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Introduction: Current treatment options for BRAF V600-mutated unresectable stage III/IV melanoma include anti-PD-1 monotherapy or combination with anti-CTLA-4 or anti-LAG-3 agents, BRAF/MEK inhibitors, and clinical trials. The strategy of combination immunotherapy with nivolumab and ipilimumab has shown promising results, achieving higher response rates, longer duration of response, improved progression-free survival, and enhanced overall survival. The optimal sequence of treatments remains a topic of interest, with preliminary data suggesting a greater effectiveness of immunotherapy as the first-line approach. Preclinical trials have indicated that the efficacy of this sequence may be due to the modification of the immune environment by BRAF kinase inhibitors, leading to immune escape by tumor cells and resistance to immune checkpoint inhibitors., Case Presentation: We present a case of a 72-year-old woman with high-burden metastatic melanoma who failed to respond to prior targeted therapy with BRAF/MEK inhibitors and exhibited a successful response to the second-line treatment with ipilimumab and nivolumab. We discuss the potential reasons for this positive outcome contributing to the current debate concerning treatment sequences, resistance mechanisms, and biomarkers predictive of response to immune checkpoint inhibitors in metastatic melanoma., Conclusion: We believe that in few years the therapeutic algorithms in BRAF V600-mutated unresectable stage III/IV melanoma will be more complex since they will define clearly the correct therapeutic sequences with the inclusion of new immune checkpoint inhibitor drugs and multiple predictive biomarkers of response to better select patients eligible to immunotherapy., Competing Interests: The authors disclose any possible conflicts of interest., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Aim: The aim of our study was to assess if there were any differences in clinical presentation, management, and outcome, between younger and elderly patients with acute diverticulitis (AD)., Material of Study: 279 patients with diagnosis of AD treated at the General Surgery Department of Trieste from January 2007 to December 2015 were retrospectively examined and then followed for a minimum of 4 years. We divided patients in two categories: young ≤ 50 years and elderly > 50. Gender, American Society of Anesthesiologists status (ASA score), Hinchey's stage, type and timing of surgery, morbidity, length of hospital stay, recurrence, and overall mortality were retrospectively analyzed., Results: There were 279 patients, 64 (22,9 %) were young and 215 (77,1%) were elderly. Female gender was more frequent in elderly cohort (150 pts 69,7 % F vs 65 pts 30,3 % M) than in the young (16 pts, 25% F vs 48 pts, 75% M), (p<0,001). Higher ASA scores were registered in elderly patients with statistically significant correlation with Hinchey's stage. 229 patients ( 82,07 %) received as initial treatment antibiotic therapy (conservative treatment), 50 (17,93 %) pts underwent EM-S, and 11 underwent to DEL-S., Discussion: In our experience, none significant differences were recorded about Hinchey's stage, timing of surgery, morbidity, length of hospital stay, and recurrence; whereas, regarding the type of surgery (resection-anastomosis (R-A), Hartmann's procedures, and Lavage/Drainage) there were a significant difference (p=0,04)., Conclusions: Hartmann's procedures have been effectuated more frequently in the elderly than in the young with recanalization in less than half of elderly. These data seems to confirm that there is no significant difference in incidence or the natural course of acute and complicated colonic diverticulitis among the young or the elderly. The best surgical treatment, with the least morbidity, may be resection with primary anastomosis., Key Words: Diverticular Disease, Elderly Patients, Sigmoidectomy, Young Patients.

Purpose: The aim of the study was to assess whether the reliability of Touch Imprinting Cytology (TIC) of Sentinel lymph node biopsy (SLNB) in skin melanoma patients allows intraoperative decisions regarding simultaneous radical lymphadenectomy to be made. Previous experiences have shown that the limit of TIC in extemporaneous diagnosis was represented by the minimal deposits of the tumor. Many current data seem to show that in this situation radical lymphadenectomy is no longer necessary, so we wondered if TIC could regain importance in the intraoperative management of these patients., Methods: TIC results of Sentinel Lymph Nodes Biopsy (SLN) were compared with those of standard histopathological and immunohistochemical examinations., Results: A total number of 110 SLN were detected from 50 melanoma patients.TIC revealed the presence of metastases only in 1 out of 13 melanoma-positive SLN (sensitivity 7.6%). There were no false-positive results of TIC (specificity 100%). The negative predictive value was 75.5%, the positive one 100% with a total diagnostic accuracy of 76%., Conclusions: TIC for SLNs is a reliable method, relatively fast and not very expensive. Although with a very high specificity, its sensitivity was very low, and almost exclusively limited to macro-metastases (>2mm). Furthermore, it was not possible to identify a subgroup of patients, based on the characteristics of the primary tumor, in which the method could have been more useful. Finally, even in positive cases, the method rarely reduced the need of a tactic in two stages, principally for the management of the operating room., Key Words: Melanoma, Sentinel lymph node (SLN), Touch Imprinting Cytology (TIC).

Purpose: The study aimed to evaluate the QoL in patients who underwent elective surgery for uncomplicated diverticulitis using a recently developed diverticulitis quality of life questionnaire (DV-QoL)., Methods: All consecutive patients who underwent surgery for uncomplicated diverticulitis or who were hospitalized and treated conservatively for acute uncomplicated diverticulitis episodes in three referral centers, in a 5-year period, were included in the study. The 36-Item Short Form Survey and the DV-QoL were administered to the patients to assess their QoL before and after treatment of diverticular disease., Results: Ninety-seven patients who underwent surgery, 44 patients who were treated conservatively, and 44 healthy volunteers were included in the study. DV-QoL scores correlated with SF-36 scores (p < 0.0001). The surgically treated patients reported a worse quality of life before treatment with respect to the patients treated conservatively (mean 21.12 surgical vs 15.41 conservative, p = 0.0048). The surgically treated patients presented better post-treatment global scores with respect to the conservatively treated patients (mean: 6.90 surgical vs 10.61 conservative, p = 0.0186). Covariance analysis confirmed that the differences between the pre- and post-treatment DV-QoL scores were significantly higher in the surgical (p = 0.0002) with respect to the non-surgical patients. As far as single items were concerned, differences between the two groups were found in the pre- and post-treatment "concerns" and "behavioral changes" DV-QoL items., Conclusions: Sigmoidectomy reduces concerns about diverticulitis and behavioral changes due to the disease. Quality of life should be considered when referring patients with uncomplicated diverticulitis to surgery. Prospective studies are required to confirm this result.

Purpose: Surgical site infection (SSI) is the most common complication of colorectal surgery, resulting in significant burden in terms of morbidity and length of hospital stay. The aims of this study were to establish the incidence of SSI in patients undergoing colorectal surgeries and to identify potentially modifiable risk factors to reduce overall SSI rates., Methods: This retrospective study analyzed patients who underwent colorectal resection at our Department. Patients were identified using a prospective SSI database. Univariate and multivariate analyses were used to identify risk factors., Results: A total of 687 patients were enrolled in the study and the overall SSI rate was 19.9% (137 patients). Superficial incisional surgical site infections (SSSIs) developed in 52 (7.6%) patients, deep incisional surgical site infections (DSSIs) developed in 15 (2.2%), and organ/space infections (OSIs) developed in 70 (10.1%). Univariate and multivariate analyses confirmed that age, diabetes, emergency surgery, and a high infection risk index are risk factors for SSI., Conclusions: There are some modifiable and non-modifiable risk factors for SSI. IRI and age are non-modifiable, whereas the timing of surgery and diabetes can be modulated by trying to defer some emergency procedures to elective ones and normalizing the glycemia of diabetic patients.

Aim: Aim of this study was to evaluate bowel function after colonic resection for diverticular disease and assess its impact on patients' quality of life., Material of Study: 47 patients who underwent urgent or elective surgery for diverticular disease were either personally contacted or interviewed by telephone and given a questionnaire. The Memorial Bowel functional index, the short form (36) health survey questionnaire, and the fecal incontinence severity index were used., Results: Fecal Urgency was found in 4,25% of cases, Incomplete Evacuation in 17,03%, and the Lifestyle/Diet Modification Score in 23,4% of patients. Incontinence cases were not found. After surgery we found reduction of abdominal pain (p=0.017) and improved bowel function (p=0.001). The quality of life correlated to bowel function was defined good or very good in 87.2% of cases whereas 4.3% of patients reported poor bowel function. This condition was related to female patients (p=0.02), urgent surgery (p=0.05), and to post-operative complication (p=0.05)., Discussion and Conclusions: In our experience, both bowel function and abdominal pain improved after surgery and 91.4% of patients were satisfied with the choice of surgery and would agree to do it again. The presence of not recognized inflammatory bowel syndromes can occasionally be responsible for persistent disorders after surgery., Key Words: Bowel function, Diverticular disease, Sigmoidectomy.

The development of new blood and lymphatic vessels is a crucial event for cancer growth, metastatic spread and relapse after therapy. In this work, the expression levels of chemokines, angiogenic and angiostatic factors and their receptors were determined in paired mucosal and tumour samples of patients with colorectal carcinoma and correlated with clinical and histological parameters by advanced multivariate analyses. The most important predictors to discriminate between tumour and paired normal mucosa turned out to be the levels of expression of plexin-A1 and stromal cell-derived factor 1 (SDF-1), the former overexpressed and the latter downregulated in tumours. The levels of osteopontin and Tie-2 transcripts discriminated between the presence and absence of lymph node infiltration, the former overexpressed in the presence of infiltration whilst the latter providing a protective role. These results add support to the notion that the expression levels of selected genes involved in new blood and lymphatic vessel formation represent trustable biomarkers of tumour development and invasion and contribute to the identification of novel molecular classifiers for colorectal carcinoma.

The aim of this retrospective study is to evaluate the immediate and late outcomes of the surgical and conservative treatment of adhesive small bowel obstruction. A series of 163 consecutive patients affected by adhesive occlusion were analysed. 63 patients were submitted to emergency surgery and 100 to conservative treatment; 15 of these ones were operated on because they did not improve or deteriorated. The in-hospital mortality and morbidity, the length of the ileus, the time required for the operation, the length of the recovery, and the late results after a median follow-up of 3.6 years (range: 1-6 years) are reported. The overall mortality was 3.26% and there was no significant difference (p = 0.764) between the treatment modalities. The patients submitted to conservative therapy had a lower morbidity, shorter length of the ileus and shorter hospital stay and a better outcome at follow-up. In the surgical group, the patients submitted to emergency surgery had a lower mortality, a shorter ileus and shorter hospital stay than the patients submitted to delayed surgery. Conservative treatment of adhesive occlusions should be opted for when the indications are correct (no intestinal ischaemia, no occlusion by a bridle). In doubtful cases, the patient should be submitted to emergency surgery to avoid the risks of surgical delay.

We report a case of inflammatory pseudotumour of the liver in a 53-year-old woman who over the previous month had presented malaise, fever and right-sided hypochondralgia. On physical examination the liver was tender at palpation 2 cm below the right costal margin. Laboratory data were normal. Abdominal ultrasonography revealed a focal lesion, measuring 5 cm in diameter, located between the sixth and seventh segments of the liver, just beneath the liver capsule, characterised by a uniformly low level of echogenicity, a round shape with ill-defined margins and very good sound transmission. CT scan disclosed an unexpected and somewhat ambiguous pattern, with coexistence of inflammatory and neoplastic patterns. The patient was therefore submitted to a diagnostic US-guided percutaneous liver biopsy. The microbiological examination proved sterile, while the histological features revealed chronic inflammatory tissue, with fibroblasts and a number of necrotic components. For this reason, despite a strong orientation towards an inflammatory process, we could not rule out the possibility of a necrotic tumour. After two weeks of antibiotic therapy without results, the patient underwent a hepatic bisegmentectomy and a cholecystectomy. Pathological examination of the surgical specimen confirmed the biopsy findings and was suggestive of an inflammatory pseudorumour of actinomycotic origin. The patient was discharged on postoperative day 14 in good general condition, and today, after a follow-up of 5 years, she is still well without any recurrence of disease. Inflammatory pseudotumour of the liver is an unusual lesion that can mimic hepatic malignancy in its presentation and imaging. Despite the clear inflammatory nature of the mass it is almost impossible to detect any aetiological agent. Histologically, the lesion consists in interlacing bands of fibrous connective tissue, containing microscopic suppurative foci, granulocytes, neutrophils, lymphocytes, plasma cells, foamy histiocytes and a few sulphur granules suggestive of actinomycosis. The diagnosis can be made only histologically by US/CT guided-biopsy or, in a limited number of cases, directly by intraoperative frozen sections. Treatment for hepatic inflammatory pseudotumours is controversial: some Authors report cases with spontaneous regression of the disease with or without antibiotic/steroid therapy, while others favour early resection in patients unresponsive to medical therapy. This latter surgical approach is justified not only by the difficult diagnosis but also by the need to prevent complications related to the clinical course of the disease.

The authors report the case of a 26-year-old woman, with a palpable abdominal mass, dyspepsia, pain and weight loss. These symptoms were caused by a non-functioning or biologically inactive neuroendocrine tumour (BINT), weighing 510 g and located in the tail of the pancreas. The treatment opted for was a surgical resection consisting in a distal pancreatectomy. The results of the operation were satisfactory and the woman is now alive and in good health, without recurrence, after 7 years. The authors then go on to analyse the concept of non-functioning neuroendocrine tumours and the problems relating to their symptoms, location and nature. These tumours, which arise, from the pancreatic islet cells, fail to produce a clinical syndrome owing to insufficient peptide production or insufficient release, or concurrent secretion, of inhibitory peptides by the tumour or production of biologically inactive molecular forms of the peptides (without clinical effects). The value of tumour markers and the indications and type of surgery are also discussed according to the different patterns of tumour spread (local, locoregional and metastatic disease). It is stressed that a complete surgical resection is the only curative treatment for these tumours. Encouraging results have been recently obtained by adjuvant treatment with somatostatin analogues, chemotherapeutic agents and/or inteferon.

Aim and Background: The problem of understaging the lymph node status in colorectal cancer because of missed micrometastases led authors to investigate the role of sentinel node (SN) mapping also in colorectal malignancies. The aim of this study was to evaluate the feasibility of the technique and to correlate the results with some characteristics of the primary tumor., Methods: Sentinel lymph node mapping was performed in 23 patients who underwent a standard lymphadenectomy for colorectal cancer. The vital dye Patent Blue had been injected into the peritumoral subserosa in vivo in 17 cases and ex vivo in seven, including one case where the in vivo method did not allow to identify the sentinel node. The nodes that took up the dye were removed and analyzed with standard hematoxylineosin staining in serial sections. Immunohistochemistry (AE1-AE3 cytokeratin markers) was performed in hematoxylineosin-negative nodes. SN status was related to the status of the other lymph nodes in the surgical specimen analyzed with the standard technique and to the following characteristics of the primary tumor: stage, grade and diameter., Results: The in vivo technique allowed to identify the SN in 16/17 cases (94.1%), the ex vivo technique in 7/7. A total of 336 lymph nodes dissected from the surgical specimens was analyzed, with an average of 14.6 nodes per patient (range, 7-35). Of these nodes 58 were SNs, with an average of 2.5 nodes per patient (range, 1-8). In the 19 cases where the SN was tumor negative, the non-SNs were also negative (specificity: 100%), whereas in the four cases where the non-SNs were positive, in two cases the SN was positive and in two cases of pT3 rectal carcinoma the SN was negative (sensitivity: 50%). Immunohistochemistry did not modify the negative results of the standard hematoxylin-eosin evaluation., Conclusions: The method used to identify the SN using vital dye proved to be easy to use both in vivo and ex vivo and allowed to identify the SN in all cases. The preliminary results indicate that there is a risk of false negative findings and therefore further studies are required to improve the sensitivity and the specificity of the technique and to evaluate the role of SN mapping in colorectal cancer management.

Carcinoembryonic antigen is an acid glycoprotein, the levels of which may increase in patients with colorectal carcinoma. The prognostic significance of preoperative carcinoembryonic antigen levels and their relationship to other risk factors are still debatable issues. Among 512 patients operated on for colorectal cancer, whose preoperative carcinoembryonic antigen concentrations were evaluated, linear correlations were established between carcinoembryonic antigen overexpression and carcinoma staging, diameter and grading, though these were not statistically significant. Moreover, metastatic cancers were significantly more frequent in patients with increased plasma concentrations of the marker (> 60 ng/ml). There were no correlations between increased carcinoembryonic antigen levels and age, ploidy, or site and shape of the cancers. As regards survival, patients with normal preoperative carcinoembryonic antigen levels had a better prognosis in terms both of lower local recurrence rates and long- term survival. In addition. In Dukes stages B and C elevation of carcinoembryonic antigen above the cut-off point can be considered a significant prognostic factor capable of identifying a group of patients at high risk who may be candidates for aggressive adjuvant therapies and follow-up. The findings of this study suggest that preoperative carcinoembryonic antigen levels are of prognostic importance in relation both to cancer staging and to long-term survival, which may have significant clinical applications.

The treatment of Crohn's disease is still a debatable issue especially as regards the integrated implementation of medical and surgical therapy, the timing of surgery and the choice of surgical technique. Prognostic factors seem to be important in the choice and planning of therapeutic procedures. The authors retrospectively review 81 patients, 31 of whom submitted to surgery. The parameters observed were the presenting symptoms, the time from onset of symptoms to surgery, previous medical treatment, disease location, and complications. Bowel resection and the treatment of fistulas and abscesses were carried out. Emergency resections were performed in 14 patients (45%): 11 for bowel obstruction, 2 for perforation and 1 for bleeding. The mean follow-up (which included laboratory tests and endoscopy) was 132 months (range: 6 months to 32 years). In-hospital mortality was 2.3% and morbidity 12.9%. Long-term mortality amounted to 3 patients, only 1 of whom died of complications related to recurrence of the disease. Statistical analysis showed that the recurrence rate was 51.3% at 5 years after the first surgical treatment, 65.4% at 10 years and 88.1% at 20 years. Recurrences requiring surgery amounted to 15.3%, 20.5% and 42.5%, respectively. No statistically significant correlations were observed between recurrence rate and time of onset of the disease (p = 0.5601), time of the first surgical treatment, disease location, or specific medical therapy, (p = n.s.). Recurrence requiring surgical treatment was observed in 33.3% of patients when the disease was located only in the ileum, in 33.3% when it was located in both the ileum and colon, and in 28.6% when only the colon was involved (p = 0.9767). The quality of life was good in 66.6% of patients, fair in 26.6%, and poor in 6.6%. The authors conclude that the treatment of Crohn's disease must be multidisciplinary and surgery must be limited to complications. When surgery is indicated, it must be performed promptly, because, in these cases, persisting with medical treatment increases the postoperative morbidity. Short resections must be performed in order to preserve the bowel as much as possible. As far as risk factors are concerned, the most important are the location and the aggressiveness of the disease, whilst biological and laboratory parameters do not seem to influence the results.