A giant pelvic infiltrating schwannoma misdiagnosed as an ovarian neoplasm that was resected using a laparoscopic approach: A case report

Introduction and importance: Large retroperitoneal schwannomas are rare and present significant challenges in surgical management, particularly when located in the pelvic region. Gynecologists can encounter rare problems when a pelvic schwannoma is mistaken for an adnexal pathology. Case Presentation: A 62-year-old woman presented with a giant retroperitoneal mass suspected of a potentially malignant ovarian tumor preoperatively. Computed tomography revealed a large mixed solid-cystic mass near the right adnexa measuring 118 x 100 x 80 mm. The cancer antigen 125 level was 196 U/mL. We performed a diagnostic-operative laparoscopy, which showed a retroperitoneal neoformation below the cava and aortic bifurcation adherent to the sacrum, right pelvic vessels, and hypogastric nerve up to the vagina. We carefully detached the mass from the nearby tissues using the most appropriate laparoscopic devices. The entire neoplasm was removed through the vagina into a surgical bag. The surgery lasted 180 min without complications. Histology revealed a grade I benign schwannoma. At the 12-month follow-up, the patient was asymptomatic without signs of recurrence. Clinical Discussion: Pelvic retroperitoneal schwannomas can mimic ovarian carcinomas; misdiagnosis may occur due to their rarity and the difficulty of interpreting preoperative imaging. In case of unexpected giant presacral schwannomas surgical management is challenging due to their peculiar location. Conclusion: This case underscores the need for a skilled, experienced team of gynecological oncologists to achieve favorable outcomes when performing laparoscopic surgery of giant pelvic retroperitoneal schwannoma. Adequate knowledge of the complex pelvic anatomy, careful surgical planning, and familiarity with the most appropriate surgical tools are critical points

Complicated enterocele: timely resolution with bowel resection via a vaginal approach: case report

Background: Enterocele is an uncommon, serious condition that requires accurate and early diagnosis to prevent complications such as intestinal obstruction, incarceration, and strangulation, with consequent intestinal ischemia, necrosis, and evisceration. We report a rare case of a patient with a voluminous enterocele and initial signs of intestinal ischemia who underwent urgent vaginal surgery. Case description: An 80-year-old woman presented with a voluminous mass protruding from the vagina, associated abdominopelvic pain, a 10-day history of bowel sub-occlusion, and numerous episodes of profuse vaginal bleeding. She was diagnosed with an enterocele with early signs of complications. Owing to her advanced clinical condition and comorbidities, we opted for an urgent vaginal procedure. Intestinal loops with initial signs of ischemia were resected via a transvaginal approach, leading to good clinical outcomes. She was discharged on postoperative day 5. Conclusions: This rare case highlights a surgical emergency that was managed with transvaginal resection of the intestine. Early identification of the initial signs of complications allowed for this less invasive approach, resulting in reduced morbidity and length of hospital stay

Pathogenic and Prognostic Roles of Paraneoplastic Leukocytosis in Cervical Cancer: Can Genomic-Based Targeted Therapies Have a Role? A Literature Review and an Emblematic Case Report

Tumor-associated leukocytosis has been associated with poor prognosis in cervical cancer. Leukemoid reaction (i.e., white blood cell count > 40,000/µL) is defined paraneoplastic (PLR) when it occurs in the presence of a cytokine-secreting tumor (CST) without neoplastic bone marrow infiltration. Cervical cancers displaying PLR represent a peculiar entity characterized by a rapidly progressive behavior typically associated with chemo-radioresistance. The present paper aims to review the literature about the pathogenetic mechanisms of PLR and its prognostic role in cervical cancer. Moreover, it reports the emblematic case of a patient with an advanced cervical cancer associated with PLR that was chemotherapy resistant. The patient underwent a palliative cytoreductive surgery of high complexity, obtaining a temporary regression of PLR. The tumor sample stained positive for G-CSF and IL-6, thus indicating a CST. Notably, the tumor genomic analysis revealed a PI3CKA mutation. Therefore, at the instrumental evidence of a rapidly progressive disease relapse, which was accompanied by reappearance of PLR, we started a targeted treatment with a selective PIK3 inhibitor alpesilib combined with the JAK1-2 inhibitor ruxolitinib. We achieved a relief of symptoms and leukocytosis; however, severe side effects necessitated the treatment suspension. In conclusion, as therapeutic strategies for cancer with PLR are scarcely reported in literature, our study could contribute to expand our understanding of the topic and provide a basis for further research

Survival as a clinical outcome and its spiritual significance in a cohort of patients with advanced central pelvic neoplastic disease undergoing total pelvic evisceration: a poorly debated issue

Background Patients with either treatment-resistant or relapsing advanced central pelvic neoplastic disease present with a condition responsible for debilitating symptoms and consequently poor quality of life (QoL). For these patients, therapeutic strategies are very limited and total pelvic evisceration is the only option for relieving the symptoms and increasing survival. Of note, taking charge of these patients cannot be limited to increasing their lifespan but must also be aimed at improving the clinical, psychological, and spiritual conditions. This study aimed to prospectively evaluate the improvement in survival and QoL, focusing on spiritual wellbeing (SWB), in patients with poor life expectancy who underwent total pelvic evisceration for advanced gynecological cancers at our center. Patients and methodsThe QoL and SWB were assessed using the European Organisation for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30), EORTC QLQ-SWB32, and SWB scale, which were repeatedly administered: 30 days before surgery, 7 days after the procedure, 1 and 3 months after surgery, and then every 3 months until death or the last follow-up assessment. Operative outcomes (blood loss, operative time, hospitalization, and incidence of complications) were evaluated as secondary endpoints. The patients and their families were included in a dedicated psycho-oncological and spiritual support protocol, which was managed by specifically trained and specialized personnel who accompanied them during all phases of the study. ResultsA total of 20 consecutive patients from 2017 to 2022 were included in this study. Of these patients, 7 underwent total pelvic evisceration by laparotomy and 13 underwent laparoscopy. The median survival was 24 months (range: 1-61 months). After a median follow-up of 24 months, 16 (80%) and 10 patients (50%) were alive at 1 year and 2 years after surgery, respectively. The EORTC-QLQ-C30 scores significantly improved yet at 7 days and at 1, 3, 6, and 12 months, as compared with the preoperative values. In particular, an early improvement in pain, overall QoL, and physical and emotional functions was observed. With respect to the SWB, the global SWB item score of the EORTC QLQ-SWB32 questionnaire significantly increased after 1 month and 3 months, as compared with preoperative values (p = 0.0153 and p = 0.0018, respectively), and remained stable thereafter. The mean SWB scale score was 53.3, with a sense of low overall SWB in 10 patients, a sense of moderate SWB in eight patients, and a sense of high SWB in two patients. The SWB scale score significantly increased after 7 days, 1 month, and 3 months, as compared with the preoperative value (p = 0202, p = 0.0171, and p = 0.0255, respectively), and remained stable thereafter. ConclusionTotal pelvic evisceration is a valid approach for improving both survival and QoL in selected patients with advanced pelvic neoplasms and poor life expectancy. Our results particularly underline the importance of accompanying the patients and their families during the journey with dedicated psychological and spiritual support protocols

Effect of Cancer-Related Cachexia and Associated Changes in Nutritional Status, Inflammatory Status, and Muscle Mass on Immunotherapy Efficacy and Survival in Patients with Advanced Non-Small Cell Lung Cancer

Immune checkpoint inhibitor (ICI)-based immunotherapy has significantly improved the survival of patients with advanced non-small cell lung cancer (NSCLC); however, a significant percentage of patients do not benefit from this approach, and predictive biomarkers are needed. Increasing evidence demonstrates that cachexia, a complex syndrome driven by cancer-related chronic inflammation often encountered in patients with NSCLC, may impair the immune response and ICI efficacy. Herein, we carried out a prospective study aimed at evaluating the prognostic and predictive role of cachexia with the related changes in nutritional, metabolic, and inflammatory parameters (assessed by the multidimensional miniCASCO tool) on the survival and clinical response (i.e., disease control rate) to ICI-based immunotherapy in patients with advanced NSCLC. We included 74 consecutive patients. Upon multivariate regression analysis, we found a negative association between IL-6 levels (odds ratio (OR) = 0.9036; 95%CI = 0.8408–0.9711; p = 0.0025) and the miniCASCO score (OR = 0.9768; 95%CI = 0.9102–0.9999; p = 0.0310) with the clinical response. As for survival outcomes, multivariate COX regression analysis found that IL-6 levels and miniCASCO-based cachexia severity significantly affected PFS (hazard ratio (HR) = 1.0388; 95%CI = 1.0230–1.0548; p < 0.001 and HR = 1.2587; 95%CI = 1.0850–1.4602; p = 0.0024, respectively) and OS (HR = 1.0404; 95%CI = 1.0221–1.0589; p < 0.0001 and HR = 2.3834; 95%CI = 1.1504–4.9378; p = 0.0194, respectively). A comparison of the survival curves by Kaplan–Meier analysis showed a significantly lower OS in patients with cachexia versus those without cachexia (p = 0.0323), as well as higher miniCASCO-based cachexia severity (p = 0.0428), an mGPS of 2 versus those with a lower mGPS (p = 0.0074), and higher IL-6 levels (>6 ng/mL) versus those with lower IL-6 levels (≤6 ng/mL) (p = 0.0120). In conclusion, our study supports the evidence that cachexia, with its related changes in inflammatory, body composition, and nutritional parameters, is a key prognostic and predictive factor for ICIs. Further larger studies are needed to confirm these findings and to explore the potential benefit of counteracting cachexia to improve immunotherapy efficacy

Leptin as a surrogate immune-metabolic marker to predict impact of anti-cachectic therapy: results of a prospective randomized trial in multiple solid tumors

Description of the work: Leptin is a reliable predictive and surrogate marker of the efficacy of multitargeted treatment of cancer cachexia. Purpose: To the best of our knowledge, no study has assessed the predictive role of biomarkers in establishing the effectiveness of anti-cachectic treatment, which remains a complex issue. Herein, we aimed to find a marker that can detect early response to anti-cachectic treatment. Patients and methods: From January 2012 to December 2022, all consecutive eligible advanced cancer patients with cachexia were prospectively enrolled in an exploratory and validation cohort according to eligibility criteria. All patients received a combined anti-cachectic treatment consisting of megestrol acetate plus celecoxib plus L-carnitine plus antioxidants that showed efficacy in a previous phase III randomized study. Primary endpoints were an increase in lean body mass (LBM), a decrease in resting energy expenditure (REE), a decrease in fatigue, and improvement in global quality of life. Results: A total of 553 consecutive patients were recruited. Twenty patients dropped out, equally distributed over the exploratory (11 patients) and validation (9 patients) cohorts, for early death due to disease progression. Then, 533 patients were deemed assessable. Leptin level changes inversely correlated with circulating levels of inflammatory mediators and reflected the improvement of body composition, energy metabolism, functional performance, and quality of life. At multivariate regression analysis, at week 8, leptin change was an independent predictor of LBM, skeletal muscle index (SMI), grip strength increase, and REE; at week 16, leptin change was an independent predictor of the same parameters and improvement in Eastern Cooperative Oncology Group performance status. The ability of leptin to predict changes in LBM, SMI, REE, and grip strength was superior to that of other inflammatory markers when comparing the receiver operating curves. Moreover, increasing delta leptin values were associated with significantly better outcomes in LBM, SMI, REE, grip strength, and fatigue. Conclusions: Leptin is a reliable predictive marker for multitargeted anti-cachectic treatment outcomes. Thus, it can be an ideal candidate for monitoring and predicting the effects of anti-cachectic treatment and a surrogate marker of the immune-metabolic actions of the selected drugs

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

NF1 truncating mutations associated to aggressive clinical phenotype with elephantiasis neuromatosa and solid malignancies

Background/aim: Von Recklinghausen disease is a syndrome characterized by a wide phenotypic variability giving rise to both, cutaneous and visceral benign and malignant neoplasms. The first include cutaneous neurofibromas, subcutaneous and plexiform neurofibromas. The latter can undergo malignant transformation and/or determine elephantiasis neuromatosa. Visceral tumors may include malignant peripheral nerve sheet tumors, gastrointestinal stromal tumors, cerebral gliomas and abdominal neurofibromas. In the present study, the authors discuss the clinical and biomolecular characterization of a cohort of 20 families with a diagnosis of type 1 neurofibromatosis. Patients and methods: Clinically, the cohort includes three probands with elephantiasis neuromatosa and a peculiarly high incidence of breast and gastrointestinal cancer. Results: Among the 14 NF1 mutations documented, 10 encoding for a truncated protein have been associated to particularly aggressive clinical phenotypes including elephantiasis neuromatosa, malignant peripheral nerve sheet tumors, breast cancer, gastrointestinal stromal tumors. Conclusion: This effect on protein synthesis, rather than the type of NF1 mutation, is the key to the explanation of the genotype-phenotype correlations in the context of neurofibromatosis type 1