Predicting locally advanced rectal cancer response to neoadjuvant therapy with 18F-FDG PET and MRI radiomics features.

PURPOSE: Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15-30% of cases, therefore it would be useful to assess if pretreatment of 18F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC. METHODS: Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models. RESULTS: In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index). CONCLUSIONS: If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.

Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma.

BACKGROUND: Effective target therapies for intrahepatic cholangiocarcinoma (ICC) have not been identified so far. One of the reasons may be the genetic evolution from primary (PR) to recurrent (REC) tumors. We aim to identify peculiar characteristics and to select potential targets specific for recurrent tumors. Eighteen ICC paired PR and REC tumors were collected from 5 Italian Centers. Eleven pairs were analyzed for gene expression profiling and 16 for mutational status of IDH1. For one pair, deep mutational analysis by Next Generation Sequencing was also carried out. An independent cohort of patients was used for validation. RESULTS: Two class-paired comparison yielded 315 differentially expressed genes between REC and PR tumors. Up-regulated genes in RECs are involved in RNA/DNA processing, cell cycle, epithelial to mesenchymal transition (EMT), resistance to apoptosis, and cytoskeleton remodeling. Down-regulated genes participate to epithelial cell differentiation, proteolysis, apoptotic, immune response, and inflammatory processes. A 24 gene signature is able to discriminate RECs from PRs in an independent cohort; FANCG is statistically associated with survival in the chol-TCGA dataset. IDH1 was mutated in the RECs of five patients; 4 of them displayed the mutation only in RECs. Deep sequencing performed in one patient confirmed the IDH1 mutation in REC. CONCLUSIONS: RECs are enriched for genes involved in EMT, resistance to apoptosis, and cytoskeleton remodeling. Key players of these pathways might be considered druggable targets in RECs. IDH1 is mutated in 30% of RECs, becoming both a marker of progression and a target for therapy.

Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome.

BACKGROUND: This study evaluated the safety of portal vein embolization (PVE), its impact on future liver remnant (FLR) volume and regeneration, and subsequent effects on outcome after liver resection. METHODS: Records of 112 patients were reviewed. Standardized FLR (sFLR) and degree of hypertrophy (DH; difference between the sFLR before and after PVE), complications and outcomes were analysed to determine cut-offs that predict postoperative hepatic dysfunction. RESULTS: Ten (8.9 per cent) of 112 patients had PVE-related complications. Postoperative complications occurred in 34 (44 per cent) of 78 patients who underwent hepatic resection and the 90-day mortality rate was 3 per cent. A sFLR of 20 per cent or less after PVE or DH of not more than 5 per cent (versus sFLR greater than 20 per cent and DH above 5 per cent) had a sensitivity of 80 per cent and a specificity of 94 per cent in predicting hepatic dysfunction. Overall, major and liver-related complications, hepatic dysfunction or insufficiency, hospital stay and 90-day mortality rate were significantly greater in patients with a sFLR of 20 per cent or less or DH of not more than 5 per cent compared with patients with higher values. CONCLUSION: DH contributes prognostic information additional to that gained by volumetric evaluation in patients undergoing PVE.

Suprapubic approach for robotic complete mesocolic excision in right colectomy: Oncologic safety and short-term outcomes of an original technique.

INTRODUCTION: Right-sided colon cancer has a worse prognosis than left-sided colon cancer. Complete mesocolic excision (CME) with central vessels ligation (CVL) reduces local recurrence, but is technically demanding, particularly with a laparoscopic approach. Aim of this study is to describe a new robotic approach to right colectomy with CME and CVL and to report oncologic safety and short term outcomes. METHODS: Twenty consecutive patients were included. All patients had a right colon adenocarcinoma and underwent right colectomy with a suprapubic approach. Surgery was realized with the Da Vinci Xi® system and all trocars were placed along a horizontal line 3-6 cm above the pubis. CME with CVL was realized in all the patients. Data analysed were: duration of surgery, conversions to open surgery, intraoperative and postoperative complication by Clavien Dindo classification, margins of resections, length of specimen and number of lymph nodes retrieved. RESULTS: Patients median age was 69 years, median body mass index was 27 kg/m2. Median operative time was 249 min, blood loss was negligible, no conversions to open or laparoscopic surgery occurred. Median hospital stay was six days; two postoperative grade IIIa Clavien-Dindo complications occurred, no 30-days postoperative death was registered. Resection margins were negative in all patients; median tumour diameter was 3.6 cm, median specimen length was 40 cm, median number of harvested lymph nodes was 40. CONCLUSIONS: Robotic right colectomy with CME using a suprapubic approach is a feasible and safe technique that allows for an extended lymphadenectomy and provides high quality surgical specimens.

Assessing the role of primary tumour resection in patients with synchronous unresectable liver metastases from pancreatic neuroendocrine tumour of the body and tail. A propensity score survival evaluation.

BACKGROUND: The role of primary tumour surgery in pancreatic neuroendocrine tumours (PNETs) with unresectable liver metastases is controversial and international guidelines do not recommend surgery in such cases. Resectability of the primary tumour has never been considered in outcome comparisons between operated and non-operated patients. METHODS: From two institutional prospective databases of patients affected by PNET and unresectable liver metastases, 63 patients who underwent a left-pancreatectomy at diagnosis were identified and compared with a group of 30 patients with a potentially resectable but not-resected primary tumour located in the body or tail. The endpoint was overall survival (OS). RESULTS: The two groups significantly differed at baseline with regard to liver tumour burden Ki-67 labelling index, site of pancreas, results of the 18FDG PET-CT and age. In the operated patients, surgical morbidity comprised 7 cases of pancreatic fistula. Postoperative mortality was nil. Median OS for patients undergoing left-pancreatectomy was 111 months vs 52 for the non operated patients (p = 0.003). At multivariate analysis after propensity score adjustment, no surgery as well as liver tumour burden>25% and higher Ki-67 index were associated with an increased risk of death during follow-up. In patients with unresectable primary tumour, OS was similar in comparison to that in the resectable but non-resected patients, and significantly worse than that in the resected patients (p = 0.032). CONCLUSION: In PNETs located in the body or tail and diffuse liver metastases distal pancreatectomy may be justified in selected patients. Randomized studies may be safely proposed in future on this topic.

A case of pleomorphic lipoma of the hypopharynx.

We report the first case of pleomorphic lipoma in the hypopharynx. A 69-year-old man was admitted because of a 12 year history of dysphagia and cough. Direct laryngo-pharyngoscopy revealed a polypoid, yellow, smooth, submucosal tumor with well defined borders. At CT scan the tumor showed a hypodense pattern and measured 3 cm. Microscopically the neoplasm was composed mainly by typical lipomatous tissue, bundles of collagen and pleomorphic multinucleated cells, some with floret-like appearance. Lipoblasts and mitoses were not found. Six months after resection there was no evidence of recurrence.

Randomized clinical trial of liver resection with and without hepatic pedicle clamping.

BACKGROUND: The purpose of this study was to compare the perioperative outcome of liver resection with and without intermittent hepatic pedicle clamping. METHODS: Between June 2002 and June 2004, 126 consecutive patients with resectable liver tumours were randomized to undergo resection with (63 patients) or without (63 patients) intermittent hepatic pedicle clamping. RESULTS: The transection time was significantly higher in the group without hepatic pedicle clamping. The blood loss per cm(2) was similar in the two groups: 2.7 ml/cm(2) in the group with versus 3.2 ml/cm(2) in group without hepatic pedicle clamping (P = 0.425). In the subset of patients with an abnormal liver, there were no differences in blood loss per transection surface: 3.1 ml/cm(2) in the group with versus 2.9 ml/cm(2) in the group without clamping (P = 0.829). The rate of blood transfusions was not higher in the non-clamping group. No differences were observed in the postoperative liver enzyme serum levels, the in-hospital mortality (one patient in each group) or the number of complications. CONCLUSION: This study showed clearly that liver resection without hepatic pedicle clamping is safe, even in patients with a diseased liver.

Prospective randomized study of steroids in the prevention of ischaemic injury during hepatic resection with pedicle clamping.

BACKGROUND: The major drawback of hepatic pedicle clamping is ischaemia-reperfusion injury with impairment of liver function. Perioperative steroid administration has been advocated to reduce liver damage. The aim of this prospective, randomized study was to determine whether steroid administration can reduce liver injury and improve short-term outcome. METHODS: Fifty-three patients undergoing liver resection were randomized to a steroid group (group 1) or to a control group (group 2); patients in group 1 received methylprednisolone 30 mg/kg 30 min before liver resection whereas those in group 2 did not. Serum levels of interleukin (IL) 6, total bilirubin, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and prothrombin time (PT) were measured. Length of stay, and type and number of complications were recorded. RESULTS: Serum IL-6 levels were significantly lower in the steroid group than in the control group 24 h after surgery. Steroid administration significantly modified AST, ALT and PT levels only in patients with chronic liver disease. Overall and lung-related morbidity were not significantly different between the two groups. CONCLUSIONS: Steroid administration suppresses serum IL-6 levels, but has no effect on short-term outcome.