Diagnosis and staging of small intestinal neuroendocrine tumors with CT enterography and PET with Gallium-68: preoperative risk stratification protocol.

PURPOSE: Pre-operative diagnosis and staging of small intestine neuroendocrine tumors (SI-NETs) remain sub-optimal, with open palpation during surgery still considered the gold standard. This limits a standardized implementation of minimally invasive surgery (MIS). The aim of this single-center retrospective study was to assess a tailored diagnostic work-up to identify candidates at low risk of undetected disease who may benefit from MIS. METHODS: Patients diagnosed with SI-NETs between 2013 and 2022 who underwent contrast-enhanced computed tomography enterography (CTE) and Ga68-DOTATOC-positron emission tomography-CT (68 Ga DOTATATE PET/CT) preoperatively and subsequently underwent open surgical resection were included. Imaging studies were reassessed by two radiologists. Combined use of CTE and 68 Ga DOTATATE PET/CT in determining primary lesion disease burden (number of lesions) and LN disease stage (distal and proximal relative to superior mesenteric vessels) was assessed, using surgical reports and pathology as gold standard. RESULTS: Overall, 56 patients were included. Sensitivity of CTE and 68 Ga DOTATATE PET/CT for at least one primary SI-NET was 100% and 94%, respectively. In the presence of concordance between studies, combined use of CTE and 68 Ga DOTATATE PET/CT for detection of single primary tumors improved specificity to 89% (n = 25/28) with a positive predictive value of 87.5% (n = 21/24). Distal LN disease was identified in 89.2% of cases (n = 33/37). The association of single lesion and distal LN disease was found pre-operatively in 32% of patients (n = 18). CONCLUSION: Combined use of CTE and 68 Ga DOTATATE PET/CT enables identifying low-risk surgical candidates (single SI-NET lesions with distal LN disease).

Cost effectiveness of different central venous approaches for port placement and use in adult oncology patients: evidence from a randomized three-arm trial.

BACKGROUND: No randomized trials have so far investigated the cost effectiveness of different methods for implantation and use of central venous ports in oncology patients. PATIENTS AND METHODS: Overall, 403 patients eligible for receiving intravenous chemotherapy for solid tumours were randomly assigned to implantation of a single type of port, either through a percutaneous landmark access to the internal jugular vein, an ultrasound (US)-guided access to the subclavian vein, or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Insertion and maintenance costs were estimated by obtaining the charges for an average implant and use, while the costs of the management of complications were analytically assessed. The total cost was defined as the purchase cost plus the insertion cost plus the maintenance cost plus the cost of treatment of the complications, if any. RESULTS: A total of 401 patients were evaluable-132 with the internal jugular vein, 136 with the subclavian vein and 133 with the cephalic vein access. No differences were found for the rate of early complications. The US-guided subclavian insertion site had significantly lower failures. Infections occurred in 1, 3, and 3 patients (internal jugular, subclavian, and cephalic access, respectively; p = 0.464), whereas venous thrombosis was observed in 15, 8, and 11 patients, respectively (p = 0.272). Mean cost for purchase, implantation, diagnosis and treatment of complications in each patient was 2,167.85 for subclavian US-guided, 2,335.87 for cephalic, and 2,384.10 for internal jugular access, respectively (p = 0.0001). CONCLUSION: US real-time guidance to the subclavian vein resulted in the most cost-effective method of central venous port placement and use.

Totally implantable vascular access devices 30 years after the first procedure. What has changed and what is still unsolved?

The first placement of a totally implantable central venous access device (TIVAD) was performed in 1982 at the MD Anderson Cancer Center in Houston by John Niederhuber, using the cephalic vein­exposed by surgical cut-down­as route of access to central veins. After that, TIVADs proved to be safe and effective for repeated administration of drugs, blood, nutrients,and blood drawing for testing in many clinical settings, especially in the oncologic applications. They allow for administration of hyperosmolar solutions, extreme pH drugs, and vescicant chemotherapeutic agents,thus improving venous access reliability and overall patients' quality of life. Despite the availability of a variety of devices, each showing different features and performances, many issues are still unsolved. The aim of this review article is to point out what has changed since the first implant of a TIVAD, and what it is still matter of debate, thus needing more investigation. Topics analyzed here include materials, choice of the veins and techniques of implantation, role of ultrasound (US) guidance in central venous access, position of catheter tip assessment, TIVAD-related infection and thrombosis, and quality of life issues.

Complementary molecular approaches reveal heterogeneous CDH1 germline defects in Italian patients with hereditary diffuse gastric cancer (HDGC) syndrome.

Germline inactivation of the E-cadherin gene (CDH1) is associated with hereditary diffuse gastric cancer (HDGC), a rare autosomal dominant syndrome predisposing to both diffuse gastric cancer (DGC) and lobular breast cancer (LBC). We searched for CDH1 germline defects in 32 HDGC Italian probands selected according to international consensus criteria and in 5 selected relatives. We used a series of molecular methods, including: DNA sequencing, multiplex ligation-dependent probe amplification, single-nucleotide primer extension, bisulfite sequencing, reverse-transcription PCR, and bioinformatics tools. We identified pathogenic mutations in 6 out of 32 probands (19%): one truncating and two missense mutations, one large deletion, one allelic expression imbalance and one splicing defect. Three out of six CDH1 constitutive alterations were novel. Our data support the need for a multimethod approach for CDH1 genetic testing, demonstrating that both DNA and RNA analyses are required to increase the detection rate of pathogenic mutations, thus reducing the number of patients without a clear molecular diagnosis. On the whole, our results indicate that not only DGC patients, but also subjects with personal or family history of LBC might benefit from CDH1 genetic testing. Moreover, our findings support the notion that prophylactic gastrectomy should be offered to asymptomatic CDH1 mutation carriers; indeed, while endoscopic analysis with histological examination of random gastric biopsies can miss cancer foci, gastrectomy performed in these subjects always revealed foci of cancer cells.

Factors predicting worse prognosis in patients affected by pT3 N0 colon cancer: long-term results of a monocentric series of 137 radically resected patients in a 5-year period.

BACKGROUND AND PURPOSE: For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial. The purpose of this study was to identify clinical and/or pathological findings related to a worse prognosis in this category of patients. PATIENTS AND METHODS: We retrospectively analyzed the data of consecutive patients, extracted by an institutional Tumour Registry, admitted to an affiliated University Hospital in Milan (European Institute of Oncology) for adenocarcinoma of the colon (all sites), between 2000 and 2005, and having a final pT3 N0 pathology staging after curative surgery. Adjuvant chemotherapy was decided as a result of a medical decision within a multidisciplinary Tumor Board. RESULTS: Data of 137 patients were obtained, with a median follow-up of 77 months (range 6-131). Patients who received chemotherapy were younger than patients who did not. Nine patients out of 137 (6.5 %) died as a consequence of colon cancer recurrence; four of them had received adjuvant chemotherapy. Only histological grade III and mucinous histotype were found to impact on cumulative incidence of colon-related events (p 0.03 and 0.02, respectively); no impact was found on cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.74 and 0.74, respectively). Number of analyzed LNs (lymph nodes) emerged as a factor possibly affecting the cumulative incidence of colon-related events (p 0.09) as well as the cumulative incidence of colonic neoplasm recurrence-related deaths (p 0.10). The risk of events was inversely proportional to the number of dissected LNs, even over 20 up to about 25 LNs. Never-smokers exhibited a lower incidence of colon-related events, although the difference was not statistically significant (p 0.09). All other analyzed variables did not show any impact on survival rate, including age, gender, ASA score, BMI, site of colonic neoplasm, multifocality, perivascular invasion, and use of adjuvant chemotherapy. CONCLUSIONS: Histology grading G3 and mucinous histotype were predictors of worse outcome. Efforts to improve LN evaluation should result in clinically significant improvements in outcome, and also the quality of care for patients with radically resected stage II colon cancer.

Operative blood loss and use of blood products after full robotic and conventional low anterior resection with total mesorectal excision for treatment of rectal cancer.

To date, no studies have investigated the estimated blood loss (EBL) after full robotic low anterior resection (R-LAR) in a case-matched model, comparing it with the conventional open approach (O-LAR). Forty-nine patients in the R-LAR and 105 in the O-LAR group were matched for age, gender, BMI (body mass index), ASA (American Society of Anesthesiology) class, tumor-node-metastasis (TNM) classification and UICC (Union for International Cancer Control) stage, distance of the lower edge of the tumor from the anal verge, presence of comorbidities, and preoperative hemoglobin (Hb). EBL was significantly higher in the O-LAR group (P < 0.001); twelve units of packed red blood cells were globally transfused in the O-LAR group, compared to one unit only in the R-LAR (P = 0.051). A significantly higher postoperative Hb drop (3.0 vs. 2.4 g/dL, P = 0.015) was registered in the O-LAR patients. The length of hospital stay was much lower for the R-LAR group (8.4 vs. 12.4 days, P < 0.001). The number of harvested lymph nodes (17.4 vs. 13.5, P = 0.006) and extent of distal margin (2.9 vs. 1.9 cm, P < 0.001) were significantly higher in the R-LAR group. Open surgery was confirmed as the sole variable significantly associated (P < 0.001) with blood loss (odds ratio = 4.41, 95% CI 2.06-9.43). It was a confirmed prognosticator of blood loss (P = 0.006) when a preoperative clinical predictive model was built, using multivariate analysis (odds ratio = 3.95, 95% CI 1.47-10.6). In conclusion, R-LAR produced less operative blood loss and less drop in postoperative hemoglobin when compared to O-LAR. Other clinically relevant outcomes were similar or superior to O-LAR.

Surgical and pathological outcomes after right hemicolectomy: case-matched study comparing robotic and open surgery.

OBJECTIVE: To compare the surgical and pathological outcomes of patients with right-sided colon cancers operated on by means of open and robotic surgery with extracorporeal anastomosis. METHODS: Thirty-three consecutive patients who underwent robotic right hemicolectomy due to right-sided colon cancer were retrospectively well matched with 102 patients operated on by the open approach. Data were included in a prospectively maintained database. RESULTS: Mean operative time was longer in the robotic group (P < 0.001), 191.7 min (134-250) versus 136.2 (45-240) min in the open group. Estimated intraoperative blood loss was less in the robotic group, which presented a mean of 6.1 ml versus 94.8 ml in the open group (P < 0.001). Despite the similar length of the surgical specimen and number of lymph nodes retrieved between both groups, 15 or more lymph nodes were found in the specimen in 90 out of 102 patients (88.2%) operated on by the open technique versus 33 out of 33 patients (100%) who underwent robotic hemicolectomy (P = 0.038). The median length of postoperative hospital stay was shorter in the robotic group, 5 versus 8 days (P < 0.001). No other statistically significant difference was observed in terms of pathological and postoperative results. CONCLUSIONS: Robotic right hemicolectomy is an oncologically safe and effective procedure. The number of lymph nodes retrieved in the robotic group compared with the open group of our series was more homogeneous, and none of the patients operated on with this technique had a suboptimal lymphadenectomy. Further clinical trials are needed to confirm current evidence and determine whether this can influence the prognosis.

Excisão total do mesorreto por técnica robótica: resultados cirúrgicos e oncológicos iniciais / Robotic total mesorectal excision: early surgical and oncological outcomes

OBJETIVOS: avaliar os resultados cirúrgicos e oncológicos imediatos em pacientes com câncer de reto extraperitoneal submetidos à excisão total do mesorreto (ETM) robótica. MÉTODOS: de janeiro de 2007 a março de 2010 um total de 60 pacientes foram operados de forma consecutiva por técnica robótica. Os dados cirúrgicos e os desfechos oncológicos iniciais foram prospectivamente registrados em um banco de dados. RESULTADOS: foram operados 35 homens e 25 mulheres. A idade média foi de 60,3 ± 11,7 anos. Cirurgia com preservação esfincteriana foi possível em 52 pacientes. A média da amostra linfonodal foi de 18,7 ± 8,8 linfonodos. A média da margem cirúrgica distal foi de 2,9 ± 1,7 cm, enquanto a margem radial foi negativa em todos os pacientes. O tempo de seguimento pós-operatório foi de 14,3 meses. Apenas uma recidiva pélvica foi observada. As taxas de sobrevida geral e sobrevida câncer-específica foram respectivamente de 97,6 por cento e 98,3 por cento. CONCLUSÕES: ETM robótica é uma cirurgia exequível e segura. Apresenta resultados iguais ou mesmo melhores que as técnicas aberta e laparoscópica em termos de morbimortalidade, taxa de preservação esfincteriana e desfechos oncológicos iniciais.

OBJECTIVES: to evaluate the surgical and oncological outcomes of patients with extraperitoneal rectal cancer who underwent robotic total mesorectal excision (TEM). METHODS: from January 2007 to March 2010 a total of 60 patients were consecutively operated on through robotic technique. Data regarding surgical data and oncological outcomes were prospectively registered in a database. RESULTS: 35 men and 25 women underwent surgery. The mean age was 60.3 ± 11.7 years. Sphincter preserving surgery was possible in 52 patients. The mean number lymph node harvested was 18.7 ± 8.8 lymph nodes. The mean distal surgical margin was 2.9 ± 1.7 cm, while the radial margin was negative in all patients. The duration of postoperative follow-up was 14.3 months. Only one local recurrence was observed. The overall and the cancer-specific survival were respectively 97.6 percent and 98.3 percent. CONCLUSIONS: robotic TEM is feasible and safe. It is equal or superior to open and laparoscopic techniques in terms of morbidity and mortality rates, sphincter preservation rates and early oncological outcomes.

No impact of central venous insertion site on oncology patients' quality of life and psychological distress. A randomized three-arm trial.

PURPOSE: Though totally implantable access ports (TIAP) are extensively used, information from randomized trials about the impact of insertion site on patient's quality of life (QoL) and psychological distress is unavailable. PATIENTS AND METHODS: Four hundred and three patients eligible for receiving intravenous chemotherapy for solid tumours were randomly assigned to implantation of a single type of TIAP, either through a percutaneous landmark access to the internal jugular or an ultrasound-guided access to the subclavian or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Patients' QoL and psychological distress were investigated at regular intervals by means of EORTC QLQ-C30 and HADS (Hospital Anxiety and Depression Scale) questionnaires, using univariate and multivariate repeated measure linear mixed models. A post hoc analysis investigated the impact of type of administered chemotherapy (adjuvant vs palliative). RESULTS: Three hundred and eighty-four patients (95.2%) were evaluable, 126 with the internal jugular, 132 with the subclavian and 126 with the cephalic vein access. The median follow-up was 361 days (range, 0-1,087). Mean score changes for the items of the EORTC QLQ-C30 scales were significantly associated with type of administered chemotherapy only (P < 0.001), and not with implantation site. Frequency distribution of patients with depression and anxiety score greater than 10 at HADS was not significantly different, with respect either to type of administered chemotherapy or TIAP implantation site. CONCLUSION: Central venous insertion sites had no impact on patients' QoL and psychological distress. Patients undergoing palliative therapies showed worse EORTC QLQ-C30 scales.

Full robotic left colon and rectal cancer resection: technique and early outcome.

OBJECTIVE: The technique for robotic resection of the left colon and anterior resection of the rectum with total mesorectal excision is not well defined. In this study we describe a method that standardizes robot and trocar position, and allows for a complete mobilization of the left colon and the rectum, without repositioning of the surgical cart. Outcome and pathology findings are also reported. METHODS: From January 2007 to May 2008 a total of 55 consecutive patients affected by rectal and left colon cancer were operated on, with full robotic technique, using the Da Vinci robot. Data regarding outcome and pathology reports were prospectively collected in a dedicated database. RESULTS: The following procedures were performed 27 left colectomies, 17 anterior resections, 4 intersphincteric resections, 7 abdominoperineal resections. There were 21 female and 34 male patients with a mean age of 63 +/- 9.9 years. Mean operative time was 290 +/- 69 minutes, ranging from 164 to 487 min., none were converted to open surgery. The median number of lymph nodes harvested was 18.5 +/- 8.3 (range 5-45), and circumferential margin was negative in all cases. Distal margin was 25.15 +/- 12.9 mm (range 6-55) for patients with rectal cancer, and 31.6 +/- 20 mm for all the patients in this series. Anastomotic leak rate was 12.7% (7/55); in all cases conservative treatment was successful. CONCLUSIONS: Full robotic colorectal surgery is a safe and effective technique that exploits the advantages of the Da Vinci robot during the whole intervention, without the need to make use of hybrid operations. Outcome and pathology findings are comparable with those observed in open and laparoscopy procedures.

Extended lymph node dissection without routine spleno-pancreatectomy for treatment of gastric cancer: low morbidity and mortality rates in a single center series of 250 patients.

BACKGROUND AND OBJECTIVES: To verify the hypothesis that avoidance of routine splenectomy and distal pancreatectomy in a modified D-2 resection for gastric cancer can significantly lower the complications rate of this procedure in a population of Western patients. METHODS: A series of 250 consecutive Italian patients suffering from localized, histology-proven gastric cancer was submitted to gastrectomy and extended D-2 lymphadenectomy for treatment of their disease during an 8-year period (1994-2002) at the European Institute of Oncology in Milano, Italy. Caudal pancreas and spleen were routinely preserved, unless the tumor was not closely adjacent to or directly invading these organs. Postoperative morbidity, overall mortality, and length of hospital stay were recorded. RESULTS: One hundred forty patients underwent total gastrectomy and 110 a subtotal distal one; splenectomy was performed in 8 cases and spleno-pancreatectomy in 15. The postoperative morbidity rate was 18%, the mortality rate was 1.2% and 9 patients experienced re-operation. The median length of stay was 14.8 days. CONCLUSIONS: These results compete favorably with those reported after standard D-1 gastrectomy in Western patients series. D-2 gastrectomy with spleen and pancreas routine preservation can be considered a safe treatment for gastric cancer in Western patients, at least in experienced centers.

Genetic polymorphisms and modulation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adducts in human lymphocytes.

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is the most abundant heterocyclic amine derived from food, possibly involved in human carcinogenesis. We evaluated the formation of PhIP-DNA adducts in lymphocytes from 76 incident colorectal cancer patients likely to be exposed to dietary PhIP. To address the role of the metabolic polymorphisms relevant to PhIP-DNA adduct formation, the patients were genotyped for common polymorphisms in the N-acetyltransferase (NAT1 and NAT2), sulfotransferase (SULT1A1) and glutathione S-transferase (GSTM1 and GSTA1) genes. PhIP released from adducted DNA after hydrolysis was quantitated by liquid chromatography-tandem mass spectrometry. Overall, adducts were 3.24 +/- 3.58/10(8) nucleotides (mean +/- SD); they were not related to sex, smoking habits or age, though levels were not significantly higher in smokers, young subjects and high meat consumers. High vegetable intake significantly reduced PhIP-DNA adducts (Mann-Whitney U, p = 0.044). Individuals with the GSTM1 null genotype showed colon cancer onset at earlier age (58.8 +/- 1.8 vs. 63.5 +/- 1.6 years; Mann-Whitney U, p = 0.047). None of the genetic polymorphisms studied significantly affected PhIP-DNA adducts. However, individuals carrying 2 mutated GSTA1 alleles and younger than the median age had higher adduct levels than homozygous wild-type and heterozygous ones (Kruskal-Wallis p = 0.0008). In conclusion, these preliminary data indicate that PhIP-DNA adducts are formed in people likely to be exposed to this carcinogen through the diet, suggesting this biomarker may be useful to detect human exposure and DNA damage. Overall, the genetic polymorphisms considered had limited effect on PhIP-DNA levels, but young people with lower detoxification capacity may form a subgroup particularly susceptible to dietary carcinogen.