Andrea Pisani Ceretti

Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells

Summary Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or non-small-cell lung cancers were compared to transcriptomes of the same subsets from normal tissues and validated at the single-cell level. We found that tumor-infiltrating Treg cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2 (IL1R2), programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine, which were not previously described on Treg cells. Remarkably, high expression in whole-tumor samples of Treg cell signature genes, such as LAYN, MAGEH1, or CCR8, correlated with poor prognosis. Our findings provide insights into the molecular identity and functions of human tumor-infiltrating Treg cells and define potential targets for tumor immunotherapy.

Gastrointestinal stromal tumors: a "benign" tumor with hepatic metastasis after 11 years.

Gastrointestinal stromal tumors (GIST) constitue the largest category of primary non-epithelial neoplasms of the stomach and small bowel. They are characterized by a remarkable cellular variability and their malignant potential is sometimes difficult to predict. Very recent studies, using mitotic count and tumor size as the best determinants of biological behavior, divide GISTs into three groups: benign, borderline and malignant tumors. We report on a male patient who underwent a right hepatectomy for a large metastasis 11 years after the surgical treatment of an antral-pyloric gastric neoplasm, histologically defined as leiomyoblastoma and with clinical, morphological and immunohistochemical features of benignity (low mitotic count, tumor size < 5 cm, low cellular proliferation index). Histological and immunohistochemical analysis of the hepatic metastasis showed the cellular proliferation index (Ki-67) to be positive in 25% of neoplastic cells, as opposed to the primary gastric tumor in which Ki-67 was positive in only 5% of neoplastic cells. In conclusion, although modern immunohistochemical techniques are now available to obtain useful prognostic information, the malignant potential of GISTs is sometimes difficult to predict: neoplasms clinically and histologically defined as benign could metastasize a long time after oncologically correct surgical treatment. Therefore, benign GISTs also require consistent, long-term follow-up.

Is there still a role for laparoscopy combined with laparoscopic ultrasonography in the staging of pancreatic cancer

PurposeThis study was designed to compare our laparoscopic ultrasonography (LUS) experience in the resectability evaluation of pancreatic or periampullary cancers (PAC) in two different periods: before and after the introduction of multidetector CT (MDCT).MethodsWe prospectively enrolled 104 CT-resectable patients with PAC. During Step 1 (1995–1999), we performed LUS on all patients, whereas during Step 2 (2002–2007), LUS was performed selectively according to Pisters’ criteria.ResultsLUS was satisfactorily performed in all cases. At Step 1 accuracy of LUS in predicting pancreatic resectability was high (96%) but it was markedly lower in a subgroup of patients with close contact between tumor and portal vein (sensibility of 57%). At Step 2, selective LUS was performed on 9 of 64 patients (14%). LUS confirmed the MDCT finding of unresectability in 8 of 9 cases, and allowed curative resection in 1 case. Only 1 of 55 of the patients who did not undergo LUS would have benefited from the procedure. The yield of LUS decreased from 45% before to 1.8% after MDCT.ConclusionsIn resectable-MDCT patients, routine LUS is unjustified. However, in doubtful MDCT cases, LUS has yet a good yield. In the event of close vascular contact, neither MDCT nor LUS seem to be conclusive, and laparotomy is still the only solution.

Liver transplantation for spontaneous intrapartum rupture of a hepatic adenoma

BACKGROUND: Hepatocellular adenomas can rupture during pregnancy with high fetal and maternal associated mortality. CASE: A primipara underwent an emergency cesarean delivery at 37 weeks of gestation for abruptio placentae. A few hours later she developed hemorrhagic shock, and laparotomy revealed the rupture of the right lobe of the liver. Bleeding was controlled with perihepatic gauze packing and she was transferred to a transplant center for emergency orthotopic liver transplantation. Histologic examination revealed the presence of an intrahepatic hematoma caused by the rupture of a 12-cm hepatocellular adenoma. At 48 months after transplantation she and her infant were both in good condition. CONCLUSION: Emergency orthotopic liver transplantations performed for acute rupture of an hepatocellular adenoma represents a valid therapy provided that bleeding can be controlled long enough to locate a suitable donor.

Vascular Map Combined with CT Colonography for Evaluating Candidates for Laparoscopic Colorectal Surgery

Contrast-enhanced computed tomography colonography (CE-CTC) is a useful guide for the laparoscopic surgeon to avoid incorrectly removing the colonic segment and the failure to diagnose of synchronous colonic and extra-colonic lesions. Lymph node dissection and vessel ligation under a laparoscopic approach can be time-consuming and can damage vessels and organs. Moreover, mesenteric vessels have extreme variations in terms of their courses and numbers. We describe the benefit of using an abdominal vascular map created by CE-CTC in laparoscopic colorectal surgery candidates. We describe patients with different diseases (colorectal cancer, diverticular disease, and inflammatory bowel disease) who underwent CE-CTC just prior to laparoscopic surgery.

Technical quality of CT colonography in relation with diverticular disease

OBJECTIVE The aim of the study is to explore how the technical quality of the examination was affected by diverticular disease. MATERIALS AND METHODS We retrospectively evaluated a consecutive series of 78 subjects who underwent CTC for screening (n=58) or staging (n=20) colorectal cancer, 38 of them (49%) after an incomplete optical colonoscopy. Patients were administered a mild laxative and a iodinated contrast material for fecal tagging. We scored both the bowel preparation and the overall colon distension as poor, good, or optimal and measured the mean sigmoid colon diameter. We counted the number of diverticula and classified patients as having or not a severe diverticular disease (SDD). The number of the prompts of computer aided diagnosis (CAD) per patient was also considered. Mann-Whitney U and χ(2) tests were performed. RESULTS No CTC complications occurred. The bowel cleansing was poor in 8 (10%) patients, good in 29 (37%) and optimal in 41 (53%); colon distension was poor in 7 (9%) patients, good in 38 (49%), and optimal in 33 (42%). Fifty-four (69%) showed diverticula and 30 (38%) had an SDD. Bowel cleansing and distension were not significantly impaired by neither diverticula (p>0.590) nor the SDD (p>0.110). Mean sigmoid colon diameter was reduced in presence of diverticula (28 mm versus 23 mm, p=0.009) or SDD (26 mm versus 22 mm, p=0.016). The mean number of CAD prompts per patient was not significantly increased by the presence of SDD (p=0.829). CONCLUSIONS Bowel cleansing and distension at CTC were not influenced by the presence of diverticular disease.

Contrast-Enhanced Computed Tomography Colonography in Preoperative Distinction between T1-T2 and T3-T4 Staging of Colon Cancer

RATIONALE AND OBJECTIVES To predict the T stage of nonrectal colon cancer using contrast-enhanced computed tomography colonography. MATERIALS AND METHODS Sixty-one patients with 67 nonrectal colon cancers consecutively underwent contrast-enhanced computed tomography colonography after an incomplete colonoscopy. Two readers evaluated wall deformity and perilesional fat abnormality on three-dimensional double contrast enema-like views and multiplanar reconstructions. Pathology was used as the standard of reference. McNemar, Fisher, and Cohen κ statistics were used. RESULTS At pathologic examination, we found the following stages: T1 (n = 5), T2 (n = 10), T3 (n = 41), T4a (n = 6), and T4b (n = 5). Intraobserver and interobserver reproducibilities were almost perfect for wall deformity (κ = 1.00 and κ = 0.88, respectively), substantial for perilesional fat abnormality (κ = 0.79 and κ = 0.74, respectively). Using the results of the more experienced reader, accuracy of wall deformity ≥50% (apple-core) alone for T ≥ 3 was 62 of 67 (0.93, 95% confidence interval [CI] 0.83-0.97) and that of perilesional fat abnormality alone was 37 of 67 (0.55, 95% CI 0.43-0.67) (P < .001). Predictive value for ≥ T3 of the association wall deformity ≥50% with perilesional fat abnormality was 22 of 22 (1.00, 95% CI 0.85-1.00), higher, but not significantly, than that of wall deformity ≥50% with normal perilesional fat 29 of 33 (0.88, 95% CI 0.72-0.97) (P = .148, Fisher exact test). CONCLUSIONS The presence of apple-core wall deformity, regardless of perilesional fat abnormality, is highly predictive of stage T3 or higher.

The Great Pretender: Rectal Syphilis Mimic a Cancer

Rectal syphilis is a rare expression of the widely recognised sexual transmitted disease, also known as the great imitator for its peculiarity of being confused with mild anorectal diseases because of its vague symptoms or believed rectal malignancy, with the concrete risk of overtreatment. We present the case of a male patient with primary rectal syphilis, firstly diagnosed as rectal cancer; the medical, radiological, and endoscopic features are discussed below.

Laparoscopic Splenectomy for Splenic Hamartoma: A Case Report

Hamartoma is a rare splenic benign tumor usually accidentally detected as a radiologic finding. Preoperative diagnosis poses a challenge and thus surgery becomes necessary to confirm the clinical suspicion. Laparoscopic splenectomy has gained consensus as a standard surgical procedure particularly for autoimmune hematological diseases. This former experience has allowed this technique to be extended to other splenic pathologies. Here we report a case of total laparoscopic splenectomy for a bulky splenic hamartoma in a young male patient.

Risk Factors for Prolonged Postoperative Ileus In Adult Patients Undergoing Elective Colorectal Surgery: An Observational Cohort Study

PURPOSE Prolonged Postoperative Ileus (PPOI) after abdominal surgery may affect unfavourably the patient recovery. The aim of this study was to estimate the incidence of PPOI in patients elective for colorectal resection and investigate perioperative variables associated with PPOI. METHODS A consecutive series of 428 patients undergoing colorectal resection (median age 72, range 24-92, years; men/women ratio 1.14) were analyzed. Data were extracted retrospectively throughout a five-year period from an electronic prospectively maintained database. PPOI was defined as the need for postoperative insertion of a nasogastric tube in a patient experiencing nausea and two episodes of vomiting and further showing absence of adequate bowel function (absence of flatus/stool) with lack of bowel sounds and abdominal distension. RESULTS Incidence of PPOI was 7% [95% confidence interval (95%CI), 4.8-9.9%]. Mean hospital stay was 8 days longer in patients with PPOI. Male gender, cancer, cardiac and respiratory co-morbidity, rectal resection, open/converted access, duration of operation, stoma formation and body mass index were associated with PPOI at univariate analysis (0.001< P< 0.048). PPOI was independently associated with male gender [adjusted odds ratio (OR), 4.2; 95%CI, 1.5-11.5], stoma formation (OR, 2.8; 95%CI, 1.2-6.8) and obesity (OR of obese vs. normal weight patients, 3.8, 95%CI, 1.2-12.0). CONCLUSION After colorectal resection, PPOI leads to a prolonged hospital stay and slower patients recovery. An international standardized definition of PPOI is strongly needed to make comparable results from researches and to reliably identify patients with increased risk, also to improve the therapeutic preventive policies in these patients.