In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO.

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam's Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan.

The Accuracy of Simple and Adjusted Aldosterone Indices for Assessing Selectivity and Lateralization of Adrenal Vein Sampling in the Diagnosis of Primary Aldosteronism Subtypes.

OBJECTIVE: This study aimed to evaluate the reliability of simple and corrected aldosterone indices for assessing the selectivity and lateralization of adrenal vein sampling (AVS) in patients with primary aldosteronism. METHODS: Data of all consecutive patients with primary aldosteronism who underwent AVS for subtype diagnosis, followed at two Italian referral centers, were analyzed retrospectively. RESULTS: AVS achieved bilateral selectivity in 112/144 patients. Unilateral disease was diagnosed in 60 cases (53.6%) and idiopathic hyperaldosteronism in 52 individuals (46.4%). The aldosterone index (aldosterone ratio between an adrenal vein and the inferior vena cava) showed a high accuracy in predicting selectivity, compared to a cortisol selectivity index of 1.1, and a moderate accuracy, compared to cortisol cut-offs of 2 and 3. The simple aldosterone index showed a moderate accuracy in predicting ipsi/contralateral aldosterone hypersecretion, while lesion side- and hypokalemia-corrected aldosterone index revealed a significant improvement in predicting ipsi/contralateral disease. Moreover, the comparative aldosterone index (aldosterone ratio in the dominant vs the non-dominant adrenal vein) revealed a high accuracy in predicting unilateral primary aldosteronism. For an immediate clinical application of our results, the adjusted cut-offs were calculated, according to the Youden's criterion and to a pre-established specificity of 90%, for all possible combinations of lesion side at imaging and presence/absence of hypokalemia. CONCLUSIONS: This study demonstrated the diagnostic accuracy of simple and clinical-/imaging-corrected aldosterone indices for adrenal vein sampling in subtype diagnosis of primary aldosteronism and suggests the potential application of these tools to select patients for adrenalectomy when standard indices cannot be performed.

Minimally invasive adrenalectomy for large pheochromocytoma: not recommendable yet? Results from a single institution case series.

BACKGROUND: Minimally invasive adrenalectomy represents the treatment of choice of pheochromocytoma (PCC). For large or invasive PCCs, an open approach is currently recommended, in order to ensure complete tumor resection, prevent tumor rupture, avoid local recurrence, and limit perioperative hemodynamic instability. The aim of this study is to analyze perioperative outcomes of laparoscopic adrenalectomies (LAs) for large adrenal PCCs. METHODS: All consecutive LAs for PCC performed at a single institution between 1998 and 2020 were included. Two groups were defined: lesions larger (group 1) and smaller (group 2) than 5 cm. Short-term outcomes were compared in order to find any significant difference between the two groups. OUTCOMES: One hundred fourteen patients underwent LA during the study period: 46 for lesions larger and 68 for lesions smaller than 5 cm. No significant differences were found in patients' characteristics, median operative time, conversion rate, intraoperative hemodynamic and metabolic parameters, postoperative intensive care unit (ICU) admission rate, complications rate, and length of hospital stay. Long-term oncologic outcomes were similar, with a recurrence rate of 5.1% in group 1 vs 3.6% in group 2 (p = 1). CONCLUSION: Minimally invasive adrenalectomy seems to be safe and effective even in large PCC. The recommendation to prefer an open approach for large PCCs should probably be reconsidered.

Localization of anatomical changes in patients during proton therapy with in-beam PET monitoring: A voxel-based morphometry approach exploiting Monte Carlo simulations.

PURPOSE: In-beam positron emission tomography (PET) is one of the modalities that can be used for in vivo noninvasive treatment monitoring in proton therapy. Although PET monitoring has been frequently applied for this purpose, there is still no straightforward method to translate the information obtained from the PET images into easy-to-interpret information for clinical personnel. The purpose of this work is to propose a statistical method for analyzing in-beam PET monitoring images that can be used to locate, quantify, and visualize regions with possible morphological changes occurring over the course of treatment. METHODS: We selected a patient treated for squamous cell carcinoma (SCC) with proton therapy, to perform multiple Monte Carlo (MC) simulations of the expected PET signal at the start of treatment, and to study how the PET signal may change along the treatment course due to morphological changes. We performed voxel-wise two-tailed statistical tests of the simulated PET images, resembling the voxel-based morphometry (VBM) method commonly used in neuroimaging data analysis, to locate regions with significant morphological changes and to quantify the change. RESULTS: The VBM resembling method has been successfully applied to the simulated in-beam PET images, despite the fact that such images suffer from image artifacts and limited statistics. Three dimensional probability maps were obtained, that allowed to identify interfractional morphological changes and to visualize them superimposed on the computed tomography (CT) scan. In particular, the characteristic color patterns resulting from the two-tailed statistical tests lend themselves to trigger alarms in case of morphological changes along the course of treatment. CONCLUSIONS: The statistical method presented in this work is a promising method to apply to PET monitoring data to reveal interfractional morphological changes in patients, occurring over the course of treatment. Based on simulated in-beam PET treatment monitoring images, we showed that with our method it was possible to correctly identify the regions that changed. Moreover we could quantify the changes, and visualize them superimposed on the CT scan. The proposed method can possibly help clinical personnel in the replanning procedure in adaptive proton therapy treatments.

"Never Trust to General Impressions, My Boy, but Concentrate Yourself upon Details": An Unusual and Challenging Presentation of Pheochromocytoma.

We present the case of a 45-year-old woman admitted to our unit with acute heart failure and cardiogenic shock, requiring an intra-aortic balloon pump insertion and inotropes and vasopressors infusion. Despite such treatment, the patient developed multi organ failure and intravascular disseminated coagulation with haemolysis. The initial diagnosis of acute myocarditis was subsequently denied by the finding of bilateral adrenal masses by MRI scan, and urine and plasma metanephrines measurements confirmed a pheochromocytoma (PCC). Genetic analysis revealed a mutation in the neurofibromatosis type 1 (NF1) gene, and an accurate physical examination drew attention to small cafè-au-lait spots, usually associated with this syndrome. PCC diagnosis should be promptly considered in patients presenting with unexplained acute heart failure and cardiogenic shock of unknown origin, considering its life-threatening complications and the good prognosis after radical surgery.

The diagnostic accuracy of adjusted unconventional indices for adrenal vein sampling in the diagnosis of primary aldosteronism subtypes.

OBJECTIVE: Simple unconventional indices did not demonstrate a satisfactory accuracy for diagnosing unilateral primary aldosteronism when adrenal vein sampling is not bilaterally selective. This study aimed to evaluate the reliability of clinical/imaging-corrected unconventional indices for adrenal vein sampling in predicting unilateral primary aldosteronism. METHODS: Data of all consecutive patients with primary aldosteronism subtyped with adrenal vein sampling, referred to two Italian centers, were analyzed retrospectively. All patients with proved unilateral aldosterone hypersecretion underwent adrenalectomy. RESULTS: Unilateral disease was diagnosed in 58 cases (54.2%) and idiopathic hyperaldosteronism in 49 individuals (45.8%). The monoadrenal index (aldosterone-to-cortisol ratio in the adrenal vein) showed high accuracy in predicting ipsilateral disease and moderate accuracy in predicting contralateral aldosterone hypersecretion. The monolateral index (aldosterone-to-cortisol ratio in the adrenal vein vs. peripheral blood) revealed moderate accuracy in predicting ipsilateral disease and high accuracy in predicting contralateral aldosterone hypersecretion. Lesion side- and hypokalemia-corrected ROC curves for these unconventional indices revealed a significant improvement in the reliability of predicting ipsilateral/contralateral disease, reaching high accuracy in all models. For an immediate clinical application of our results, the adjusted cut-offs were calculated, according to the Youden's criterion and to a pre-established specificity of 95%, for all possible combinations of lesion side at imaging and presence/absence of hypokalemia. CONCLUSION: This study demonstrated the high diagnostic accuracy of clinical-/imaging-corrected unconventional indices for adrenal vein sampling in the diagnosis of primary aldosteronism subtypes and suggests the use of these adjusted indices to select patients for adrenalectomy when adrenal vein sampling is not bilaterally selective.

Prevalence of primary aldosteronism and association with cardiovascular complications in patients with resistant and refractory hypertension.

OBJECTIVES: To assess the prevalence of primary aldosteronism and its association with cardiometabolic complications in patients with resistant and refractory hypertension. METHODS: One hundred and ten consecutive patients with true resistant hypertension [insufficient blood pressure control despite appropriate lifestyle measures and treatment with at least three classes of antihypertensive medication, including a diuretic] and without previous cardiovascular events were screened for secondary hypertension. Refractory hypertension was diagnosed in case of uncontrolled blood pressure despite the use of at least five antihypertensive drugs. RESULTS: Primary aldosteronism was diagnosed in 32 cases (29.1%). The multivariate analysis showed that primary aldosteronism is a strong factor positively associated with left ventricular hypertrophy [odds ratio (OR) = 12.98, 95% confidence interval (CI) 3.82-60.88; P < 0.001], microalbuminuria (OR = 3.67, 95% CI 1.44-9.78; P = 0.007), carotid intima-media thickness at least 0.9 mm (OR = 2.69, 95% CI 1.02-7.82; P = 0.037), aortic ectasia (OR = 4.08, 95% CI 1,18-15.04; P = 0.027) and atrial fibrillation (OR 8.80, 95% CI 1.53-73.98; P = 0.022). Moreover, primary aldosteronism was independently associated with the presence of at least one (OR = 8.60, 95% CI 1.73-69.88; P = 0.018) and at least two types of organ damage (OR = 3.08, 95% CI 1.19-8.24; P = 0.022). Thirteen patients (11.8%) were affected by refractory hypertension. This group was characterized by significantly higher values of carotid intima-media thickness, higher rate of aldosterone-producing adenoma and atrial fibrillation, compared with the other individuals with resistant hypertension. CONCLUSION: The current study indicates that primary aldosteronism is a frequent cause of secondary hypertension and cardiovascular complications among patients with resistant and refractory hypertension, suggesting a crucial role of aldosterone in the pathogenesis of severe hypertensive phenotypes and cardiovascular disease.

Predictors of recurrence of pheochromocytoma and paraganglioma: a multicenter study in Piedmont, Italy.

The available data on the natural history of pheochromocytomas and paragangliomas after radical surgery are heterogeneous and discordant. The aim of our retrospective multicenter study was to find predictors of recurrence in patients with pheochromocytomas and sympathetic paragangliomas submitted to radical surgery in Piedmont (a region in northwest Italy). We collected data from 242 patients diagnosed between 1990 and 2016. Forty-two patients (17.4%) had disease recurrence. Multivariate analysis showed that genetic mutation (HR = 3.62; 95% CI 1.44-9.13; p = 0.006), younger age (HR = 0.97; 95% CI 0.95-0.99; p = 0.031) and larger tumor size (HR = 1.01; 95% CI 1.00-1.02; p = 0.015) were independently associated with a higher recurrence risk of pheochromocytoma and paraganglioma; in pheochromocytomas, genetic mutation (HR = 3.4; 95% CI 1.00-11.48; p = 0.049), younger age (HR = 0.97; 95% CI 0.94-0.99; p = 0.02), higher tumor size (HR = 1.01; 95% CI 1.00-1.03; p = 0.043) and PASS value (HR = 1.16; 95% CI 1.03-1.3; p = 0.011) were associated with recurrence. Moreover, tumor size was the only predictor of metastatic pheochromocytoma and paraganglioma (HR = 4.6; 95% CI 1.4-15.0; p = 0.012); tumor size (HR = 3.93; 95% CI 1.2-16.4; p = 0.026) and PASS value (HR = 1.27; 95% CI 1.06-1.53; p = 0.007) were predictors of metastatic pheochromocytoma. In conclusion, our findings suggest that the recurrence of pheochromocytoma and sympathetic paraganglioma develops more frequently in younger subjects, patients with a family history of chromaffin tissue neoplasms, mutations in susceptibility genes, larger tumors and higher values of PASS. We recommend genetic testing in all patients with PPGL and strict follow-up at least on an annual basis.

Online proton therapy monitoring: clinical test of a Silicon-photodetector-based in-beam PET.

Particle therapy exploits the energy deposition pattern of hadron beams. The narrow Bragg Peak at the end of range is a major advantage but range uncertainties can cause severe damage and require online verification to maximise the effectiveness in clinics. In-beam Positron Emission Tomography (PET) is a non-invasive, promising in-vivo technique, which consists in the measurement of the ß+ activity induced by beam-tissue interactions during treatment, and presents the highest correlation of the measured activity distribution with the deposited dose, since it is not much influenced by biological washout. Here we report the first clinical results obtained with a state-of-the-art in-beam PET scanner, with on-the-fly reconstruction of the activity distribution during irradiation. An automated time-resolved quantitative analysis was tested on a lacrimal gland carcinoma case, monitored during two consecutive treatment sessions. The 3D activity map was reconstructed every 10 s, with an average delay between beam delivery and image availability of about 6 s. The correlation coefficient of 3D activity maps for the two sessions (above 0.9 after 120 s) and the range agreement (within 1 mm) prove the suitability of in-beam PET for online range verification during treatment, a crucial step towards adaptive strategies in particle therapy.

TRIMAGE: A dedicated trimodality (PET/MR/EEG) imaging tool for schizophrenia.

Simultaneous PET/MR/EEG (Positron Emission Tomography - Magnetic Resonance - Electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here within the framework of the European Union Project TRIMAGE. The trimodal, cost-effective PET/MR/EEG imaging tool makes use of cutting edge technology both in PET and in MR fields. A novel type of magnet (1.5T, non-cryogenic) has been built together with a PET scanner that makes use of the most advanced photodetectors (i.e., SiPM matrices), scintillators matrices (LYSO) and digital electronics. The combined PET/MR/EEG system is dedicated to brain imaging and has an inner diameter of 260 mm and an axial Field-of-View of 160 mm. It enables the acquisition and assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. The dopaminergic system and the glutamatergic system in schizophrenic patients are investigated via PET, the same physiological/pathophysiological conditions with regard to functional connectivity, via fMRI, and its electrophysiological signature via EEG. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases. The preliminary performances of two components of the imaging tool (PET and MR) are discussed. Initial results of the search of possible candidates for suitable schizophrenia biomarkers are also presented as obtained with PET/MR systems available to the collaboration.

The Thunderbeat and Other Energy Devices in Laparoscopic Colorectal Resections: Analysis of Outcomes and Costs.

BACKGROUND: The THUNDERBEAT™ (TB) is a recently developed energy-based device. To date, there are no clinical studies comparing TB and other energy sources, such as standard electrosurgery (ES), ultrasonic coagulating shears (US) and electrothermal bipolar vessel sealers (EBVS) in patients undergoing laparoscopic colorectal resection (LCR). The aim of this study was to compare outcomes and costs in patients undergoing LCR with TB, US, EBVS, or ES for both benign and malignant colorectal diseases. METHODS: This study is a retrospective analysis of a prospective database of patients undergoing LCR. Unselected consecutive patients who had the laparoscopic dissection conducted by using TB were compared with consecutive patients undergoing LCR with US, EBVS, or ES. RESULTS: Mean operative time did not significantly differ between the groups (P = .947). Estimated blood loss was significantly higher in the ES group (P < .001). Device-related complications occurred in 2.5% of ES patients, in 2.5% of US patients, and in 5% of EBVS patients, while no complications occurred in TB patients (P = .768). No significant differences were observed in postoperative complication rates between the groups. Mean postoperative hospital stay was similar in the groups. Cost analysis showed no significant differences between US (1519.1 ± 303 €), EBVS (1474.4 ± 372.8 €), and TB (1474.3 ± 176.3 €) (P = .737). CONCLUSION: This is the first clinical study comparing TB and other energy-based devices in LCR. They all appear to be equally safe and effective. Costs of surgery are very similar. Further large randomized controlled trials are needed to confirm these data.

INSIDE in-beam positron emission tomography system for particle range monitoring in hadrontherapy.

The quality assurance of particle therapy treatment is a fundamental issue that can be addressed by developing reliable monitoring techniques and indicators of the treatment plan correctness. Among the available imaging techniques, positron emission tomography (PET) has long been investigated and then clinically applied to proton and carbon beams. In 2013, the Innovative Solutions for Dosimetry in Hadrontherapy (INSIDE) collaboration proposed an innovative bimodal imaging concept that combines an in-beam PET scanner with a tracking system for charged particle imaging. This paper presents the general architecture of the INSIDE project but focuses on the in-beam PET scanner that has been designed to reconstruct the particles range with millimetric resolution within a fraction of the dose delivered in a treatment of head and neck tumors. The in-beam PET scanner has been recently installed at the Italian National Center of Oncologic Hadrontherapy (CNAO) in Pavia, Italy, and the commissioning phase has just started. The results of the first beam test with clinical proton beams on phantoms clearly show the capability of the in-beam PET to operate during the irradiation delivery and to reconstruct on-line the beam-induced activity map. The accuracy in the activity distal fall-off determination is millimetric for therapeutic doses.

10-Year Oncologic Outcomes After Laparoscopic or Open Total Mesorectal Excision for Rectal Cancer.

BACKGROUND: Only few studies have compared laparoscopic total mesorectal excision (LTME) and open total mesorectal excision (OTME) for rectal cancer with follow-up longer than 5 years. The aim of this study was to compare 10-year oncologic outcomes after LTME and OTME for nonmetastatic rectal cancer. METHODS: We conducted a retrospective analysis of a prospective database of rectal cancer patients undergoing LTME or OTME. Statistical analyses were performed on an ''intention-to-treat'' basis and by actual treatment. Overall survival (OS) and disease-free survival (DFS) were compared by using the Kaplan-Meier method. A multivariable analysis was performed to identify predictors of poor survival. RESULTS: Between April 1994 and August 2005, a total of 153 LTME patients and 154 OTME patients were included. Similarly, 10-year OS and DFS after LTME and OTME were observed: 76.8 versus 70.6 % (P = 0.138) and 69.1 versus 67.6 % (P = 0.508), respectively. Conversion to OTME did not adversely affect OS and DFS. Stage-by-stage comparison showed no significant differences between LTME and OTME. No significant differences were observed in local recurrence rates after LTME and OTME (6.5 vs. 7.8 %, P = 0.837). Median time until local recurrence was 24.5 (range, 12-56) months after LTME and 22 (6-64) months after OTME (P = 0.777). Poor tumor differentiation, lymphovascular invasion, and a lymph node ratio of 0.25 or more were the independent predictors of poorer OS and DFS. CONCLUSION: This retrospective study with long follow-up did not show significant differences between the two groups in OS and DFS.

Issues in the Diagnosis and Treatment of Primary Aldosteronism.

Primary aldosteronism (PA) is associated with a high rate of cardio- and cerebrovascular complications and metabolic alterations. PA is also recognized as the most frequent, although often unrecognized, secondary form of hypertension. Guidelines have been released to assist clinicians in the diagnostic work-up and subtype differentiation of PA. In this review we discuss and compare the available guidelines in the context of our professional experience and evaluate diagnostic and therapeutic aspects that are still a matter of debate.

Laparoscopic colon resection: To prep or not to prep? Analysis of 1535 patients.

BACKGROUND: Mechanical bowel preparation (MBP) before elective open colon resection does not reduce the rate of postoperative anastomotic leakage. However, MBP is still routinely used in many countries, and there are very limited data regarding the utility of preoperative MBP in patients undergoing laparoscopic colon resection (LCR). The aim of this study was to challenge the use of MBP before elective LCR. METHODS: It is a retrospective analysis of a prospectively collected database. All patients undergoing elective LCR with primary anastomosis and no stoma were included. Preoperative MBP with polyethylene glycol solution was used routinely between April 1992 and December 2004, and then it was abandoned. The early postoperative outcomes in patients who had preoperative MBP (MBP group) and in patients who underwent LCR without preoperative MBP (No-MBP group) were compared. RESULTS: From April 1992 to December 2014, 1535 patients underwent LCR: 706 MBP patients and 829 No-MBP patients. There were no differences in demographic data, indication for surgery and type of procedure performed between MBP and No-MBP group patients. The incidence of anastomotic leakage was similar between the two groups (3.4 vs. 3.6 %, p = 0.925). No differences were observed in intra-abdominal abscesses (0.6 vs. 0.8 %, p = 0.734), wound infections (0.6 vs. 1.4 %, p = 0.149), infectious extra-abdominal complications (1.8 vs. 3 %, p = 0.190), and non-infectious complications (6.1 vs. 6.8 %, p = 0.672). The overall reoperation rate was 4.6 % for MBP patients and 5 % for No-MBP patients (p = 0.813). CONCLUSION: The use of preoperative MBP does not seem to be associated with lower incidence of intra-abdominal septic complications after LCR.

Laparoscopic versus open resection for transverse colon cancer.

BACKGROUND: Previous large randomized controlled trials comparing laparoscopic (LR) and open resection (OR) for colon cancer have not specifically analyzed the outcomes in patients with transverse colon cancer. The aims of this study were to evaluate the feasibility and safety of LR transverse colon cancer resection and to compare our findings with the results available in the literature. METHODS: We performed a retrospective analysis of consecutive patients undergoing LR or OR for histologically proven adenocarcinoma of the transverse colon. RESULTS: A total of 123 patients were included in this study: 66 LR and 57 OR. Median operating time was similar in the two groups. Median blood loss was higher in the OR group, even though the difference was not statistically significant. The rate of conversion from LR to OR was 16.7 %. Return of bowel function occurred significantly earlier in the LR group. The incidence and severity of 30-day postoperative complications and mortality rates were similar in the two groups. The median hospital stay was significantly shorter in the LR group. There was a trend toward a greater number of lymph nodes harvested in the OR group than in the LR group, although the difference was not statistically significant. The time to first flatus and bowel movement was significantly earlier in the LR group. Five-year overall survival and disease-free survival rates were similar in the LR and OR groups (86.4 vs. 88.6 %, p = 0.770 and 80.4 vs. 77.3 %, p = 0.516, respectively). CONCLUSIONS: LR of transverse colon cancer is feasible and safe, with similar early short-term outcomes when compared to OR. Larger prospective comparative studies with long-term follow-up are needed to assess the oncological equivalence of the two approaches.

Laparoscopic versus open resection for colon cancer: 10-year outcomes of a prospective clinical trial.

BACKGROUND: Laparoscopic resection (LR) and open resection (OR) for colon cancer have similar oncologic outcomes at 5-year follow-up. However, results from studies with longer follow-up are limited. This study aimed to compare 10-year oncologic outcomes of LR and OR for non-metastatic colon cancer. METHODS: A prospective non-randomized trial comparing patients undergoing LR or OR for non-metastatic colon cancer at a single institution was conducted. Statistical analyses were performed on an ''intention-to-treat'' basis and by actual treatment. Kaplan-Meier curves were compared to analyze overall survival (OS) and disease-free survival (DFS). A multivariate analysis was performed to identify predictors of poor survival. RESULTS: The study included 304 colon cancer patients: 154 patients underwent LR and 150 underwent OR. Fifteen (9.7 %) had LR converted to OR. During a median follow-up period of 138 (range, 120-220) months, no significant differences were observed between LR and OR patients in 10-year OS and DFS rates: 87.2 % versus 78.7 % (P = 0.182) and 80.9 % versus 76.8 % (P = 0.444), respectively. Conversion to open surgery was associated with a non-significant reduction in OS and DFS. Stage-by-stage comparison showed no significant differences between the two groups. Both OS and DFS were similar between right colon and left-sided colon cancer patients. On multivariate analysis, pT4 cancer and a lymph node ratio of 0.20 or more were the only independent predictors of both OS and DFS. CONCLUSIONS: The 10-year follow-up results confirm the oncological effectiveness of the laparoscopic approach to non-metastatic colon cancer.

Metastatic lymph node ratio as a prognostic factor after laparoscopic total mesorectal excision for extraperitoneal rectal cancer.

BACKGROUND: The lymph node ratio (LNR; number of positive nodes divided by total nodes harvested) has been demonstrated to be a prognostic factor in colon cancer, but its role in extraperitoneal rectal cancer is still debated; furthermore, no data are available on laparoscopic rectal resection. The aim of this study was to evaluate the prognostic impact of LNR on long-term outcomes after laparoscopic total mesorectal excision (LTME) for extraperitoneal cancer in consecutive patients with a 5-year minimum follow-up. METHODS: This study is a prospective analysis of consecutive patients who underwent LTME for adenocarcinoma of the extraperitoneal rectum. RESULTS: LTME was performed in 158 patients. The median number of LN harvested was 12 (range = 3-25). The proportion of specimens with fewer than 12 examined LN was significantly higher in patients who had neoadjuvant chemoradiotherapy (p < 0.001). During a median follow-up period of 122 months, the local recurrence rate was 8 %. At univariate analysis, disease-free survival and overall survival significantly decreased with increasing LNR (p < 0.001). Multivariate analysis showed that the distal margin ≤ 1 cm was the only independent predictor of local recurrence (p = 0.028). LNR (cutoff value = 0.25) and lymphovascular invasion were significant prognostic factors for both disease-free (p = 0.015 and p = 0.046, respectively) and overall survival (p = 0.031 and p = 0.040, respectively). Even in the subgroup of patients in whom fewer than 12 LN were examined, LNR confirmed its prognostic role, with a statistical trend toward worse disease-free survival and overall survival. CONCLUSION: Metastatic LNR is an independent prognostic factor for disease-free survival and overall survival after LTME for extraperitoneal rectal cancer.

Transanal endoscopic microsurgery vs. laparoscopic total mesorectal excision for T2N0 rectal cancer.

OBJECTIVE: The aim was to compare transanal endoscopic microsurgery (TEM) and laparoscopic resection (LR) in terms of short-term and oncologic outcomes in patients with a preoperatively diagnosed T2N0 extraperitoneal rectal cancer. METHODS: We conducted a retrospective analysis of a prospective database. All patients with a preoperatively staged T2N0 extraperitoneal rectal adenocarcinoma were considered for LR. Patients refusing LR or medically unfit for LR were considered for TEM, which was associated with neoadjuvant RT in the last cases. Only patients with a minimum follow-up of 36 months were included. RESULTS: Seventy-eight patients were included. TEM was indicated or preferred in 43 patients; of these, 11 underwent neoadjuvant RT. Morbidity was significantly lower after TEM (p < 0.001). The median follow-up was 70 (36-140) months. A higher local recurrence rate was noted after TEM (26 %), compared to neoadjuvant RT + TEM (0 %) and LR (9 %) (p = 0.070). Overall, 5-year survival rate was 76 % after TEM, 77.8 % after RT + TEM, and 96 % after LR, respectively (p = 0.134). CONCLUSIONS: While TEM alone may only be considered a palliative treatment, it might allow similar oncologic results to abdominal resection in responders to neoadjuvant RT. Large prospective randomized trials are awaited to confirm these findings.