Ultrasound-guided robotic surgical procedures: a systematic review.

INTRODUCTION: Ultrasound has been nicknamed "the surgeon's stethoscope". The advantages of laparoscopic ultrasound beyond a substitute for the sense of touch are considerable, especially for robotic surgery. Being able to see through parenchyma and into vascular structures enables to avoid unnecessary dissection by providing a thorough assessment at every stage without the need for contrast media or ionising radiation. The limitations of restricted angulation and access within the abdominal cavity during laparoscopy can be overcome by robotic handling of miniaturised ultrasound probes and the use of various and specific frequencies will meet tissue- and organ-specific characteristics. The aim of this systematic review was to assess the reported applications of intraoperative ultrasound-guided robotic surgery and to outline future perspectives. METHODS: The study adhered to the PRISMA guidelines. PubMed, Google Scholar, ScienceDirect and ClinicalTrials.gov were searched up to October 2023. Manuscripts reporting data on ultrasound-guided robotic procedures were included in the qualitative analysis. RESULTS: 20 studies met the inclusion criteria. The majority (53%) were related to the field of general surgery during liver, pancreas, spleen, gallbladder/bile duct, vascular and rectal surgery. This was followed by other fields of oncological surgery (42%) including urology, lung surgery, and retroperitoneal lymphadenectomy for metastases. Among the studies, ten (53%) focused on locating tumoral lesions and defining resection margins, four (15%) were designed to test the feasibility of robotic ultrasound-guided surgery, while two (10.5%) aimed to compare robotic and laparoscopic ultrasound probes. Additionally two studies (10.5%) evaluated the robotic drop-in probe one (5%) assessed the hepatic tissue consistency and another one (5%) aimed to visualize the blood flow in the splenic artery. CONCLUSION: The advantages of robotic instrumentation, including ergonomics, dexterity, and precision of movements, are of relevance for robotic intraoperative ultrasound (RIOUS). The present systematic review demonstrates the virtue of RIOUS to support surgeons and potentially reduce minimally invasive procedure times.

Survival associated with the use of one-step nucleic acid amplification (OSNA) to detect sentinel lymph node metastasis in cervical cancer.

INTRODUCTION: Sentinel lymph node (SLN) biopsy is part of surgical treatment of apparent early-stage cervical cancer. SLN is routinely analyzed by ultrastaging and immunohistochemistry. The aim of this study was to assess the survival of patients undergoing SLN analyzed by one-step nucleic acid amplification (OSNA) compared with ultrastaging. METHODS: Single-center, retrospective, cohort study. Patients undergoing primary surgery and SLN mapping ( ±pelvic lymphadenectomy) for apparent early-stage cervical cancer between May 2017 and January 2021 were included. SLN was analyzed exclusively with OSNA or with ultrastaging. Patients with bilateral SLN mapping failure, with SLN analyzed alternatively/serially with OSNA and ultrastaging, and undergoing neo-adjuvant therapy were excluded. Baseline clinic-pathological differences between the two groups were balanced with propensity-match analysis. RESULTS: One-hundred and fifty-seven patients were included, 50 (31.8%) in the OSNA group and 107 (68.2%) in the ultrastaging group. Median follow up time was 41 months (95%CI:37.9-42.2). 5-year DFS in patients undergoing OSNA versus ultrastaging was 87.0% versus 91.0% (p = 0.809) and 5-year overall survival was 97.9% versus 98.6% (p = 0.631), respectively. No difference in the incidence of lymph node recurrence between the two groups was noted (OSNA 20.0% versus ultrastaging 18.2%, p = 0.931). In the group of negative SLN, no 5-year DFS difference was noted between the two groups (p = 0.692). No 5-year DFS and OS difference was noted after propensity-match analysis (87.6% versus 87.0%, p = 0.726 and 97.4% versus 97.9%, p = 0.998, respectively). CONCLUSION: The use of OSNA as method to exclusively process SLN in cervical cancer was not associated with worse DFS compared to ultrastaging. Incidence of lymph node recurrence in the two groups was not different.

The potential role of systemic inflammatory markers in predicting recurrence in early-stage cervical cancer.

INTRODUCTION: The influence of systemic inflammatory markers on early-stage cervical cancer (ECC) patients is contradictory. No previous study analyzed whether these markers may be suggestive of recurrence. The aim of this study was to assess whether the inflammatory markers level of patients with recurrence during surveillance was different from those of patients without recurrence representing a risk factor for recurrence. METHODS: Retrospective, single-center, observational study. Patients with 2009 FIGO EEC surgically treated between 2012 and 2019 were included. Baseline inflammatory markers were evaluated on the results of the complete blood count (CBC) and coagulation tests. Inflammatory markers of relapsed patients were evaluated on the last CBC performed before the relapse diagnosis. Inflammatory markers of patients with no recurrence were evaluated on the available CBC taken at the same median follow-up time as the one from relapsed patients. RESULTS: 174 patients were included. Baseline Systemic immune inflammation index (SII) > 663 and Systemic inflammation response index (SIRI) > 0.98 were associated with significant risk of recurrence. SII>663 and Neutrophil to lymphocyte ratio (NLR) > 2.41 were associated with increased risk of death. Significant changes between relapsed (n = 23) and non-relapsed (n = 151) patients in median values of SII (615 versus 490, p-value = 0.001), SIRI (0.74 versus 1.05, p-value = 0.005), NRL (2.95 versus 2.15, p-value = 0.0035), and MLR (0.26 versus 0.22 p-value = 0.020), showed that different levels of inflammatory markers could help identifying recurrent disease during surveillance. CONCLUSION: Baseline SII>663 and SIRI>0.98 were associated with increased risk of recurrence. Higher median values of SII, SIRI, NLR and MLR in relapsed patients highlight their potential association with recurrence.

Reporting a single case of cystic echinococcosis in retroperitoneal mass of uncertain origin.

Echinococcal disease (hydatid disease (HD) is an endemic parasitosis caused by Echinococcus granulosus in the larval stage, and it is typically due to the production of unilocular cystic lesions, usually involving the liver for the majority of patients and the lungs in 25%, but also any other organs can be potentially involved in developing echinococcal disease. We report a case of extrahepatic, retroperitoneal echinococcal disease, caused by Echinococcus granulosus. The patient underwent a surgical removal of the abdominal mass, revealed by abdominal ultrasound and computerized tomography scanning, and in the founded clinical and radiological suspicion of echinococcal disease, multiple bioptical samples were sent for microbiological analysis and albendazole therapy was started; Echinococcus granulosus protoscolices were found on the bioptical sample, and the diagnosis was successfully confirmed. According to the current parasitology literature on echinococcal disease, extrahepatic localization, although rare, can be found, and it should be considered in the differential diagnosis of an abdominal mass when epidemiological risk factors and anamnestic data are present, regardless of the usual site of the disease.

Ultrastaging of the Parametrium in Cervical Cancer: A Clinicopathological Study.

Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment. The primary endpoint of the present study was to assess the rate of positive parametrial lymph nodes and of microscopic continuous or discontinuous parametrial involvement. This is a retrospective, single-center, observational study including patients with FIGO 2018 stage IA1-IIA1 and IIIC1p in whom bilateral sentinel lymph node (SLN) detection and ultrastaging of SLN were performed according to institutional protocol, with surgery as primary treatment performed between May 2017 and February 2021, as well as type B2/C1/C2 (Querleu-Morrow) radical hysterectomy and usual histology (squamous cell, adenocarcinoma and adenosquamous carcinoma). Thirty-one patients were included in the study period. Six (18.7%) patients had metastatic lymph nodes, of whom four had only SLN metastasis (two cases of ITC, one case of micrometastasis and one case of macrometastasis). We found a macroscopic deposit of cancer cells in the parametrial lymph node of one patient (3.1%). There was a positive statistical correlation between the incidence of parametrial lymph node involvement and the metastatic pelvic lymph nodes (p = 0.038). When performed per patient, the sensitivity, negative predictive value and accuracy of parametrial lymph node involvement in predicting pelvic lymph node metastasis were 16.7%, 83.3% and 83.9%, respectively. Ultrastaging of parametrial tissue did not identify any occult continuous or discontinuous parametrial metastasis. In conclusion, the incidence of lymph node parametrial involvement in a retrospective series of early-stage cervical cancer was 3.1% of all included patients. Lymph node involvement of the parametrium was associated with lymph node metastasis. The sensitivity of parametrial lymph node involvement to predict pelvic lymph node metastasis was low. The lack of parametrial involvement revealed by parametrial ultrastaging could be related to the number of patients with tumors with a pathologic diameter < 2 cm (54.8%). Further prospective studies are needed to analyze the role of parametrial ultrastaging in early-stage cervical cancer and to assess whether it can be considered the "sentinel" of the sentinel lymph node.

Prognostic Significance of Ultrasound Characteristics and Body Mass Index in Patients with Apparent Early-Stage Cervical Cancer: A Single-Center, Retrospective, Cohort Study.

The primary aim of the present study was to investigate the prognostic impact (defined as disease-free-DFS and overall survival-OS) of the ultrasound scan tumor parameters, patients' anthropometric parameters, and their combination in early-stage cervical cancer. The secondary aim was to assess the relation between ultrasound characteristics and pathological parametrial infiltration. This is a retrospective, single-center, observational cohort study. Consecutive patients with clinical FIGO 2018 stage IA1-IB2 and IIA1 cervical cancer who underwent preoperative ultrasound examination and radical surgery between 02/2012 and 06/2019 were included. Patients who underwent neo-adjuvant treatment, fertility sparing surgery, and pre-operative conization were excluded. Data from 164 patients were analyzed. Body mass index (BMI) ≤20 Kg/m2 (p < 0.001) and ultrasound tumor volume (p = 0.038) were related to a higher risk of recurrence. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI were significantly related to a higher risk of recurrence (p = 0.011, p = 0.031, and p = 0.017, respectively). The only anthropometric characteristic related to a higher risk of death was BMI ≤20 Kg/m2 (p = 0.021). In the multivariate analysis, the ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter (with 37 as the cut-off) was significantly associated with pathological microscopic parametrial infiltration (p = 0.018). In conclusion, a low BMI was the most significant anthropometric biomarker impairing DFS and OS in patients with apparent early-stage cervical cancer. The ratios between ultrasound tumor volume and BMI, ultrasound tumor volume and height, and ultrasound largest tumor diameter and BMI significantly affected DFS but not OS. The ratio between ultrasound-measured largest tumor diameter and cervix-fundus uterine diameter was related to parametrial infiltration. These novel prognostic parameters may be useful in pre-operative workup for a patient-tailored treatment in early-stage cervical cancer.

Fertility-sparing treatment for endometrial cancer and atypical endometrial hyperplasia in patients with Lynch Syndrome: Molecular diagnosis after immunohistochemistry of MMR proteins.

Introduction: Lynch Syndrome (LS) represents the hereditary condition that is most frequently associated with endometrial cancer (EC). The aim of this study is to assess the presence of Lynch Syndrome (LS) in young women with mismatch repair (MMR)-deficient atypical endometrial hyperplasia (AEH) and non-myoinvasive FIGO G1 endometrioid EC and its possible impact on the outcome of conservative treatment. Methods: Six MMR-deficient cases identified from a previous cohort of 69 conservatively treated patients were selected to be screened for germline mutations in MMR genes. In each patient, the outcomes of conservative treatment for AEH and EEC, including response, relapse, progression, and pregnancy, were assessed. Results: Five out of 6 patients underwent genetic test for LS. Three out of these 5 patients showed a positive genetic test. Patient 1 showed the c.942 + 2 T>A heterozygous variant of MSH2 mutation; after 12 months of complete response, she had relapse and progression of disease. Patient 4 showed the c.2459-1G>C variant of MSH2 mutation; after complete response, she failed to achieve pregnancy; she had relapse after 24 months and underwent hysterectomy. Patient 6 showed the c.803 + 1 heterozygous variant of PMS2 mutation; she had relapse of disease after 18 months from the first complete response and then underwent hysterectomy. Conclusions: In this series, 3 out of 6 women with MMR-deficiency had LS. None of the patients achieved pregnancy, and those who responded to treatment had subsequent relapse of disease. Patients undergoing fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer should perform MMR immunohistochemical analysis in order to screen LS.

Clinical Impact of Pathologic Residual Tumor in Locally Advanced Cervical Cancer Patients Managed by Chemoradiotherapy Followed by Radical Surgery: A Large, Multicenter, Retrospective Study.

BACKGROUND: Exclusive chemoradiation (E-CT/RT) represents the standard of treatment for locally advanced cervical cancer (LACC). Chemoradiation (CT/RT) followed by radical surgery (RS) may play a role for patients with a suboptimal response to CT/RT or in low-income countries with limited access to radiotherapy. Histologic assessment of residual tumor after CT/RT and RS allows accurate definition of prognostic categories. METHODS: Data on patients with FIGO stages 1B2 to 4A cervical cancer managed by CT/RT and RS from June 1996 to March 2020 were retrospectively analyzed. Pathologic response on the cervix was defined as complete (pCR), microscopic (persistent tumor foci ≤ 3 mm) (pmicroR), or macroscopic (persistent tumor foci > 3 mm) (pmacroR). Lymph node (LN) residual tumor was classified as absent or present. RESULTS: The 701 patients in this study underwent CT/RT and RS. Of the 701 patients, 293 (41.8%) had pCR, 188 (26.8%) had pmicroR, and 220 (31.4%) had pMacroR. Residual tumor was found in the pelvic lymph nodes of 66 (9.4%) patients and the aortic lymph nodes of 29 (4.1%) patients. The 5-year DFS and OS were respectively 86.6% and 92.5% in the pCR cases, 80.3% and 89.1% in the pmicroR cases, and 56.2% and 68.8% in the pmacroR cases. Among the patients with lymph node residual tumor, the 5-year DFS and OS were respectively 16.7% and 40% in the pCR cases, 35.4% and 53.3% in the pmicroR cases, and 31.7% and 31.1% in the pmacroR cases. Cervical residual tumor,, positive pelvic LNs, and positive aortic LNs were associated with worse DFS and OS in both the uni- and multivariate analyses. CONCLUSIONS: Persistence of pathologic residual tumor on the cervix and LNs after CT/RT are reliable predictors of survival for LACC patients undergoing CT/RT and adjuvant surgery.

The role of semiquantitative evaluation of lympho-vascular space invasion in early stage cervical cancer patients.

OBJECTIVE: Lymph vascular space involvement (LVSI) is one of the most important prognostic factors in early stage cervical cancer. Its qualitative evaluation represents a milestone for patient risk stratification and treatment choice, but a semi-quantitative analysis of LVSI may offer a more truthful risk model, as already demonstrated for endometrial cancer. The present study aims to investigate the performances of a semi-quantitative evaluation of LVSI in terms of patient risk assessment. METHODS: In this retrospective study were enrolled patients underwent surgical treatment for early cervical cancer from January 2009 to October 2018. A semi-quantitative evaluation such as the "three-tiered approach" was used to classify the LVSI pathway: negative vs. focal vs. diffuse. RESULTS: Diffuse LVSI was found to be a risk factor for lymph node metastasis (OR: 9.844, p < 0.001), and parametrial involvement (OR: 5.566, p < 0.001). Lymph nodal recurrences were more frequent in diffuse LVSI group (LVSI negative vs. focal LVSI p = 0.369; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.214); and so distant recurrences (LVSI negative vs. focal LVSI p = 0.623; LVSI negative vs. diffuse LVSI p = 0.002; Focal LVSI vs. diffuse LVSI p = 0.026). Patients with diffuse LVSI showed a worse disease-free survival (DFS) than patients with focal or absent involvement (DFS LVSI negative vs. focal LVSI p = 0.938; LVSI negative vs. diffuse LVSI p < 0.001; focal LVSI vs. diffuse LVSI p = 0.036). CONCLUSION: Semi-quantitative evaluation of LVSI may be useful to identify risk patients for shorter disease-free survival and lymphatic and distant recurrences in patients with early stage.

Sentinel lymph node mapping with indocyanine green in cervical cancer patients undergoing open radical hysterectomy: a single-institution series.

PURPOSE: To assess the rate of bilateral sentinel lymph node (SLN) detection with indocyanine green (ICG), to evaluate the sensitivity and the negative predictive value of cervical cancer patients undergoing open radical hysterectomy; to compare open versus minimally invasive SLN biopsy performance and to assess factors related to no/unilateral SLN mapping. METHODS: We retrospectively reviewed consecutive patients with FIGO 2018 stage IA1 with lymph-vascular space involvement to IIB and IIIC1p cervical carcinoma who underwent SLN mapping with ICG followed by systematic pelvic lymphadenectomy between 05/2017 and 06/2020. Patients were divided according to surgical approach for statistical analysis. RESULTS: Eighty-five patients met inclusion criteria. Twenty-seven (31.8%) underwent open and 58 (68.2%) underwent minimally invasive SLN mapping. No difference in any SLN mapping (laparotomy 92.6% and minimally invasive 91.4%) or in SLN bilateral detection (laparotomy 72.0% and minimally invasive 84.9%) (p = 0.850 and p = 0.222, respectively), in median number of SLNs mapped and retrieved (2 in both groups, p = 0.165) and in site of SLN mapping per hemi-pelvis (right side, p = 0273 and left side, p = 0.618) was evident between open and minimally invasive approach. Per-patient sensitivity of SLN biopsy in laparotomy was 83.3% (95% CI 35.9-99.6%) and the negative predictive value was 95.0% (95% CI 76.0-99.1%). No difference in per-patient sensitivity was noted between two approaches (p = 0.300). None of the analyzed variables was associated with no/unilateral SLN mapping. CONCLUSION: The use of ICG to detect SLN in cervical cancer treated with open surgery allows a bilateral detection, sensitivity and negative predictive value comparable to minimally invasive surgery with potential advantages of ICG compared to other tracers.