Increased production of 27-hydroxycholesterol in human colorectal cancer advanced stage: Possible contribution to cancer cell survival and infiltration.

So far, the investigation in cancer cell lines of the modulation of cancer growth and progression by oxysterols, in particular 27-hydroxycholesterol (27HC), has yielded controversial results. The primary aim of this study was the quantitative evaluation of possible changes in 27HC levels during the different steps of colorectal cancer (CRC) progression in humans. A consistent increase in this oxysterol in CRC mass compared to the tumor-adjacent tissue was indeed observed, but only in advanced stages of progression (TNM stage III), a phase in which cancer has spread to nearby sites. To investigate possible pro-tumor properties of 27HC, its effects were studied in vitro in differentiated CaCo-2 cells. Relatively high concentrations of this oxysterol markedly increased the release of pro-inflammatory interleukins 6 and 8, monocyte chemoattractant protein-1, vascular endothelial growth factor, as well as matrix metalloproteinases 2 and 9. The up-regulation of all these molecules, which are potentially able to favor cancer progression, appeared to be dependent upon a net stimulation of Akt signaling exerted by supra-physiological amounts of 27HC.

Parafibromin-deficient (HPT-JT Type, CDC73 Mutated) Parathyroid Tumors Demonstrate Distinctive Morphologic Features.

The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma. Therefore loss of parafibromin expression by immunohistochemistry may triage genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with malignant behavior in atypical parathyroid tumors. We share our experience that parafibromin-negative parathyroid tumors show distinctive morphology. We searched our institutional database for parathyroid tumors demonstrating complete loss of nuclear expression of parafibromin with internal positive controls. Forty-three parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing immunohistochemistry were identified. Thirty-three (77%) were external consultation cases; the estimated incidence in unselected tumors was 0.19%. Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%) noninvasive but parafibromin-negative tumors subsequently metastasized. Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated distinctive morphology including extensive sheet-like rather than acinar growth, eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin, perinuclear cytoplasmic clearing, a prominent arborizing vasculature, and, frequently, a thick capsule. Microcystic change was found in 21 (48.8%). In conclusion, there are previously unrecognized morphologic clues to parafibromin loss/CDC73 mutation in parathyroid tumors which, given the association with malignancy and syndromic disease, are important to recognize.

Early versus delayed laparoscopic cholecystectomy for acute cholecystitis.

AIM: Laparoscopic cholecystectomy, currently the gold standard treatment for cholelithiasis, has been extended to treating acute cholecystitis as well. However, operation timing remains controversial. The aim of this retrospective study was to compare our data on the timing of surgery for early and delayed laparoscopic cholecystectomy for acute cholecystitis. METHODS: From January 1, 2006 to December 31, 2010, 508 laparoscopic cholecystectomy procedures were performed, 149 of which for acute cholecystitis: 122 operations were defined as early (performed within 72 hours of symptom onset) and 27 as delayed (72 hours to 9 days from symptom onset). RESULTS: There were no statistically significant differences in operating time, conversion or complications rates between early and delayed procedures. The total length of hospital stay was longer for patients who had undergone a delayed procedure. The success rates were similar irrespective of the surgeon's level of experience. CONCLUSION: Patients operated on for acute cholelithiasis between 72 hours and up to 9 days after symptom onset may benefit similarly as from an earlier operation. Delayed laparoscopic cholecystectomy for acute cholelithiasis is a feasible and safe procedure that compares favorably with early laparoscopic cholecystectomy.

"Fast track surgery" in the north-west of Italy: influence on the orientation of surgical practice.

Fast track surgery is a peri-operative management model, including different strategies to improve patients' convalescence, avoid metabolic alterations, reduce complications, and shorten hospital stay. Prerequisite is coordination between different practitioners (surgeon, anaesthetist, nurse, nutritionist, physiotherapist). The purpose of our investigation is to understand the level of fast track surgery application in Piedmont and to evidence analogies and differences among departments. We projected an investigation proposing, to every surgery department in Piedmont, a multiple-choice questionnaire evaluating the level of fast track surgery peri-operative interventions' application. Data analysis was conducted in two points of view: the transversal one with an overview of answer's percentages, the longitudinal one correlating data through Pearson's index (r). We collected answers by 78 % of balloted departments (38 on 49). Transversal analysis, including the evaluation of percentages of each question, shows that intra-operative period is the most influenced by fast track principles, and that only 12 departments of 38 apply complete protocols. Longitudinal analysis, estimating the whole of each department's answers, demonstrates the absence of statistical significance in the correlation between fast track surgery application and territorial (r = 0.18), economic (r = 0.31), or age (r = 0.06) variables. Influence of fast track surgery is significantly present in our territory, even though it is not fully concretized in protocols. The choice of fast track depends on the instruction, the environment and the sensibility of each surgeon. Knowledge of geographic distribution of departments applying this model can be useful to organize common protocols, starting from more experienced hospitals.

A novel technique for rectocele repair in elderly women.

We have developed a transvaginal technique for rectocele repair which we believe to be particularly suitable for older woman. A transverse incision was made in the mucocutaneous border of the vaginal introitus. The rectal wall was separated from the rectovaginal septum. The vaginal wall was divided in the middle. The first flap was sewn to the second and this onto the first. This intervention permits the contemporary correction of other pathologies frequently found in older women, such as cystocele and prolapse of the uterus. Twenty-two elderly women underwent operations using this technique; the mean follow-up period was 48 months (range, 24-84 months). The need to assist evacuation digitally disappeared in all patients.

The mesorectum: hypothesis on its evolution.

BACKGROUND: Two points are controversial in the anatomy of the mesorectum: (1) its origin; and (2) the existence of the lateral ligaments. We studied these structures in animals and in human fetuses. METHODS: Dissections were performed on quadrupedal mammals (29 dogs and 32 pigs) and 28 primates (Macaca apes). Moreover, macroslices of Macaca ape and of 182 human fetuses were examined histologically. RESULTS: In quadrupedal mammals, we found no traces of any adipose masses comparable to the human mesorectum nor were there ligaments of suspension. In the ape, the adipose tissue in the mesosigmoid forms an adipose cuff that completely surrounds the extraperitoneal rectum. Two dense connective bands were found between the lateral wall of the pelvis and the perirectal tissue. Both the mesorectum and the lateral ligaments were clearly identified in the sections of human fetus only at the end of the fifth month but not earlier. CONCLUSIONS: On the basis of our analysis of 3 animal species, we conclude that the mesorectum and lateral ligaments are absent in quadrupedal mammals but are present in primates. Therefore, we hypothesize that these structures appeared with the attainment of the upright position, even though other hypotheses are possible.

The role of lymphadenectomy in gastric cancer in elderly patients.

The incidence of gastric cancer in elderly patients has significantly increased in the last few decades. Recent reports show that resective surgical procedures are the best therapeutic treatment for aged patients without important pre-existing clinical disorders. The role of lymphadenectomy in elderly patients with gastric cancer is not clear. The present study analyses literature data regarding the optimal extension of lymphadenectomy in gastric carcinoma; we reviewed the data from Japanese authors and from newer multicentric prospective European studies (German Gastric Carcinoma Study Group, Dutch Gastric Cancer Group, Medical Research Council, Italian Gastric Cancer Study Group). We also analysed the clinicopathological characteristics, the site, the symptoms, the spread and recurrence patterns of gastric carcinoma in the elderly compared with adult patients. This review shows that 75-90% of the diagnosis of gastric carcinoma in aged patients is done in advanced stage and an aggressive surgical treatment is required. A pre-existing illness and the ASA stage of the patients are directly correlated to postoperative complications. For these reasons, considering the clinicopathological features of the disease, a curative surgical operation using also an extended lymph node dissection is recommended for aged patients in good health.

Can intestinal innervation be preserved in pancreatoduodenectomy for cancer? Results of an anatomical study.

Twenty dissections were carried out, in all of which the splanchnic nerves, celiac plexuses, capital pancreatic plexus and superior mesenteric plexus were identified and traced. The capital pancreatic plexus was formed from two bundles, the first taking its origin from the right celiac plexus, the second from the superior mesenteric plexus. These two bundles joined together just behind the head of the pancreas. Two preganglionic bundles, a ganglion and two postganglionic bundles composed the superior mesenteric plexus. Postganglionic bundles received fibers from both right and left celiac plexuses. In small cancers a thin layer of nervous tissue around the superior mesenteric artery might be spared in order to avoid diarrhea from intestinal denervation. This study has provided anatomical evidence that a part of the mesenteric plexus, which receives fibers from both left and right celiac plexuses, maintains a sufficient intestinal innervation.

Clinical impact of false-negative sentinel node biopsy in primary breast cancer.

BACKGROUND: The aim was to assess the false-negative sentinel node biopsy rate in women with early breast cancer and its implications in patient treatment. METHODS: Between January 1995 and March 2001, 328 consecutive patients with clinically lymph node-negative primary operable breast cancer underwent lymphatic mapping and sentinel node biopsy using a combination of preoperative lymphoscintigraphy and/or blue dye. All underwent immediate axillary dissection. The intraoperative success rate in sentinel node identification, false-negative rate, predictive value of negative sentinel node status and overall accuracy were assessed. The clinical features and primary tumour characteristics for each false-negative case were reviewed. RESULTS: The sentinel node was identified in 285 (86.9 per cent) of 328 women. The false-negative rate was 7.9 per cent (eight of 101). Most members of the breast multidisciplinary team would have instituted adjuvant systemic therapy for six false-negative cases based on clinical features and primary tumour histology. In all, only two (0.7 per cent) of 285 women who had sentinel node biopsy may have had their management and survival prospects potentially jeopardized owing to a false-negative sentinel node. CONCLUSION: The results of this study suggest that the clinical impact of a false-negative sentinel node is low.

[Contribution to the study of innervation of the pancreas with a view to its relevance to neoplasm surgery]. / Contributo allo studio sull'innervazione del pancreas finalizzato alla chirurgia neoplastica.

Pancreaticoduodenal resection yields poor results, mainly because of cancer spread into retropancreatic nervous tissue. The aim of this study was to evaluate the feasibility of dissection capable of sparing a portion of retropancreatic nervous tissue in order to lessen, if not prevent, postoperative diarrhoea and severe malabsorption. From April 2000 to June 2001 20 dissections were carried out on 18 fresh cadavers (15 male) within 24 hours of death and on 2 frozen trunks. In all dissections the splanchnic nerves, coeliac plexuses, capital pancreatic plexus and superior mesenteric plexus were identified and traced. The capital pancreatic plexus is composed of two bundles, the first originating in the right coeliac plexus, the second in the superior mesenteric plexus. These two bundles join together just behind the head of the pancreas. The superior mesenteric plexus is composed of two preganglionic bundles, one ganglion, and another two postganglionic bundles. These latter two bundles receive fibres from both the right and left coeliac plexuses. In pancreaticoduodenal resection for cancer, the capital pancreatic plexus has to be completely removed, like the superior mesenteric plexus, as they are very often infiltrated and constitute a route for cancer spread. In small cancers, a thin layer of nervous tissue around the superior mesenteric artery might be spared in order to avoid diarrhoea due to intestinal denervation. The results of this study show that there is anatomical evidence that a thin layer of superior mesenteric plexus receiving fibres from both the left and right coeliac plexuses maintains adequate intestinal innervation.

Contribution to the surgical anatomy of the ligaments of the rectum.

PURPOSE: Many authors have discussed the presence and the importance of the lateral ligaments of the rectum. Our contribution aims at clarifying some aspects of surgical anatomy that help in the preservation of the urogenital functions and may influence the surgical practice. METHODS: From 1994 to 1998 we examined 27 fresh cadavers and five embalmed pelves. We performed all dissections with a technique similar to that used for the surgical mobilization of the rectum. RESULTS: The lateral ligaments of the rectum are trapezoid structures originating from mesorectum and are anchored to the endopelvic fascia; as lateral extensions of the mesorectum, they must be included in the surgical specimen. According to our results, three main structures can be recognized laterally to the rectum: 1) the lateral ligament, which does not contain important structures; 2) the inferior hypogastric plexus and the urogenital bundle; and 3) the lateral neurovascular pedicle of the rectum that comprises the nervi recti and the middle rectal artery, both running under the lateral ligament, although at different angles. CONCLUSION: At the point of insertion into the endopelvic fascia, the lateral ligaments run close to the urogenital bundle. Nevertheless, the dissection at its attachment is safe if the urogenital bundle is kept under visual control.

The lateral ligaments of the rectum: myth or reality?

The modern approach to rectal surgery aims at preserving the nerves to the urogenital system. The relationships between the lateral aspects of the rectum and the surrounding structures represent one of the most controversial points in the surgical anatomy of this area. This study was conducted on 27 fresh cadavers and 5 frozen pelvises. All dissections were performed with a technique similar to that used for the surgical mobilisation of the rectum. The lateral ligaments can be considered extensions of the mesorectum; they originate laterally to the middle portion of the rectum and descend posterolaterally to anchor to the endopelvic fascia. The lateral neurovascular pedicle of the rectum, comprising the middle rectal artery and the transverse autonomic nervous fibres, courses partially beneath the lateral ligament. The urogenital nervous bundle runs close to the point of insertion of the lateral ligaments in the endopelvic fascia, but is not covered with the same layer that forms the ligament itself. Anatomical dissection of cadavers is of invaluable help to the surgeon as it represents the basis for easy recognition of all the various structures in the rectal area.

[The nutrition of the elderly surgical patient]. / La nutrizione nel paziente anziano operato.

The key concepts regarding nutrition of elderly patients prior to surgery are outlined. The main metabolic changes that occur during surgical stress, paying special attention to the characteristics of elderly patients, are described. Lastly, the caloric-energy intake required by postoperative geriatric patients is evaluated and the methods of food intake compared to the benefits obtained are analysed.