Impact of perineural invasion on the outcome of patients with synchronous colorectal liver metastases treated with neoadjuvant chemotherapy and surgery.

PURPOSE: To analyze the prognostic value of variables of the primary tumor in patients with synchronous liver metastases in colorectal cancer (CLRMs) treated with neoadjuvant chemotherapy and surgery. METHODS/PATIENTS: From a prospective database, we retrospectively identified all patients with synchronous CLRMs who were treated with neoadjuvant chemotherapy and liver resection. Using univariate and multivariate analyses, we identified the variables associated with tumor recurrence. Overall survival and disease-free survival were calculated using the Kaplan-Meier method with differences determined by the Cox multiple hazards model. Results were compared using the log-rank test. RESULTS: Ninety-eight patients with synchronous CLRMs were identified. With a median follow-up of 39.8 months, overall survival and disease-free survival at 5 and 10 years were 53%, 41.7%, 29% and 29%, respectively. Univariate analysis identified three variables associated with tumor recurrence: location in the colon (p = 0.025), lymphovascular invasion (p = 0.011) and perineural invasion (p = 0.005). Multivariate analysis identified two variables associated with worse overall survival: perineural invasion (HR 2.36, 95% CI 1.162-4.818, p = 0.018) and performing frontline colectomy (HR 3.286, 95% CI 1.256-8.597, p = 0.015). Perineural invasion remained as the only variable associated with lower disease-free survival (HR 1.867, 95% CI 1.013-3.441, p = 0.045). Overall survival at 5 and 10 years in patients with and without perineural invasion was 68.2%, 54.4% and 29.9% and 21.3%, respectively (HR 5.920, 95% CI 2.241-15.630, p < 0.001). CONCLUSIONS: Perineural invasion in the primary tumor is the variable with most impact on survival in patients with synchronous CLRMs treated with neoadjuvant chemotherapy and surgery.

Predictors of postoperative complications and readmissions in laparoscopic pancreas resection: Results of a cohort 105 consecutive cases. A retrospective study.

INTRODUCTION: Laparoscopic resection of the pancreas (LRP) has been implemented to a varying degree because it is technically demanding and requires a long learning curve. In the present study we analyze the risk factors for complications and hospital readmissions in a single center study of 105 consecutive LRPs. METHODS: We conducted a retrospective study using a prospective database. Data were collected on age, gender, BMI, ASA score, type of surgery, histologic type, operative time, hospital stay, postoperative complications, degree of severity and hospital readmission. RESULTS: The cohort included 105 patients, 63 females and 42 males with a median age and BMI of 58 (53-70) and 25.5 (22,2-27.9) respectively. Eighteen (17%) central pancreatectomies, 5 (4.8%) enucleations, 81 (77.6%) distal pancreatectomies and one total pancreatectomy were performed. Fifty-six patients (53.3%) experienced some type of complication, of which 13 (12.3%) were severe (Clavien-Dindo > IIIb) and 11 (10.5%) patients were readmitted in the first 30 days after surgery. In the univariate analysis, age, male gender, ASA score, central pancreatectomy and operative time were significantly associated with the development of complications (P <0.05). In the multivariate analysis, male gender (OR 7.97; 95% CI 1.08-58.88)), severe complications (OR 59.40; 95% CI, 7.69-458.99), and the development of intrabdominal collections (OR 8.97; 95% CI, 1.28-63.02)) were associated with hospital readmission. CONCLUSIONS: Age, male gender, ASA score, operative time and central pancreatectomy are associated with a higher incidence of complications. Male gender, severe complications and intraabdominal collections are associated with more hospital readmissions.

Delays to surgery following chemoradiotherapy lead to poorer oncologic outcomes in patients with localized pancreatic adenocarcinoma.

BACKGROUND: although neoadjuvant chemoradiotherapy (NCRT) and surgery are accepted as treatments for pancreatic ductal adenocarcinoma (PDAC), some authors have highlighted the risks of delaying surgery. The objective of this study was to analyze the impact of prolonging the time interval between NCRT and surgery (NCRT-TTS) in PDAC. METHODS: patients treated with NCRT and pancreatoduodenectomy (PD) were identified. Clinical, histopathological variables were analyzed about whether NCRT-TTS was greater or less than 50 days. Five- and ten-year overall survival (OS) and disease-free survival (DFS) were analyzed depending on whether the delay was greater than 50 days or not. RESULTS: one hundred (8.3 %) of 120 eligible patients underwent PD (61 male, median age of 63.7 years). In 71 (71 %) patients, the median NCRT-TTS was 39 (24-50) days and in 29 (29 %) 61 days. There were no differences between the two groups except for carbohydrate antigen 19-9 (CA 19-9) levels, the incidence of cholangitis, American Society of Anesthesiologists (ASA) score, intraoperative blood transfusions and degree of histopathologic response (all p < 0.001). Median DFS when the NCRT-TTS was less than 50 days was higher than when the interval exceeded 50 days (51.0 months [95 % CI: 20.3-81.6] vs 17.0 months [95 %: CI 10.9-23.0]; HR [95 % CI 1.08-3.46], p = 0.026). Five-year DFS was higher in the subgroup with NCRT-TTS of less than 50 days compared to the group with an interval of more than 50 days (43.5 % vs 23.65 % [HR 1.812, 95 % CI: 1.001-3.280], p = 0.050). CONCLUSIONS: an increase in the NCRT-TTS > 50 days is associated with poorer OS and DFS in patients with localized PDAC treated with NCRT and PD.

Predictive Risk Factors for Postoperative Complications and Its Impact on Survival in Laparoscopic Resection for Colon Cancer.

BACKGROUND: Laparoscopic resection is the ideal treatment of colon cancer. The aim of the study was to analyze the predictive factors for postoperative complications and their impact on oncologic outcomes in laparoscopic resections in colon cancer. MATERIALS AND METHODS: In all patients undergoing elective laparoscopic surgery the number and degree of severity of postoperative complications were recorded and classified according to Clavien-Dindo. A univariate analysis was made of the demographic, surgical, and oncologic variables of patients with and without complications. The statistically significant variables were then entered into a multivariate model. In both groups overall and disease-free survival were analyzed using Kaplan-Meier estimates. RESULTS: Of 524 patients, 138 (26.3%) experienced some type of complication, 110 less severe (79.7%) and 28 (20.4%) severe. Twenty-nine conversions to open surgery occurred (5.5%) and hospital mortality was 0.2%.In the multivariate analysis, use of corticosteroids [odds ratio (OR): 3.619], oral anticoagulants (OR: 3.49), blood transfusions (OR: 4.30), and conversion to open surgery (OR: 3.93) were significantly associated with the development of complications. However, sigmoid resections were associated with fewer complications (OR: 0.45).Overall 5-year and 10-year survival in both groups, was 83.3%, 74.1%, 76.0%, and 67.1%, respectively (P=0.18). Disease-free survival at 5 and 10 years, excluding stage IV tumors, was 88.6% and 90.4%, respectively (P=0.881). CONCLUSIONS: The use of corticosteroids, oral anticoagulants, blood transfusions, and conversion to open surgery are all independent predictive factors of postoperative complications. Sigmoid resections are associated with fewer complications. In laparoscopic resections of the colon, complications do not negatively affect long-term oncologic outcomes.

Prognostic significance of lymph node count in high-risk node-negative colon carcinoma.

BACKGROUND: the prognostic value of the number of lymph nodes isolated (< 12 versus ≥ 12) in the surgical specimen continues to be controversial. In this study, the impact of isolating fewer or more than 12 lymph nodes in stage II colon cancer with a high-risk biologic phenotype was analyzed, such as the presence of perineural invasion. METHODS: all cases of stage II disease (T3-4N0M0) with perineural invasion (PNI+) were retrospectively identified from a prospective database of patients undergoing surgery for colon cancer. The cohort was divided into two groups depending on the number of lymph nodes isolated (< 12 vs ≥ 12). Apart from clinical and surgical data, the patterns of recurrence, overall (OS) and disease-free survival (DFS) at five and ten years were analyzed. RESULTS: sixty patients met the inclusion criteria, 31.7 % had < 12 lymph nodes isolated and 68.3 % had more than 12 isolated. There were no clinical or surgical differences between the two groups. OS at five and ten years was significantly lower in the patients with < 12 lymph nodes isolated (84.2 %, 62.7 % vs 94.6 % and 91.6 %, p = 0.01). DFS at five and ten years was 51 % vs 86.5 %, respectively (p = 0.005). CONCLUSION: the number of lymph nodes isolated (with a cutoff of 12) in stage II colon cancer with PNI+ has prognostic value and should therefore be borne in mind when planning adjuvant chemotherapy.

Minimally Invasive Surgical Approach for the Treatment of Superior Mesenteric Artery Syndrome: Long-Term Outcomes.

BACKGROUND: Latero-lateral duodenojejunostomy is the treatment of choice for superior mesenteric artery syndrome (SMAS). The present study analyzes the long-term outcomes in 13 patients undergoing laparoscopic surgery for SMAS. MATERIALS AND METHODS: A retrospective study of 10 females and three males undergoing surgery between 2001 and 2013 was performed. Demographic, clinical and radiologic data and long-term surgical outcomes were recorded. In 12 patients latero-lateral duodenojejunostomy and in one patient distal laparoscopic gastrectomy with Roux-en-Y reconstruction were performed. The median age was 24 years (20-28), and the median duration of symptoms was 24 months (5-24). The most frequent symptoms were abdominal pain (n = 11; 92.3%), nausea and vomiting (n = 10; 77%) and weight loss (n = 9; 69.2%). The median operating time was 98 min (86-138) and hospital stay was 3 days (1-14). RESULTS: No reconversions occurred, and one patient experienced gastric emptying delay in the immediate postoperative period with spontaneous resolution. In four patients, SMAS was associated with severe stenosis of the celiac trunk which was treated in the same operation, and four patients presented stenosis of the left renal vein (the "nutcracker" phenomenon). With a median follow-up of 94 months (SD 65.3), eight patients (61.5%) had excellent results. One patient had a relapse of symptoms 4 years after surgery requiring distal gastrectomy, two patients presented delay in gastric emptying following temporary improvement and one patient experienced no improvement. CONCLUSIONS: Latero-lateral duodenojejunostomy yields good results in SMAS although it requires other gastric motility disorders to be ruled out for appropriate treatment to be established.

Neoadjuvant chemotherapy without radiotherapy for patients with locally advanced rectal cancer. Oncologic outcomes.

BACKGROUND: the standard treatment for locally advanced rectal cancer is neoadjuvant chemo-radiotherapy, surgery and adjuvant chemotherapy. Only 50% of patients receive the adjuvant treatment due to the surgical complications and toxicity of radiotherapy. Recently, neoadjuvant chemotherapy has been investigated in the locally advanced rectal cancer setting, with the aim of guaranteeing an uninterrupted systemic treatment. The objective of the present study was to assess the safety and efficacy of neoadjuvant chemotherapy in locally advanced rectal cancer. METHODS AND PATIENTS: patients treated with neoadjuvant chemotherapy and surgery were identified from a prospective database of patients with rectal cancer (cII-III). The primary outcomes were the assessment of the number of R0 resections, the degree of pathologic response, patterns of recurrence and overall and disease-free survival. Treatment schedule: patients received 6-8 cycles of oxaliplatin and fluoropyrimides based chemotherapy. RESULTS: twenty-seven patients who received neoadjuvant chemotherapy were identified. Twenty-six anterior resections and one Hartmann intervention were performed. An R0 resection was performed in 27 (100%) patients and no involvement of the circumferential margin was observed. Complete pathologic response (ypT0N0) was confirmed in four (14.8%) patients. The median follow-up was 35 months (range: 10-81) and four distant recurrences were recorded. Overall and disease-free survival at five years was 85% and 84.7%, respectively. Twenty-seven (100%) patients received all the cycles of chemotherapy, with a mean of six cycles (range 5-8) per patient. CONCLUSIONS: neoadjuvant chemotherapy is a promising alternative in the locally advanced rectal cancer setting and further phase III clinical trials are clearly warranted.

Neoadjuvant therapy for locally advanced gastric cancer patients. A population pharmacodynamic modeling.

BACKGROUND: Perioperative chemotherapy (CT) or neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC) has been shown to improve survival compared to an exclusive surgical approach. However, most patients retain a poor prognosis due to important relapse rates. Population pharmacokinetic-pharmacodynamic (PK/PD) modeling may allow identifying at risk-patients. We aimed to develop a mechanistic PK/PD model to characterize the relationship between the type of neoadjuvant therapy, histopathologic response and survival times in locally advanced GC and GEJC patients. METHODS: Patients with locally advanced GC and GEJC treated with neoadjuvant CT with or without preoperative CRT were analyzed. Clinical response was assessed by CT-scan and EUS. Pathologic response was defined as a reduction on pTNM stage compared to baseline cTNM. Metastasis development risk and overall survival (OS) were described using the population approach with NONMEM 7.3. Model evaluation was performed through predictive checks. RESULTS: A low correlation was observed between clinical and pathologic TNM stage for both T (R = 0.32) and N (R = 0.19) categories. A low correlation between clinical and pathologic response was noticed (R = -0.29). The OS model adequately described the observed survival rates. Disease recurrence, cTNM stage ≥3 and linitis plastica absence, were correlated to a higher risk of death. CONCLUSION: Our model adequately described clinical response profiles, though pathologic response could not be predicted. Although the risk of disease recurrence and survival were linked, the identification of alternative approaches aimed to tailor therapeutic strategies to the individual patient risk warrants further research.

Cystic tumors of the pancreas. An update of the surgical experience in a single institution.

BACKGROUND: the aim of the present study was to analyze the clinicopathological features of patients undergoing pancreatic surgical resections due to cystic neoplasms of the pancreas. MATERIAL AND METHODS: demographic data, form of presentation, radiologic images and location of the tumors within the pancreas were analyzed. Data was also collected on the type of surgery (open/laparoscopic), postoperative complications and their severity and oncologic outcomes. RESULTS: eighty-two pancreatic resections were performed. The mean age of patients was 57 years and 49 (59%) were female. Forty-one tumors (50%) were incidental and the most frequent symptoms in the group of symptomatic patients were abdominal pain (63.4%) and weight loss (36.5%). Thirty-two tumors (39%) were located in the tail of the pancreas, 25 (30.5%) in the head and 20 (24.4%) in the body. Thirty-nine (47.5%) distal pancreatectomies, 16 central, ten duodenal pancreatectomies and one enucleation were performed; 40 (48.5%) were carried out laparoscopically. Mean hospital stay was ten days and eight patients (7%) experienced severe complications, one was a pancreatic fistula. Sixty-six tumors (80.5%) were recorded as non-invasive and 16 (19.5%) as invasive: seven intraductal mucinous papillary tumors, one cystic mucinous tumor, four solid pseudopapillary tumors and four cystic neuroendocrine tumors. There was a median follow-up of 64 months; disease-free survival at five and ten years was 97.4% in the patients with non-invasive tumors and 84.6% and 70.5% in the invasive tumors group (p < 0.01). CONCLUSIONS: fifty percent of cystic neoplasms of the pancreas are incidental. Two phenotypes exist, invasive and non-invasive.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas: clinicopathological features and long-term outcomes following a pancreatectomy.

OBJECTIVE: the objective of this study was to analyze the anatomical and clinical features and long-term oncologic outcomes of 25 patients that underwent surgery due to intraductal papillary mucinous neoplasm of the pancreas. MATERIAL AND METHODS: patients undergoing surgery for intraductal papillary mucinous neoplasm of the pancreas were identified from a prospective database of pancreatic resections. Demographic data, symptoms, type of surgery and type of lesion (branch type, main duct or mixed) were recorded. The lesions were classified into invasive (high grade dysplasia and carcinoma) and noninvasive (low- or intermediate-grade dysplasia). Postoperative complications were analyzed as well as the pattern of recurrence and disease-free survival at five and ten years. RESULTS: the most common symptoms in the 25 patients (14 males and eleven females) were abdominal pain and weight loss. Eight (32%) cases were diagnosed incidentally. Twelve (48%) of the lesions were of the branch type, three affected the main duct and ten (40%) were mixed. Twelve cephalic duodenopancreatectomies and seven total pancreatectomies were performed; three were central; two, distal; and one, enucleation. Seven cases (32%) had an invasive phenotype. Three patients had locoregional and distant recurrence at six, 16 and 46 months after surgery with a median follow-up of 7.7 years. Disease-free survival at five and ten years for the noninvasive type was 94% and 57% for invasive phenotypes (p < 0.05). CONCLUSIONS: intraductal papillary mucinous neoplasm is a heterogeneous entity with well differentiated phenotypes, which requires a tailored strategy and treatment, as established in the current consensus guidelines due to its malignant potential.

Screening-detected colorectal cancers show better long-term survival compared with stage-matched symptomatic cancers.

PURPOSE: the aim of this study was to compare overall and disease-free survival among patients with colorectal cancer detected via a screening program as compared to those with symptomatic cancer. MATERIAL AND METHODS: patients diagnosed via colonoscopy (screening group) and those with clinical symptoms (non-screening) were identified from 1995 to 2014. Demographic, clinical, surgical and pathologic variables were recorded. Stage I, II and III cancers were included. Overall and disease-free survival were calculated at five and ten years after tumor resection and survival was calculated by matching both groups for cancers at stage I, II and III. RESULTS: two hundred and fifty patients were identified as a result of screening procedures and 1,330 patients presented with symptomatic cancers. There were no significant differences in the baseline characteristics between the two groups. Pathologic stage, degree of differentiation, perineural invasion and lymphovascular invasion were lower in the screening group (p < 0.01). Overall and disease-free survival at five and ten years were higher in the screening group (p < 0.01). However, when the subjects were matched for pathologic stage, significant differences were found between the two groups with regard to stage I and III tumors. Disease-free survival in stage III at five years (79.1 vs 61.7%; p < 0.001) and ten years (79.1% vs 58.5%; p < 0.001) were significantly higher in the screening group. CONCLUSIONS: patients with stage I and III tumors that were diagnosed via a screening program have a higher overall and disease-free survival at five and ten years.

The impact of major postoperative complications on long-term outcomes following curative resection of colon cancer.

PURPOSE: The objective is to analyze the impact of severe postoperative complications in patients undergoing curative surgery for colon cancer. MATERIAL AND METHODS: From a prospective database, we identified patients with stage I-III disease (AJCC) who underwent surgery between 2000 and 2014. Patients were selected with major complications (IIIb on the Clavien-Dindo classification) and with no major complications. Variables were analyzed in both groups. Local, peritoneal and distant recurrence together with overall survival and disease-free survival were analyzed. RESULTS: Of a total of 950 patients, 51 (5.3%) experienced major complications. Operative mortality was 2.6%. Age, ASA grade, urgent surgery, pre-operative hemoglobin, right-sided location, operative time, transfusion, conversion to open surgery, were all associated with major complications (all P < 0.05). With a median follow-up of 84.8 and 40 months in both groups, there was greater incidence of local recurrences in patients experiencing complications (2.4% vs 7.8%; P = 0.03 OR 3.39, 95% CI 1.12-10.24), being more marked in stage III patients (4.2% vs 21%; P = 0.005, OR 6.13 95% CI 1.74-21.56). In the stage III group, peritoneal recurrence was significantly greater in patients with complications (13.6% vs 31.6%; P = 0.04 OR 2.92 95% CI 1.04-8.18). Patients with major complications had a significantly lower overall survival (P = 0.024) than patients with no complications both at 5 years (78.9% vs 68.8%) and 10 years (74.6% vs 32.1%). The same trend was observed for disease-free survival (71.6% vs 48.3% and 69.8% vs 32.2%; P = 0.013). CONCLUSION: The development of major complications following colectomy for colon cancer has a negative impact on long-term oncologic outcomes, especially in stage III disease.

NLRP3 Inflammasome: A Possible Link Between Obesity-Associated Low-Grade Chronic Inflammation and Colorectal Cancer Development.

Emerging evidence reveals that adipose tissue-associated inflammation is a main mechanism whereby obesity promotes colorectal cancer risk and progression. Increased inflammasome activity in adipose tissue has been proposed as an important mediator of obesity-induced inflammation and insulin resistance development. Chronic inflammation in tumor microenvironments has a great impact on tumor development and immunity, representing a key factor in the response to therapy. In this context, the inflammasomes, main components of the innate immune system, play an important role in cancer development showing tumor promoting or tumor suppressive actions depending on the type of tumor, the specific inflammasome involved, and the downstream effector molecules. The inflammasomes are large multiprotein complexes with the capacity to regulate the activation of caspase-1. In turn, caspase-1 enhances the proteolytic cleavage and the secretion of the inflammatory cytokines interleukin (IL)-1ß and IL-18, leading to infiltration of more immune cells and resulting in the generation and maintenance of an inflammatory microenvironment surrounding cancer cells. The inflammasomes also regulate pyroptosis, a rapid and inflammation-associated form of cell death. Recent studies indicate that the inflammasomes can be activated by fatty acids and high glucose levels linking metabolic danger signals to the activation of inflammation and cancer development. These data suggest that activation of the inflammasomes may represent a crucial step in the obesity-associated cancer development. This review will also focus on the potential of inflammasome-activated pathways to develop new therapeutic strategies for the prevention and treatment of obesity-associated colorectal cancer development.

Clinico-pathological and oncological differences between right and left-sided colon cancer (stages I-III): analysis of 950 cases.

PURPOSE: The objective of the study was to analyze the clinico-pathological differences and the oncologic outcomes between right and left-sided colon cancer. PATIENTS AND METHODS: The patients cohort was identified from a prospective register of colon cancer, 950 patients underwent surgery (stages I, II and III), of which 431 had right-sided colon cancer and 519 had left-sided colon cancer. RESULTS: More laparoscopic resections were performed (101 vs 191; p < 0.001) and operating times were longer (146 min vs 165 min; p < 0.001) in the left-sided colon group. Patients with right-sided colon cancer more frequently received transfusions (18.8% vs 11.3%; p < 0.001) and experienced a greater number of complications (28.5% vs 20.9%, p = 0.004), although severity and operative mortality were similar in both groups (1.2% vs 0.2%). Mucinous adenocarcinomas and undifferentiated tumors were more frequent in the right-sided group (12% vs 6.5%; p < 0.001). Early stage was predominant in the left-sided colon tumors (28.2% vs 34.5%, p = 0.02). There were no differences in disease-free survival (DFS) in stages I and II after a median follow-up of 103 months. However, a greater survival at five and ten years in left-sided, stage III tumors was observed, with a trend towards statistical significance (p = 0.06). No differences were found with regard to the patterns of recurrence. CONCLUSIONS: Right-sided colon cancer exhibits phenotypical differences with regard to left-sided colon cancer. In stage III disease, left-sided colon cancer has a greater survival with a trend towards statistical significance. Overall, tumor location is a variable that should be taken into consideration in clinical studies of colon cancer.

Laparoscopic Treatment of Median Arcuate Ligament Syndrome: Analysis of Long-Term Outcomes and Predictive Factors.

BACKGROUND: Laparoscopic arcuate ligament release has been demonstrated a valid therapeutic option for arcuate ligament syndrome. Nevertheless, long-term follow-up and predictive factors have not been described for this treatment. METHODS: Clinical and surgical data and short- and long-term outcomes together with the impact of the degree of stenosis of the celiac trunk were analyzed in 13 consecutive patients who underwent laparoscopic arcuate ligament release between 2001 and 2013. RESULTS: Thirteen patients (12 F/1 M) underwent surgery. The median age was 32 years old, and their mean body mass index was 20.7 (range 14.7-25). The 13 patients presented with intense postprandial abdominal pain. Ten cases were associated with weight loss. The median duration of symptoms was 24 months (range 2-240). Three patients presented symptoms associated with superior mesenteric artery syndrome. Median operative time was 120 min (range 90-240), and there were no conversions to open surgery. Median hospital stay was 3 days (range 2-14). Over a median follow-up of 117 months (range 45-185), nine patients had excellent results although two required endovascular procedures at 70 and 24 months after surgery. Four patients (30.7%) experienced poor outcomes. When we analyzed the impact of the degree of occlusion of the celiac trunk, we observed that in patients with severe occlusion (> 70%), better results were obtained, with complete resolution of symptoms in 71% of cases. CONCLUSION: Laparoscopic arcuate ligament release constitutes an excellent treatment for arcuate ligament syndrome. The degree of occlusion of the celiac trunk may be a factor predictive of long-term outcomes.

Short-term outcome of patients with colon cancer diagnosed by symptoms and screening.

Colon cancer diagnosed as part of a screening program, showed better short-term outcomes following surgery. These advantages seem to have impact on long-term outcomes as well.

Cystic pancreatic neuroendocrine tumors (cPNETs): a systematic review and meta-analysis of case series.

Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387) were sporadic tumors and 10.3% (n = 40) corresponded to multiple endocrine neoplasia endocrine type 1. Were diagnosed incidentally 44.6% (n = 135). Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338), and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb), and 12.2% were advanced (III-IV). Disease-free survival at 5 years in stages (I-IIIa) and (IIIb-IV) was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001) in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5%) and multifocal (28.1%) tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.

IL-32α-induced inflammation constitutes a link between obesity and colon cancer.

Growing evidence indicates that adipose tissue inflammation is an important mechanism whereby obesity promotes cancer risk and progression. Since IL-32 is an important inflammatory and remodeling factor in obesity and is also related to colon cancer (CC) development, the aim of this study was to explore whether IL-32 could function as an inflammatory factor in human obesity-associated CC promoting a microenvironment favorable for tumor growth. Samples obtained from 84 subjects [27 lean (LN) and 57 obese (OB)] were used in the study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (49 without CC and 35 with CC). We show, for the first time, that obesity (p = 0.009) and CC (p = 0.026) increase circulating concentrations of IL-32α. Consistently, we further showed that gene (p < 0.05) and protein (p < 0.01) expression levels of IL-32α were upregulated in VAT from obese patients with CC. Additionally, we revealed that IL32 expression levels are enhanced by hypoxia and inflammation-related factors in HT-29 CC cells as well as that IL-32α is involved in the upregulation of inflammation (IL8, TNF, and CCL2) and extracellular matrix (ECM) remodeling (SPP1 and MMP9) genes in HT-29 cancer cells. Additionally, we also demonstrate that the adipocyte-conditioned medium obtained from obese patients stimulates (p < 0.05) the expression of IL32 in human CC cells. These findings provide evidence of the potential involvement of IL-32 in the development of obesity-associated CC as a pro-inflammatory and ECM remodeling cytokine.

Short- and long-term outcomes of laparoscopic organ-sparing resection in pancreatic neuroendocrine tumors: a single-center experience.

BACKGROUND: Laparoscopic organ-sparing pancreatectomy (LOSP) is an ideal therapeutic option in selected cases of pancreatic neuroendocrine tumors (PNETs). Nevertheless, given the low frequency of PNETs, there is scarce evidence regarding short and particularly long-term outcomes of LOSP in this clinical setting. METHODS: All patients with PNETs who underwent surgery (under a LOSP policy) were retrospectively reviewed from a prospective database maintained at our center. Preoperative characteristics, operative data, pathological features and postoperative outcomes were analyzed. RESULTS: Between December 2003 and December 2015, 36 patients with PNETs underwent laparoscopic resections. Ten were functional tumors, 26 non-functional and 16 were "incidental" cases. The following procedures were performed: one enucleation, eight central pancreatectomies (LCP), one resection of the uncinate process and 26 distal pancreatectomies (DP) (15 of them laparoscopic vessels-preserving). There were no conversions to open surgery, and no drains were routinely left. Mean operative time was 288 min (SD 99). Hospital stay was 6 days. Eighteen patients (50%) experienced some complication of which most were mild (Clavien-Dindo I/II). Three postoperative bleedings occurred: two grade B/one grade C; two required laparoscopic reoperation. Thirteen (36.1%) patients developed peripancreatic fluid collections: two were symptomatic and were managed with transgastric drainage (one presented post-puncture abscesification requiring surgical drainage and splenectomy). Four patients (11%)-one DP and three LCP-developed new-onset pancreatogenic diabetes mellitus (NODM) in the long term. According to the European Neuroendocrine Tumor Society, 19 cases were stage I, seven IIA, two IIIA, one IIIB and seven stage IV. Over a mean follow-up of 51 months, two patients died, one due to recurrence of the tumor and another due to cirrhosis. CONCLUSIONS: The existing different surgical options must be individually considered according to the location and particular characteristics of every tumor. Results from this single-center study document the effectiveness of LOSP in selected cases of PNETs.