.6 ± 43.6 ng/mL) during the luteal phase were found in a small study of breast cancers patients undergoing controlled ovarian stimulation (COS) with letrozole plus recombinant FSH. Results highlight the need to further evaluate this in larger series. While waiting, the clinical significance of high progesterone levels can be drawn from epidemiological and experimental data here reviewed in order to give reassurance to the clinician involved in fertility preservation. If the progesterone increase will be confirmed, epidemiological and experimental data do not seem to indicate a detrimental effect or they could even be protective. As this possible rise of levels is a very short event in the very long lasting and multifactorial breast carcinogenesis, it is unlikely that it will significantly influence breast cancer prognosis.

Ospemifene: a safe treatment of vaginal atrophy.

OBJECTIVE: Vaginal atrophy is a chronic, progressive medical condition that affects fifty percent of postmenopausal women, causing symptoms like dyspareunia, vaginal dryness, and vaginal irritation. Until recently, the only prescription options were systemic and vaginal estrogen therapies that might be limited by concerns about long-term safety and breast cancer risk. The objective is to analyze the literature about ospemifene, a tissue-selective estrogen receptor modulator (SERM) recently approved for the treatment of vulvovaginal atrophy and dyspareunia and to compare its effects with those of the other SERMs to assess its safety. MATERIALS AND METHODS: Review. Medline search. RESULTS: Ospemifene treats vaginal atrophy, and, if compared with other SERMS, it has no or not significant effects on endometrium and thromboembolism. Experimental and animal models suggest an inhibitory effect on the growth of malignant breast tissue. The available clinical data support ospemifene breast safety. CONCLUSIONS: Ospemifene relieves moderate to severe symptoms of vulvovaginal atrophy, like dryness, irritation and soreness around the genital area, and painful sexual intercourse, in menopausal women. It is well tolerated, and it has neutral effects on endometrium and coagulation. Clinical trials and even long-term studies on breast cancer effects support ospemifene overall safety.

Rational selection of predictive pharmacogenomics test for the Fluoropyrimidine/Oxaliplatin based therapy.

OBJECTIVE: Both Fluoropyrimidine and Oxaliplatin (FluOx) are the most common anticancer drugs used to treat colorectal, ovarian, and gastrointestinal cancers. Nevertheless, the efficacy of FluOx-based therapy is often compromised by the severe risk of neurotoxicity, cardiotoxicity, and gastrointestinal toxicity. Stratification of patients for their individual response to drugs is a promising approach for cancer treatment and cost-effectiveness. Here we evaluate the most recent findings on the most appropriate gene variants related to the toxicity in patients receiving FluOx chemotherapy. MATERIALS AND METHODS: A systematic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted to identify all clinical studies of any association between DPYD and 5-FU correlated to allelic status of 6 validated polymorphisms in five genes Dihydropyrimidine Dehydrogenase (DPYD), Thymidylate Synthase (TYMS), Glutathione S-Transferase (GSTP1), and DNA-repair genes (ERCC2 and XRCC1). RESULTS: The stratification of the patients into three genotype profiles group, who are most likely responders to FluOx treatments, provide informations about toxicity and/or resistance before starting therapy. Also, early evaluation cost of panel testing proposed is averaged about €100,00 per sample. The evaluation costs of genotyping before starting treatment could be a good cost-effectiveness strategy. CONCLUSIONS: Based on the individual genomic profile, the oncologists will have new possibilities, based on the individual genetic profile, to make treatment decisions for their patients and to redefine scheduling and dosage of FluOx-based therapy.

Antiblastic treatment of haematological malignancies during pregnancy: a crucial decision.

Antiblastic treatment of hematological malignancies during pregnancy poses a number of issues related to the curability of the maternal disease, the need of a prompt treatment and the potential toxicity of chemotherapy for the fetus. Here we report the results of a systematic literature search about the management of the most frequent hematological malignancies that may occur during pregnancy, focusing on specific issues related to gestational age at diagnosis, fetal toxicity and efficacy on the maternal side. The standard approach in non-pregnant women is illustrated as reference.

Antiblastic treatment, for solid tumors, during pregnancy: a crucial decision.

Cancer is the second leading cause of death during the reproductive years complicating between 0.02 percent and 0.1 percent of pregnancies. The incidence is expected to rise with the increase in age of childbearing. The most common types of pregnancy-associated cancers are: cervical cancer, breast cancer, malignant melanoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma and ovarian cancer. The relatively rare occurrence of pregnancy-associated cancer precludes conducting large, prospective studies to examine diagnostic, management and outcome issues. The treatment of pregnancy-associated cancer is complex since it may be associated with adverse fatal effects. In pregnant patients diagnosed with cancer during the first trimester, treatment with multidrug anti-cancer chemotherapy is associated with an increased risk of congenital malformations, spontaneous abortions or fetal death, and therefore, should follow a strong recommendation for pregnancy termination. Second and third trimester exposure is not associated with teratogenic effect but increases the risk of intrauterine growth retardation and low birth weight. There are no sufficient data regarding the teratogenicity of most cytotoxic drugs. Almost all chemotherapeutic agents were found to be teratogenic in animals and for some drugs only experimental data exist. Moreover, no pharmacokinetic studies have been conducted in pregnant women receiving chemotherapy in order to understand whether pregnant women should be treated with different doses of chemotherapy. This article reviews the available data regarding the different aspects of the treatment of cancer during pregnancy.

Obstetrical, fetal and postnatal effects of gestational antiblastic chemotherapy: how to counsel cancer patients.

At least one in a thousand pregnancies is complicated by cancer and, as the maternal age at pregnancy increases, numbers are growing. If chemotherapy cannot be postponed, both doctors and patients face complex medical and ethical issues. There is a conflict between optimal maternal therapy and fetal wellbeing. Treatment during the first trimester increases the risk of congenital malformations, spontaneous abortions and fetal death. Second and third trimester exposure is less risky, but it can cause intrauterine growth retardation and low birth weight. Other effects on pregnancy after the first trimester include premature birth, stillbirth, impaired functional development, myocardial toxicity and myelosuppression. Counseling and management of these cases are difficult, because literature is mostly represented by case reports or retrospective series while randomized prospective studies or guidelines are lacking. Moreover, personal experience is often scanty due to the rarity of the condition. This article reviews the available data regarding the different aspects of systemic treatment of cancer during pregnancy to help oncologist and obstetricians in counseling their patients and treat them accordingly.

Effect of one-month treatment with vaginal promestriene on serum estrone sulfate levels in cancer patients: a pilot study.

UNLABELLED: Vaginal promestriene was tested in gynecological cancer patients who suffered from severe vaginal dryness and dyspareunia. This form of estrogen has a low level of vaginal absorption and proved to be effective for vaginal atrophy. METHOD: 17 patients were treated with a 10mg soft vaginal suppository daily for one month. Plasma levels of estrone sulfate (E1S), used as the marker of overall estrogenicity, were measured by liquid chromatography in combination with mass spectrometry. RESULTS: Mean E1S levels changed from 533 (22-2920) to 374 (81-856) pg/ml (p=0.39). CONCLUSION: In highly symptomatic gynecological cancer patients the level of circulating estrone sulfate was not significantly affected by vaginal promestriene treatment overall, but a wide range of levels was noted pre and post treatment in individual patients.

Non-hormonal treatment of vasomotor symptoms in gynecological cancer patients.

Gynaecological cancer patients generally suffer from an earlier and more severe menopausal syndrome than the general female population. Hormone replacement therapy is often contraindicated and there are non-hormonal treatments that are proven to be more effective than placebo in randomized controlled trials, e.g., some antidepressants, gabapentine and clonidine. The main limits to the use of these drugs in controlling hot flashes are the off-label use for this purpose, the very short follow-up and the fact that data come from studies performed on breast cancer, not on gynecological cancer patients. Patients believe that drugs derived from plants could be effective in relieving hot flashes and that they are harmless. Evidence is contrary to this belief and estrogen-sensitive cancer patients should be warned of the potential, though very weak, estrogenic effect of phytoestrogens and other "natural" drugs, and that their efficacy is close to that of a placebo.

[Treatment of atrophic and irritative vulvovaginal symptoms with an anhydrous lipogel and its complementary effect with vaginal estrogenic therapy: new evidences]. / Trattamento dei disturbi trofici e irritativi vulvovaginali con un lipogel anidro e suo effetto complementare alla terapia estrogenica per via vaginale: nuovi approfondimenti.

It is sometimes difficult to treat vulvovaginal itching and dryness, which represent frustrating symptoms for both patients and doctors. In case that the etiological agent is Candida albicans, effective antimycotic therapies are available; however, itching is often caused by aspecific allergic-irritative factors, which are difficult to be defined. In these cases, patients are invited to limit local irritative factors; nevertheless, this advice is not always taken and sometimes it turns out to be insufficient. Besides behavioral suggestions, a therapeutic support would be useful; medical doctors habitually prescribe local symptomatic treatments which, however, do not target numerous causes of irritative vulvovaginal symptomatology, though they are formulated for vulvovaginal application. If there is estrogenic deficit, the best therapeutic approach is based on topical estrogenic therapy, which is sometimes ineffective on vulvar symptoms. Frequently, it is necessary to choose a complementary therapeutic tool for vaginal application in order to alleviate itching, burning, erythema, dryness. The aim of this study was to evaluate the efficacy of an innovative anhydrous lipogel containing vitamin E and boswellic acids. Results of this study, performed on 34-58-year-old patients, confirmed the efficacy of the lipogel on irritative vulvovaginal symptoms. In postmenopausal women, the lipogel is a useful synergistic complement to topical hormonal therapy.

Middle-term expansion of hematopoietic cord blood cells with new human stromal cell line feeder-layers and different cytokine cocktails.

Cord blood (CB) is a source of hematopoietic stem cells (HSCs) and is an alternative to bone marrow for allogenic transplantation in patients with hematological disorders. The improvement of HSC in vitro expansion is one of the main challenges in cell therapy. Stromal components and soluble factors, such as cytokines, can be useful to induce in vitro cell expansion. Hence, we investigated whether feeder-layers from new stromal cell lines and different exogenous cytokine cocktails induce HSC expansion in middle-term cultures. CB HSC middle-term expansion was carried out in co-cultures on different feeder-layers exposed to three different cytokine cocktails. CB HSC expansion was also carried out in stroma-free cultures in the presence of different cytokine cocktails. Clonogenic tests were performed, and cell growth levels were evaluated. Moreover, the presence of VCAM-1 mRNA was assessed, and the mesenchymal cell-like phenotype expression was detected. All feeder-layers were able to induce a significant clonogenic growth with respect to the control culture, and all of the cytokine cocktails induced a significant increase in CB cell expansion indexes, even though no potential variation dependent on their composition was noted. The modulative effects of the different cocktails, exerted on each cell line used, was dependent on their composition. Finally, all cell lines were positive for CD73, CD117 and CD309, similar to mesenchymal stem cells present in adult bone marrow and in other human tissues, and negative for the hematopoietic markers. These data indicate that our cell lines have, not only a stromal cell-like phenotype, but also a mesenchymal cell-like phenotype, and they have the potential to support in vitro expansion of CB HSCs. Moreover, exogenous cytokines can be used in synergism with feeder-layers to improve the expansion levels of CB HSCs in preparation for their clinical use in allogenic transplantation.

Rational reconstitution of the immune repertoire in AIDS with autologous, antigen-specific, in vitro-expanded CD4 lymphocytes.

HIV infection leads to decrease of CD4 lymphocytes. In particular, loss of CD4 cells specific for opportunistic pathogens results in active opportunistic infections, that are the chief cause of morbidity and mortality in AIDS. Highly active anti-retroviral therapy (HAART) has been shown to have dramatic effects in a large fraction of treated individuals, such as decrease of viral load and increase of CD4 cells. It has not been clearly established, though, whether CD4 cells that appear during HAART represent a functional repertoire (i.e. a CD4 repertoire that encompasses all specificities, including T-cells responding to opportunistic pathogens, as in immunocompetent individuals) or an amplified mirror image of a defective repertoire. Therefore we propose that the immune repertoire can be reconstituted with autologous CD4 lymphocytes collected at early stages of infection, selected for specificity for opportunistic pathogens, expanded and stored for future use when laboratory or clinical signs indicate a depletion of antigen-specific CD4 cells. Since the reinfused CD4 cells are themselves susceptible to HIV infection-replication, we suggest that in vitro gene therapy of these cells may confer a genetic resistance that is permanently maintained in these cells.

Anti-HIV genetic treatment of antigen-specific human CD4 lymphocytes for adoptive immunotherapy of opportunistic infections in AIDS.

HIV-1 infection results in the loss of CD4+ T helper lymphocytes which make up the immune repertoire. This leads to opportunistic infections that define AIDS. Here, we show that CD4 T cell lines from normal donors with specificity for different antigens can be rendered resistant to HIV-1 replication by retroviral transduction with an antisense vector directed to the HIV-1 tat gene. The genetic treatment did not affect the properties of antigen-specific CD4 lymphocytes such as proliferative response, lymphokine production and phenotypic markers. The HIV-1 challenge dose that resulted in productive infection was two to four logs higher for transduced cells as compared with control cells. Resistance was shown with the HXB2 strain, whose tat sequence was used to design the antisense gene, and with the SF2 strain, whose targeted tat sequence carries five nucleotide mismatches. Retroviral transduction was also performed on a Candida-specific T cell line from a seropositive individual. This line, derived from T cells infected in vivo, produced infectious virus when stimulated in vitro with antigen, but was no longer productive after transduction. In addition, a four log higher HIV-1 challenge dose was needed for a productive superinfection of this T cell line. The production of antigen-specific CD4 T cells resistant to HIV-1 replication to be used in adoptive immunotherapy of opportunistic infections may represent a new form of gene therapy of AIDS.

A new antisense tRNA construct for the genetic treatment of human immunodeficiency virus type 1 infection.

Different strategies proposed in the literature to attempt gene therapy of AIDS are based mainly on the intracellular production of RNA and protein therapeutics. This report describes the construction and the anti-human immunodeficiency virus type 1 (HIV-1) activity of a new type of antisense tRNA directed against a nucleotide region in the first coding exon of HIV-1 tat (nucleotides 5924 to 5943; Los Alamos data bank) which is conserved among many HIV-1 clones. The anti-tat antisense sequence was inserted into a tRNA(Pro) backbone by replacement of the anticodon loop, without altering the tRNA canonic tetraloop structure. The antisense tRNA was able to interact effectively with its target in vitro. Jurkat cells that constitutively expressed the anti-tat tRNA following retroviral vector transduction exhibited significant resistance to HIV-1 de novo infection. Resistance seemed to correlate with the level of antisense expression. This is the first time that such a tRNA antisense strategy has been shown to be effective as a genetic treatment of HIV-1 infection in tissue culture. The construct design proposed in this report has some intrinsic advantages: the transcript is driven by a polymerase III promoter, the short length of the RNA minimizes effects of intramolecular base pairing that may impair target recognition, and the antisense RNA has the stability and intracellular fate of a native tRNA molecule.

Endometrial stage I carcinoma treated with surgery and adjuvant irradiation: a retrospective analysis.

AIMS AND BACKGROUND: Data from the literature show that the incidence of pelvic recurrences in poor prognosis endometrial carcinoma is significantly reduced by combined surgery and radiotherapy compared to surgery alone. METHODS: In this paper we analyze the results of the combined treatment surgery and adjuvant irradiation in patients with endometrial carcinoma with regard to survival, site of progression, and toxicity. The surgical treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy in 40 patients. Pelvic and para-aortic node dissection was performed in 19 patients and lymph node sampling in 5. RESULTS: Overall 5-year survival was 85%. One patient had local failure, and 5 patients with local control of disease had distant metastases. Toxicity was mild and transient. CONCLUSIONS: Our experience confirms the data of the literature. Postoperative irradiation is a safe and well-tolerated treatment that can achieve a good local control in high risk, stage I, endometrial carcinoma. The control of distant metastases remains an open question.

[Combined surgical and radiotherapy treatment in endometrial cancer]. / Il trattamento combinato chirurgico e radioterapico del cancro dell'endometrio.

Early stage endometrial carcinoma is usually treated by surgery and radiotherapy if there is a substantial risk of recurrence. The aim of this study was to evaluate early and late toxicity, to determine the sites of recurrence and the prognostic factors which were statistically correlated with survival in patients who were treated with surgery plus external beam radiotherapy. MATERIALS AND METHODS. We have carried out a retrospective analysis of the records of 87 patients treated with hysterectomy plus external beam pelvic radiotherapy (50 Gy/28 Fractions), at the Radiotherapy Division of the CRO Aviano PN Italy, between 1985 and 1990. The median length of follow-up was 32.42 months. RESULTS. The treatment was well tolerated. The median time to recurrence was 6.56 months. There were 4.7% local, 5.8% distant and 3.5% local plus distant recurrences. As of May 1993 83.2% of the patients were still alive. All deaths occurred within two years from the beginning of treatment. The prognostic factors which were significantly correlated with survival were the stage of the disease (p = 0.0479), depth of myometrial invasion (p = 0.0429), age greater than 64 years (p = 0.0357) and performance status < = 80 at diagnosis (p = 0.0002). CONCLUSIONS. Our study confirms that post operative external beam pelvic RT is well tolerated and effective in achieving a good locoregional control. All the factors investigated were prognostic for survival, except histological grade, lymph node involvement and RT dose.