Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.

BACKGROUND: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. OBJECTIVE: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. PATIENTS AND METHODS: This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. RESULTS: Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). CONCLUSIONS: Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

Tumor-non-tumor discrimination by a ß- detector for Radio Guided Surgery on ex-vivo neuroendocrine tumors samples.

This paper provides a first insight of the potential of the ß- Radio Guided Surgery (ß--RGS) in a complex surgical environment like the abdomen, where multiple sources of background concur to the signal at the tumor site. This case is well reproduced by ex-vivo samples of 90Y-marked Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP NET) in the bowel. These specimens indeed include at least three wide independent sources of background associated to three anatomical districts (mesentery, intestine, mucose). The study is based on the analysis of 37 lesions found on 5 samples belonging to 5 different patients. We show that the use of electrons, a short range particle, instead of γ particles, allows to limit counts read on a lesion to the sum of the tumor signal plus the background generated by the sole hosting district.The background on adjacent districts in the same specimen/patient is found to differ up to a factor 4, showing how the specificity and sensitivity of the ß--RGS technique can be fully exploited only upon a correct measurement of the contributing background. This locality has been used to set a site-specific cut-off algorithm to discriminate tumor and healthy tissue with a specificity of 100% and a sensitivity, on this test data sample, close to 100%. Factors influencing the sensitivity are also discussed. One of the specimens set allowed us evaluate the volume of the lesions, thus concluding that the probe was able to detect lesions as small as 0.04 mL in that particular case.

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.

Robotic colectomy: is it necessary?

More than 20 years ago the introduction of laparoscopic surgery represented a paradigm shift in the management of colorectal cancer. In most recent years robotic surgery is becoming a viable alternative to laparoscopic and traditional open surgery. The major clear advantages of robotic surgery in comparison with laparoscopy are the lower conversion to open surgery rates and the shorter learning curve. However, the role of robotics in colorectal surgery is still largely undefined and different with respect to its application in abdominal versus pelvic surgery. As for colon cancer there are emerging data that laparoscopic and robotic surgery have the same advantages in terms of faster recovery, although robotic-assisted colectomy is associated with costs increase of care without providing clear reduction in overall morbidity or length of stay. Long-term outcomes for laparoscopic versus robotic colonic resections remain still largely undetermined and randomized controlled clinical trials are required to establish a possible difference in outcomes. Interesting issues for the educational aspects are associated with robotic surgery, as the double console allows the resident to take part actively at the surgical procedure since the beginning of his surgical experience.

Role of robotic surgery in colorectal resections for cancer.

In recent years, robotic surgery is becoming a valid alternative in colorectal diseases treatment to laparoscopic and traditional open surgery. The most relevant reported technical advantages of the robotic surgery are 3D-view, tremor-filtering, seven degree-free motion and a higher comfortable setting for the surgeon. Both case series and comparative studies available in Literature report only short and mid-term outcomes. These studies are able to demonstrate that robotic surgery is as safe and feasible as laparoscopic surgery regarding perioperative outcomes. Trials with long term follow up are needed to establish the real safety and effectiveness of the robotic surgery especially concerning resections for cancer. The robotic surgery could be considered a promising surgical field. The high costs represent one of the most relevant drawbacks.

Retroperitoneal pararenal isolated neurofibroma: report of a case and review of literature.

The neurofibroma is a tumour of neural origin. This kind of neoplasm, though, is generally skin located. Rare cases in deep organs or in the peritoneal cavity are also reported in the literature. There are two types of neurofibromas, localized and diffuse; the latter is associated with von Recklinghausen disease and always occurs together with skin neurofibromas. Here we report the case of a 47-year-old man affected by retroperitoneal neurofibroma, but not associated with von Recklinghausen disease. A computed tomography (CT) scan described a retroperitoneal pararenal lesion with no clear involvement of adjacent viscera. We describe the diagnostic modality, treatment planning and the timing of treatment of this neoplasm, reviewing also the literature.

Comparison of oral polyethylene glycol plus a large volume glycerine enema with a large volume glycerine enema alone in patients undergoing colorectal surgery for malignancy: a randomized clinical trial.

AIM: Recent meta-analyses and randomized clinical trials have concluded that mechanical bowel preparation (MBP) before elective colorectal surgery is not associated with a reduction of surgical site infection (SSI). The aim of this randomized clinical trial was to evaluate the impact of preoperative MBP for colon and rectal cancer surgery in comparison with a single glycerine enema. METHOD: Patients scheduled for radical colorectal resection for malignancy with primary anastomosis were randomized to preoperative MBP (4 l of polyethylene glycol) (group 1, 114 patients) plus a glycerine 5% enema (2 l) or a single glycerine 5% enema (2 l) (group 2, 115 patients). The postoperative incidence of SSI was recorded prospectively. Patients undergoing minimally invasive surgery (laparoscopy or robotic) accounted for 55 and 51 in groups 1 and 2 respectively. RESULTS: In all, 229 patients were included in the study, 114 in group 1 and 115 in group 2. At least one SSI was reported in 16 (14.0%) group 1 and in 20 (17.8%) group 2 patients (P=0.475). Perioperative mortality was nil. The incidence of SSI was comparable also in the 73 patients who had a low anterior resection (seven of 33 vs eight of 40, P=1.000), and for the 106 patients who underwent a minimally invasive procedure (nine of 55 vs four of 51, P=0.241). CONCLUSION: A single large-volume glycerine enema is effective bowel preparation before colorectal resection whether performed by an open or minimally invasive technique.

[Robotic rectal resection in rectal cancer: short term results in a monocentric prospective study]. / Trattamento chirurgico del cancro del retto con tecnica robotica: risultati a breve termine di uno studio prospettico monocentrico.

AIM: The aim of this study was to evaluate technical feasibility, oncological safety and short-term clinical results of robotic rectal resection for cancer. METHODS: From January 2008 to July 2010, 46 patients (27 males and 19 females, median age 69 years, median BMI 24.6 kg/m2) with histologically-proven adenocarcinoma of medium and distal rectum were enrolled in a prospective database. Preoperative assessment was performed with colonoscopy with biopsies, thoraco-abdominal CT scan, pelvic MRI and endorectal-ultrasound (ERUS). In the case of locally advanced non metastatic disease (T3/4 or N1/2), patients received preoperative radiotherapy (45 Grays in 5 weeks) and chemotherapy (oral Capecitabine). The robotic system was a four-arms Da Vinci® (Intuitive Surgical, Sunnyvale, CA, USA); arms position is not modified during the entire surgical procedure. RESULTS: Twenty-five patients received a preoperative radio-chemotherapy. Surgical procedure was an abdomino-perineal amputation in nine patients and an anterior resection in the remaining 37, with temporary ileostomy in 16 cases and a laparoscopic mobilization of splenic flexure in 25. Median operative time was 251 minutes, median time of first bowel movements 1.7 days and median hospital stay 6.7 days. Major complications requiring reoperation verified in 2 patients, while overall complication rate is 15.2%. Median number of harvested lymph nodes per patient was 18; median distance of the tumour from distal resection margin was 2 cm; distance of the tumour from circumferential margin was superior to 1 mm in all of the patients. At a median follow up of 11 months, all patients are alive and disease-free. CONCLUSION: Robotic rectal resection is a feasible technique which can provide good oncological and short-term clinical results.

The management of colorectal liver metastases: Expanding the role of hepatic resection in the age of multimodal therapy.

Colorectal cancer (CRC) caused nearly 204,000 deaths in Europe in 2004. Despite recent advances in the treatment of advanced disease, which include the incorporation of two new cytotoxic agents irinotecan and oxaliplatin into first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patient's treatment and the integrated use of targeted monoclonal antibodies, the 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with colorectal liver metastases, liver resection offers the only potential for cure. This review, based on the outcomes of a meeting of European experts (surgeons and medical oncologists), considers the current treatment strategies available to patients with CRC liver metastases, the criteria for the selection of those patients most likely to benefit and suggests where future progress may occur.

Correlation between administered treatment and patient's living will.

Respecting the wishes of an adequately informed patient should be a priority in any health structure. A patient with advanced or terminal cancer should be allowed to express their will during the most important phases of their illness. Unfortunately, this is seldom the case, and in general instructions regarding an individual's medical care preferences, i.e., their 'living will', expressed when healthy, often change with the onset of a serious illness.At the European Institute of Oncology (IEO), a clinical study is ongoing to verify whether, during clinical practice, the patient is adequately informed to sign an 'informed consent', in a fully aware manner, that will allow the patient and doctor to share in the decisions regarding complex treatment strategies (living will). A further aim of the study is to verify if health workers, both in hospital and at home, respect the patient's will.The observational study 'Respecting the patient's wishes: Correlation between administered treatment and that accepted by the patient in their Living Will' was approved by the IEO Ethical Committee in April 2008.

Surgical 'damage control' treatment of a large retroperitoneal liposarcoma encasing a horseshoe kidney.

Damage control is a surgical strategy for severely compromised trauma patients based on speed control of life-threatening injuries that aims to rapidly resuscitate patients in an intensive care unit (ICU). We report on the use of such therapeutic strategy in a patient affected by a retroperitoneal sarcoma concomitant to a horseshoe kidney, a relatively rare anatomical malformation.

Resection of colorectal liver metastases following neoadjuvant chemotherapy.

BACKGROUND/AIMS: Hepatic resection in metastatic disease from colorectal cancer offers the best chance in selected cases for long-term survival. Neoadjuvant chemotherapy (NACT) has been advocated in some cases initially deemed irresectable, with few reports of the efficacy of such a strategy and the influence of the response to chemotherapy on the outcome of radical hepatic resection. METHODOLOGY: Between December 1995 and May 2005, 27 patients with colorectal liver metastases (seven males, 20 females, mean age: 58 ± 8 years; range: 40-75) were treated with neoadjuvant chemotherapy. A seven-year survival analysis was performed. Chemotherapy included mainly 5-fluorouracil, leucovorin and either oxaliplatin or irinotecan for a median of eight courses. RESULTS: A total of 16 patients (59%) had synchronous and 11 (41%) metachronous metastases. During pre-operative chemotherapy, tumour regression occurred in ten cases (37%), stable disease in a further ten patients (37%) and progressive disease developed in seven cases (26%). The five-year overall survival for NACT responders was 64% and only 15% for non-responders (p=0.044). CONCLUSIONS: The response to chemotherapy is likely to be a significant prognostic factor affecting survival after liver resection for cure.

Surgical outcomes for colorectal cancer patients including the elderly.

BACKGROUND/AIMS: The aim of this study was to compare the short- and long-term outcome of older and younger colorectal cancer patients resected for cure. METHODOLOGY: Three hundred and forty-six consecutive colorectal cancer patients who underwent some form of surgery were analyzed. One hundred and forty-four patients were < 65 years old (group 1), 151 patients were 65-79 years old (group 2), and 51 patients were 80 years or more (group 3). RESULTS: The overall perioperative mortality rate was 1.7% (n = 6). The median length of hospital stay was 19 days (range: 3-86 days). By univariate analysis, intraoperative bleeding (500 mL or more) (P = 0.009), duration of operations (240 min or more) (P = 0.03), and the presence of rectal cancer (P = 0.001), were strongly associated with higher incidence of postoperative complications. In multiple logistic regression analysis, only rectal cancer (P = 0.02) was significantly associated with serious postoperative complications. No age-related difference was noted concerning 5-year cancer-specific survival rates for patients with < 65, 65-79, and > or = 80 years who underwent surgery for cure (85%, 76%, and 69%, respectively) (P = 0.3). Using logistic regression analysis, tumor stage (P = 0.0001) and perioperative blood transfusions (500 mL or more) (P = 0.05) were strongly associated with outcome. CONCLUSIONS: Colorectal curative surgery for malignancy can be performed safely in the elderly with acceptable morbidity and mortality rates and long-term survival.

Prognostic value of the modified TNM (Izumi) classification of hepatocellular carcinoma in 53 cirrhotic patients undergoing resection.

BACKGROUND/AIMS: Few studies have assessed the significance of prognostic factors in cirrhotic patients undergoing resection for hepatocellular carcinoma. METHODOLOGY: Overall survival and disease-free survival were evaluated in 53 cirrhotic patients undergoing hepatic resection for supervening hepatocellular carcinoma. The value of the UICC TNM classification, and the Izumi modified staging system on prognosis were analyzed. RESULTS: In multivariate analysis lack of micro/macrovascular invasion were predictive for long-term outcome. The difference between stages 1 and 2 or stage 3 and 4A using the UICC TNM classification was not significant with respect to survival or disease-free survival. UICC TNM classification was modified as follows; stage 1, solitary tumor without vascular invasion; stage 2, solitary or multiple tumor(s) involving adjacent vessel branch; stage 3, tumor(s) involving major vessel branch or with regional lymph node metastases; stage 4, tumor(s) with distant metastases. TNM (modified in accordance with Izumi) showed a significant difference between each stage with respect to survival and disease-free survival. CONCLUSIONS: A uniform tumor classification of hepatocellular carcinoma is advocated. Our results show that the UICC TNM classification for hepatocellular carcinoma is inadequate and may even on occasion lead to unnecessary resection. The modified staging system of Izumi is superior in determining outcome for cirrhotic patients with supervening hepatocellular carcinoma undergoing resection.

Curative resection for colorectal cancer in the elderly. Prognostic factors and five-year follow-up.

The purpose of this perspective study was to evaluate which prognostic factors predict long-term survival and disease-free survival (DFS) of elderly patients (> or = 65 years) who underwent surgery for colorectal carcinoma. Between January 1992 and December 1998, 196 colorectal cancer patients > or = 65 years (114 M; 82 F; mean age: 75 years; range: 65-92) underwent surgery. One hundred forty-five (74%) of them underwent curative surgery and emergency surgery was more common in patients > or = 75 years of age than among those younger than 75 years (39% vs 23%; p = 0.01). The overall peroperative mortality rate was 3% (n = 6). The median length of hospital stay was 18 days (range: 3-86 days). By univariate analysis, intraoperative bleeding (> or = 500 cc; p = 0.002), length of surgery (> or = 240 min.; p = 0.004), and rectal cancer (p = 0.0001) were associated with complications. By multivariate analysis, only rectal cancer (p = 0.002) was associated with complications. The overall 1, 3-, and 5-year survival rate and DFS rate were 97%, 82%, 74%, and 86%, 64% and 60% respectively. Using multivariate analysis only tumour stage (p < 0.0001) and peroperative blood transfusions (> or = 500 cc; p = 0.006) were associated with outcome. Treatment decisions in elderly patients with colorectal carcinoma should not be influenced by the chronologic age of the patient.