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Following exposure to human plasma (HP), nanoparticles (NPs) are coated with a biomolecular layer referred to as a protein corona. We recently revealed that characterizing the protein coronas of various NPs may provide a unique opportunity for cancer identification and discrimination. In other words, protein corona profiles of several NPs, when being analyzed using classifiers, would provide a unique “fingerprint” for each type of disease. Here, we probed the capacity of the protein corona for the identification and discrimination of breast and prostate cancer patients from healthy individuals. Using three lipid NP formulations with distinct physical–chemical properties as a cross-reactive sensor array and a supervised random forest classifier, we identified a set of proteins that showed a significant difference in cancer patients and control subjects. Our data show that many of the corona proteins with the highest discrimination ability between oncological patients and healthy individuals are related to cellular and molecular aspects of breast and prostate cancers.

To asses drains amylase (DA) cut-offs for the risk of clinically relevant postoperative pancreatic fistula (POPF) and define the optimal timing of drains removal based on daily DA assay and abdominal CT scan finding after pancreatoduodenectomy (PD). Different algorithms able to identify patients at higher risk of POPF and to assess the optimal time for drains removal after PD have been proposed. The most accurate DA cut-offs in the assessment of the risk of clinically relevant POPF were retrospectively identified. Data from a prospective trial for optimal timing of drains removal were analyzed. Then, to validate the cut-offs identified in the first phase, they were applied to the patients enrolled in the prospective trial. Patients with POD1 DA ≥ 666 U/L were at higher risk of clinically relevant POPF (p 0.0001). POD3 DA value ≥ 252 U/L predicted 88% of clinical relevant fistulas. POD3 DA level ≥ 207 U/L was able to predict 68% of biliary fistulas. Patients with abdominal collection ≥ 5 cm, showed a significantly higher rate (60% vs. 23%, p

The value of minimally invasive pancreatic surgery (MIPS) is still uncertain, despite the growing number of publications, including reviews and meta-analyses, and the quick diffusion of these procedures worldwide. The Italian Group of Minimally Invasive Pancreas Surgery (IGoMIPS) was created under the auspices of three Scientific Societies: Associazione Italiana Studio Pancreas (AISP), Associazione Italiana Chirurgia Epato-Bilio-Pancreatica (AICEP, former IT-IHPBA), and Società Italiana di Chirurgia Endoscopica (SICE). The main aim of IGoMIPS is to develop and implement a national registry for MIPS. IGoMIPS was founded on February 22, 2019 in Pisa. The IGoMIPS registry became operational in September 2019, following approval by the Ethic Committees of founding Institutions, inscription into the Registry of Patient Registries (RoPR), and a wrap-up meeting held in Bologna during the Annual Congress of the Italian Surgical Society. During this meeting IGoMIPS members approved that the Italian Registry will provide data to the European Registry, while retaining the right to analyze and publish Italian data. An audience survey was also conducted to obtain information on perceived value and current implementation of MIPS in founding Institutions. MIPS is performed in 94.7% of IGoMIPS centers, including pancreaticoduodenectomy in 42.1%. Robotic assistance was employed in 52.6% of Institutions. The annual volume of MIPS was 6–10 cases in 38.9% of the centers, 11–20 cases in 16.7%, 21–30 cases in 22.2%, and > 30 cases in 22.2%. The registry was felt to be extremely important for both safety improvement and educational purposes by 94.5% of the centers.

Pancreatic ductal adenocarcinoma (PDAC) early diagnosis is crucial and new, cheap and user-friendly techniques for biomarker identification are needed. "Protein corona" (PC) is emerging a new bio-interface potentially useful in tumor early diagnosis. In a previous investigation, we showed that relevant differences between the protein patterns of PCs formed on lipid NPs after exposure to PDAC and non-cancer plasma samples exist. To extend that research, We performed this pilot study to investigate the effect of PDAC tumor size and distant metastases on PC composition.Twenty PDACs were clinically staged according to the UICC TNM staging system 8 t h Edition. Collected plasma samples were let to interact with lipid NPs; resulting PCs were characterized by SDS-PAGE. To properly evaluate changes in the PC, the protein intensity profiles were reduced to four regions of molecular weight:25 kDa, 25-50 kDa, 50-120 kDa,120 kDa. RESULTS: Data analysis allowed to distinguish T1-T2 cases from T3 and above all from metastatic ones (p 0.05). Discrimination power was particularly due to a subset of plasma proteins with molecular weight comprised between 25-50 kDa and 50-120 kDa.PC composition is critically influenced by tumor size and presence of distant metastases in PDAC. If our findings will be further confirmed, we envision that future developments of cheap and user-friendly PC-based tools will allow to improve the accuracy of PDAC clinical staging, identifying among resectable PDACs with potentially better prognosis (i.e. T1 and T2) those at higher risk of occult distant metastases.

Ideal time interval between end of neoadjuvant radio-chemotherapy (NRCT) and surgery for rectal cancer is debated. Effect that different time intervals have on postoperative complications with particular regard to anastomotic dehiscence (AD) was evaluated on 167 patients who underwent surgery after long-course NRCT. Three different time intervals were considered: (0–42; 43–56; > 57 days). A time interval > 57 days was significantly protective for AD (p = 0.04, Odds ratio = 0.35; 95% CI 0.1254–0.9585) without influence on early oncological outcomes. Optimal time interval after end of NRCT and surgery may help achieving the best pathological response with lowest postoperative morbidity. Trial registration number: Clinical Trial. Gov NCT04013347. https://clinicaltrials.gov/ct2/results?cond=&term=NCT04013347&cntry=&state=&city=&dist= ).

Introduction The current Tumor Node Metastasis staging system (TNM) for gastric cancer classifies the extent of lymph node metastasis based upon the number of lymph nodes involved. Choi et al. have recently proposed a new anatomical classification based upon the regionality of the involved nodes. This new classification seems to have a better predictive prognostic value than the traditional one. We investigated the prognostic role of the new anatomical based classification, reviewing our institutional gastric cancer database. Methods We performed a retrospective chart review of 329 patients who underwent gastrectomy at our Institution from 2003 to 2017. We excluded from data analysis any patient with distant metastases at the time of first diagnosis and or surgery, pathology other than adenocarcinoma, lymphadenectomy less than D2, impossibility to identify location of lymph nodes (LNs) on pathological report and neoadjuvant chemotherapy. The extent of D2 lymphadenectomy was defined according to Japanese Gastric Cancer Association criteria. LN metastasis were reclassified into three topographic groups (lesser, greater curvature, and extraperigastric nodes) and staged according to Choi. The new N stage was combined with the current pT according to the 8th edition of TNM and a new hybrid TNM stage was established. All patients were followed up until June 2019. The prognostic performance of the new stage and of the current anatomical numeric based system (TNM) was analyzed and assessed by the C-index, AIC and likelihood ratio χ2 value. Results In predicting both Overall Survival (OS) and Disease free Survival (DFS) the new N stage and the new TNM staging system had the highest C-index and likelihood ratio χ2 value and the lowest Akaike Information Criterion (AIC), showing a better accuracy and displaying a better prognostic performance. Conclusions Our study is the first from the Western world to compare the new hybrid classification, based on the anatomical location of metastatic nodes, to the 8th of American Joint Committee on Cancer (AJCC) TNM staging system. Our findings on a small, monocentric sample suggest that hybrid topographic lymph node staging system is more accurate than TNM.

Background and aim Endoscopic full-thickness resection (EFTR) provides complete en-bloc resection with a histopathological evaluation of submucosal, muscular, and serosal layers. The aim of this study was to investigate the efficacy and safety of a novel over-the-scope device for colorectal EFTR. Material and methods In this retrospective, observational, open-label case study, a total of 20 patients with superficial colorectal neoplasms, underwent EFTR using a new endoscopic full-thickness resection device (FTRD; Ovesco Endoscopy, Tubingen, Germany). Endoscopic treatment outcomes (technical success, rate of EFTR, adverse events) and early follow-up at three months, were analyzed. Results We reported a 100% of technical success, defined as full-thickness resection. Among the R1 resections, histology was negative for neoplasm. Non-lifting adenomas had histology positive for adenocarcinoma: seven T1/G1/sm1; one T1/G1/sm2; one, who underwent a surgical resection, T1/G1/sm3. Mean size of the resected lesions was 26 mm, ranging from 10 to 42 mm. One (5%) patient developed abdominal pain, fever and leukocytosis and was treated conservatively with medical therapy. In all specimens, histological complete resection was confirmed. Conclusions EFTR is a feasible and effective technique that could become a valid alternative to EMR and ESD in the management of recurrent adenomas, no-lifting lesions and scars of R1 resections. However, prospective studies are needed to further evaluate the device and technique.

Background Surgical-site infections (SSIs) remain a serious complication of colorectal surgery, causing a significant financial burden to the health care system. The aim of this study is to investigate whether the use of an O-ring retractor can be effective in preventing the incidence of wound infections after elective laparoscopic colorectal surgery. Methods A retrospective case-control study from January 2014 to June 2018 was performed. Data were analyzed from a retrospective colorectal database. SSI was defined according to criteria published by the European Centre for Disease Prevention and Control and analyzed as a primary outcome. Results Three hundred twelve consecutive patients (n = 312) were enrolled in our study. Among them, 158 patients (Group A) in which an O-ring retractor device was used during surgery was compared with a control group of 154 patients (Group B) in which an O-ring retractor device was not used. Primary outcome was to determine SSIs rates among the 2 groups. No statistically differences were observed with regard to baseline characteristics between both groups. A total of 9 patients (5.69%) and 24 (15.58%) with SSIs were identified in Group A and B, respectively, and the difference was statistically significant (OR, 0.32; 95% CI, 0.14-0.72; P = .0045). The median postoperative hospital stay length was 6.7 days in group A and 7.6 days in group B (P ≤ .05). Conclusions SSIs infections rates were significantly higher in patients in which an O-ring retractor device was not used. This study suggests that the use of a wound protector device can be considered for routine use in elective colorectal surgery.

Microscopic residual tumor (R1) affects prognosis of resected pancreatic head cancer patients. Surgeon’s ability, caseload and accuracy of pathological staging affect the rate of R1 resections. The goal of this study was to verify if a standardized histopathological workup of the specimen affects the rate of microscopic residual tumor after PD for cancer. Two groups of specimens were managed with (Group 1, Standardized Group, SG) or without (Group 2, Non Standardized Group, NSG) a standardized histopathological workup reported by the Royal College of Pathologists. Group 1 included 50 cases of PD for periampullary cancer treated between October 2010 and July 2012. Group 2 included 50 cases of PD for periampullary cancer treated between September 2005 and September 2010. The primary endpoint of the study was to verify the differences in terms of R1 rate in the two groups. Correlation between presence/absence of microscopic residual tumor status and local recurrence was also evaluated. The cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma (PDAC) (SG: 35; NSG: 31), 15 distal common bile duct cancer (SG: 9; NSG: 6) and 19 cancer of the ampulla of Vater (SG: 6; NSG: 13). The rate of R1 resections resulted higher in the SG (66% vs 10%, p

HER2 (human epidermal growth factor receptor-2) assessment in histological samples of gastric cancer is essential to determine which patients might benefit from trastuzumab therapy. HER2 is often evaluated in primary tumor even if trastuzumab therapy is used to treat metastatic disease. However, the exact relationship in terms of HER2 status between primary and metastatic tumors has not been fully clarified. We aimed to evaluate the HER2 status concordance between primary gastric cancer and corresponding distant metastasis. HER2 status was evaluated by IHC (immunohistochemistry) and/or FISH ( fluorescence in situ hybridization) in 41 patients in primary gastric cancer and in paired metastasis. HER2 was assessed according scoring criteria applied in clinical approach. HER2 positivity was found in 14,6 % primary tumors and in 24,4%corresponding metastasis. HER2 concordance rate between primary and metastasis was 80,5 % (K-value = 0,388). Eight/41 (19,5 %)cases resulted discordant: 6 patients with metastatic HER2 positive lesions were found HER2 negative in primary cancers while 2 patient HER2 positive in primary lesion showed a negative conversion in metastasis. Our results showed a good concordance in terms of HER2 status between primary and metastatic lesions, as well as in biopsy and surgical removed specimens. However, the higher rate of HER2 positive status found in metastatic lesions underlined the importance of HER2 assessment in all samples obtained from different sites of gastric cancer disease.

OBJECTIVES R1 resection rate after pancreaticoduodenectomy (PD) for cancer is highly variable. The aim of this study was to verify if a standardized histopathological work-up of the specimen affects the rate of R1 resection after PD for cancer. METHODS Two groups of specimens were managed with (standardized method [SM] group) or without (non-standardized method [NSM] group) a SM of histopathological work-up. Each group included 50 cases of PD for periampullary cancer. Differences in terms of R1 resection rate between the 2 groups were evaluated. Correlation between R1 status and local recurrence was also evaluated. RESULTS The cohort of 100 patients consisted of 66 pancreatic ductal adenocarcinoma, 15 cholangiocarcinoma, and 19 ampullary cancer. The R1 resection rate resulted statistically higher in the SM group (66% vs 10%). Local recurrence was more frequently related to R1 resection in the SM group (34.3% of cases) than in NSM group (20% of cases). CONCLUSIONS The use of the SM of pathological evaluation of the specimen after PD for cancer determines a significant increase of R1 resection. This remarkable difference seems to be due to the different definition of minimum clearance. The SM seems to better discriminate patients in terms of risk of local recurrence.

BackgroundStandard lymphadenectomy during pancreaticoduodenectomy (PD) for peri‐ampullary cancer does not include the routine removal of para‐aortic lymph nodes (PALN) (station 16, according to the JPS staging system). The aim of this study was to report the incidence and the prognostic value of PALN metastases in patients undergoing PD for peri‐ampullary cancer.Materials and methodsOne hundred thirty‐five consecutive patients who underwent PD and PALN dissection for peri‐ampullary cancer were prospectively evaluated. The relationship between clinicopathological factors, including PALN metastases and survival was evaluated at univariate and multivariate analysis.ResultsPALN metastases (N16+) were found in 11.1% of cases. At univariate analysis, R1 resection, metastatic nodes different from para aortic (N1) and N16+ significantly affected patients' prognosis. Compared with N16+, the median overall survival (OS) of N0 patients was significantly longer (32 versus 69 months, respectively; P 0.05). At multivariate analysis, only R1 resection reached statistical significance and was confirmed an independent prognostic factor.ConclusionsNeoplastic involvement of PALN in peri‐ampullary cancer is frequent and, so, their removal during PD could be justified. Moreover, PALN metastases should be not considered an absolute contraindication to radical surgery.

BACKGROUND Risk of nodal involvement in T1 colorectal cancer is assessed by tumor histological features. In several tumors, the ratio between neutrophils and lymphocytes (NLR) or platelets and lymphocytes (PLR) have been applied to lymph-node metastases prediction. The aim of this study was to evaluate the role of NLR, derived NLR (dNLR) and PLR in predicting nodal involvement in T1 colorectal cancers. METHODS NLR, dNLR and PLR in surgical resected T1 colorectal cancers were retrospectively calculated and analysed in nodal positive and negative cases. RESULTS Data regarding 102 patients were considered. Nodal involvement rate was 10.8%. NLR values were higher in node positive patients (P=0.04). A trend toward significance (P=0.05) was found for higher dNLR values and positive nodal status. For NLR, ROC curve analysis allowed to choose a predictive cut-off value of 3.7 (AUC of 0.69; 95% CI: 0.48-0.89). Nodal positivity was reported in 71.5% of high NLR patients; only two N0 cases (28.5%) were registered in high NLR group (P

Clinical phenotype variability in MEN1 syndrome exists and evidence for an established genotype-phenotype is lacking. However, a higher aggressiveness of MEN1-associated gastro-entero-pancreatic (GEP) (neuro)endocrine tumours (NETs) tumours has been reported when MEN1 gene truncating mutations are detected. We found a novel germline truncating mutation of MEN1 gene at exon 10 in a subject with an aggressive clinical behavior of GEP-NETs. Successively, other two mutant-affected familial members have been identified. The aim of this observational study was to investigate genotype-phenotype correlation in these three members, with attention to GPE-NETs behavior over the years. The genetic and clinical data obtained and the follow-up screening program (2012–2016) were according to the International Guidelines in a multidisciplinary academic reference center. The familial history collected strongly suggested MEN1 GEP-NETs in at least other four members from different generations. Three MEN1 patients (aged 30–69 years at MEN1 diagnosis) were clinically screened for MEN1 GEP-NETs, both functioning and nonfunctioning. Biochemical, imaging, and nuclear medicine tests and fine-needle agobiopsy were performed, depending on found/emerging clinical symptoms/biochemical abnormalities, and made when necessary. Our clinical survey found strong genotype-phenotype correlation with aggressive MEN1 GEP-NETs (G1, G2-NETs, and multiple ZES/gastrinomas) over the years. The familial history strongly suggested ZES/gastrinoma in progenitors from previous generations. This novel MEN1 truncating mutation correlates with an aggressive evolution and behavior of MEN1 GEP-NETs in studied affected subjects, confirming the need for MEN1 individuals to be evaluated by a skilled multidisciplinary team, as also stated by International Guidelines.

Background: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. Methods: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-KrasG12D/+,LSL-Trp53R175H/+ transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. Results: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. Conclusions: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

There is not a clear consensus regarding the optimal treatment of locally advanced pancreatic disease. There is a potential role for neoadjuvant therapy to treat micrometastatic disease with chemotherapy, as well as for the treatment of local disease with radiotherapy. We evaluated the safety and efficacy of induction chemotherapy with oxaliplatin and gemcitabine followed by a high weekly dose of gemcitabine concurrent to radiation therapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer. In our study, 41 patients with pancreatic cancer were evaluated. In all cases an accurate pre-treatment staging was performed. Patients with evidence of metastatic disease were excluded, and thus a total of 34 patients were consequently enrolled. Of these, twenty-seven patients (80%) had locally advanced unresectable tumours, seven patients (20%) had borderline resectable disease. This protocol treatment represents a well-tolerated promising approach. Fifteen patients (55.5%) underwent surgical radical resection. With a median follow-up of 20 months, the median PFS and OS were 20 months and 19.2 months, respectively. The median OS for borderline resectable patients was 21.5 months compared with 14 months for unresectable patients (p = 0.3). Continued optimization in multimodality therapy and an accurate patient selection remain crucial points for the appropriate treatment of these patients.

Introduction: Gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas. The hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response. The programmed death 1–programmed death-ligand 1 (PD-1/PD-L1) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms. Patient's concerns case study and outcome: We report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis. He is alive without disease 10 months after surgery. We focused the study on factors that potentially modulate the prognosis. In this setting we demonstrate, for the first time in this type of tumor, by immunohistochemistry a strong PD-L1 expression in neoplastic cell and the presence of PD-1 positive infiltrating lymphocytes. Conclusion: The applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery.

Several studies showed how serum levels of lactate dehydrogenase (LDH) are related with a worse prognosis and response to therapy. Its role in colorectal cancer is not still assessed. The aim of this study was to assess the prognostic role of serum level of LDH in non-metastatic, previously untreated, T2–T3–T4 colorectal tumours undergoing surgery. Data regarding preoperative serum levels of LDH have been retrospectively collected. A group with normal levels of serum LDH (group A) and a group with high levels of serum LDH (group B) have been identified and compared in relation with disease staging and outcome. A series of 96 cases have been analysed. Only age was significantly associated with increased LDH serum level (p 0.001). No significant differences between serum LDH levels, staging pT (p 0.721), pN (p 0.080) and grading (0.849) have been found. Test’s sensitivity and specificity were 76 and 46.5 %, respectively. Preoperative serum levels of LDH alone failed to demonstrate a prognostic role in a selected series of colorectal cancer patients. Low rates of sensitivity and specificity have been found.

Bevacizumab is largely used in colorectal cancer patients. Postsurgical healing complications have been described for patients following treatment with Bevacizumab. We report three cases of spontaneous intestinal perforation following infusion of Bevacizumab. From January 2002 through October 2010, Bevacizumab was delivered in 143 patients. Spontaneous intestinal perforation occurred in 3 cases (2.1 %). Bevacizumab may result in severe complications. Therefore, it is important to consider every patient treated with Bevacizumab at risk for life-threatening gastro-intestinal complications.

Objectives Aortic valve replacement through conventional sternotomy still represents the gold-standard surgical approach for aortic valve disease. However, given the increasing number of patients with comorbidities, strategies that can improve operative results are always sought. Minimally invasive aortic valve surgery, although related to a steep learning curve, might be associated with improved postoperative outcomes. The main aim of this study was to assess whether significant differences exist in terms of operative and early results between a mini-sternotomy and a right mini-thoracotomy approach for isolated aortic valve replacement without sutureless technologies. Methods This is an observational retrospective multicentre study from nine Italian cardiac centres that analyses prospectively collected data of patients who underwent isolated minimally invasive aortic valve replacement between January 2010 and December 2014. Two approaches are considered (mini-sternotomy and mini-thoracotomy) and compared in terms of operative and early outcomes. Results After interrogation of the centralized database, a total of 1130 patients were retrieved (854 mini-sternotomy and 276 mini-thoracotomy). Patients in the mini-sternotomy group had a higher risk profile. There was no difference in terms of early mortality; cardiopulmonary bypass and cross-clamp time did not differ significantly between the groups; and a significantly higher number of reoperations for bleeding was observed in the right mini-thoracotomy group. Conclusions Both mini-sternotomy and mini-thoracotomy could be performed safely, with low mortality and postoperative morbidity. The mini-thoracotomy approach was associated with a significantly higher rate of reoperation for bleeding. Uptake among cardiac centres was low. Sutureless technologies could potentially increase surgical volume by simplifying the mini-thoracotomy procedure.

Background and aim: A debate over alternative therapeutic strategies for multivessel coronary disease is currently ongoing. We aimed at analyzing the results of myocardial revascularization with arterial conduits. Methods: We retrospectively reviewed 10,752 patients undergoing isolated coronary bypass surgery within our hospital's group. Average follow-up was 37.2 months. Through propensity-matching, we generated three groups (3584 patients each) on the basis of the revascularization strategy: use of one mammary artery plus venous grafts, use of two mammary arteries plus venous graft, and total arterial revascularization. Results: Overall operative mortality was 2.8%. Patient-related factors (renal failure, advanced age, recent myocardial infarction, depressed LVEF, diabetes) were identified as predictors of mortality (logistic regression). Although mortality was not statistically different among groups, patients receiving more than one arterial conduit displayed in the long-term better freedom from cardiac death and from adverse cardiac events (repeat revascularization, myocardial infarction, recurrent angina) (Kaplan–Meier analysis). Use of only one arterial conduit, diabetes and depressed LVEF predicted cardiac mortality, and adverse events (Cox regression). No differences in any endpoint emerged among patients receiving two arterial conduit plus venous grafts or total arterial revascularization. Conclusions: These data strongly support the practice of using two arterial conduits rather than one. The operative and late results of coronary surgery with arterial conduits are optimal and should serve as a current benchmark for the comparison with state-of-the-art percutaneous interventions. (J Card Surg 2012;27:427-433)

Background— Age >90 years represents in many centers an absolute contraindication to cardiac surgery. Nonagenarians are a rapidly growing subset of the population posing an expanding clinical problem. To provide helpful information in regard to this complex decision, we analyzed the operative and 5-year results of coronary and valvular surgical procedures in these patients. Methods and Results— We retrospectively reviewed 127 patients aged ≥90 years who underwent cardiac surgery within our hospital group in the period 1998 to 2008. Kaplan–Meier and multiple logistic regression analyses were performed. A longer follow-up than most published studies and the largest series published thus far are presented. Mean age was 92 years (range, 90 to 103 years). Mean logistic EuroSCORE was 21.3±6.1. Sixty patients had valvular surgery (including 11 valve repairs), 49 patients had coronary artery bypass grafting, and 18 had valvular plus coronary artery bypass grafting surgery (55 left mammary artery grafts implanted). Forty-five patients (35.4%) were operated on nonelectively. Operative mortality was 13.4% (17 cases). Fifty-four patients (42.5%) had a complicated postoperative course. There were no statistically significant differences in the rate and type of complications between patient strata on the basis of type of surgery performed. Nonelective priority predicted a complicated postoperative course. Predictors of operative mortality were nonelective priority and previous myocardial infarction. Kaplan–Meier survival estimates at 5 years were comparable between patient groups on the basis of procedure performed. Conclusions— Although the rate of postoperative complications remains high, cardiac surgery in nonagenarians can achieve functional improvement at the price of considerable operative and follow-up mortality rates. Cardiac operations in these very elderly subjects are supported if appropriate selection is made and if the operation is performed earlier and electively. Our results should contribute to the development of guidelines for cardiac operations in nonagenarians.

ObjectiveIt is unclear (1) whether the use of 2 arterial conduits rather than a single conduit in multivessel coronary artery bypass grafting significantly improves results despite the concomitant use of saphenous vein grafts and (2) whether any among different configurations of composite grafts (left/right thoracic arteries and radial artery) offers an advantage over the others.MethodsEight hundred fifteen patients were randomized to one of 3 different strategies of revascularization by using the left thoracic artery plus the right thoracic artery or using the left thoracic artery plus the radial artery. Venous grafts were used for the remaining targets. Patients randomized to receive 1 arterial graft served as control subjects. Operative mortality and morbidity were comparable among groups.ResultsThe rate of cerebrovascular complications was not statistically lower among patients receiving 2 arterial grafts. At 2 years, overall survival was not significantly different among groups (P = .59). Cardiac event–free survival was significantly better in patients receiving 2 arterial grafts versus control subjects (P < .0001), even among elderly patients (P = .022). The 3 investigated strategies using 2 arterial conduits were similar concerning early and midterm results.ConclusionsRevascularization with 2 arterial conduits offers better midterm event-free survival than a single arterial graft, irrespective of which second-choice arterial conduit is used (radial artery or right thoracic artery), the simultaneous use of saphenous vein grafts, and the patient's age.

Background: Promyelocytic leukemia (PML) tumor suppressor gene plays a key role in acute PML pathogenesis but its involvement in pathogenesis and prognosis of solid cancers has not been defined yet. Patients and methods: In all, 62 ampullary adenocarcinoma patients who underwent curative surgery between 1996 and 2005 were included. Expression analysis of PML was carried out by immunohistochemical staining and correlated with disease-free survival (DFS) and overall survival (OS). Results: In 24 tumor specimens (38.7%), PML was classified as absent, in 16 (25.8%) as focally expressed and in 22 (35.5%) as diffusely expressed. By univariate analysis, DFS was significantly influenced by pathological T stage (P = 0.03), lymph nodal involvement (P = 0.002), and PML expression (P = 0.001). DFS in patients without PML expression was 28.0 months versus 45.1 and 75.5 for patients with focal and diffuse expression, respectively. OS in the group of patients without PML expression, with focal expression, and with diffuse expression was 40, 48, and 77 months, respectively (P = 0.002). By a multivariate analysis, PML expression was the strongest prognostic factor for DFS (P = 0.003) and the only statically significant prognostic factor for OS (P = 0.009). Conclusions: Our preliminary data suggest PML as a novel prognostic tool for ampullary cancer patients.

Background: Alexithymia refers to a set of cognitive and emotional deficits. Its effect on surgical outcome has been demonstrated but no studies have been published on colorectal cancer patients. Study Design: A series of 60 consecutive colorectal cancer patients were enrolled in a 3-year prospective study on quality of life by using the SF-36 test and Toronto Alexithymia Scale questionnaires. Patients were investigated pre- and postoperatively (before discharge and then 1 and 3 months thereafter). The control group consisted of patients undergoing laparoscopic cholecystectomy for cholelithiasis. These two groups were divided into two subsets: high-level alexithymia (HA) and low-level alexithymia (LA). The prevalence of HA was 34% in colorectal patients and 35% in cholelithiasis patients. Results: During the postoperative period, in the colorectal group the SF-36 score was significantly higher in HA than in LA subsets. This result was confirmed in the cholelithiasis group. During follow-up, a progressive reduction of the SF-36 score was observed in both HA populations. Discussion: Results emerging from this investigation demonstrate that surgery significantly improves the quality of life in HA patients. These findings suggest that alexithymia might be advantageous in evaluating the adaptation after surgery in the short follow-up period.

Background Radio-chemotherapy is one of the steps of multidisciplinary management in locally advanced pancreatic cancer. The Epidermal Growth Factor Receptor (EGFR) plays an important role in the disease pathway. The purpose of this prospective study is to evaluate the feasibility and the efficacy of radiotherapy in combination with gemcitabine and EGFR targeting therapy for patients with locally advanced disease. Materials and methods From November 2008 through January 2012, 34 patients were included in this study. In all cases an accurate pre-treatment staging including CT scan, Endoscopic Ultra-Sonography (EUS), 18F - fluorodeoxyglucose (18F-FDG) PET-CT and laparoscopy with peritoneal washing was performed. External beam radiation was delivered with a total dose of 50.4 Gy (1.8 Gy per fraction). Patients were treated using 3D- conformal radiotherapy, and the clinical target volume was the primary tumor and involved lymph nodes. Gemcitabine 300 mg/m2 and Cetuximab were given weekly during radiation therapy. Results Ten patients (29.4 %) were excluded from the protocol because of the evidence of metastatic disease at the pre-treatment staging. Three patients refused radiochemotherapy. Twenty-one patients completed the therapy protocol. During the combined therapy grade 3–4 toxicities observed were only haematological (leukopenia 47,6 %, trombocytopenia 4.8 %, elevated gamma-GT 23.8 %, elevated alkaline phosphatase 4,8 %). Non-haematological toxicity grade 3–4 was never reported. Post-treatment workup showed partial response in five patients (24 %), stable disease in 11 patients (52 %) and disease progression in 5 patients (24 %). Two-year Local Control was 49 % (median, 18.6 months), 2-year Metastases Free Survival was 24 % (median, 10.8 months). One and two-year Overall Survival were 66 % and 28 % respectively, with a median survival time of 15.3 months. Conclusions The combination of cetuximab and gemcitabine with concurrent radiation therapy provides a feasible and well tolerated treatment for locally advanced pancreatic cancer. Patients’ selection is crucial in order to treat patients appropriately.

Epidemiological studies suggest that regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with reduced incidence of gastrointestinal cancer. Several lines of evidence indicate that the antineoplastic effect of NSAIDs is attributable to COX-2 inhibition. The aim of our study was to assess COX-2 expression in a series of primary untreated ampullary carcinomas and its possible correlation with clinicopathological parameters. In the present study, 45 surgical specimens of invasive ampullary carcinomas were histologically classified into pancreaticobiliary, intestinal, and unusual types. COX-2 expression by immunohistochemical method was analyzed. High COX-2 expression was detected in 35 (77.8%) ampullary carcinomas. Among these, 20/21 (95.2%) were classified as intestinal, 9/18 (50%) pancreaticobiliary, and 6/6 (100%) unusual type. A significant statistical difference in terms of COX-2 expression was found between pancreaticobiliary vs intestinal type (P=0.002). Furthermore, a negative significant statistical correlation was found between T factor and COX-2 expression (P=0.047). The different COX-2 expression among histopathological types supports the concept of histogenetical difference of ampullary carcinomas. Furthermore, the high rate of COX-2 expression in the intestinal subtype of ampullary carcinoma may represent the rational for a histotype-tailored therapy targeting COX-2.

The epidermal growth factor receptor (EGFR), which participates in signalling pathways that are deregulated in cancer cells, is frequently mutated in colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We evaluated the efficacy of cetuximab in weekly combination with irinotecan in metastatic colorectal cancer patients refractory to previous treatments based on oxaliplatin or irinotecan. We included 55 heavily pretreated patients (colon/rectum: 34/11, M/F: 16/29, median age 63 years, range: 27-79) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy and a irinotecan-based second-line regimen. Patients were followed for tumour response and were also evaluated for the time to tumour progression, and safety of treatment. Cetuximab was given at an initial dose of 400 mg m(-2), followed by weekly infusions of 250 mg m(-2). Irinotecan was administered weekly at the dose of 90 mg m(-2). All patients were assessable for treatment efficacy and safety response rate was 25.4% (95% CI: 21.7-39.6%); 38.2% (95 CI: 18.6-39.8%) of patients showed a disease stability as the best response. As a consequence, the overall tumour control rate was 63.6% (95% CI: 46.4-70.6%). The median time to progression was 4.7 months (95% CI: 2.5-7.1 months) and the median survival time was 9.8 months (95% CI: 3.9-10.1 months). The most common G3-4 noncutaneous side toxicities were: diarrhoea (16.4%), fatigue (12.7%) and stomatitis (7.3%). 89.1% of patients developed skin toxicity and 32.6% of cases was of grade 3-4. No allergic reactions were identified at any courses in any patients. Fever was documented in 27.3% of patients and was most commonly recorded after the first administration. Cetuximab has clinically significant activity even in heavily pretreated colorectal cancer patients progressed after both oxaliplatin and irinotecan-based chemotherapy regimens.

Purpose: To identify potential prognostic molecular factors in ampullary adenocarcinoma that could be of significant importance. To this end, we examined the possible prognostic significance of cyclooxygenase-2 (Cox-2) and Survivin expression and the apoptotic index in a cohort of uniformly treated patients with ampullary cancer treated with radical surgical excision. Experimental Design: The entry criteria were that the patients have a pathologic diagnosis of ampullary cancer which had been resected. Expression analysis for Cox-2 and Survivin was done by immunohistochemical staining. Apoptotic cells were identified by the terminal deoxyribonucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL) method. Results: Thirty-nine tumor specimens from resected ampullary adenocarcinoma patients were included. By univariate analysis, overall survival was affected by Cox-2 expression and TUNEL staining (respectively, P = 0.0003 and 0.03). Survivin expression did not influence the overall survival in our patient population (P = 0.123). Patients' clinicopathologic features (gender, age, and T and N factors) did not influence outcome. In multivariate Cox regression analysis, Cox-2 expression (relative risk, 4.330; P = 0.005) was the only variable that significantly affected overall survival. Conclusions: The results of the present article provide, for the first time, evidence that Cox-2 expression, but not Survivin expression, may represent a significant prognostic factor after surgical resection in patients affected by cancer of the ampulla of Vater. Further studies are required to determine whether Cox-2 inhibitors may be useful for the therapy or prevention of ampullary carcinoma.

Objectives: The aim of the study was to define the feasibility and efficacy of Xelox (capecitabine and oxaliplatin) administered through a new and original schedule in advanced pretreated colorectal cancer (CRC) patients. Methods: 36 metastatic CRC patients resistant at least to a previous 5-fluorouracil- and irinotecan-based chemotherapy line were included in the study. Treatment: Oxaliplatin 70 mg/m2 as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on days 1, 8 plus chronomodulated capecitabine 1,750 mg/m2/day per os (8.00 a.m. 25% of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on days 1–14 every 21 days. 16 (44.4%) patients had previously received only 1 chemotherapy line for metastatic disease and 20 patients (55.6%) 2 chemotherapy lines. Moreover, 12 patients (33.3%) progressed after a first or second line of oxaliplatin-based regimen as well. Results: Most frequent related G3–4 adverse reactions were diarrhea (11.6%), nausea/vomiting (8.3%), neuropathy (8.3%), mucositis (8.3%), asthenia (16.7%) and hand-foot syndrome (5.5%). G3–4 anemia, leucopenia and liver toxicities were not observed. The overall response rate was 30.6% (11/36 patients). Disease stabilization was observed in 13 patients (36.1%) and progression in 12 patients (34.3%). Between the 12 oxaliplatin-resistant patients, the overall response rate was 25% (3 patients); 6 patients (54.5%) obtained a stable disease, and only 3 patients (25%) progressed. The median overall survival was 11.3 months (95% confidence interval 7.0–15.7 months), the median response duration 2.8 months (95% confidence interval 1.2–5.6 months) and the median time to progression 6.7 months (95% confidence interval 5.7–6.3 months). The 1-year survival rate was 53.8%. Conclusions: The high overall tumor growth control, the remarkable median time to progression and overall survival and the good safety profile are of particular interest for patients with heavy pretreated metastatic CRC.

In the present study, the prognostic impact of factors involved in the apoptosis pathway were tested on 67 consecutive patients treated with surgical resection. Included in the study were all patients resected for pancreatic adenocarcinoma from 1988 to 2003. Expression analysis for p53, Bax, and Bcl-2 were performed by immunohistochemical staining. Apoptotic cells were identified by the TUNEL method. These data were correlated with survival. Sixty-seven tumor specimens were included in the study. A strong positive correlation was recorded between p53 overexpression and Bax expression levels (P < 0.001). By univariate analysis, overall survival seemed to be improved with Bcl-2 and Bax expression (respectively, P = 0.0379 and 0.0311). The median survival time in patients with low apoptotic index was better versus those with a high index (P = 0.0127). Lymph node involvement was the only clinico-pathologic parameter that significantly correlated with overall survival (P = 0.0202). By a multivariate Cox regression analysis, the only immunohistochemical parameter that influenced overall survival was the apoptotic index (P = 0.040). Tumor's overexpression of both Bax and Bcl-2 resulted the strongest independent prognostic factor (P = 0.013). This is the first study to report a statistically significant association of apoptosis to overall survival for pancreatic cancer patients treated with surgical resection. The contemporary overexpression of Bax and Bcl-2 represents the strongest prognostic factor.

Introduction After complete local excision of pT1 colorectal cancers, prediction of the absence of lymph-node involvement represents an interesting perspective in order to avoid unnecessary additional radical surgery, reducing morbidity, mortality and costs of care. We aimed to identify independent risk factors predictive of nodal involvement in pT1 colorectal cancer patients. Methods Data regarding depth of submucosal invasion, histological grading, tumour budding and lymphovascular invasion in a consecutive series of 48 pT1 surgically resected colorectal cancers have been retrospectively collected and related to the nodal status. Results A 12.5% rate of nodal involvement has been found. The poor differentiation was found as the only independent predictor of nodal metastases in pT1 colorectal cancer ( p = 0.01). Conclusions Poor differentiation was the only independent significant predictor of nodal involvement in pT1 colorectal tumours. Our and literature's data confirm that risk factors must be prospectively collected and reported; further genetic and epigenetic predictive factors have to be investigated in order to carefully evaluate the needing of major surgery for pT1 colorectal cancer.

Objective: Total arterial myocardial revascularization may be achieved by using the ‘Y-graft’ techniques with different free arterial conduits anastomosed off the side of an in situ internal thoracic artery to reach distal coronary segments. This study was assessed to measure intraoperative graft flow, resistance and clinical outcomes. Methods: Seventy-six patients who underwent coronary artery bypass grafting during a time period of 27 months were enrolled in this prospective study. All patients received sequential grafting by using both internal thoracic arteries, inferior epigastric and right gastroepiploic artery joined as a composite Y graft. Intraoperative graft flow, resistance and derived variables were measured. Results: All patients except one showed good flow (ml/min and waveform) in either branch of composite graft. In one case, a low-flow situation through the graft was registered requiring surgical correction. Temporary occlusion of either branch did not significantly affect flow in the other side of the arterial Y. Mid-term follow-up (3 and 15 months) and angiographic studies showed a high graft patency rate. Conclusion: Composite arterial grafts provide excellent early and mid-term clinical results. Flow reserve of the left internal thoracic artery did not affect blood flow and resistance on either branch of the Y graft when temporary occlusion on the other side of the arterial Y was performed. q 2000 Elsevier Science B.V. All rights reserved.

Background and Objectives: Surgical resection offers the only potential cure for pancreatic carcinoma. Several recent series have reported an encouraging increase in 5-year survival rate exceeding 20% and have emphasized the importance of patient selection based on reproducible prognostic factors. The impact on survival of demographic, intraoperative, and histopatologic factors are investigated in this study. Methods: Seventy-three patients with adenocarcinoma of the pancreas, treated at the Department of Surgery of the Catholic University of Rome during 1988-1998, were retrospectively analyzed. Survival data were reviewed, and potential prognostic factors were compared statistically by univariate and multivariate analyses. Results: There was no operative mortality, and the morbidity rate was 37%. Actuarial overall and disease-specific survival rates for all 73 patients were, respectively, 27% and 31% at 3 years and 13% and 21% at 5 years, with a median survival time of 16 months. T stage and nodal status significantly affected survival according to univariate analysis (P = 0.0017 and 0.04). An impact on survival, even if not of statistical significance, was shown for other pathologic or intraoperative factors. Conclusions: T and nodal stage are the strongest independent predictors of survival. Limited intraoperative transfusion, reduced operative time, and clear margins also may play a role, which requires further confirmation in a larger series.

A very unusual clinical presentation of non-Hodgkin's lymphoma (NHL) of the liver is reported herein. The patient was a 35-year-old male who had been HIV-positive since 1987. Following an episode of acute pain in the right upper abdominal quadrant, ultrasonography (US) and computed tomography (CT) were performed, revealing a nodular tomography (CT) were performed, revealing a nodular lesion, 2.5 cm in diameter, localized in the eight segment of the liver. Despite the fact that the lesion became significantly enlarged over a 6-month period, three repeated percutaneous biopsies proved negative. Finally, his increasing pain and the lack of a definitive diagnosis prompted us to perform a right hepatectomy. The patient had an uneventful postoperative course and is well 1 year after his operation. Establishing a diagnosis of extranodal lymphoma can be difficult, especially in HIV-positive or AIDS patients. Thus, performing a laparotomy is justified to confirm a diagnosis and decide upon the most appropriate treatment. However, in about 10% of these patients, only surgical resection allows for the diagnosis. In accordance with other reports, our experience confirms that, in contrast with AIDS patients, HIV-positive patients have a similar prognosis as non-HIV patients, and are suitable candidates for even major surgical procedures.

Background: Endoscopic sphincterotomy (ES) plays an important role in treatment of biliary stones; however, there remain some controversies concerning complications of ES, which in most cases seem not to be predictable. Methods: The aim of this study was a retrospective analysis of complications in 546 consecutive patients (267 males, 279 females, average age 63.7 years) who underwent endoscopic retrograde cholangiography (ERCP) for biliary stones from 1988 to 1995. Results: ES was performed in 535 patients (98%), and extraction of stones was successful in 493 (92%). In all, 29 complications (5.4%) were observed, including bleeding 13, cholangitis seven, cholecystitis four, pancreatitis three, retroduodenal perforation two; of these, four (14%) required an operation. Overall mortality was 0.3%. Conclusion: While a significant decrease of the incidence of complications was observed in the course of the study, due to constantly improving experience, no correlation between risk factors and complications was identified.

The objective of the study was to verify if histopathological differentiation of ampullary carcinoma after surgical resection may be related to survival.The prognostic role of an accurate histological and immunohistochemical classification has been investigated in a multicentric series of carcinoma of the ampulla of Vater. Immunohistochemical expression of cytokeratin 7 (CK7) and CK20 were analyzed in the different morphological histotypes of ampullary cancers, and results were compared with overall survival.Of 72 ampullary cancers, 48.6% were classified as pancreaticobiliary-type carcinomas, 43.1% were classified as intestinal-type carcinomas, and 8.3% were classified as "unusual"-type carcinomas. Cytokeratin 20 was expressed in 28 (90.3%) of the 31 intestinal-type carcinomas, whereas it was always negative in the pancreaticobiliary histotype; CK7 was expressed in 32 (91.4%) of the 35 pancreaticobiliary-type carcinomas and in 18 (58.1%) of the 31 intestinal-type carcinomas. By univariate analysis, overall survival was influenced significantly by pathological T factor, lymph node involvement, and histological/immunohistochemical subtyping. Furthermore, using a multivariate Cox regression model, lymph node metastasis and CK20 were identified as significant independent factors related to prognosis.Our results prove the clinical use of ampullary cancer subclassification based on different histotypes and indicate the useful role of the CK7/CK20 expression profile for consistent histopathological classification and prognostic relevance.

Following Lichtenstein’s technique, over the last 15 years several variation have been proposed, such as Trabucco’s sutureless technique and the use of two self-regulating prostheses, proposed by Valenti that have given excellent results. The aim of this prospective and randomised study was to determine whether there are differences in the results obtained with these three techniques. Of 812 patients submitted to inguinal hernia repair, we selected and randomised 162 patients into three groups of 54 patients each: Lichtenstein (Group L), Trabucco (Group T) and Valenti (Group V). Surgical procedures were performed in all cases by residents in surgery using local anaesthesia. Primary endpoint was intensity of postoperative pain. Median follow-up was 8 years. The primary analysis of postoperative pain at 48 h did not report any significant difference between the three groups as for secondary analyses except that the Trabucco procedure took less operative time than the Lichtenstein, and the Valenti group was more painful than the Lichtenstein group at the third postoperative day. In our series median operation time was 60 min. Recurrence rate was 1.85 %. Surgical repair of inguinal hernia according to the Lichtenstein, Trabucco and Valenti techniques is safe and easy to perform regardless of the surgical experience of the operator, with excellent results and no differences due to technique used as regards almost all of the parameters studied.

Epigenetic alterations, such as CpG islands methylation and histone modifications, are recognized key characteristics of cancer. Glycogenes are a group of genes which epigenetic status was found to be changed in several tumors. In this study, we determined promoter methylation status of the glycogene beta-1,4-galactosyltransferase 1 (B4GALT1) in colorectal cancer patients. Methylation status of B4GALT1 was assessed in 130 colorectal adenocarcinomas, 13 adenomas, and in paired normal tissue using quantitative methylation specific PCR (QMSP). B4GALT1 mRNA expression was evaluated in methylated/unmethylated tumor and normal specimens. We also investigated microsatellite stability and microsatellite instability status and KRAS/BRAF mutations. Discriminatory power of QMSP was assessed by receiving operating curve (ROC) analysis on a training set of 24 colorectal cancers and paired mucosa. The area under the ROC curve (AUC) was 0.737 (95% confidence interval [CI]:0.591-0.881, P = 0.005) with an optimal cutoff value of 2.07 yielding a 54% sensitivity (95% CI: 35.1%-72.1%) and a specificity of 91.7% (95% CI: 74.1%-97.7%). These results were confirmed in an independent validation set where B4GALT1 methylation was detected in 52/106 patients. An inverse correlation was observed between methylation and B4GALT1 mRNA expression levels (r = -0.482, P = 0.037). Significant differences in methylation levels and frequencies was demonstrated in invasive lesions as compared with normal mucosa (P = 0.0001) and in carcinoma samples as compared with adenoma (P = 0.009). B4GALT1 methylation is a frequent and specific event in colorectal cancer and correlates with downregulation of mRNA expression. These results suggest that the glycogene B4GALT1 represent a valuable candidate biomarker of invasive phenotype of colorectal cancer.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, and account for 0.1%-1% of gastrointestinal malignancies. Meckel's diverticulum (MD) is the most prevalent congenital abnormality of the gastrointestinal tract (0.3%-4.0%).Their clinical presentation is strongly related to the occurrence of complications or the development of a neoplasm. Tumors and perforation of MD are infrequent. The case presented here is to our knowledge the fourth published case of a small intestine GIST causing perforation of the Meckel's diverticulum.Although there is no compelling evidence in the current literature to support prophylactic diverticulectomy for patients with MD, our and other similar cases could justify the use of simple laparoscopic tangential resection during elective operations for healthy patients.

Objective: The results of mitral repair for complex Barlow valves are adequate and support earlier intervention. It is unknown whether these results are reproducible in the context of minimally invasive surgery via right minithoracotomy. Methods: We randomized patients with Barlow mitral disease (bileaflet prolapse) to have conventional open repair via median sternotomy (MS group) or minimally invasive (MI group) repair. Repair was done using polytetrafluoroethylene chordal reimplantation for both leaflets. In the MI group, we adopted right minithoracotomy, peripheral cannulation, external aortic clamping, and surgery under direct vision. Results: Both groups comprised 70 patients. The operative and the cardiopulmonary bypass times were significantly longer in the MI group (P = .003 and P = .012). Mitral repair was successful in 98.5% MI patients and 100% MS patients. Operative mortality was comparable. The mean mechanical ventilation time, intensive care unit stay, and hospital stay were lower in the MI group (P = .014, P =.02, and P = .03,). Mean pain score was lower in the MI group at postoperative days 2 and 4. At follow-up, the freedom from moderate (2+) or severe (3+ or 4+) mitral regurgitation was 98% versus 97% (P = .9). Two patients underwent reoperation (1 in each group) for late failure of repair. The Kaplan-Meier analysis confirmed these results. Conclusions: Our data indicate that the optimal standard-of-care results of mitral repair for complex disease (Barlow) are reproducible in the minimally invasive settings through right minithoracotomy and direct vision. The minimally invasive technique can be proposed for complex mitral disease and early referral of these patients can be encouraged. Copyright © 2011 by The American Association for Thoracic Surgery.

A 12-year-old neurologically impaired boy with recurrent peptic stenosis of the esophagus was treated successfully with use of a self-expanding metallic stent that remained for 3 months.

We present a case of a transsexual patient who underwent a partial pelvectomy and genital reconstruction for anal cancer after chemoradiation. This is the first case in literature reporting on the occurrence of anal cancer after male-to-female sex reassignment surgery. We describe the surgical approach presenting our technique to avoid postoperative complications and preserve the sexual reassignment.

Introduction: Pancreatic cancer is one of the most aggressive gastrointestinal cancer with less than 10% long-term survivors. The apoptotic pathway deregulation is a postulated mechanism of carcinogenesis of this tumor. The present study investigated the prognostic role of MUC2 and MUC5 apomucin expression in a series of surgically resected pancreatic cancer patients. Results: By univariate analysis, survival was influenced by MUC2 expression but not by MUC5 expression. The MUC2 overexpression was associated with better prognosis (p = 0.003). By a multivariate Cox regression analysis, MUC2 overexpression maintained the prognostic statistical value. In particular, patients with high MUC2 staining showed a longer survival. Moreover the present study does report the absence of a prognostic role of MUC5 expression in this type of cancer. Material and methods: All patients affected by pancreatic ductal adenocarcinoma and treated with surgical resection from 1988-2003 were considered for the study. MUC2 and MUC5 expression were evaluated by immunohistochemical staining. Tumor specimens of 59 resected patients were included in the study. Conclusions: the study demonstrated the prognostic relevance of MUC2 expression in pancreatic cancer and underlined its potential role as target gene in the field of therapy research. ©2009 Landes Bioscience.

BACKGROUND: The aim of the current study was the investigation of the value of bevacizumab + 5-fluorouracil(5–FU)/folinic acid in patients with advanced colorectal cancers who have exhausted standard chemotherapy options. METHODS: The authors included 48 heavily pretreated patients (colon:rectum, 33:15; men:women, 23:25; median age, 63 years; range, 27-79 years) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy, an irinotecan-based second-line regimen, and a third-line treatment with cetuximab plus weekly irinotecan. Bevacizumab was given at a dose of 5 mg/kg. 5-FU/folinic acid was administered according to the de Gramont schedule. RESULTS: The response rate was 6.25%, and 30.4% of patients demonstrated stable disease as the best response. The median time to disease progression was 3.5 months (95% confidence interval [95% CI], 2.3-6.9 months), and the median survival time was 7.7 months (95% CI, 3.9-11.9 months). The most common grade 3 to 4 side toxicities (graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) were: diarrhea (20.8%), fatigue (14.5%), and stomatitis (12.5%). Grade 3 to 4 hemorrhage occurred in 8 patients (16.6%), including 4 cases of bleeding in the gastrointestinal tract. Other relatively common adverse events such as hypertension, thrombosis, and bowel perforation were reported in 50%, 18.7%, and 4.16%, of patients respectively. CONCLUSIONS: The data from the current study suggest a modest but significant clinical benefit of bevacizumab + de Gramont schedule in heavily pretreated colorectal cancer patients. Cancer 2009. © 2009 American Cancer Society.

Intestinal tuberculosis is rare in Western countries, with incidence rates of 35.7 and 0.43 per 100,000 per year for the immigrant and native populations, respectively. Despite a clear increase in the frequency of extrapulmonary tuberculosis in immunosuppressed patients, the clinical features of intestinal tuberculosis are seen rarely. A typical clinical presentation includes abdominal pain, weight loss, fever, weakness, nausea, vomiting, obstruction, and bleeding. Intestinal tuberculosis often mimics inflammatory bowel disease or malignant neoplasia, and its preoperative diagnosis is a challenge. Microbiologic diagnosis often is difficult because the causative microorganism requires a long incubation period.Two case reports and review of the pertinent literature.We report two cases of colonic tuberculosis mimicking cecal carcinoma in one patient and periappendiceal abscess in the other. A 75 year-old man underwent right hemicolectomy for a right colon mass. Preoperative laboratory, radiologic, and endoscopic evaluations were negative for tuberculosis and carcinoma. The QuantiFERON-TB Gold test was positive. Surgical specimen histologic review showed non-caseating granulomas and rare Ziehl-Neelsen-positive bacilli. A 35 year-old man, born in Sri Lanka but living in Italy for 10 years, came to our attention for a periappendiceal abscess. Multiple peritoneal micro-nodules were found at laparotomy. Their extemporaneous histologic examination showed granulomas and giant-cell inflammation. A right hemicolectomy was performed. The QuantiFERON-TB Gold test, performed on peritoneal fluid and blood, was positive in both.The QuantiFERON-TB Gold test may hold promise for use in intestinal inflammatory diseases when tuberculosis is suspected but conventional workup is not diagnostic.

Objectives: We compared two different approaches to right laparoscopic transperitoneal adrenalectomy for large tumors (>5 cm): the anterior transperitoneal (AT) and lateral transperitoneal (LT) approaches. Methods: 40 patients with a right large adrenal mass >5 cm underwent right adrenalectomy: 20 patients underwent the AT procedure and 20 patients the LT procedure. Preoperative characteristics were similar for both groups: mean tumor size for the AT and LT groups was 6.52 cm (range 5.2–8.5) and 6.59 cm (range 5.4–8.1), respectively. Mean patient’s age was 53 years (23–75 in the AT group and 20–77 in the LT group). AT and LT approaches were compared in terms of operative time, intraoperative blood loss, time to first oral intake and postoperative convalescence. Results: No difference was found between two groups in terms of estimated blood (100 ml for the AT group and 105.3 ml for the LT group), time to first oral intake (2.0 days for both groups) and convalescence (3.5 and 3 days, respectively). The mean operative times of the AT and LT procedures were 75.25 and 84.75 min, respectively: this difference was statistically significant at the Student’s t test (p = 0.0423). Conclusions: Both approaches proved to be safe and minimally invasive. We believe that the shorter operative time of AT procedures was related to the better visibility of familiar anatomic landmarks, easier access to the vessels and a larger operative field. For these reasons, we prefer the AT approach in the management of large adrenal masses.

Background Gemcitabine is an acceptable alternative to best supportive care in the treatment of advanced biliary tract cancers. The human equilibrative nucleoside transporter 1 (hENT1) is a ubiquitous protein and is the major means by which gemcitabine enters human cells. Moreover, recent reports indicate a significant correlation between immunohistochemical variations of hENT1 in tumor samples and survival after gemcitabine therapy in patients with solid tumors. Materials and methods We used immunohistochemistry to assess the abundance and distribution of hENT1 in tumor samples from radically resected cancer of the ampulla, and sought correlations between immunohistochemical results and clinical parameters including disease outcomes. Results In the 41 individual tumors studied, 12 (29.3%) had uniformly high hENT1 immunostaining. Statistical analysis showed a significant correlation between hENT1 and Ki-67 (P = 0.04). No statistical significant differences were found between immunohistochemical findings and patient characteristics (sex, age, and tumor–node–metastasis). On univariate analysis, hENT1 and Ki-67 expression were associated with overall survival (OS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.022) and those with high Ki-67 staining showed a shorter survival (P = 0.05). Conclusions hENT1 expression is a molecular prognostic marker for patients with resected ampullary cancer and holds promise as a predictive factor to assist in chemotherapy decisions.

Background To compare tumor necrosis in hepatoma induced in rats by a single percutaneous injection of ethanol (PEI) or acetic acid (PAI). Methods BW7756 hepatomas of 1 mm3 were implanted in the liver of 40 male healthy rats. After 14 days, the 36 surviving rats were treated, in a single session, by ultrasound-guided injection of 300 μl of 95% ethanol (n = 17) or 100 μl of 50% acetic acid (n = 19). They were sacrificed 14 days after treatment and explanted tumoral livers were examined. The same PAI procedure was repeated on 13 additional rats to exclude a suspected occurrence of technical failures during the experiment, due to a surprisingly high rate of deaths within 30 minutes after PAI. Results Four rats died within four days after tumor implantation; after PEI, 1/17 (6%) died, whereas after PAI 9/19 (47%) died. The remaining 26 rats, after 14 days post-percutaneous ablation, were sacrificed. Gross and microscopic examinations showed that the hepatoma's nodules treated with PEI had 45.3 ± 19.4% tumor necrosis compared to 49 ± 23.3% (P = NS) for those treated with PAI. Complete tumor necrosis was not found in any animal. Peritoneal invasion was present in 4/16 (25%) and 2/10 (20%) rats treated with PEI or PAI, respectively (P = NS). Autopsy was performed in the 5 additional rats that died within 30 minutes after PAI. Conclusion Our results show that there is no significant difference in the percentage of tumor necrosis between two local ablation methods in spite of the different dosages used. However, mortality in the PAI-treated group was greater than in PEI-treated group, presumably due to greater acetic acid systemic diffusion and its metabolic side effects. In human subjects, HCC occurs in the setting of cirrhosis, where the non-tumoral tissue is firmer than the tumor structure, with consequent reduction of drug diffusion. This could be the reason why some human studies have concluded similar or even better safety and efficacy with PAI compared to PEI.