Risk factors for difficult thyroidectomy and postoperative morbidity do not match: retrospective study from an endocrine surgery academic referral centre.

Hyperthyroidism, goiter and thyroiditis have been associated with complex thyroidectomy. Difficult thyroidectomies may implicate longer operating times and higher complication rates, while literature on quantification and prediction of difficulty in thyroidectomy is scant. We aim at assessing the impact of preoperative and intraoperative factors on the technical difficulty of total thyroidectomy (TT) and on the incidence of postoperative complications. We conducted a retrospective study on 197 TT from 343 thyroidectomies performed with intraoperative neuromonitoring between October 2019 and June 2022 (excluding lobectomies, nodal dissection, extra-thyroidal procedures). Operating time (surrogate of TT difficulty), postoperative hypocalcaemia, recurrent laryngeal nerve palsy and postoperative bleeding were assessed in relation to pre- and intraoperative characteristics. Vocal fold palsy(VFP) was defined as recovering < 12 months postoperatively. There were 87 thyroid cancers and 110 multinodular goiters (21 hyperfunctioning, 51 mediastinal). Median operating time was 136 min (range 51-310). Within 17.4 months overall median follow-up we recorded two transient VFPs and 12% symptomatic transient hypocalcaemia. At univariable analysis male sex (p = 0.005), BMI (p < 0.001), thyroiditis (p < 0.05), hypervascular goiter (p = 0.003) and thyroid adhesions to surrounding anatomical structures (p < 0.001) were associated with longer operating time. At multivariable analysis male male sex (p = 0.01), obesity (p = 0.001) and thyroid adhesions (p = 0.008) were factors for prolonged operating time. Above-normal anti-thyroid peroxidase antibodies correlated to transient symptomatic hypocalcemia (p < 0.001). Risk factors for complex TT were identified and did not correlate with morbidity rates. Results from this study may help optimizing operating room schedule and inform case selection criteria for training programs in thyroid surgery. Further research is required to confirm these findings.

Prophylactic thyroidectomy in children with multiple endocrine neoplasia type 2.

BACKGROUND: In patients with multiple endocrine neoplasia type 2 (MEN2) syndrome, genetic testing offers early diagnosis, stratifies the risk of developing medullary thyroid cancer (MTC) and informs the timing of thyroidectomy. The efficacy of treatment, which depends on timely and safe surgery, is not well established. METHODS: This was a retrospective review of diagnostic and clinicopathological outcomes of prophylactic thyroidectomy in children with MEN2 between 1995 and 2013 in the UK. American Thyroid Association (ATA) 2009 guidelines were used as a benchmark for adequate treatment. RESULTS: Seventy-nine children from 16 centres underwent total thyroidectomy. Thirty-eight patients (48 per cent) underwent genetic testing and 36 (46 per cent) had an operation performed above the age recommended by the ATA 2009 guidelines; pathology showed MTC in 30 patients (38 per cent). Late surgery, above-normal preoperative calcitonin level and MTC on pathology correlated with late genetic testing. Twenty-five children had lymphadenectomy; these patients had more parathyroid glands excised (mean difference 0·61, 95 per cent c.i. 0·24 to 0·98; P = 0·001), and were more likely to have hypocalcaemia requiring medication (relative risk (RR) 3·12, 95 per cent c.i. 1·54 to 6·32; P = 0·002) and permanent hypoparathyroidism (RR 3·24, 1·29 to 8·11; P = 0·010) compared with those who underwent total thyroidectomy alone. Age did not influence the development of complications. CONCLUSION: Late genetic testing may preclude age-appropriate surgery, increasing the risk of operating when MTC has already developed. Early genetic testing and age-appropriate surgery may help avoid unnecessary lymphadenectomy and improve outcomes.

Role of contrast-enhanced ultrasound to define prognosis and predict response to biotherapy in pancreatic neuroendocrine tumors.

PURPOSE: The incidence of neuroendocrine tumors (NETs) is progressively increasing. Most cases arise from the digestive system, where ileum, rectum and pancreas represent the commonest site of origin. Liver metastases are frequently detected at diagnosis or during the follow-up. Contrast-enhanced ultrasound (CEUS) is used in patients with pancreatic NETs (P-NETs) and liver metastases from P-NET but its role has not been standardized. The aim of this retrospective study was to investigate CEUS in patients with P-NETs and liver metastases from P-NET both as prognostic factor and predictor of response to therapy with somatostatin analogues (SSAs). METHODS: CEUS was performed at the diagnosis of NET and 3, 6 and 12 months after the beginning of SSAs. CEUS pattern was compared with contrast-enhanced computed tomography (CT) pattern. RESULTS: There was a significant association between CEUS and CT pattern (X 2 = 79.0; p < 0.0001). A significant association was found between CEUS pattern and Ki-67 index (X 2 = 24.6; p < 0.0001). The hypervascular homogeneous CEUS typical pattern was associated with low tumor grading (G1 or G2) (X 2 = 24.0; p < 0.0001). CEUS pattern changed from hypervascular homogeneous in baseline to hypovascular/hypervascular inhomogeneous after SSA therapy, with a significant association between tumor response at CT scan and appearance of hypervascular inhomogeneous pattern at CEUS evaluation (6 months: X 2 = 57.0; p < 0.0001; 12 months: X 2 = 49.8; p < 0.0001). CONCLUSIONS: In patients with P-NET, CEUS pattern correlates with tumor grading, being homogeneous in G1-G2 but not in G3 tumors. After therapy with SSAs, CEUS is predictive of response to SSAs. These findings seem to support a role of CEUS as prognostic and predictive factor of response.

Inguino-scrotal herniation of the ureter containing stones.

BACKGROUND: Inguino-scrotal herniation of the ureter is a rare and difficult situation for a surgeon, especially if only recognized during inguinal hernia repair. METHODS: An 83-year-old gentleman, with a previous history of radiation treatment for squamous anal cancer, presented with a large left inguinoscrotal hernia causing occasional pain at the base of the scrotum. Follow-up, post-radiation therapy CT scan showed a hernia sac containing the bladder and large bowel. Calcifications in the sac were interpreted as bladder stones, in keeping with the history of left renal calculi. RESULTS: During hernia repair careful dissection revealed a herniated portion of the left ureter located alongside a large hernia sac, complicated by ureteral calculi. Following stones extraction and ureteral repair, hernia repair with mesh was successfully accomplished. Pathogenesis of ureteric herniation is reviewed. CONCLUSION: A herniated ureter is potentially a source of serious renal or ureteral complications. When discovered, ureteric hernias should be surgically repaired. If preoperative detection of a ureter herniation alongside an inguinal hernia is missed, awareness of the existence of this condition may help avoid iatrogenic ureteral damage injury during a complex hernioplasty. Documentation of unexplained, sizeable and distinct calcifications in an inguino-scrotal hernia sac, particularly in a patient with a history of urolithiasis, may suggest the presence of a herniated, calculus-filled ureter. In such cases, retrograde pyelograms may be considered for a definitive diagnosis prior to surgery.

The pull-through: back to the future.

BACKGROUND: Historically, colo-anal pull-through (P-T) has been the first surgical procedure adopted to facilitate a handmade lower anastomosis. Very popular around mid twentieth century, P-T has had poor diffusion, mainly as a consequence of the technical simplifications brought by staplers. Recent literature seems poor on this specific topic, despite description of P-T appears in published series during the reconstructive phase of total laparoscopic protectomies. A comeback of P-T has also been observed as an option with deferred anastomosis, to allow and protect a colo-anal anastomosis in situations at greater risk of dehiscence, avoiding a temporary faecal diversion. After reviewing the most significant aspects of classic techniques of P-T, we report our experience with transanal laparoscopic P-T for distal rectal cancer, presenting a new, modified P-T with deferred anastomosis aimed at improving defecatory compliance. PATIENTS AND METHODS: Between January 2008 and June 2011 we operated in 258 rectal cancers (0-14 cm from the anal verge), 62.79% of which by laparoscopic access (VL), with 218 restorative procedures (84.49%). The colo-anal anastomoses (CAA) were globally 68 (26.35%), of which 48 in VL procedures (70.58%). In 27 of these CAAs we utilised the P-T procedure, with immediate CAA (I-CAA) in 11 cases (all VL) and delayed CAA (D-CAA) in 16 (2 VL), by selective indications. All CAAs were manually fashioned; 6 D-CAA had the addition of a transverse coloplasty. Site of tumor was the lower rectum in 24 patients, with 21 patients receiving preoperative chemoradiation. RESULTS: There was no operative mortality. Early morbidity: DCAA: 3 pelvic abscesses with stoma formation. I-CAA: 1 intraoperative re-resection and colo-anal anastomosis with stoma formation for defective distal vascular supply. Late morbidity: anastomotic stenosis in 5/12 I-CAA and 4/14 D-CAA controlled by mechanical dilation. Function: 4/7 D-CAA and 4/6 I-CAA nearly complete functional recovery (Kirwan's 1 or 2). CONCLUSION: There are selective indications to P-T, when resection and anastomosis is not feasible in one step, or also as a primary restorative option in elective cases when a covering stoma is refused or dangerous.

Quantification of surgical trauma: comparison of conventional and minimally invasive surgical techniques for pertrochanteric fracture surgery based on markers of inflammation (interleukins).

BACKGROUND: Fixation of pertrochanteric fracture is undoubtedly an additional trauma after the fracture itself. In elderly patients, it might have an important impact on the whole organism. In the literature we find various techniques to perform this type of surgery. Up to now, there are no parameters validated for quantification of the invasiveness of a surgical procedure; it is therefore still not demonstrated that any method is less invasive than any other. In an effort to find a way to quantify the invasiveness of a surgical procedure, inflammatory markers were collected in patients undergoing fixation of trochanteric fracture with gliding hip screw [dynamic hip screw (DHS)] using either a conventional (DHS conv) or minimally invasive (DHS MIO) technique. METHOD: Two groups of patients were investigated prospectively; 36 of them were treated with conventional DHS technique and 32 with minimally invasive technique. Mean age was 84.7 ± 7.20 and 82.78 ± 7.71 years, respectively. Fracture type was classified according to the AO classification. Interleukin (IL)-6, IL-10, IL-8, and tumor necrosis factor (TNF)-α were measured 1 h before and 1 h after surgery. Student's t test, chi-square test, and multivariate logistic regression were used for statistical analysis. RESULTS: Preoperative levels of interleukins showed no significant differences between the two groups. In contrast, the postoperative blood level of IL-6 in patients operated with DHS conv technique (78.41 ± 67.04 pg/ml) was on average higher than in patients operated by DHS MIO technique (39.02 ± 37.36 pg/ml), the mean difference being 39.39 pg/ml [95 % confidence interval (CI) 12.65-66.13 pg/ml; p = 0.0045]. Multivariate logistic regression (backward method with limit of significance 0.05) confirmed that patients operated by conventional technique were significantly more likely to have increased IL-6 after surgery than those operated by MIO technique. IL-8 was measured in only 36 patients (20 for DHS conv, 16 for DHS MIO). No significant differences were found between the two groups; however, there was a drastic decrease postoperatively (p < 0.0001) regardless of the type of surgery performed. IL-10 and TNF-α were tested in all subjects, but did not show significant differences between the two groups. Average length of incision was significantly different (4.61 cm, 95 % CI 3.50-5.71 cm; p < 0.001) between the two groups, being 11.65 ± 2.64 cm for DHS conv and 7.05 ± 1.77 cm for DHS MIO. Similarly, average units of red blood cells (RBCs) transfused [performed for hemoglobin (Hb) <9 g/dl and/or hematocrit (HCT) <27 %] was higher (2.22 ± 0.99) in the DHS conv group compared with the DHS MIO group (1.09 ± 1.20), with average difference of 1.13 (95 % CI 0.59-1.66; p < 0.001). CONCLUSIONS: This attempt to quantify the invasiveness of internal fixation for trochanteric fracture comparing two techniques (DHS conv versus DHS MIO) based on inflammatory markers (IL-6) has given encouraging results. Measurement of systemic inflammatory response to local tissue damage caused by osteosynthesis using IL-6 as marker seems to confirm the lower invasiveness of MIO techniques. These results for trauma cases seem in line with those published for hip prosthesis. Ongoing further studies analyzing the effect of nailing will confirm or invalidate these preliminary results.

Dendritic cell functional improvement in a preclinical model of lentiviral-mediated gene therapy for Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency caused by the defective expression of the WAS protein (WASP) in hematopoietic cells. It has been shown that dendritic cells (DCs) are functionally impaired in WAS patients and was(-/-) mice. We have previously demonstrated the efficacy and safety of a murine model of WAS gene therapy (GT), using stem cells transduced with a lentiviral vector (LV). The aim of this study was to investigate whether GT can correct DC defects in was(-/-) mice. As DCs expressing WASP were detected in the secondary lymphoid organs of the treated mice, we tested the in vitro and in vivo function of bone marrow-derived DCs (BMDCs). The BMDCs showed efficient in vitro uptake of latex beads and Salmonella typhimurium. When BMDCs from the treated mice (GT BMDCs) and the was(-/-) mice were injected into wild-type hosts, we found a higher number of cells that had migrated to the draining lymph nodes compared with mice injected with was(-/-) BMDCs. Finally, we found that ovalbumin (OVA)-pulsed GT BMDCs or vaccination of GT mice with anti-DEC205 OVA fusion protein can efficiently induce antigen-specific T-cell activation in vivo. These findings show that WAS GT significantly improves DC function, thus adding new evidence of the preclinical efficacy of LV-mediated WAS GT.

Effects of cooling and freezing on the motility of Ostrea edulis (L., 1758) spermatozoa after thawing.

The aim of this work was to evaluate the effects of temperature, cryoprotectant agents and freezing curves on sperm motility of Ostrea edulis. All phases of cryopreservation were studied (evaluation of semen motility pattern, choice of cryoprotectants and freezing rates) to restore after thawing the motility characteristics distinctive of fresh semen. To assess the temperature effects on sperm motility, semen was activated using four different temperatures (25, 18, 10 and 3°C). Sperm aliquots were maintained inactive at these temperatures for 1 and 3h, then activated with FSW at same temperature of conservation. Sperm was activated and incubated to 3°C with dimethylsulfoxide (Me(2)SO), ethylene glycol (EG), 1-2 propylene glycol (PG) (5%, 7%, 10% and 15% final concentrations), glycerol (GlOH; 5%, 10% and 15% final concentrations) and methanol (MetOH; 4% and 10% final concentrations) for 10, 20 and 30min. A first evaluation of freezing rates was made by testing four freezing curves: -1, -3, -6 and -10°C/min. Then, an optimization was made by testing four freezing curves: -2.5, -3.0, -3.5 and -4°C/min. The selected temperature for short term conservation has been 3°C, because only this temperature has allowed good sperm motility conservation after 3h of dry-storage; this is a time sufficient to conduct cryopreservation procedures. The sperm showed a particular sensitivity to GlOH and PG to all tested concentrations and to 15% Me(2)SO. EG and MetOH to all concentrations and Me(2)SO to concentrations lower than 15% have not shown significant toxic effects. The freezing rate -3°C/min using 15% EG has shown an highest percentage of RVF (rapid, vigorous and forward) spermatozoa (class 3, about 75% of fresh semen) and an highest sperm motility duration.

Feasibility of laparoscopic portal vein ligation prior to major hepatectomy.

BACKGROUND: Patients noted to have an inadequate future liver remnant on pre operative volumetric assessment are considered to be candidates for portal vein embolization (PVE). A subset of patients undergo laparoscopic intervention prior to PVE for staging purposes or to address the primary in Stage IV colon cancer. These patients usually undergo PVE as a subsequent additional procedure by the transhepatic route. The aim of this study was to assess the feasibility of portal vein ligation by the laparoscopic approach in suitable patients. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database was performed to identify patients that underwent laparoscopic portal vein ligation (LPVL). The demographic, clinical, radiographic, operative and volumetric details were collected to determine the feasibility of portal vein ligation. RESULTS: A total of nine patients underwent LPVL as part of a two stage procedure in preparation for subsequent major hepatectomy. With a median age of 67 yrs, the diagnoses included: colorectal metastasis (five patients), cholangiocarcinoma (three patients) and hepatocellular carcinoma (one patient). The ligation involved the right portal vein in all and was performed with silk ligature (seven patients) and clips (two patients). Volumetric data was available in six patients which showed a mean increase from 209.1 cc+/-97.76 to 495.83 cc+/-310.91 (increase by 181.5%) In two patients, inadequate hypertrophy mandated later embolization by percutaneous technique. Five patients underwent subsequent major hepatic resection as planned. The remaining four patients were noted to have progression of disease that precluded the planned procedure. There were no complications associated with LPVL. CONCLUSIONS: LPVL is feasible and can be safely performed. In a select group of patients, it may be considered as an alternative to subsequent embolization and thereby potentially absolve the need for an additional procedure with its attendant complications.

Restorative proctectomy with colon pouch-anal anastomosis by laparoscopic transanal pull-through: an available option for low rectal cancer?

BACKGROUND: There are sporadic reports, with different verdicts, of restorative proctectomy by laparoscopic transanal pull-through (LTPT) without the use of a minilaparotomy for a part of the procedure. This study aimed to explore the applicability and advantages of LTPT with colon pouch-anal anastomosis for low rectal cancer, and to evaluate the results. METHODS: From January 2002 to July 2003, 10 of 12 patients (6 men and 4 women) undergoing a laparoscopic procedure for low rectal cancer (<6 cm from the anal verge) underwent LTPT. The mean age of these patients was 58 years. The results have been compared with those for 12 similar non-pull-through procedures performed during the same period. RESULTS: There was no operative mortality. An anastomotic leakage and a hemorrhagic gastropathy occurred in the LTPT group. During a mean follow-up period of 18 months (range, 12-26 months), there was no local relapse. Four patients manifested moderate incontinence. No significant differences in functional outcome were observed between the LTPT and control groups. CONCLUSION: The authors' experience supports use of the LTPT procedure with colonic pouch-anal anastomosis for selected lower rectal cancers with indications for a laparoscopic approach as an appropriate and reproducible surgical treatment.

CD44s adhesive function spontaneous and PMA-inducible CD44 cleavage are regulated at post-translational level in cells of melanocytic lineage.

Adhesion between the CD44s receptor and hyaluronic acid plays an important role in cell migration, tumour growth and progression. Although the alternative splicing of CD44 variant exons represents the principal regulatory mechanism of CD44-mediated functions, CD44v spliced variants are scantily expressed in melanoma cells. For this reason, we have investigated the possibility that post-translational modifications of the CD44 standard receptor could play a pivotal role in regulating CD44-mediated functions in melanoma. Using metabolic inhibitors of N- and O-glycosylation, as well as melanoma transfectants expressing CD44s O-glycosylation site-specific mutants, we performed structural and functional analysis of N- and O-deglycosylated CD44s molecules expressed in melanoma cells. We discovered that complete N- and O-glycosylation is not required by CD44s to be correctly expressed on the melanoma cell surface. Indeed, variably glycosylated and functionally different CD44s molecules were constitutively expressed in primary and metastatic lesions. Furthermore, we observed that changes in N- and O-glycosylation of CD44s could modulate its cleavage. In fact, spontaneous CD44s shedding was dependent on the presence of partial or complete O-glycosylation of four serine-glycine motifs localized in the membrane-proximal CD44 ectodomain. Mutation of these serine residues, as well as an extensive metabolic O-deglycosylation, strongly impaired spontaneous CD44 shedding. Furthermore, an O-glycosylation-independent mechanism of CD44 cleavage has been identified. This alternative mechanism of receptor cleavage is phorbol 12-myristate-13-acetate (PMA) inducible, mediated by metalloproteinase and requires the presence of N-linked sugar residues. Our findings demonstrate that the post-translational modification of CD44s represents the principal regulatory mechanism of CD44s-mediated functions in melanoma.

What's right when the gallbladder's left? A case report.

During laparoscopic cholecystectomy for cholelithiasis in a 40-year-old woman, we came upon a case of incidentally discovered left-sided gallbladder (LSG). Two anatomic variants of LSG are known: (a) "true LSG," in which, according to Gross, an accessory gallbladder originates from the left hepatic duct (LHD), the right embryonic bud is readsorbed, and the cystic duct joins either the CBD from the left or the LHD directly. Otherwise, a normal right-sided gallbladder adheres to the inferior left hepatic lobe, and the cystic duct joins the CBD from the right side (as in our case); (b) gallbladder under the fourth hepatic segment, medial to a right-sided round ligament, probably resulting from a prenatal obliteration of the right umbilical vein. Left-sided gallbladder is a paraphysiologic condition that when identified before surgery, must be studied by CT or MRI, when incidentally discovered during surgery must be promptly recognized by the surgeon, who must be aware of the unpredictable confluence of the cystic duct into the CBD. The following operative precautions are useful for avoiding a lesion of the CBD: The surgeon should start dissection of Calot's triangle as close as possible to the gallbladder margin, prepare and clip the cystic duct as close as possible to the infundibulum, and a 30 degrees angled telescope. If in doubt, the surgeon should perform an intraoperative cholangiography.

Nine novel APC mutations in Italian FAP patients.

Familial adenomatous polyposis (FAP) is a common hereditary syndrome characterized by early development of colorectal cancer consequent to extensive adenomatous polyps of the colon. In addition to the colonic manifestations the syndrome presents several extracolonic features including polyps of the upper gastrointestinal tract, congenital hypertrophy of the retinal pigment, jaw cysts, osteomata and desmoid tumors. In this study the entire APC coding region has been analysed for mutation in a panel of one Turcot and 33 unrelated Italian FAP patients using SSCP analysis, PTT and DNA sequencing. We detected APC mutations in 23 of them and identified nine which, to our knowledge were not previously reported. All of these novel mutations are in exon 15, including two nonsense mutations, 6 deletions or insertions leading to premature termination of the protein and one missense mutation (7697G>A). This last mutation occurs in the EB1-binding domain of the APC protein and segregates in four relatives of the patient with three of them presenting 2-3 adenomatous polyps.

[Role of intersphincter resection among the surgical options for cancer of the distal rectum]. / Il ruolo della resezione intersfinterica fra le opzioni chirurgiche per il cancro del retto distale.

The surgical treatment of low rectal cancer has yet to be standardised. The aims of the study were to define the curative role of intersphincteric resection and to evaluate its indications and functional results through a retrospective clinical experience. From 1988 to 2000, out of 783 operations for primary rectal cancers (resectability rate 96%; restorative resections 83% and APR 10%) an intersphincteric resection was performed in 48 patients (31 male, 17 female, average age 62) for tumours located at a mean distance of 4.5 cm from the anal verge. Clinical stage: 27 T3 (56.3%), 12 T2, 5 T4 and 4 T1. All the operations were rated R0. TME with N-S, endo-anal distal transection and manual colo-anal anastomosis with a protective stoma were systematically performed. The mean follow-up was 46 months (range: 12-80). Functional results were evaluated with a prospective standardised questionnaire. There was no hospital mortality (30 days). The total morbidity rate was 22% with anastomotic leakage (clinical or X-ray evidence) in 12.5%. Four anal stenoses needed dilatation. Only one local recurrence six years after operation (2.1%). Nine patients died of systemic metastases within 3 years of surgery; the others are still alive and disease-free. Minor faecal incontinence with frequency and urgency occurred in 68.7% of cases at 3 months after protective stoma closure and in 37.5% after 6 months. After one year continence was good in 85.4% of survivors. Only one case required a permanent stoma for poststenotic total incontinence. The best functional results were achieved by colonic pouch reconstruction. For selected low rectal cancers (T2/T3) without voluntary sphincter infiltration, intersphincteric resection is safe and effective for oncological and functional purposes. The procedure requires accuracy in dissecting the anorectal junction. Preoperative radiotherapy may increase the indications for intersphincteric resection as well as the availability of a disease-free margin. A manual colo-anal anastomosis with colonic pouch interposition is strongly recommended.