The INTERNATIONAL MISSION study: minimally invasive surgery in ovarian neoplasms after neoadjuvant chemotherapy.

OBJECTIVES: The aim of this retrospective multicenter study was to investigate the extent, feasibility, and outcomes of minimally invasive surgery at the time of interval debulking surgery in different gynecological cancer centers. METHODS/MATERIALS: In December 2016, 20 gynecological cancer centers were contacted by e-mail, to participate in the INTERNATIONAL MISSION study. Seven centers confirmed and five were included, with a total of 127 patients diagnosed with advanced epithelial ovarian cancer after neoadjuvant chemotherapy and minimally invasive interval surgery. Only women with a minimum follow-up time of 6 months from interval surgery or any cancer-related event before 6 months were included in the survival analysis. Baseline characteristics, chemotherapy, and operative data were evaluated. Survival analysis was evaluated using the Kaplan-Meier method. RESULTS : All patients had optimal cytoreduction at the time of interval surgery: among them, 122 (96.1%) patients had no residual tumor. Median operative time was 225 min (range 60 - 600) and median estimated blood loss was 100 mL (range 70 - 1320). Median time to discharge was 2 days (1-33) and estimated median time to start chemotherapy was 20 days (range 15 - 60). Six (4.7%) patients experienced intraoperative complications, with one patient experiencing two serious complications (bowel and bladder injury at the same time). There were six (4.7%) patients with postoperative short-term complications: among them, three patients had severe complications. The conversion rate to laparotomy was 3.9 %. Median follow-up time was 37 months (range 7 - 86): 74 of 127 patients recurred (58.3%) and 31 (24.4%) patients died from disease. Median progression-free survival was 23 months and survival at 5 years was 52 % (95% CI: 35 to 67). CONCLUSIONS: Minimally invasive surgery may be considered for the management of patients with advanced ovarian cancer who have undergone neoadjuvant chemotherapy, when surgery is limited to low-complexity standard cytoreductive procedures.

MetaShot: an accurate workflow for taxon classification of host-associated microbiome from shotgun metagenomic data.

SUMMARY: Shotgun metagenomics by high-throughput sequencing may allow deep and accurate characterization of host-associated total microbiomes, including bacteria, viruses, protists and fungi. However, the analysis of such sequencing data is still extremely challenging in terms of both overall accuracy and computational efficiency, and current methodologies show substantial variability in misclassification rate and resolution at lower taxonomic ranks or are limited to specific life domains (e.g. only bacteria). We present here MetaShot, a workflow for assessing the total microbiome composition from host-associated shotgun sequence data, and show its overall optimal accuracy performance by analyzing both simulated and real datasets. AVAILABILITY AND IMPLEMENTATION: https://github.com/bfosso/MetaShot. CONTACT: graziano.pesole@uniba.it. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Laparoscopic staging of apparent early stage ovarian cancer: results of a large, retrospective, multi-institutional series.

OBJECTIVE: The aim of this study is to analyze the safety, adequacy, perioperative and survival figures in a large series of laparoscopic staging of patients with apparent early stage ovarian malignancies (ESOM). PATIENTS AND METHODS: Retrospective data from seven gynecologic oncology service databases were searched for ESOM patients undergoing immediate laparoscopic staging or delayed laparoscopic staging after an incidental diagnosis of ESOM. Between May 2000 and February 2014, 300 patients were selected: 150 had been submitted to immediate laparoscopic staging (Group 1), while 150 had undergone delayed laparoscopic staging (Group 2) of ESOM. All surgical, pathologic, and oncologic outcome data were analyzed in each group and a comparison between the two was carried out. RESULTS: Longer operative time, higher blood loss, more frequently spillage/rupture of ovarian capsule and conversion to laparotomy occurred in Group 1. No significant differences of post-operative complications were observed between the two groups. Histological data revealed more frequently serous tumors (0.06), Grade 3 (p=0.0007) and final up-staging (p=0.001) in Group 1. Recurrence and death of disease were documented in 25 (8.3%), and 10 patients (3.3%%), respectively. The 3-year disease free survival (DFS) and overall survival (OS) rates were 85.1%, and 93.6%, respectively in the whole series. There was no difference between Group 1 and Group 2 in terms of DFS (p value=0.39) and OS (p value=0.27). CONCLUSION: In this very large multi-institutional study, it appears that patients with apparent ESOM can safely undergo laparoscopic surgical management.

Robotic single-site hysterectomy (RSS-H) vs. laparoendoscopic single-site hysterectomy (LESS-H) in early endometrial cancer: a double-institution case-control study.

OBJECTIVE: To report our experience with single-site robotic platform for IS3000 "Da Vinci" Si Surgical System to perform robotic single site hysterectomy (RSS-H), and to compare peri-operative results with a historical series of laparoendoscopic single site hysterectomies (LESS-H). METHODS: This is a retrospective case-control study, performed at the Gynecologic Oncologic Unit, National Cancer Institute "Regina Elena", Rome, and at the Gynecologic Oncologic Unit, Catholic University of the Sacred Heart, Rome, Italy between December 2011 and January 2013. RESULTS: 19 women underwent RSS-H (cases) and 38 patients were submitted to LESS-H (controls) for early endometrial cancer. Pre-surgical procedures (port placement and docking) required a median time of 8 min in the RSS-H group and a median time of 2 min in the LESS-H group (p=0.0001). The median estimated blood loss was 75 ml in the cases and 30 ml in the controls (p=0.005). The median operative time, calculated from the beginning of intraperitoneal procedures to the skin closure, was 90 min in the cases and 107 ml in the controls (p=ns). The median time to discharge from the hospital was postoperative day two for both techniques. CONCLUSIONS: The few differences we registered do not seem clinically relevant, thus making the two procedures comparable.

Is the sarcomatous component (homologous vs heterologous) the prognostic "driving force" in early-stage uterine carcinosarcomas? A retrospective multicenter study.

PURPOSE: Uterine carcinosarcomas (UCSs) are aggressive biphasic malignancies, with a carcinomatous/epithelial component and a sarcomatous/mesenchymal counterpart. The aim of this study was to evaluate the impact of the sarcomatous component (homologous vs heterologous) on the overall survival (OS) and progression-free survival (PFS). METHODS: This is a multicenter observational retrospective study conducted in patients with stage I and II UCSs. RESULTS: Ninety-five women with histological diagnosis of early-stage UCSs were retrieved: 60 (63.2%) had tumors with homologous sarcomatous components, and 35 (36.8%) with heterologous. At univariate analysis, a stromal invasion ≥ 50%, the presence of clear cell, serous or undifferentiated carcinomatous component, the heterologous sarcomatous component and FIGO stage IB and II were shown to be variables with a statistically significant negative impact on PFS. Similarly, a depth of invasion ≥ 50%, the heterologous sarcomatous component and FIGO stage IB and II were statistically negative prognostic factors also concerning OS. At multivariate analysis, only the heterologous sarcomatous component was confirmed to be a statistically significant negative prognostic factor both on PFS (HR 2.362, 95% CI 1.207-4.623, p value = 0.012) and on OS (HR 1.950, 95% CI 1.032-3.684, p = 0.040). CONCLUSION: Carcinomatous and sarcomatous components both played a role in tumor progression and patients' survival. However, only the sarcomatous component retained a statistical significance at the multivariable model suggesting its preeminent prognostic role in early-stage UCSs.

A multicenter phase II randomized trial of docetaxel/gemcitabine versus docetaxel/capecitabine as first-line treatment for advanced breast cancer: a Gruppo Oncologico Italia Meridionale study.

OBJECTIVE: To evaluate two docetaxel-based regimens as first-line treatment in advanced breast cancer patients. METHODS: Patients were randomly assigned to docetaxel/gemcitabine (arm A: docetaxel 75 mg/m(2) on day 1, gemcitabine 1,000 mg/m(2) on days 1 and 8) or docetaxel/capecitabine (arm B: docetaxel 75 mg/m(2) on day 1, capecitabine 1,250 mg/m(2) twice daily on days 1-14); both chemotherapy regimens were repeated every 21 days. The primary objective of the study was to evaluate the response rate. RESULTS: Seventy-two patients were enrolled (36 each in arms A and B). Responses according to intention-to-treat analysis were as follows: arm A, 41.7% [95% confidence interval (CI) 25.6-57.8]; arm B, 38.9% (95% CI 23-54.8). Median progression-free survival was 10.9 months (95% CI 8.1-13.7) in arm A and 10 months (95% CI 8.8-11.2) in arm B. Overall survival was 26 months (95% CI 22.0-30.0) in arm A and 28 months (95% CI 23.4-32.6) in arm B. Both treatments were well tolerated; myelosuppression was the dose-limiting toxicity, with grade 3-4 neutropenia in 13.8 and 19.4% of the patients in arms A and B, respectively. No relevant differences in other toxicities were observed in the two arms, except for diarrhea (13.9%) and hand-foot syndrome (11.1%), which occurred only in arm B. CONCLUSIONS: Both regimens were active and well tolerated in advanced breast cancer.

MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study.

BACKGROUND: In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. METHODS: We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). RESULTS: In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. CONCLUSIONS: Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.

Pattern of recurrence in patients with endometrial cancer: A retrospective study.

INTRODUCTION: Endometrial cancer (EC) known prognostic factors are not sufficient to predict either outcome or recurrence rate/site: to investigate EC recurrence patterns according to ESMO-ESGO-ESTRO risk classes, could be beneficial for a more tailored adjuvant treatment and follow-up schedule. METHODS: 758 women diagnosed with EC, and a 5-years follow-up, were enrolled: they were divided into the ESMO-ESGO-ESTRO risk classes (low LR, intermediate IR, intermediate-high I-HR, and highrisk HR) and surgically treated as recommended, followed by adjuvants therapies when appropriate. RESULTS: Higher recurrence rate (RR) was significantly detected (p < 0,001) in the HR group (40,3%) compared to LR (9,6%), IR (16,7%) and I-HR (17,1%). Recurrences were detected more frequently at distant sites (64%) compared to pelvic (25,3%) and lymph nodes (10,7%) recurrences (p < 0,0001): only in LR group, no differences were detected between local and distant recurrences. 5-Year distant-free (LR 99%, IR 94%,I-HR 86%, HR 88%) and local-free survivals (LR 99%, IR 100%,I-HR 98%, HR 95%) significantly differ between groups (p < 0,0001 and p = 0,003, respectively). Adjuvant therapy modifies RRs only in LR group (p = 0,01). CONCLUSION: To identify biological factors to stratify patients at higher risk of relapse is needed. Distant site relapse could be the main reason of endometrial cancer failure follow-up, independently or in addition to their risk class prognosis.

Endometrial biopsy by means of the hysteroscopic resectoscope for the evaluation of tumor differentiation in endometrial cancer: a pilot study.

AIMS: To assess the diagnostic accuracy of endometrial biopsy by means of the hysteroscopic resectoscope (EBHR) in evaluating tumor differentiation in patients with endometrial cancer. METHODS: Between January and December 2005, all the women with a diagnosis of endometrioid adenocarcinoma of the uterus, when admitted to hospital, were enrolled for this study. Patients eligible for surgical treatment underwent a preoperative work-up consisting in pelvic magnetic resonance imaging (MRI) and EBHR. In all patients submitted to a hysterectomy, a comparison between pre- and postoperative tumor grade was carried out. RESULTS: 42 women were enrolled in the study. Hysteroscopic biopsy was carried out in 39 patients (mean age 62.5 years, range 33-79; FIGO stage I: 34, stage II-IV: 5). No complication related to hysteroscopy was observed. The preoperative tumor grade by hysteroscopy correlated with the final grade in 97.1% of cases. No patient had positive peritoneal washing and after a median follow-up of ten months no intraperitoneal tumor relapse was observed. CONCLUSION: EBHR is a very accurate diagnostic procedure for assessing the preoperative tumor grade in patients with endometrial cancer.

Robotic single site staging in endometrial cancer: A multi-institution study.

OBJECTIVE: To evaluate the feasibility and the safety of robotic single site hysterectomy (RSSH) plus or less pelvic lymphadenectomy in FIGO stage I-II endometrial cancer. MATERIALS AND METHODS: We prospectively collected patient demographics, operative times, complications, pathologic results, and length of stay on all patients who underwent RSSH plus or less pelvic lymphadenectomy for clinical FIGO stage I or occult stage II endometrial carcinoma. RESULTS: From January 2012 to February 2015, 125 patients were included in our study. The median age of the patients was 59 years (range, 35-84 years) and the median body mass index was 27 kg/m(2) (range, 19-52 kg/m(2)). One patient was converted to vaginal surgery due to problems of hypercapnia. The median docking time, console time, and total operative time was 11 min (range, 4-40 min), 80 min (range, 20-240 min) and 122 min (range, 35-282 min), respectively. The median blood loss was 50 ml (range, 10-250 ml). No laparoscopic/laparotomic conversion was registered. Twenty one patients underwent pelvic lymphadenectomy (16.8%) and the median pelvic lymph nodes was 13 (range, 3-32). The median time to discharge was 2 days (range, 1-3 days). No intra-operative complications occurred, while we observed 10 (8%) early post-operative complications. CONCLUSION: RSSH plus or less pelvic lymphadenectomy is technically feasible, safe and reproducible and could be the treatment of choice for patients affected by FIGO stage I-II endometrial cancer. However, randomized controlled trials are needed to confirm these results.

Radical hysterectomy after chemoradiation in FIGO stage III cervical cancer patients versus chemoradiation and brachytherapy: Complications and 3-years survival.

BACKGROUND: To compare patterns and rates of early and late complications, and survival outcome in FIGO stage III cervical cancer patients underwent to radical hysterectomy after chemo-radiation (CT-RT) vs. chemo-radiation alone. METHODS: Between May 1996 and April 2013 150 FIGO stage III cervical cancer patients were treated. We divide patients according to type of treatment: 77 were submitted to standard treatment (Group A), and 73 to completion hysterectomy after chemo-radiation (Group B). RESULTS: The baseline characteristics of the 2 groups were superimposable. We observed lower intra-operative and treatment-related early urinary and gastro-intestinal complications in Group B with respect to Group A (p < 0.001). Vascular complications were registered only in Group B (p < 0.001). We found a significantly higher rate of local recurrences in the Group A than in the Group B (p < 0.002). We registered 29 deaths in the Group A and 22 in the Group B (p = 0.021). The 3-years disease-free survival rate in the Group A and in the Group B was 62.9% and 68.3%, respectively (p = 0.686), and the 3-years overall survival rate in the Group A and in the Group B was 63.2% and 67.7%, respectively (p = 0.675). CONCLUSIONS: This study confirms that radical hysterectomy after CT-RT is an effective therapeutic approach for advanced cervical cancer. Further prospective and randomized studies should be performed in order to solve the question about the standard approach, and how the different pattern of complication could impact on the quality of life.

Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

Mini-laparoscopic versus robotic radical hysterectomy plus systematic pelvic lymphadenectomy in early cervical cancer patients. A multi-institutional study.

OBJECTIVE: The aim of this study was to verify possible differences in terms of perioperative outcomes and complications between mini-laparoscopic radical hysterectomy with lymphadenectomy (mLRH) and robotic radical hysterectomy with lymphadenectomy (RRH) in patients with early cervical cancer (ECC). MATERIAL AND METHODS: In this retrospective study, thirty women with early stage cervical cancer who underwent mini-laparoscopic radical hysterectomy plus lymphadenectomy (mLRH) were compared with a cohort of thirty women who underwent robotic multiport radical hysterectomy (RRH). The study involved patients, between August 2010 and December 2012, from three Italian institutions: National Cancer Institute of Rome, University of Insubria, Varese, and the Catholic University of the Sacred Heart of Rome. RESULTS: No significant differences between groups were observed in terms of age, BMI, previous abdominal surgery or FIGO stage. Operative time, blood loss, need of blood transfusion, risk of intra- and post-operative complications, and lymph nodes yield were similar between mLRH and RRH in patients with ECC. The median length of hospital stay was 2 days in the mLRH group and 3 days in the RRH group (p < 0.05). CONCLUSIONS: The few differences we registered do not seem clinically relevant, thus making the two procedures comparable. The decision on how to gain best access for radical hysterectomy considers the surgeon's skill and experience with the different possible approaches. Further randomized trials are needed to determine whether mini-laparoscopic techniques truly offer any advantages.

Surgical and oncological outcome of robotic surgery compared to laparoscopic and abdominal surgery in the management of endometrial cancer.

OBJECTIVE: To compare different techniques of minimally invasive surgery (laparoscopy and robotics) to abdominal surgery in order to identify the optimal surgical technique in the treatment of endometrial cancer. METHODS AND MATERIALS: A single-institutional, matched, retrospective, cohort study was performed. All patients with clinical stage I or occult stage II endometrial cancer who underwent robotic hysterectomy, bilateral salpingo-oophorectomy ± lymphadenectomy from August 2010 and December 2013 were identified. Surgical and oncological outcomes were compared with patients matched by age, body mass index, tumor histology, and grade, who underwent abdominal or laparoscopic surgery between January 2001 and December 2013. RESULTS: Three groups were identified: 177 laparotomies (group A), 277 laparoscopies (group B) and 72 robotics (group C). There were no statistically significant differences between the three groups in terms of age, BMI and FIGO stage. The operative time was shortest in group B (p = 0.0001). Blood loss and transfusions were equivalent in group B and C, while they were greater in group A (p = 0.0001). The intra-operative, early and late postoperative complications, rate of conversion, the re-intervention and median hospital stay were lower in group C. The rate of recurrence and death from disease was similar in all three groups. CONCLUSIONS: Minimally invasive surgery was superior to abdominal surgery in terms of surgical outcomes. Robotic surgery was superior to laparoscopy in terms of intra- and post-operative complications, conversion rates, length of hospital stay and re-interventions. In terms of oncological outcomes the three groups were equivalent.

Laparoscopic versus robotic radical hysterectomy after neoadjuvant chemotherapy in locally advanced cervical cancer: a case control study.

OBJECTIVE: To compare the surgical outcome of robotic radical hysterectomy (RRH) versus laparoscopic radical hysterectomy (LRH) for the treatment of locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). MATERIALS AND METHODS: From August 1st 2010 to July 1st 2012 a prospective data collection of women undergoing RRH for cervical cancer stage FIGO IB2 to IIB, after neoadjuvant chemotherapy, was conducted at National Cancer Institute "Regina Elena" of Rome. All patients deemed operable underwent class C1 RRH with pelvic lymphadenectomy within 4 weeks from the last chemotherapy cycle. RESULTS: A total of 25 RRH were analyzed, and compared with 25 historic LRH cases. The groups did not differ significantly in body mass index, stage, histology, number of pelvic lymph nodes removed. The median operative time was the same in the two groups with 190 min respectively. The median estimated blood loss (EBL) was statistically significant in favor of RRH group. Median length of stay was shorter, for the RRH group (4 versus 6 days, P = 0.28). There was no significant difference in terms of intraoperative and postoperative complications between groups but in the RRH group we observed a greater number of total complications compared to the control group. CONCLUSION: This study shows that RRH is safe and feasible in LACC after NACT compare to LRH. However, a comparison of oncologic outcomes and cost-benefit analysis is still needed and it has to be carefully evaluated in the future.

Analysis of chromosomes 3, 7, X and the EGFR gene in uterine cervical cancer progression.

The aim of this study was to investigate the possible role of genetic alterations in the genesis and progression of cervical carcinomas. We analysed the 3, 7, X aneusomy of chromosomes and the status of the epidermal growth factor receptor (EGFR) gene by fluorescence in situ hybridisation (FISH) analysis. Polysomy of chromosomes 3 and X defined the transition from high-grade squamous intraepithelium lesions (HSIL) to cervical carcinoma. Chromosome 7 monosomy and polysomy did not show any statistical significant differences between the groups examined. When we compared the chromosomal aneusomies in all of the specimens using the Kruskal-Wallis test, significant differences (P = 0.0001, P = 0.0001 for chromosomes 3 and X, respectively) were observed. Using a ratio of the EGFR gene signals and chromosome 7 centromeric signals, no samples showed gene amplification. Our results demonstrate the importance of chromosomal 3 and X aneusomies in the development and progression from HSIL to cervical carcinoma, highlighting their usefulness as genetic markers for identifying SILs at high-risk of progression.

The three-dimensional architecture of the myosalpinx in the rat (Rattus norvegicus) as revealed by scanning electron microscopy.

The three-dimensional (3-D) architecture of myosalpinx in the rat has been investigated by means of scanning electron microscopy after microdissection and removing interstitial connective tissue with 6N NaOH digestion. In the extramural portion of tube-uterine junction the myosalpinx shows circularly arranged fibers originating from the uterus, together with oblique fibers typical for the salpinx, which occur more frequently in the deeper layers. As fibers approach the mucous folds they assume a plexiform arrangement, which is maintained through all tubal segments. In the isthmus surface fibers form wide muscle rings around the elbow of loops, peculiar to the rat tubal morphology. Surface fibers in the ampulla and pre-ampulla have an even circular course. Our 3-D results reveal that the muscular architecture of rat tube is mainly organized in concentric, monolayered shells with a plexiform arrangement tightly fastened together. Functionally, this muscular arrangement seems to be capable of stirring rather than pushing the embryo and gametes. Finally, such a plexiform network might work as a mechanism of "tube locking" in proximity of isthmic loops as well as at the level of the ampullary-isthmic junction.

The collagen skeleton of the human umbilical cord at term. A scanning electron microscopy study after 2N-NaOH maceration.

The organization of the collagen fibrils in the human umbilical cord at term is directly visualized by means of a scanning electron microscopy cell maceration method. This technique clearly reveals that there is a much more extensive collagen fibrillar architecture within the umbilical cord than that reported in the classical histological descriptions. The Wharton's jelly, in fact, appears as a spongy network of interlacing collagen fibres and small woven bundles apparently arranged at random and forming a continuous soft skeleton that encases the umbilical vessels. The collagen fibrillar network shows the presence of a wide system of interconnected cavities consisting of canalicular-like structures as well as cavernous and perivascular spaces. This system of cavities might play a mechanical role allowing the storing of the ground substance of the jelly and its diffusion during twisting or compression. Furthermore, it may have an important role facilitating the diffusion throughout the jelly of diffused materials (i.e. water and trophic metabolites) either from or to the umbilical vessels and the amniotic cavity, thus overcoming the lace of a proper vasculature with the jelly.

Vaginal reconstruction by skin grafts: a scanning electron microscopic evaluation.

In order to evaluate the morphofunctional pattern of transplanted skin structural and ultrastructural studies on biopsies taken from surgically created neovaginae in three cases of vaginal agenesis were performed one and two years postoperatively. Two of the cases were associated with a rudimentary uterus, while the remaining one involved testicular feminization. Neovaginae were constructed by directly prolonging a pre-existing perineal introitus, to form a vesicorectal pouch, which was lined inside with gluteal skin autografts. All three patients reported satisfactory psychosexual behavior one year after operation. Light microscopy of the bioptic fragments demonstrated, even two years after surgery, features generally similar to those of the normal dermis and epidermis, and a keratinization rate as a rule, that did not range significantly from the norm. Scanning electron microscopy also confirmed the maturation of the cornified cells, since these were often seen to be desquamating and exhibited structures usually found in normal skin, such as double edges on the luminal surface--usually considered to be the morphological expression of squamous cell overlapping--and microwrinkles on disrupted apical and basal cytoplasmic flaps, which are considered reciprocal cell-gearing devices. Our results seem to indicate, therefore, that the transplanted skin, maintaining, on the whole, its integrity and viability despite an environment differing somewhat from the external one with regard to moisture, pH and temperature, shows a good adaptability, at least until the above mentioned time lapses.