Acute cholecystitis management in high-risk, critically ill, and unfit-for-surgery patients: the Italian Society of Emergency Surgery and Trauma (SICUT) guidelines.

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.

Unresectable locally advanced pancreatic cancer: a multimodal treatment using neoadjuvant chemoradiotherapy (gemcitabine plus stereotactic radiosurgery) and subsequent surgical exploration.

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.

New therapeutic approaches to liver fibrosis: a practicable route?

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.

Spontaneously metachronous ruptures of adrenocortical carcinoma and its contralateral adrenal metastasis.

Adrenocortical carcinomas (ACCs) are rare neoplasms. In spite of its rarity, ACCs are the second most lethal endocrine cancer after anaplastic thyroid carcinomas. Currently, the only chance for a cure is an early diagnosis and a radical surgical resection. We present the case of a previously unreported bilateral adrenal hemorrhage occurring in a 59-year-old Caucasian male who was admitted to our surgical division with the diagnosis of a right retroperitoneal spontaneous hemorrhage. Imaging revealed a 10-cm ruptured right adrenal mass with no other abdominal lesions, endocrine screening results were normal, and a right adrenalectomy was performed. Pathology revealed a ruptured ACC. The postoperative period was uneventful and the patient was discharged. While recovering, 3 weeks after the operation, the patient showed the same symptoms on the contralateral side. Imaging once again revealed a retroperitoneal hemorrhage due to a 5-cm ruptured left adrenal mass. Endocrine screening showed a frank peripheral hypercortisolism and imaging showed a huge metastatic dissemination to the liver, lungs, and retroperitoneal space. An urgent left adrenalectomy was performed and pathology showed a metastatic ruptured ACC. The patient was placed in substitutive therapy but never recovered and died of penta lobar pneumonia on postoperative day 31. An extensive review of the current literature on the issue was performed. ACC is confirmed to be a lethal cancer. Rupture is the rarest clinical presentation and appears to be caused by the tumor's growth rate more than the tumor dimensions itself. The use of endocrine screening on such hemodynamically unstable patients is questionable.

Twelve years of experience treating Spigelian hernia.

BACKGROUND AND AIMS: A Spigelian hernia (SH) is an acquired ventral hernia that most commonly occurs in the Spigelian belt. Patients may experience pain or a bulge in the abdominal area, but in most cases there are no symptoms. If left untreated the hernia may become strangulated, which could lead to bowel obstruction. MATERIAL AND METHODS: We reviewed 28 surgical patients with SH between January 2002 and December 2013. We evaluated the incidence of complications, recurrences, and the length of hospital stay with comorbidities, body mass index, clinical presentation, and operative techniques. RESULTS: The 28 patients included 10 males and 18 females, with a mean age of 67 years. Seven patients (26.9%) received emergency operations, and the remaining patients received elective operations. An "open-direct" operative approach was used in 16 cases and a laparoscopic approach in 12. The overall complication rate was 7.6% and the recurrence rate was 3.8% with a median follow-up of 3 years. The median hospital stay was 1 day (range, 1-7). Only the presence of local complications at diagnosis showed a significant impact on length of hospital stay. None of the considered variables had a significant impact on hernia recurrence. CONCLUSION: No differences were noted among the operative techniques, wound infections, complications rate, and length of hospital stay. Laparoscopy seems to cause more early postoperative pain that reverses in about 2 weeks.

Accuracy of magnetic resonance cholangiography compared to operative endoscopy in detecting biliary stones, a single center experience and review of literature.

AIM: To compare diagnostic sensitivity, specificity and accuracy of magnetic resonance cholangiopancreatography (MRCP) without contrast medium and endoscopic ultrasound (EUS)/endoscopic retrograde cholangiopancreatography (ERCP) for biliary calculi. METHODS: From January 2012 to December 2013, two-hundred-sixty-three patients underwent MRCP at our institution, all MRCP procedure were performed with the same machinery. In two-hundred MRCP was done for pure hepatobiliary symptoms and these patients are the subjects of this study. Among these two-hundred patients, one-hundred-eleven (55.5%) underwent ERCP after MRCP. The retrospective study design consisted in the systematic revision of all images from MRCP and EUS/ERCP performed by two radiologist with a long experience in biliary imaging, an experienced endoscopist and a senior consultant in Hepatobiliopancreatic surgery. A false positive was defined an MRCP showing calculi with no findings at EUS/ERCP; a true positive was defined as a concordance between MRCP and EUS/ERCP findings; a false negative was defined as the absence of images suggesting calculi at MRCP with calculi localization/extraction at EUS/ERCP and a true negative was defined as a patient with no calculi at MRCP ad at least 6 mo of asymptomatic follow-up. Biliary tree dilatation was defined as a common bile duct diameter larger than 6 mm in a patient who had an in situ gallbladder. A third blinded radiologist who examined the MRCP and ERCP data reviewed misdiagnosed cases. Once obtained overall data on sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) we divided patients in two groups composed of those having concordant MRCP and EUS/ERCP (Group A, 72 patients) and those having discordant MRCP and EUS/ERCP (Group B, 20 patients). Dataset comparisons had been made by the Student's t-test and χ (2) when appropriate. RESULTS: Two-hundred patients (91 men, 109 women, mean age 67.6 years, and range 25-98 years) underwent MRCP. All patients attended regular follow-up for at least 6 mo. Morbidity and mortality related to MRCP were null. MRCP was the only exam performed in 89 patients because it did show only calculi into the gallbladder with no signs of the presence of calculi into the bile duct and symptoms resolved within a few days or after colecistectomy. The patients remained asymptomatic for at least 6 mo, and we assumed they were true negatives. One hundred eleven (53 men, 58 women, mean age 69 years, range 25-98 years) underwent ERCP following MRCP. We did not find any difference between the two groups in terms of race, age, and sex. The overall median interval between MRCP and ERCP was 9 d. In detecting biliary stones MRCP Sensitivity was 77.4%, Specificity 100% and Accuracy 80.5% with a PPV of 100% and NPV of 85%; EUS showed 95% sensitivity, 100% specificity, 95.5% accuracy with 100% PPV and 57.1% NPV. The association of EUS with ERCP performed at 100% in all the evaluated parameters. When comparing the two groups, we did not find any statistically significant difference regarding age, sex, and race. Similarly, we did not find any differences regarding the number of extracted stones: 116 stones in Group A (median 2, range 1 to 9) and 27 in Group B (median 2, range 1 to 4). When we compared the size of the extracted stones we found that the patients in Group B had significantly smaller stones: 14.16 ± 8.11 mm in Group A and 5.15 ± 2.09 mm in Group B; 95% confidence interval = 5.89-12.13, standard error = 1.577; P < 0.05. We also found that in Group B there was a significantly higher incidence of stones smaller than 5 mm: 36 in Group A and 18 in Group B, P < 0.05. CONCLUSION: Major finding of the present study is that choledocholithiasis is still under-diagnosed in MRCP. Smaller stones (< 5 mm diameter) are hardly visualized on MRCP.

Neoadjuvant strategies for pancreatic cancer.

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.

Hepatic colorectal metastases involving infra-hepatic inferior vena cava in high risk patients for extended resection: an alternative method for achieving radical resection in patient with borderline liver remnant.

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.

Chemoradiation treatment with gemcitabine plus stereotactic body radiotherapy for unresectable, non-metastatic, locally advanced hilar cholangiocarcinoma. Results of a five year experience.

BACKGROUND: Hilar cholangiocarcinoma (Klatskin tumor-KT) accounts for about 0.5-1.5% of all gastrointestinal cancers and for 40-60% of all biliary malignancies. Tumor resection is attainable in about 30-50% of patients. When resection is not possible other treatment options have little or no impact on survival. We present the results of hypofractionated Stereotactic Body Radiotherapy (SBRT) on a small series of non resectable locally advanced KT patients. MATERIALS AND METHODS: Ten patients with histologically proven KT underwent SBRT plus gemcitabine. Radiotherapy (30Gy) was delivered in three fractions. Treatment toxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE v. 3.0). Alive patients with less than 1 year of follow up were excluded from the present study. Local control was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Two grade 1 and Two grade 2 acute toxicities were observed, moreover one grade 2 late toxicity was recorded. The overall local response ratio was 80% (4 PR+2 SD). SBRT showed a good efficacy in achieving local control. Median time to progression was 30 months. Two-year survival was 80% and four-year survival 30%. Six patients developed metastatic disease. Response to treatment and nodal metastases were the only independent indicators of prolonged survival. CONCLUSIONS: The chemoradiation given by SBRT plus gemcitabine is a promising treatment for non-metastatic unresectable KT. High local control rates, even compared to historical data from conventional radiotherapy, can be achieved with minimal toxicity.

Unusual Development of Iatrogenic Complex, Mixed Biliary and Duodenal Fistulas Complicating Roux-en-Y Antrectomy for Stenotic Peptic Disease of the Supraampullary Duodenum Requiring Whipple Procedure: An Uncommon Clinical Dilemma.

Complex fistulas of the duodenum and biliary tree are severe complications of gastric surgery. The association of duodenal and major biliary fistulas occurs rarely and is a major challenge for treatment. They may occur during virtually any kind of operation, but they are more frequent in cases complicated by the presence of difficult duodenal ulcers or cancer, with a mortality rate of up to 35%. Options for treatment are many and range from simple drainage to extended resections and difficult reconstructions. Conservative treatment is the choice for well-drained fistulas, but some cases require reoperation. Very little is known about reoperation techniques and technical selection of the right patients. We present the case of a complex iatrogenic duodenal and biliary fistula. A 42-year-old Caucasian man with a diagnosis of postoperative peritonitis had been operated on 3 days earlier; an antrectomy with a Roux-en-Y reconstruction for stenotic peptic disease was performed. Conservative treatment was attempted with mixed results. Two more operations were required to achieve a definitive resolution of the fistula and related local complications. The decision was made to perform a pancreatoduodenectomy with subsequent reconstruction on a double jejunal loop. The patient did well and was discharged on postoperative day 17. In our experience pancreaticoduodenectomy may be an effective treatment of refractory and complex iatrogenic fistulas involving both the duodenum and the biliary tree.

FNA cytology and frozen section examination in patients with follicular lesions of the thyroid gland.

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.

Image-guided robotic stereotactic radiosurgery for unresectable liver metastases: preliminary results.

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.