Improving the TIR3B oncological stratification: try to bridge the gap through a comprehensive presurgical algorithm.

PURPOSE: Indeterminate cytology still puzzles clinicians, due to its wide range of oncological risks. According to the Italian SIAPEC-IAP classification, TIR3B cytology holds up to 30% of thyroid cancer, which justifies the surgical indication, even if more than half of cases do not result in a positive histology. The study aim is to identify potential clinical, ultrasound or cytological features able to improve the surgical indication. METHODS: Retrospective analysis. A consecutive series of TIR3B nodules referred to the Endocrine Unit of Careggi Hospital from 1st May 2014 to 31st December 2021 was considered for the exploratory analysis (Phase 1). Thereafter, a smaller confirmatory sample of consecutive TIR3B diagnosed and referred to surgery from 1st January 2022 to 31st June 2022 was considered to verify the algorithm (Phase 2). The main clinical, ultrasound and cytological features have been collected. A comprehensive stepwise logistic regression was applied to build a prediction algorithm. The histological results represented the final outcome. RESULTS: Of 599 TIR3B nodules referred to surgery, 451 cases were included in the exploratory analysis. A final score > 14.5 corresponded to an OR = 4.98 (95% CI 3.24-7.65, p < 0.0001) and showed a PPV and NPV of 57% and 79%, respectively. The Phase 2 analysis on a confirmatory sample of 58 TIR3B cytology confirmed that a threshold of 14.5 points has a comparable PPV and NPV of 53% and 80%, respectively. CONCLUSIONS: A predictive algorithm which considers the main clinical, US and cytological features can significantly improve the oncological stratification of TIR3B cytology.

Clinical impact of the new SIAPEC-IAP classification on the indeterminate category of thyroid nodules.

BACKGROUND: The increasing frequency in the diagnosis of thyroid nodules has raised a growing interest in the search for new diagnostic tools to better select patients deserving surgery. In 2014, the major Italian Societies involved in the field drafted a new cytological classification, to better stratify pre-surgical risk of thyroid cancer, especially for the indeterminate category, split into TIR3A and TIR3B subclasses, associated to different therapeutic decisions. MATERIALS AND METHODS: This retrospective cross-sectional survey analyzed thyroid fine-needle aspiration biopsy performed at our outpatient clinic before and after the introduction of the new SIAPEC-IAP consensus in May 2014. RESULTS: 8956 thyroid nodules were included in the analysis: 5692 were evaluated according to the old classification and 3264 according to the new one. The new criteria caused the overall prevalence of TIR3 to increase from 6.1 to 20.1%. Of those, 10.7 and 9.4% were included in the TIR3A and TIR3B subgroups, respectively. Each of the 213 TIR3B nodules underwent surgery and 86 (40.4%) were diagnosed as thyroid cancer, while among the 349 TIR3A nodules, only 15 of the 60 that underwent surgery were found to be thyroid cancer. CONCLUSIONS: This analysis shows that the new SIAPEC-IAC criteria significantly increased the proportion of the overall TIR3 diagnosis. The division of TIR3 nodules into two subgroups (A and B) allowed a better evaluation of the oncologic risk and a better selection of patients to be referred to surgery.

hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.

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-Kras(G12D/+),LSL-Trp53(R175H/+) 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.

VEGF-A clinical significance in gastric cancers: immunohistochemical analysis of a wide Italian cohort.

PURPOSE: The clinical significance of VEGF-A expression in gastric cancer (GC) has been reported with contradicting results. We analyzed the expression and clinical significance of VEGF-A in a wide Italian cohort of GC specimens. METHODS: VEGF-A expression was tested by immunohistochemistry in 507 patients with GC of all clinical stages. The impact of VEGF-A on overall survival (OS) was evaluated in conjunction with clinical and pathological parameters. RESULTS: In the Italian cohort we studied VEGF-A was not an independent prognostic factor neither at the univariate nor at multivariate analysis. CONCLUSIONS: Although frequently expressed, in our study VEGF-A was not able to discriminate between groups of patients with different risk.

Gallbladder neoplasm: a single institution experience according to the standard current management.

AIM: The aim of this paper was to determine if an aggressive surgical approach, with an increase in R0 resections, has resulted in improved survival for patients with gallbladder cancer. Gallbladder cancer is a silent disease, despite the efforts, the prognosis remains dismal. Consensus among surgeons regarding the indications for the extent of resection, lymph node dissection, port site resection, bile duct management has not been reached. METHODS: A retrospective review of all patients with gallbladder cancer admitted during 12 years period was conducted. Sixteen patients were identified. Cases were divided into 2 cohorts surgical treated group (STG, N.=10) and non surgical treated group (NSTG, N.=6). RESULTS: In NSTG the disease was metastatic (stage IV): liver (33.3%), peritoneum (50%), liver and peritoneum (16.7%). In STG 13 procedures were performed, 6 liver resection (2 en bloc resection, 2 bisegmentectomy, 2 wedge resection) 7 cholecystectomies. 6 R1, 7 R0 resections. All the liver resections were R0. 0% mortality, 30.7% of morbidity, all the complications were managed conservatively. Length of stay was 10 days for the STG, and 5 days for the NSTG. The median overall survival was 10 months (Std Error 2.381 CI 5.333-14.667), while in the STG 16 months (Std Error 6.275 CI 3.701-28.299) and in the NSTG was 7 months (Std Error 2.381 CI 5.337-14.667) CONCLUSION: Whenever is possible radical resection with free margin (R0) must be achieved, being the only chance to treat efficiently.

Modular branched neurotensin peptides for tumor target tracing and receptor-mediated therapy: a proof-of-concept.

The aim of this study was to demonstrate that oligo-branched peptides can be effective either for spotlighting tumor cells that overexpress peptide receptors, or for killing them, simply by exchanging the functional moiety coupled to the conserved receptor-targeting core. Tetra-branched peptides containing neurotensin (NT) sequence are described here as selective targeting agents for human colon, pancreas and prostate cancer. Fluorophore-conjugated peptides were used to measure tumor versus healthy tissue binding in human surgical samples, resulting in validation of neurotensin receptors as highly promising tumor-biomarkers. Drug-armed branched peptides were synthesized with different conjugation methods, resulting in uncleavable adducts or drug-releasing molecules. Cytotoxicity on human cell lines from colon (HT-29), pancreas (PANC-1) or prostate (PC-3) carcinoma indicated branched NT conjugated with MTX and 5-FdU as the most active agents on PANC-1 (EC(50) 4.4e-007 M) and HT-29 (1.1e-007 M), respectively. Tetra-branched NT armed with 5-FdU was used for in vivo experiments in HT-29-xenografted mice and produced a 50% reduction in tumor growth with respect to animals treated with the free drug. An unrelated branched peptide carrying the same drug was completely ineffective. In vitro and in vivo results indicated that branched peptides are valuable tools for tumor selective targeting.

[Treatment of the pancreatic stump after pancreaticoduodenectomy. Wirsung duct occlusion versus pancreaticojejunostomy]. / Trattamento del moncone pancreatico dopo duodenocefalopancreasectomia.Occlusione del Wirsung vs anastomosi pancreatico-digiunale.

AIM: The aim of the study is to compare the results obtained using two different techniques of reconstruction after pancreaticoduodenectomy: pancreaticojejunostomy and pancreatic remnant duct occlusion. METHODS: The authors describe a retrospective study performed in 44 nonselected patients submitted to pancreaticoduodenectomy from 2000 to 2004. They have been divided into 2 groups. Patient characteristics were comparable in both groups. The first group (22 patients) received pancreaticojejunostomy. The second group (22 patients) received duct occlusion with sclerosing glue. Intraoperative finding (operative time, estimated blood loss) and postoperative morbidity and mortality were evaluated. Endocrine and exocrine function were analyzed at 3 and 12 months after surgery. RESULTS: Results showed no differences in median blood loss, duration operation and hospital day. Morbidity and mortality were higher in duct occlusion group; pancreatic fistula was more frequent after duct occlusion, but less dangerous than one from pancreaticojejeunostomy. Also exocrine function was better in anastomosis group and the incidence of diabetes mellitus was higher in patients with duct occlusion. CONCLUSION: Pacreaticojejunostomy is the procedure of choice, while duct occlusion should be performed in friable stump with small pancreatic duct (higher risk of pancreatic fistula).

Recurrences after laparoscopic ventral hernia repair: results and critical review.

We describe the whole cohort of patients operated on laparoscopically for ventral hernias at our institution. Information on early results, complications, and long-term follow-up was collected prospectively. Of 90 operations attempted, five (5.8%) required conversion. Of the remaining 85 patients, 65 (76%) had an incisional hernia, while 20 (24%) had primary defects. Three trocars were routinely employed (Hasson and two 5-mm). The prosthetic mesh used was ePTFE inserted through the first trocar and fixed using helicoidal staplers. Patients were periodically followed in the outpatient clinic for at least 12 months postoperatively and contacted at the time of this review. Mean operative time was 101 min. We had three small bowel injuries repaired laparoscopically. Postoperative pain was limited. Bowel movements, deambulation, and discharge were prompt. We had six (7%) urinary retentions, eight (9%) seromas, three (3.5%) cases of pneumonia, two (2%) cases of postoperative vomiting, and one (1%) prolonged ileus, which resolved spontaneously on postoperative day 2. Mean postoperative stay was 4 days. One patient was readmitted after 4 weeks with incomplete obstruction, resolved conservatively. There were three recurrences (3.5%), which developed within 1 year of the operation, and a trocar-site herniation (1%). The technique appears safe and efficacious.

Incisional hernia: repair retrospective comparison of laparoscopic and open techniques.

PURPOSE: A retrospective clinical trial was conducted to compare laparoscopic incisional hernia repair (LIHR) and open traditional repair (OR). Demographics, perioperative data, results, and follow-up data were examined to determine whether there was any difference in outcome, recurrences, and costs. METHODS: From January 2000 to June 2002, 42 consecutive, unselected patients who successfully underwent LIHR were matched with 49 consecutive, unselected patients who received OR during the same period. The operating room database, clinical files, and outpatient sheets were examined. Patient demographics, results, follow-up data, and costs were compared between the two groups. RESULTS: Demographic characteristics, obesity, ASA status, type of hernia, concomitant surgery, urgencies, and incidences of previous repair were well matched between the two groups. Hernia defect was significantly larger in the OR group (122 cm2) than in the LIHR group (83 cm2; p = 0.0006). The operative times and the overall complications rates were similar, but wound infections were more common in the OR group (12% vs 0%; p = 0.04). The analgesic requirement was smaller (mean ketorolac injections, 2 vs 5; p < 0.0001; additional opiates, 0% vs 24%; p = 0.0006) and the hospital stay was shorter (5 vs 8 days; p < 0.0001) in the LIHR group. No recurrences were noted in the LIHR group, but there were three recurrences (6%) in the OR group ( p = 0.30, not statistically significant). The cost of the prosthesis was higher for laparoscopic procedure, although the reduction in the hospital stay largely balanced the overall cost ( p = 0.017). CONCLUSIONS: In this study, LIHR appeared to be as safe as OR. Despite the fact that LIHR raised the prosthesis-related costs, the findings showed that LIHR has clinical (less wound complications, shorter hospital stay, reduced pain) and financial advantages over OR.

Caval extension of the right renal vein in cadaveric renal transplantation using the ETS 45 endoscopic stapler.

A major technical difficulty encountered with the transplantation of a cadaveric right kidney is due to the short right renal vein. The transplant surgeon usually has two different options to deal with this: the first is to mobilize the external iliac vein, ligating the internal iliac vein and the small retroiliac veins, while the second option is to increase the length of the right renal vein. Right renal vein extension is usually preferred because it is easier to work with. The technique used was to construct a conduit with the vena cava that extends the cadaveric right renal vein using an endoscopic stapler (Ethicon Endopath Linear Cutter ETS45, cod. TSW 45) for thin/vascular tissues. This procedure has been used successfully in 11 of our 155 transplanted patients. We have seen no vascular complications as a result of the stapled conduit of the vena cava. We conclude that the endoscopic stapler for thin/vascular tissues is safe and easy to use in right renal vein extension.

[Intestinal occlusion caused by strangulated Morgagni-Larrey hernia: clinical case and review of the literature]. / Occlusione intestinale da ernia di Morgagni-Larrey strozzata: caso clinico e revisione della letteratura.

Morgagni-Larrey hernia is an infrequent, asymptomatic disease discovered by chance during routine radiological examination. It is usually congenital and non-traumatic even in adults. Nevertheless, it can cause severe disturbances when complicated. We describe a case of strangulated Morgagni-Larrey hernia in a 73-year-old lady admitted to the Emergency Room for abdominal pain, symptoms of intestinal occlusion and respiratory distress. Routine abdominal and chest x-rays revealed herniation of the stomach and transverse colon filling the entire right hemithorax with several air-fluid levels. A CT scan and a water-soluble contrast medium via a nasogastric tube confirmed the presence of the stomach and omentum in the right pleural cavity. Emergency laparotomy permitted reduction of the herniation and treatment of the diaphragmatic defect without resection.

Early and late (ten years) experience with circular stapler hemorrhoidectomy.

PURPOSE: We present a retrospective clinical study concerning the preliminary experience with the circular stapler in the treatment of hemorrhoids. Early results, complications, and long-term follow-up are revisited. METHODS: Fifty-six consecutive patients with second-, third-, and fourth-degree hemorrhoids were included in the study. Data about operation, early postoperative results, and follow-up at one, two, and four weeks were collected. Patients were also contacted by phone after a long-term follow-up (mean, 33 (range, 5-120) months). RESULTS: Every operation attempted was successfully terminated. The length of the operation was less than 15 minutes. No major bleeding or anastomotic disruption occurred. Six patients (13 percent) who underwent spinal or epidural anesthesia had urinary retention. One patient (1.7 percent) had minor bleeding, and four patients (7.1 percent) experienced transient edema of the anastomotic ring after the operation. None needed further treatments. The mean analgesic requirement was 1.4 (range, zero to eight) ketorolac 30-mg injections; 23 patients (41 percent) received no analgesics, and seven patients (12 percent) required a single extra dose of opiates (10 mg morphine cloridrate). Length of hospital stay was between 0 and 11 (mean, 2.7) days, but 20 patients (35 percent) received an additional operation for coexisting surgical disease. At one week, almost all patients experienced little pain at digital inspection and little bleeding after defecations. No anastomotic leakage, wound infection, or healing delay was found. Three patients (5.3 percent) experienced wound edema and pain during defecation. Two weeks later, one patient (1.7 percent) suffered from painful defecation and ten patients (17 percent) reported minor bleeding, but all returned to normal activities. No pain during defecation, bleeding, stenosis, soiling, incontinence, or other anal symptoms were found at one month after the operation, and all patients were well. All patients were contacted by phone 5 to 120 (mean, 33) months later, and all were pleased with the results of this procedure. There were no symptomatic recurrences. DISCUSSION: Our study confirms the feasibility of circular stapler hemorrhoidectomy in the treatment of hemorrhoids. Complications and postoperative pain were minimal. There were no recurrences during long-term follow-up. CONCLUSION: Mechanical hemorrhoidectomy is a promising new option in the treatment of all patients eligible for a surgical approach.

[Surgical treatment of thyroid microcarcinoma]. / Trattamento chirurgico dei microcarcinomi tiroidei.

Thyroid microcarcinoma is nowaday defined as a tumor of one centimeter or less in the maximum diameter. It occurs in less than five per cent of all thyroid carcinomas. In personal experience four thyroid microcarcinomas have been found in specimens from 121 thyroidectomies and have been retrospectively reviewed clinical data and the long term follow-up of the patients. Total thyroidectomies nor prophylactic lymphadenectomies were never performed. All patients at present are well. Our purpose was to focus on the current surgical treatment of microcarcinoma. Many hypotheses are done to explain pathogenesis and fairly good prognosis of thyroid microcarcinomas, without univocal conclusions. Almost all authors agree that microcarcinoma of the thyroid gland is a low-aggressive tumor, with good biological behaviour, but the therapeutic strategies are not codified yet. Particularly, doubt still exists about the choice between total thyroidectomy and more conservative procedure, and lymphadenectomy, especially when tumor is found in specimens after surgery for benign disease. In conclusion, in our opinion conservative management is the best choice, provided that the patient is included in a correct long-term follow-up.

Bizarre leiomyoma of the epididymis. A case report.

A case of epididymal leiomyoma with bizarre nuclei is described. A 48-year-old man presented with a painless scrotal mass raising the suspicion of a testicular neoplasm. A seven-year follow-up revealed no evidence of local recurrence or distant metastasis. To personal knowledge, this is the first reported case of bizarre leiomyoma of the epididymis.

[Ileal duplication in adults. A very rare nosological entity]. / La duplicazione ileale dell'adulto. Una rarissima entità nosologica.

The report presents a rare case of intestinal duplication in a 43-year old female. Intestinal duplication is a rare congenital malformation and is extremely exceptional in adults. A lot of etiopathogenic theories have been advanced to explain this malformation that can occur anywhere along the alimentary tract, even if the ileum remains the most common. It may be cystic or tubular. An important aspect of mucosal histology is the possibility of gastric heterotopy, conditioning a particular treatment. The literature shows 14 cases with clinical very different presentations and instrumental exams were rarely helpful for correct diagnosis. Treatment of choice is surgical complete resection of the duplication. When contiguous structures are involved intestinal bypass or Roux-on-Y anastomosis may be necessary with mandatory stripping of the mucosa when heterotopic gastric mucosa is present in order to prevent the risk of gastrointestinal haemorrhage or malignant transformation, an event possible in about 25% of the cases reported in the literature.