High prevalence of orofacial pain in juvenile fibromyalgia as detected by a novel tool specifically devised for children and adolescents.

OBJECTIVES: To examine the prevalence of temporomandibular disorders (TMD) in patients with juvenile fibromyalgia syndrome (JFS) and identify TMD characteristics specifically associated to JFS. METHODS: Signs and symptoms of TMD were assessed using a novel clinical tool specifically devised for children that consists of: 1. a self-report multiple-choice questionnaire; 2. a protocol for the clinical examination of the orofacial region. Multivariate logistic regression model was used to identify TMD features associated with JFS. RESULTS: Thirty JFS patients (median age 15.5 years) and 45 healthy controls (median age 15.0 years) were included in this cross-sectional study. Orofacial pain was reported by 26 of 30 JFS patients (86.7%) and by 3 of 45 controls (6.7%; p<0.001). Pain on TMJ palpation was present in 18 of 30 JFS patients (60%) and in 5 of 45 controls (11.1%; p<0.001). Median values of maximum spontaneous mouth opening, voluntary active opening and assisted passive opening were significantly higher in JFS patients than in controls. On multiple regression analysis spontaneous orofacial pain (OR: 21.0; p=0.005), diffuse tenderness on palpation of the masticatory muscles (OR: 14.9; p=0.026) and TMJ hypermobility (OR 1.42; p=0.008) were independently associated with JFS. CONCLUSIONS: The high prevalence of TMD in JFS highlights the need for a broader interdisciplinary evaluation of JFS patients. TMJ hypermobility, in addition to orofacial and masticatory muscle pain, is an important clue for the diagnosis of TMD in adolescents with JFS. Elucidating the link between these disorders will advance individualised management and improve treatment efficacy.

Feasibility and safety of total laparoscopic hysterectomy for uteri weighing from 1.5 kg to 11.000 kg.

PURPOSE: To assess the feasibility and safety of total laparoscopic hysterectomy (TLH) for uteri ≥ 1.5 kg. METHODS: We prospectively evaluated all elective TLHs (with or without adnexectomy) performed for fibromatous uteri between August 2009 and August 2019 in the Department of Obstetrics and Gynecology, Sirai Hospital, Carbonia, and the Department of Gynecologic Oncology, Businco Hospital, Azienda Ospedaliera Brotzu, Cagliari. Patients with large myomatous uteri (uterine weight ≥ 1.5 kg on pathology reports) were included in the analysis. We examined all procedures and collected data about intra- and post-operative short-term and long-term complications, intraoperative blood loss, operative time, hospital stay, and time to achieve well-being. RESULTS: Seventy-eight patients were included. The median weight was 2,000 g (range 1,500-11,000 g), estimated blood loss was 100 mL (range 10-700 mL), operating time was 135 min (range 60-300 min), and hospital stay was 2 days (range 2-5 days). Conversion to laparotomy occurred in 4 patients (5.1%) with uterine weight ranging from 3 to 5.5 kg, due to severe adherence syndrome or inadequate visualization. As for intraoperative complications, 1 patient (who had the largest removed uterus weighing 11,000 g) experienced an intraoperative ureteral injury (grade III). No major postoperative complications occurred. CONCLUSIONS: This study provides the largest case series of TLH for fibromatous uteri > 1.5 kg and includes some of the largest uteri reported to date in the literature (weighing 5,320, 5,720, and 11,000 g, respectively). The study reaffirms the feasibility and safety of a minimally invasive hysterectomy even in the case of abnormally large uteri.

Laparoscopic splenectomy both for primary cytoreductive surgery for advanced ovarian cancer and for secondary surgery for isolated spleen recurrence: feasibility and technique.

BACKGROUND: This study investigated the feasibility and safety of laparoscopic splenectomy conducted in the contexts of both laparoscopic secondary surgery for isolated recurrence in the spleen and primary laparoscopic cytoreductive surgery for advanced ovarian cancer. METHODS: We performed a perspective observational study including all consecutive patients with ovarian cancer who underwent laparoscopic splenectomy as part of primary cytoreductive procedures for advanced stage ovarian cancer or secondary surgery for isolated splenic recurrence between January 2016 and May 2020. RESULTS: We enrolled 13 consecutive patients, candidate to laparoscopic splenectomy as part of primary cytoreductive procedures for advanced stage ovarian cancer (6 patients) or secondary surgery for isolated splenic recurrence of platinum-sensitive ovarian cancer (7 patients). Median operative time (509 min [range, 200-845]) for primary cytoreductive surgery varied according to surgical complexity depending on the extensiveness of the disease. Median operative time for secondary surgery for isolated splenic metastasis was 253 min (90-380). Only 1 patient with isolated splenic recurrence required conversion to an open approach. No intraoperative complication occurred, and no intraoperative blood transfusions were required. Median hospital stay was 3 days (range, 2-5) for isolated recurrence and 9 days (7-18) for primary cytoreductive surgery. Complete tumor resection was achieved in all patients. Median time from surgery to adjuvant chemotherapy was 16 days (7-24). All six patients who underwent laparoscopic splenectomy during primary cytoreductive surgery remain alive, four of whom exhibit no evidence of disease (median follow-up 25 months [4-36]). Among patients who underwent laparoscopic splenectomy during secondary surgery for isolated splenic relapse, all patients are alive and only one had a central diaphragmatic relapse 2 years after surgery (median follow-up 17 months ([5-48 months]). CONCLUSIONS: The laparoscopic approach to splenectomy is feasible and safe both in patients undergoing primary cytoreductive surgery for advanced stage disease and those with isolated recurrence of ovarian cancer, without compromising survival and allowing early initiation of postoperative systemic chemotherapy.

Laparoscopic removal of a very large uterus weighting 5320 g is feasible and safe: a case report.

BACKGROUND: Total laparoscopic hysterectomy (TLH) has demonstrated to be feasible and safe in the presence of very large uteri. However, it is currently difficult to establish the upper uterine weight limit for successful performance of a laparoscopic hysterectomy. CASE PRESENTATION: Here we report the case of a TLH performed for a very large fibromatous uteri weighing 5320 g in a 40-year-old Caucasian woman. The surgery had no complications with an operating time of approximately 220 min. The patient was discharged from the hospital on postoperative day 3 in very good condition. To our knowledge, the present paper is the only to describe a uterus of this size removed by laparoscopic hysterectomy. CONCLUSIONS: Our case demonstrates that uterine size is not a determinant for a final surgical decision to use laparoscopic hysterectomy. Therefore, if not contraindicated by the patient's comorbidities or peculiar anatomical conditions, we believe that laparoscopic hysterectomy could be performed in the presence of large uteri without hypothetical weight limits.

Long-Term Survival in a Patient With Abdominal Sarcomatosis From Uterine Leiomyosarcoma: Role of Repeated Laparoscopic Surgery in Treatment and Follow-Up.

Uterine leiomyosarcoma (LMS) in some cases may disseminate through the abdominal cavity, without extra-abdominal spreading, determining a condition of abdominal sarcomatosis, which represents a peculiar situation. Only radical surgical removal offers a chance of long-term survival in such cases of LMS. Here we describe a case of diffuse abdominal sarcomatosis from uterine LMS in a 51-year-old perimenopausal woman who underwent laparoscopic radical hysterectomy, bilateral salpingo-oophorectomy, total pelvic peritonectomy, pelvic lymphadenectomy to the mesenteric inferior artery, and omentectomy. Then, given the high probability of disease recurrence, the patient underwent a close follow-up consisting of positron emission tomography (PET)/computed tomography every 3 months and diagnostic (and if necessary operative) laparoscopy every 6 months. To date, the patient had 11 laparoscopies; 5 of them were preceded by a PET indicative of the presence of disease with high metabolic activity, which was confirmed at surgery and each time completely removed laparoscopically with no evidence of residual disease. To date, 5 years from diagnosis the patient is alive and continues her follow-up. Our report brings to light the ability of laparoscopic surgery to obtain disease control in a case of LMS with abdominal dissemination. Moreover, laparoscopic surgery, as demonstrated in our case, may have an important role in the close follow-up of the disease and allow a timely and early radical surgical approach of relapses before they become extremely large and difficult to remove radically.

Surgical outcome and complications of total laparoscopic hysterectomy for very large myomatous uteri in relation to uterine weight: a prospective study in a continuous series of 461 procedures.

PURPOSE: To analyze whether a large uterine size was associated with increased rate of intraoperative and postoperative surgical complications in patients who underwent total laparoscopic hysterectomy (TLH) for myomatous uteri. METHODS: We examined prospectively data from 461 consecutive TLHs performed by a single surgeon between August 2004 and August 2014 at the Department of Obstetrics and Gynecology, Sirai Hospital, Carbonia, and at the Department of Gynecologic Oncology, Businco Hospital, Cagliari, Italy. Demographic and surgical data were stratified by uterine weight (range 90-5500 g) into four groups: <300 g; from 300 to 500 g; from 500 to 800 g; and >800 g. Outcomes examined included blood loss, operative time, intraoperative and postoperative complications, and duration of hospital stay. A linear regression analysis was performed to identify whether uterine weight was an independent predictor affecting these outcomes. In addition, BMI, previous surgery with adhesiolysis, and endometriosis were tested as a predictor of surgical complications and outcomes. RESULTS: No significant difference was found in intraoperative and postoperative complications, as well as hospital stay, by uterine weight. Increased uterine size was significantly associated with longer operative time and increased blood loss. Beside uterine weight, prior surgery was predictive of postoperative complications. In contrast, higher BMI was not associated with increased complication rate. Independent predictors of longer operative time included previous surgery, endometriosis, and BMI. CONCLUSIONS: Our results showed that in experienced hands, TLH is feasible and safe also in presence of very large uteri. TLH results in a few complications and short hospital stay regardless of uterine weight.

Diagnostic Framework of Pelvic Massive Necrosis with Peritonitis following Chemoradiation for Locally Advanced Cervical Cancer: When Is the Surgery Not Demandable? A Case Report and Literature Review.

Concurrent platinum-based chemoradiation (CCRT) is the established treatment for locally advanced cervical cancer and has an acceptable toxicity. Radiation-induced necrosis of the uterus and pelvic tissue is a rare and usually late potential complication. Limited data are available about its management. Here, we describe a case of a patient affected by a locally advanced cervical cancer (stage IVA) who received CCRT, obtaining a partial response with persistence of bladder and rectal infiltration. Unfortunately, after the first brachytherapy dose, the patient developed a worsening clinical picture with fever and altered laboratory data indicative of sepsis; the computed tomography revealed a massive necrosis of the uterus with pelvic abscess and peritonitis. We performed a laparoscopic emergency surgery with removal of the necrotic tissue, supracervical hysterectomy, bilateral-oophorectomy, and abscess drainage. Thereafter, once the severe inflammatory condition was resolved, the patient underwent pelvic exenteration with palliative/curative intent. The postoperative PET/CT was negative for residual disease. However, the patient needed further hospitalization for re-occurrence of peritonitis with multiple abscesses. A careful diagnosis is crucial in locally advanced cervical cancer patients who, after CCRT, present persistent pain and problematic findings at imaging and laboratory parameters. In these cases, radiation-induced necrosis of the pelvis should be suspected. This case helps to clarify the central role of surgery, especially when actinic necrosis leads to complications such as abscess, fistulae, and extensive tissue destruction that cannot be conservatively medically handled. Laparoscopy represents an ideal approach to realizing the correct diagnosis, as well as enabling the performance of important therapeutic surgical procedures.

Next-Generation Sequencing Whole-Genome Analysis for Targeted Treatment Approach of Metastatic Bartholin Gland Adenocarcinoma: An Emblematic Case Report and Review of the Literature.

Bartholin gland adenocarcinoma (BGA) is extremely rare and is characterized by high rates of lymph-node recurrence and distant metastases. No effective palliative treatments are available for metastatic BGA; therefore, advanced BGA remains a challenge for gynecologic oncologists. Considering the rarity of this disease and the lack of a standardized approach, the present study aims to discuss the available literature on current therapies for BGA and to describe an emblematic case treated with a novel tailored approach. A postmenopausal woman with advanced BGA was referred to our department for an adequate evaluation, staging and treatment. Notably, we used PET/CT as a fundamental imaging technique for staging and follow-up. The patient underwent primary surgery followed by standard chemotherapy and pelvic radiotherapy. Three months later, she relapsed, with the appearance of multiple metastatic sites. Considering the evident chemoresistance to standard chemotherapy and the absence of valid therapeutic alternatives for this rare cancer, she was treated with a combination of repeated minimally invasive surgical procedures for all the resectable metastatic lesions and innovative approaches comprising, firstly, chemoimmunotherapy with Nivolumab combined with metronomic vinorelbine, which resulted in a clinical response for approximately 7 months. Upon disease progression, we used a targeted systemic approach based on the whole genomic profile of the primary tumor, which showed PTEN loss, which is predictive of a benefit from an mTOR inhibitor, and a CCND1 amplification, which predicts sensitivity to CDK4/6 inhibitors. Therefore, she received Everolimus, resulting in a significant metabolic response that lasted 12 months. Thereafter, upon further progression of the disease, the patient started Palbociclib treatment, which is currently ongoing, with evidence of a metabolic response. The patient has survived for 54 months from diagnosis, with a good performance status. In conclusion, the present paper confirms the lack of efficacy of conventional therapeutic regimens in the context of advanced, recurrent or metastatic adenocarcinomas of the Bartholin gland. The case report shows how a personalized multidisciplinary approach based on repeated minimally invasive surgery and tailored anticancer treatment based on whole-genome sequencing analysis could be effective and associated with prolonged survival in this rare gynecological cancer.

Risk of temporomandibular joint effusion related to magnetic resonance imaging signs of disc displacement.

BACKGROUND: It has been suggested that TMJ effusion may represent an inflammatory response to a dysfunctional disc-condyle relationship. The purpose of the present study was to evaluate whether the status of the disc in the temporomandibular joint, as depicted in magnetic resonance (MR) images, is predictive of the presence of temporomandibular joint (TMJ) effusion. METHODS: The relationship between disc displacement and TMJ effusion was analyzed in MR images of 154 TMJs in 77 patients complaining for pain and/or dysfunction in the TMJ area and referred from medical practitioners to specialist consultation. Logistic regression analysis was used to identify the significant correlation between presence/absence of joint effusion and disc displacement. RESULTS: Significant correlation (P<0.01) between disc displacement and joint effusion was found. OR for all type of disc displacement was 3.1, and the odds that a joint had magnetic resonance imaging findings of effusion was greater for anterior disc displacement without reduction. CONCLUSIONS: The status of the disc could represent a factor involved in the development of temporomandibular joint oedema. However, these findings suggest that disc displacement may not be regarded as the dominant factor in defining the occurrence of TMJ effusion. Certain local or systemic conditions other than the disc-condyle relationship must be considered.

Laparoscopic hysterectomy as optimal approach for 5400 grams uterus with associated polycythemia: A case report.

BACKGROUND: Uterine myomas are the most common benign gynecological soft tissue tumors in women but polycythemia associated with these tumors is rare. Polycythemia is significantly associated with risk of venous thromboembolism (VTE), which is further increased in case of a large pelvic mass and obesity. Here we report the surgical challenges in the case of an obese patient with a giant fibromatous uterus and associated polycythemia. CASE SUMMARY: A 42-year-old obese woman was referred to our department for treatment for a huge fibromatous uterus. She suffered of pelvic pressure and abdominal distension and reported severe dyspnea from several months. Laboratory analyses including hemoglobin (Hb) 19.2 g/dL and hematocrit (Hct) 59.7% were indicative of polycythemia. Arterial blood gas analysis showed arterial oxygen pressure (pO2) of 81.5 mmHg. Abdominal computed tomography confirmed a giant fibromatous uterus measuring 28.2 cm × 17 cm × 25 cm. To reduce the thromboembolic risk, the patient underwent low molecular weight heparin, phlebotomy twice before surgery, and we opted for a laparoscopic hysterectomy. The uterus weighed 5400 g and the histology confirmed a diagnosis of leiomyoma. We did not find increased erythropoietin levels in the supernatant of the myomatous uterine tissue. There were no complications. On postoperative day 1, the Hb and the Hct levels normalized to 13.3 g/dL and 41.7%, respectively. Arterial blood gas analysis after surgery showed a pO2 of 144.7 mmHg. These results suggested the diagnosis of myomatous erythrocytosis syndrome. The patient was discharged on the second postoperative day in very good condition with no symptoms. CONCLUSION: We believe this is the first reported laparoscopic hysterectomy in a patient with a giant uterus, polycythemia and obesity. Multiple VTE risk factors warranted a laparoscopic approach.

Next generation sequencing driven successful combined treatment with laparoscopic surgery and immunotherapy for relapsed stage IVB cervical and synchronous stage IV lung cancer.

BACKGROUND: The treatment of patients with multiple synchronous tumors is challenging and complex. The use of next generation sequencing (NGS) may help in identification of germline mutations in genes involved in a common etiology for both tumors thus allowing a common effective therapeutic strategy. PATIENTS AND METHODS: We describe the unexpected positive results obtained in a young woman with relapsed chemo-resistant stage IVB cervical and synchronous stage IV lung cancer, who underwent an interdisciplinary approach including palliative surgery with laparoscopic total pelvic exenteratio followed by a chemo-immunotherapy protocol with the anti-Programmed Death (PD)-1 antibody nivolumab plus metronomic cyclophosphamide. The treatment choice was based on tumor PD-Ligand 1 assessment and NGS analysis for the identification of potential treatment targets. Outcomes included tumor objective response and patient-centered outcomes (pain, performance status and overall quality of life). RESULTS: Laparoscopic surgery obtained an immediate symptom control and allowed the early start of medical treatment. One month after combined therapy start the patient achieved a significant improvement in performance status, pain, overall Quality of life and after 3 months she resumed working. After 3 and 6 months of treatment we observed an objective dimensional and metabolic response. Currently, after 24 months (and 48 cycles of nivolumab) the patient is continuing to benefit from treatment: she is in complete remission, with good performance status and she is working and leading a self-dependent life. CONCLUSION: Our study strongly affirms the efficacy of an interdisciplinary approach including surgical and innovative medical strategies based on immunotherapy in patients with advanced chemo-resistant synchronous cervical and lung cancer. The present findings support the use of NGS to drive a targeted rational treatment especially in heavily pre-treated patients.

Feasibility and safety of total laparoscopic hysterectomy for huge uteri without the use of uterine manipulator: description of emblematic cases.

BACKGROUND: Uterine manipulator is a very useful tool in performing total laparoscopic hysterectomy (TLH) for large uteri; however, in some cases, it cannot be used due to unfavorable anatomical conditions. The feasibility and safety of TLH for very large uteri without the use of uterine manipulator has not yet been established. RESULTS: We describe two emblematic cases of TLH for huge fibromatous uteri: the first one for a uterus weighing 5700 g, which is the largest uterus laparoscopically removed to date reported in literature, and the second one for a uterus of 3670 g associated with a severe lymph node neoplastic disease.In both cases, TLH was successfully and safely performed even without the use of uterine manipulator, thus allowing a rapid recovery, especially in the second case, which was essential for a fast start of the most appropriate oncological treatment, the best quality of life and undoubtedly cosmetic advantages. CONCLUSIONS: Although we believe in the great usefulness of the uterine manipulator in performing TLH for huge uteri, in the present paper, we demonstrate the feasibility and safety of such complex surgery also when the use of this tool is not possible due to unfavorable anatomical condition.

Abdominal leiomyosarcomatosis after surgery with external morcellation for occult smooth muscle tumors of uncertain malignant potential: A case report.

INTRODUCTION: Although rare, cases of abdominal sarcomatosis (AS) after laparotomy/laparoscopic interventions for uterine smooth muscle tumors of uncertain malignant potential (STUMP) have been reported. PRESENTATION OF CASE: We describe a rare case of diffuse abdominal sarcomatosis in a patient that some year earlier had undergone myomectomy for a suspected uterine myoma, which was histologically proven to be a STUMP. Once the patient was admitted at our Department, she underwent a diagnostic laparoscopy that confirmed a condition of peritoneal sarcomatosis disseminated through the entire abdomen, and then a laparotomic total hysterectomy, bilateral salpingo-oophorectomy, and total omentectomy, achieving a complete cytoreduction. Histological examination showed high-grade uterine leyomiosarcoma (LMS). Since there is no evidence of any clinical benefit of adjuvant treatment, given the risk of disease recurrence, we decided, with the patient's agreement, to conduct close follow-up with a Positron Emission Tomography (PET)/Computed Tomography (CT) scan every 3months and diagnostic laparoscopy every 6months, even in the absence of PET/CT positivity. After 2years PET/CT showed a relapse of LMS in the perigastric region and, therefore the patient underwent a diagnostic/operative laparoscopy with complete removal of the neoplastic recurrence. To date, the patient is disease-free. DISCUSSION AND CONCLUSION: STUMPs should be submitted to a frequent surveillance for their risk of recurrence, dissemination and transformation into LMS, even many years after the first diagnosis. A follow-up including surgical re-exploration with laparoscopy and PET/CT imaging may allow early detection and timely treatment of the relapse with good long-term outcome, as demonstrated by our case.

A 10-year evaluation of implants placed in fresh extraction sockets: a prospective cohort study.

BACKGROUND: The placement of an implant into a fresh extraction socket has been identified as a reliable technique, allowing a reduction in the time needed for prosthetic rehabilitation. This treatment modality is widely reported in the scientific literature; however, the long-term outcomes and the need for guided bone regeneration (GBR) are still topics of debate. The aim of this prospective study is to evaluate the clinical and radiologic findings from the 10-year follow-up of immediately placed implants, with and without the GBR procedure. METHODS: A total of 159 implants in 91 patients are included in this study; 101 implants required a GBR procedure simultaneously with placement. All implants were used to support a single crown restoration. The clinical/radiographic measurements were repeated each year up to the 10-year follow-up. At the 10-year follow-up visit, the papilla index and the apico-coronal location of mid-buccal soft tissue positions were recorded. RESULTS: The 10-year cumulative success rate was 91.8% (87.9% in the non-GBR group and 94.1% in the GBR group). The clinical attachment level (CAL) measurements were stable throughout the study, and 82% of the implants showed marginal bone loss (MBL) of 0.6 to 1.5 mm at the 10-year visit; moreover, these two parameters did not show significant differences between the GBR and non-GBR groups. Seventy percent of the implant sites showed acceptable outcomes in terms of interproximal papilla. The facial gingival level was more apical in the non-GBR group than in the GBR group (P <0.05). CONCLUSIONS: The present prospective clinical study shows that implants placed in fresh extraction sockets had a high cumulative success rate, namely 91.8% after 10 years. No differences were detected in survival and success rate of implants whether GBR procedures were performed or not. The CAL, MBL, and marginal level of soft tissue measurements were stable throughout the 10-year evaluation.

A stepwise multiple regression model to assess the odds ratio between myofascial pain and 13 occlusal features in 238 Italian women.

OBJECTIVE: To quantify the relative risk of multiple occlusal variables for muscular disorders of the stomatognathic system. METHOD AND MATERIALS: Thirteen occlusal features were clinically assessed by the same three operators: partial unilateral posterior reverse articulation, anterior open occlusal relationship, vertical anterior overlap (normal value < 4 mm), complete unilateral posterior reverse articulation, anterior overjet (normal value < 5 mm), incisor midline discrepancy (normal value < 2 mm), Angle Class I canine and molar relationship; plus dynamic occlusion features such as length and symmetry of retruded contact position-intercanine position (RCP/ICP) slides (normal value < 2 mm), occlusal guidance patterns, and mediotrusive and laterotrusive interferences. The sample consisted of 156 women with only muscular disorders according to the Group I Research Diagnostic Criteria for temporomandibular disorders and 82 healthy women (control group). A stepwise multiple logistic regression model was used to identify the significant correlation between occlusal features and disease. RESULTS: The odds ratio for myofascial pain was 2.6 for absence of canine guidance, 2.0 for laterotrusive interference, 2.3 for mediotrusive interference, and 1.9 for reverse articulation. Other occlusal variables did not reveal statistical significance. The percentage of the total log likelihood for myofascial pain explained by the significant occlusal factors was acceptable with a Nagelkerke R2 = 0.2. The final model including the significative occlusal features revealed an optimal discriminant capacity to predict patients with myofascial pain with a sensitivity of 62.2%, or healthy subjects with a specificity of 93.6%, and an accuracy of 82.8%. CONCLUSIONS: Few occlusal features show a significative predictive value for myofascial pain.

Relationship between human oral lichen planus and oral squamous cell carcinoma at a genomic level: a datamining study.

The leader gene approach is a data mining method based on the systematic search for genes involved in a specific process and their ranking according to the number of interconnections with the other genes identified. The genes with the strongest interconnections are termed leader genes, since they may be supposed to play an important role in the process. The potential of malignant progression of OLP to oral squamous cell carcinoma (OSCC) is still not completely clear. In this study, the leader gene approach is applied to investigate the association between OLP and OSCC at a molecular level. Results were integrated with those obtained in an experimental analysis (see paper 1 of this series). Genes involved in OLP and OSCC were identified by systematic queries to dedicated databases. Interconnections among identified genes were calculated and given a confidence value using STRING database. Leader genes were identified by clustering genes according to their interconnections. This theoretical analysis shows that OLP and OSCC share two leader genes: TP53 and CDKN1A, involved in the PI3K signalling events mediated by AKT pathway. This finding and those obtained in the experimental analysis suggest the possible involvement of some key genes/proteins LCK, PIK3CA, BIRC5, TP53 and CDKN1A in the malignant progression from OLP to OSCC. Moreover, these findings support the role of some molecular pathways, namely IL2 signalling events mediated by PI3K, PI3K signalling events mediated by AKT, and, possibly, Aurora A signalling in the association between OLP and OSCC.