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Dealing with acute cholecystitis in high-risk, critically ill, and unfit-for-surgery patients is frequent during daily practice and requires complex management. Several procedures exist to postpone and/or prevent surgical intervention in those patients who temporarily or definitively cannot undergo surgery. After a systematic review of the literature, an expert panel from the Italian Society of Emergency Surgery and Trauma (SICUT) discussed the different issues and statements in subsequent rounds. The final version of the statements was discussed during the annual meeting in Rome (September 2022). The present paper presents the definitive conclusions of the discussion. Fifteen statements based on the literature evidence were provided. The statements gave precise indications regarding the decisional process and the management of patients who cannot temporarily or definitively undergo cholecystectomy for acute cholecystitis. Acute cholecystitis management in high-risk, critically ill, and unfit-for-surgery patients should be multidisciplinary. The different gallbladder drainage methods must be tailored according to each patient and based on the expertise of the hospital. Percutaneous gallbladder drainage is recommended as the first choice as a bridge to surgery or in severely physiologically deranged patients. Endoscopic gallbladder drainage (cholecystoduodenostomy and cholecystogastrostomy) is suggested as a second-line alternative especially as a definitive procedure for those patients not amenable to surgical management. Trans-papillary gallbladder drainage is the last option to be reserved only to those unfit for other techniques. Delayed laparoscopic cholecystectomy in patients with percutaneous gallbladder drainage is suggested in all those patients recovering from the conditions that previously discouraged surgical intervention after at least 6 weeks from the gallbladder drainage., (© 2023. Italian Society of Surgery (SIC).)

Pancreatic cancer (PC) is the fourth cause of cancer death in Western countries, the only chance for long term survival is an R0 surgical resection that is feasible in about 10%-20% of all cases. Five years cumulative survival is less than 5% and rises to 25% for radically resected patients. About 40% has locally advanced in PC either borderline resectable (BRPC) or unresectable locally advanced (LAPC). Since LAPC and BRPC have been recognized as a particular form of PC neoadjuvant therapy (NT) has increasingly became a valid treatment option. The aim of NT is to reach local control of disease but, also, it is recognized to convert about 40% of LAPC patients to R0 resectability, thus providing a significant improvement of prognosis for responding patients. Once R0 resection is achieved, survival is comparable to that of early stage PCs treated by upfront surgery. Thus it is crucial to look for a proper patient selection. Neoadjuvant strategies are multiples and include neoadjuvant chemotherapy (nCT), and the association of nCT with radiotherapy (nCRT) given as either a combination of a radio sensitizing drug as gemcitabine or capecitabine or and concomitant irradiation or as upfront nCT followed by nRT associated to a radio sensitizing drug. This latter seem to be most promising as it may select patients who do not go on disease progression during initial treatment and seem to have a better prognosis. The clinical relevance of nCRT may be enhanced by the application of higher active protocols as FOLFIRINOX.

Resection is the only chance of cure for isolated liver metastases from colorectal cancer. In the case of extended parenchymal resections, one crucial point is the ischemic damage to the remnant liver. We report an alternative technique for extremely extended liver resections without total hilar clamping for borderline liver remnants. Two patients presented with invasion of the infrahepatic vena cava, both with an estimated live remnant ≤20 %. The crucial point of the technique is the absence of a portal triad clamping in under beating heart-extracorporeal circulation. In both patients resection margins were free of disease. No signs of liver insufficiency were noted. Survival was more than 2 years in both cases. We believe that aggressive treatment of liver colorectal metastases should be given to all suitable patients. This operation may be added to the techniques that can be offered to these patients.

Background: Pancreatic cancer accounts for approximately 3% of cancer deaths in Europe. Locally advanced pancreatic cancer (LAPC) involves vascular structures, and resectability is low, with a median survival time of 6 to 11 months. We conducted a prospective, nonrandomized study of patients with LAPC to assess the effect of stereotactic body radiotherapy (SBRT) on local response, pain control, and quality of life (QOL)., Methods: Twenty-three patients with histologically confirmed LAPC underwent SBRT. Radiotherapy (30 Gy) was delivered in three fractions, and treatment toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE v. 3.0). All patients received also gemcitabine chemotherapy and were followed up until death. Local control was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, pain control was assessed with a visual analog scale, and QOL was assessed with the SF-36 instrument (Italian v. 1.6)., Results: No grade 2 or higher acute or late toxicity was observed. The overall local response ratio was 82.6% (14 partial response, 2 complete response, 3 stable disease). SBRT showed a good short-term efficacy in controlling both pain and QOL. Median survival was 10.6 months, with a median follow-up of 9 months. The LAPC became resectable in 8% of the patients. Median time to progression of disease was 7.3 months. Six patients developed early metastatic disease., Conclusions: The SBRT method is a promising treatment for LAPC. Local control rates, even compared to historical data from conventional radiotherapy, can be achieved with minimal toxicity. Resectability can also be achieved.

Patients with solitary thyroid nodules should have fine-needle aspiration (FNA) cytology as the initial screening test, but the most of those referred to a surgeon usually undergo frozen section examination (FS). The aim of this retrospective study was to assess the usefulness of FNA cytology and FS together in patients with a solitary thyroid nodule (TN). Two-hundred and ten patients with a TN and FNA cytology suggesting follicular neoplasm underwent intraoperative FS and subsequent hemithyroidectomy or total thyroidectomy. There were 47 (22.4%) men and 163 (77.6%) women, with a median age of 43 years (range 18-76 years). In all patients, ultrasound-guided FNA was successfully performed using 22-G needle prior to surgery. Smears of the FNA samples were stained by May-Grünwald-Giemsa stain and evaluated immediately by the cytologist. Final histology was follicular carcinoma in 23 (10.9%), follicular adenoma in 181 (86.2%), and hyperplasia in 6 (2.9%) patients. No difference (p=NS) in age of the patients, and greatest diameter on the TN was found between groups. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 13.0%, 97.3%, 37.5%, 90.0%, and 88.1% for FNA cytology, and 17.4%, 100%, 100%, 90.8%, and 91.0% for FS, respectively. The combination of FNA plus FS did not significantly improve the results. In conclusion, both FNA cytology and FS are highly specific tests, but their sensitivity is low, even when they are used in combination. Thus, in patients with smears suggesting follicular neoplasm, FS should be considered unnecessary because it does not affect the intraoperative decision making. FS is most useful in those cases that are diagnosed as suspicious for papillary carcinoma by FNA.

The aim of this study was to evaluate the usefulness of image-guided robotic stereotactic radiosurgery for the local control of unresectable liver metastases from colorectal and non-colorectal cancer. Twenty-seven consecutive patients (median age 62 years, range 47-80 years) with liver metastases considered unsuitable for surgery were enrolled in the study. The diagnosis was colorectal cancer liver metastasis in 11 (41%) and other secondary malignancies in 16 (59%) patients. The patients were treated with 25 to 60 Gy (median 36 Gy) delivered in 3 consecutive fractions, and the isodose value covering the planning target volume was 80% of the prescribed dose. Overall, the mean tumour volume was 81.6+/-35.9 ml. Inhibition of growth or a reduction in size was obtained in 20 (74.1%) patients: 7 with complete response and 13 with partial response. There was a local complete response with other single lesions appearing in 3 (11.1%) patients and progressive disease in 4 (14.8%). The median post-treatment volume of the tumour was 24 ml (range 0-54 ml) among the responders. Mild or moderate transient hepatic dysfunction was evident in 9 patients and minor complications in five. Two patients with progressive disease died of liver failure. In conclusion, in patients with liver metastases unsuitable for surgery, stereotactic radiosurgery achieves high rates of local disease control, representing an acceptable alternative therapy, but should be further studied in larger series.

The progress of research on the molecular pathogenesis of liver fibrosis and the consequent discoveries are likely to open new possibilities for therapeutic approaches to the management of this disease in the future. A key step towards this goal is a deeper comprehension of both the complex molecular and cellular mechanisms and the signaling involved in the development of hepatic fibrosis. It is not yet clear, in fact, what role apoptosis, cytokines, oxidants and other molecules play and what relationships exist between them in favouring or delaying the onset of these adverse mechanisms. At present, a unique mechanism is recognized to be the main reason for the cause and development of liver fibrosis: sustained hepatic stellate cell activation and transformation. Therefore, in this review, after considering the cause, development of fibrosis and interrelation between molecular and cellular profibrotic mechanisms, the part played in counteracting both of these actions by some anti-oxidants and anti-fibrotic molecules such as cytokines, prostacyclin and others will be taken into consideration. The gene therapy and the possible therapeutic use of liver stem cells and tissue engineering will also be dealt with briefly. At the moment, however, the efficacy of these novel strategies still needs to be further validated in animal studies and confirmed in clinical trials. Some data that are already available from in vitro and animal studies demonstrating the effectiveness of novel approaches to inhibiting or treating liver fibrosis can only offer moderate hope.

Primary hyperparathyroidism is the most common cause of hypercalcemia and 80-85% of the patients have parathyroid tumors. The purpose of this retrospective review was to analyse whether differences exist between patients with parathyroid tumors treated in the 1980s and 1990s. Between 1980-1997, 253 patients underwent initial surgical neck exploration for hyperfunctioning parathyroid tumors. Renal (polyuria, nocturia, renal colic due to lithiasis), rheumatologic (bone and joint pain), neurological (fatigue, memory loss, depression) and gastrointestinal (dyspepsia, anorexia, nausea) symptoms were recorded and main biochemical parameters were measured. In all patients one or more preoperative localization procedures were carried out prior to successful parathyroidectomy, and the confirmation of imaging findings was obtained after surgery. The patients were divided in two groups. Group A: 121 (47.8%) patients who underwent surgery from 1980-1989; Group B: 132 (52.2%) patients in whom parathyroidectomy was performed from 1990-1997. There were no differences (p=NS) between the two groups in average age, preoperative serum creatinine and intact-PTH levels. Symptoms were most common in Group A, and pre-operative serum calcium levels were significantly lower in Group B. Ultrasonography (n=191) sensitivity did not improve significantly (82.8% vs 82.9%), but positive predictive value (PPV) was higher (89.8% vs 96.0%). CT-scan (n=73) sensitivity was 79.2% and 82.6%, and PPV was 95.0% and 100% in Groups A and B, respectively. 201Tl/99mTc subtraction scintigraphy (n=111, Group A) was 84.6% sensitive (PPV=92.6%) whereas 99mTc-sestamibi scanning (n=90, Group B) was 85.1% sensitive (PPV=96.1%). In conclusion, the clinical features of parathyroid tumors has changed in the nineties and increasing asymptomatic pHPT rate has been found. Although sensitivity and PPV of preoperative localization procedures has improved moderately, at present noninvasive techniques may offer excellent results and should be used in all patients with suspected parathyroid tumors.

The aim of this study was to evaluate CEA and CA 15-3 changes in patients surgically treated for breast cancer. One hundred and three women (median age 59 years, range 31-83 years) with pT1-2, pN0-1, M0 breast cancer were followed up for at least 5 years. CEA and CA 15-3 serum levels were measured before operation and every 6 months during follow-up. The diagnostic sensitivity of CEA and CA 15-3 was 22.3% and 33.3% respectively. There was a significant difference (p < 0.01) between pre- and post-operative (6 months and 5 years after surgery) mean CEA serum levels independent of TNM staging. During follow-up, 21 (20.4%) patients showed recurrence of cancer and overall CEA and CA 15-3 sensitivity was 38.1% and 61.1%, with 98.8% and 91.2% specificity, respectively. Tumor marker measurement may be useful in post-surgical follow-up, but at present they are neither sensitive nor specific enough for early diagnosis of malignancy.

Background: In breast cancer, mammography (MG) fails to reveal malignancy in 10% to 15% of patients, and its sensitivity is limited by dense breast tissue. The aim of this study was to evaluate the usefulness of 99m-Tc-sestamibi scintimammography (SMM) in conjunction with MG and fine needle aspiration (FNA) cytology in the detection of low-stage breast cancer., Methods: A total of 64 women (median age 58 years, range 32-86 years), 53 (82.8%) with palpable and 11 (17.2%) with nonpalpable breast mass, underwent SMM; 61 patients had MG and 62 underwent FNA cytology. At histological examination, breast cancer was found in 59 (92.2%) of the women (pTis = 2, pT1a = 2, pT1b = 13, pT1c = 20, pT2 = 22)., Results: Of the 61 patients who had MG, 45 (73.8%) showed signs of cancer or abnormalities. Of the 62 patients who had FNA cytology, 55 (88.7%) showed malignancy. In 5 (8.1%) patients, atypical ductal hyperplasia or complex sclerosing lesions were found. MG, SMM, and FNA cytology were 80.4%, 78.0%, and 96.5% sensitive, respectively, and their positive predictive value was 97.8%, 100%, and 100%, respectively. In all patients, cancer was at least detected by one of these three techniques., Conclusions: In women with suspicious MG or abnormal FNA cytology that required further investigations, SMM may be helpful in surgical planning and should be considered in most patients before biopsy as an additional noninvasive procedure.

We undertook a retrospective study in 16 patients with parathyroid carcinoma, with the aim of conveying experience from management of this rare cause of hyperparathyroidism (HPT). From 1980 to 1996 we operated on 309 patients with HPT, 290 of whom had primary HPT, and parathyroid carcinoma was diagnosed in 16 (5.2%) cases. In none was the malignancy diagnosed preoperatively. The average serum calcium and parathyroid hormone levels were significantly higher (p < 0.05) than in patients with parathyroid adenoma, and the mean tumor size was 2.9 cm (median 2.5 cm, range 1.5-4.5 cm). Twenty-eight operations were performed with resulting normalization of serum calcium levels for more than 6 months in 11 patients. Six patients presented prolonged postoperative hypocalcemia (2-10 months), and five patients had persistent HPT. Ten patients experienced recurrent disease; the median disease-free period was 24 months (range 4-72 months). None of the patients was treated with chemotherapy, one patient underwent radiation therapy (50 Gy in 25 sessions) but required reoperation for local recurrence 4 months later. Three patients are still alive (two with recurrence). Average survival was 40 months (median 31 months, range 11-131 months).

In 15-20% of the cases pheochromocytoma (pheo) localizes in extraadrenal sites and in about 15% of all cases it seems to be multiple. We analyze our 20-year experience in surgical treatment of pheos, studying the differences between typical and extraadrenal or multiple tumors. From 1977 to 1996 we operated 55 patients (patients) with pheos, 28 (50.9%) males and 27 females (mean age 41 years, range 10-63). Two groups have been distinguished: classic pheos (Group 1, 45 patients) and extraadrenal or multiple pheos (Group 2, 10 patients). Hypertensive crises were present in 37/45 (82.2%) patients of Group 1 and in 7/10 patients of Group 2. Five (11.1%) masses were nonfunctioning and incidentally discovered (4 in Group 1 and one in Group 2). In 4 cases association with familial syndromes was observed (3 MEN IIb, 1 von Recklinghausen syndrome); no further significant differences in clinical features and laboratory data were found between the two Groups. At immunohistochemical analysis 26/26 patients resulted positive for chromogranin A and NSE and 17/26 (11/20 in Group 1 and 4/6 in Group 2) resulted positive for S 100 protein. Five (11.1%) malignant pheos were discovered and removed (Group 1); average survival of these patients was 54.4 months, two patients underwent radioactive iodine (131-I-MIBG) therapy after surgery and only one patient is still alive at 24-month follow-up. Recurrence for benign sporadic pheo (Group 1) occurred in one patient 183 months after adrenalectomy. Ectopic, associated with familial syndromes and multiple pheos are not uncommon and although recovery in surgically treated patients is excellent, lifelong follow-up is necessary also in benign tumors.

Pheochromocytoma is a rare tumor that is found in only 0.1% of patients with diastolic hypertension. We analyze the results of our experience in management of pheochromocytomas and long-term results of its surgical treatment. From 1977 to 1996 we operated on 55 patients with a pheochromocytoma: 29 males and 27 females with an average age of 41 years (range 10-63 years). In 44 (80.0%) patients episodic hypertension or paroxysms were observed; 7 (12.7%) patients had permanent hypertension, and 4 (7.3%) had a normal arterial blood pressure (ABP). 131/123I-MIBG scintigraphy (33 patients) and magnetic resonance imaging (12 patients) showed 100% sensitivity and computed tomography (47 patients) 97.9% sensitivity. At operation five (9.1%) tumors were bilateral, five extraadrenal, and five multiple. In four (7.3%) patients an association with familial syndromes (three MEN-IIb, one von Recklinghausen disease) was observed. Five (9.1%) malignant tumors were discovered, and two patients are still alive 30 and 104 months after surgery, one of them with relapse. In 43 (78.2%) patients we preferred a flank incision, and no intraoperative deaths occurred. Mean follow-up was 88 months (6-232 months) with recurrence in only 1 (2.0%) of 50 patients without malignancy. In patients with benign pheochromocytomas the recurrence rate did not seem to be elevated in our series. Nevertheless, because the lifelong follow-up requires only annual 24-hour urinary catecholamine measurement (less than $40 per patient per year) and periodic ABP measurements, it is suggested for all patients who undergo surgery for pheochromocytoma.

Background: The incidence of unsuspected adrenal masses (incidentalomas) based on CT-scan results to be higher than in the past. The aim for our study was to establish some guidelines for an appropriate management., Methods: From 1986 to 1995, 61 patients with no history or clinical findings suggestive of adrenal mass or adrenal hyperfunction were discovered by radiologic examination to have an incidentaloma larger than 1 cm. In each patient basal biochemical evaluations were obtained to exclude the presence of adrenal cortical or medullary dysfunction. There were 28 men and 33 (54.1%) women, with a mean age of 53 years (range 16-74). 19 patients underwent CT-guided fine-needle biopsy to exclude metastatic tumors. Furthermore in 29 patients 75-Se-selenomethyl-norcholesterol was performed and 17 were studied by MRI., Results: At CT-scan mean lesion diameter was 5.48 +/- 3.76 cm (range 2-23); 32 adrenal masses were right sided and 3 (4.9%) were bilateral. 17 patients had concordant scintigraphic imaging pattern, 6 bilateral uptake and 6 had discordant imaging. CT-guided FNAB showed malignancy in 9. Adrenalectomy was performed in 45 patients according to a score calculated by 4 parameters: age of the patients, size of the mass, scintigraphic pattern, MR imaging. Twenty-four had a score greater than 9 and in the remaining 21 patients in spite of a score lower than 10 adrenalectomy was performed based on: 1) increased size at CT scan follow-up (15 pts); 2) either suspected primitive malignant neoplasm at CT-guided FNAB or history of malignancy (6 pts); 3) elevated 24-hour dopamine (4 pts). In 12 (26.7%) patients a malignant tumor was found. There were not any statistically significant differences (p > 0.05) between the age of the patients with malignant neoplasms and those with benign masses, and between the size of the masses, which were 7.58 +/- 5.93 cm (range 2-23) and 5.03 +/- 2.81 cm (range 3-17) respectively. The difference in scores between the patients with malignant masses (12.17 +/- 2.95) and those with benign ones (9.09 +/- 1.33) was statistically significant (p < 0.01)., Conclusions: Since adrenal incidentaloma have a malignancy rate higher than the other adrenal tumors, it is crucial to outlinesome criteria to sort out the patients at risk for whom adrenalectomy is to be warranted. Based on our results we believe that patients with a score > 9 should undergo adrenalectomy.