Instantaneous response to surgically induced hypoxia of hepatocellular carcinoma.
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Carcinoma, Hepatocellular↗
Biomedical subjects
Leandro Gennari
Publications and source records attributed to Leandro Gennari.
Lymphadenectomy in gastric cancer: prognostic role and therapeutic implications.
AIMS: Surgeons involved in the treatment of gastric cancer are interested in the extent of lymphadenectomy as the latter may not only influence the reliability of the tumour, node and metastasis classification but also be relevant for the long-term oncological outcome. The purpose of the study was to evaluate the prognostic role of the number of resected lymph nodes (as an indicator of the scope of lymphadenectomy) and of the number of metastatic lymph nodes on the long-term mortality for all causes and to provide clinicians with estimates of predictive survival probabilities. METHODS: The study involved 615 cancer patients subjected to a curative (R0) subtotal or total gastrectomy in a randomized Italian trial. According to the trial protocol, a D2 lymphadenectomy had been advised. The number of resected and metastatic lymph nodes was analysed as a continuous variable in multiple Cox models. RESULTS: There was no difference in operative mortality (about 1.8%) according to the number of lymph nodes in the specimen (< or =15, 16-25, >25). The risk of long-term death for all causes tended to decrease with increasing number of resected lymph nodes up to about 25, and then could be considered stable for wider lymphadenectomies. An increasing risk of death for all causes was associated with an increasing number of metastatic lymph nodes; the risk could be considered stable for more than 20 metastatic lymph nodes. CONCLUSIONS: A lymphadenectomy including more than 25 lymph nodes is suggested, provided that there is a low risk of operative mortality.
Aged↗
Methylation framework of cell cycle gene inhibitors in cirrhosis and associated hepatocellular carcinoma.
One of the main regulatory pathways reported to be altered in hepatocellular carcinoma (HCC) is that of cell cycle control involving RB1 gene-related cell inhibitors. We investigated p14(ARF), p15(INK4B), p16(INK4A), p18(INK4C), and RB1 genes in a series of HCCs and associated cirrhosis with the goal of ascertaining their pattern of inactivation by gene methylation. Thirty-three HCCs, adjacent nonneoplastic cirrhotic tissues, and 6 HCC cell lines were studied. Cirrhoses (25 of 33, 76%), HCCs (31 of 33, 94%), and 3 of 6 (50%) cell lines showed 1 or more methylated genes. Cirrhoses (17 of 33, 51%) had more frequently than HCCs (11 of 33, 33%, P =.01) only 1 methylated gene. With the exception of p18(INK4C) the genes under study showed promoter methylation with frequency ranging from 82% (p16(INK4A) in HCC) to 33% and 39% (p15(INK4B) and p16(INK4A) in cirrhoses). In cases with only 1 methylated gene, p15(INK4B) in cirrhosis (8 of 17, 47%) and p16(INK4A) in HCC (10 of 11, 91%) were the more frequently altered. An optimal correlation was found between p15 and p16 gene methylation and complete protein loss in HCC detected by immunocytochemistry, whereas a partial loss of the same proteins was a feature of methylated cirrhoses. Inactivation by DNA methylation of several genes of the RB1 pathway is common to cirrhosis and HCC. An early pattern of methylatory events (1 methylated gene) is a feature of cirrhosis rather than HCC, whereas an advanced one (> or = 3 methylated genes) is characteristic of malignancy. Early methylation changes seem to involve p15(INK4B) and p16(INK4A) in cirrhosis and p16(INK4A) in HCC. In conclusion, a stepwise progression of methylating events is a feature of the sequence cirrhosis-HCC and contributes to the process of hepatic carcinogenesis with potential clinical implications.
Aged↗
Concurrent Pheochromocytoma, Paraganglioma, Papillary Thyroid Carcinoma, and Desmoid Tumor: A Case Report with Analyses at the Molecular Level.
Reports on the association of papillary thyroid carcinoma with paraganglionic or desmoid tumors have appeared infrequently. The former setting usually affects middle-aged females; the latter is typical of familial adenomatous polyposis. We report the case of a 69-yr-old man in whom two abdominal masses had been instrumentally detected following an access of abdominal pain. Save for a moderate hypertension, he was asymptomatic and an impalpable thyroid nodule was detected by ultrasonography. A high urinary noradrenaline output and cytology of the masses raised the suspicion of pheochromocytoma. At laparotomy, an adrenal pheochromocytoma and a paracaval paraganglioma were excised. Subsequently, hemithyroidectomy was performed, and histopathology revealed papillary microcarcinoma. A nodule of desmoid tumor was also removed from the abdominal wall. An analysis of RET, APC, and TP53 gene mutations, and of RET and NTRK1 gene rearrangements, yielded negative results. No in vitro transforming activity was detected in the tumor DNA when assayed in transfection experiments. The lack of a consistent family history also made unlikely the possibility of identifying the putative germline defect by linkage analyses. Should this unusual aggregation of tumors represent a new entity, a number of genetic alterations have now been excluded.
Journal Article↗
Gastric cancer: extent of lymph node dissection and requirements for a correct staging.
AIMS AND BACKGROUND: Lymphatic spread is an important prognostic factor in gastric cancer. The TNM classification requires at least 15 lymph nodes to stage and identify three prognostic groups according to the number of metastatic lymph nodes: N1 (1-6), N2 (7-15), N3 (> 15). The aim of this study was to investigate which type of lymph node dissection allows an accurate staging. METHODS: From 1996 to 2001, we treated 140 gastric cancer patients, 27 with D1 and 113 with D2 dissection. We evaluated lymph node count, status and ratio between metastatic and total number of excised lymph nodes, keeping 20% as the cutoff value. RESULTS: The mean number of lymph nodes was 18 and 33 respectively for D1 and D2 (P < 0.001), 41% of patients in D1 and 5% in D2 had less than 15 lymph nodes (P < 0.001). 59% in D1 and 73% in D2 (P = 0.145) had lymph node metastases, but this incidence decreased to 36% (P = 0.045) and 16% (P < 0.001) respectively for D1 and D2 when less than 15 lymph nodes were available. Considering the ratio between metastatic and total number of lymph nodes, 45% of D1 versus 3% of D2 (P < 0.001) in the N1 group exceeded 20%. CONCLUSIONS: D2 lymph node dissection is better than D1 in providing at least 15 lymph nodes required for a correct staging. We confirm the risk of a downstage when less than 15 lymph nodes are available.
Adult↗
[Integrated treatments of rectal carcinoma (review)].
We have reviewed the international literature regarding the treatment of rectal carcinoma. Over the last decades the evolution of treatment methods has led to a drastic fall in the incidence of local recurrences which has gone from a wide range (15-40%) to a much lower figure (10%). This favourable result has been reached also due to improvement in surgical techniques (total mesorectal excision) and to the use of an association of preoperative radio and chemotherapy. However, the drugs and dosage of these as well as of the RT still have to be defined. In our experience the integrated treatment has brought a downstaging of the T in 60% of cases and of the N in 15%.
Combined Modality Therapy↗
[Does the Roux-en-Y-stasis syndrome still exist?].
Roux-en-Y-stasis syndrome (RYS) is a complication of subtotal gastrectomy characterized by delayed gastric emptying and vomiting. The aim of the study was to analyze RYS frequency with particular attention to diagnosis and therapy. From November 1996 to June 2004, we performed 147 distal gastrectomies with 5 cases of RYS: mean age 78 years, 3 male, 2 female, 4 adenocarcinoma and 1 GIST. Among the 5 cases, RYS was due to different causes: it was functional in 2 cases (with difficult gastric emptying due to a long gastric remnant in one patient, while the other was associated with duodenal fistula) and healed through medical therapy in both; a third patient had an edematous stenosis of the gastrojejunal anastomosis treated with medical therapy and the remaining 2 patients had jejunal obstruction due to adherences and required reoperations. RYS is a rare complication of subtotal gastrectomy determined by different causes. Recognizing the cause is very important for choice of appropriate therapy.
Adenocarcinoma↗
[Results of integrative therapy in rectal neoplasm].
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Humans↗
[The lymph node dissection in thyroid carcinoma].
Rule and indications of lymph node dissection (LD) in thyroid carcinoma is still under debate because of the biological variety of different histological types and the difficulty to have an accurate preoperative diagnosis of metastatic lymph nodes; moreover prognostic factors of metastatic lymph nodes are still unclear. The AA. have separately analyzed different thyroid carcinomas and different clinical situations requiring thyroid LD. Metastatic lymph nodes from differentiated carcinomas, including papillary and follicular type, range from 12 to 90% and apparently do not worsen the prognosis. Level II-VI LD is indicated in presence of metastatic lymph nodes or macroscopic nodal recurrence after a previous LD. No prognostic advantages have been demonstrated when LD is performed without clinical or instrumental evidence of metastatic disease, including suspected recurrence characterised only by plasma Thyreoglobulin increased values. Lymph node metastases from medullary carcinoma range from 25 to 63%. Level II-VI LD is indicated if node metastases are present, whereas prophylactic LD, confined to level VI, is always recommended. Controversies still remain about: 1) LD extension whether it is prophylactic (level VI vs. II- VI) or in case of nodal involvement (levels II- VI monolateral or bilateral), 2) LD indications in case of an increased plasma Calcitonin levels during the follow-up after total thyroidectomy, without clinical or instrumental evidence of nodes involvement. Anaplastic carcinoma represents 5% of all thyroid carcinomas; it is the most aggressive type with an early tendency to invade surrounding organs and to give metastases; prognosis is very poor. LD is indicated only for a palliation in cases with compression syndromes.
Carcinoma↗