A Case of Pulmonary Sarcoidosis during First-Line Targeted Therapy with Dabrafenib Plus Trametinib in BRAF V600E-Mutated Metastatic Melanoma.

BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) exert a cytotoxic and immune-mediated effect on metastatic melanoma. The immune-mediated mechanism can lead to some adverse events, including panniculitis, erythema, keratitis, vitiligo-like lesions, or, more rarely, sarcoid-like skin reactions. In particular, sarcoidosis-related manifestations during melanoma treatment are characterized mainly by skin involvement and are seldom associated with chest or lymph node lesions. Overall, managing these adverse events can be very challenging from the diagnostic and therapeutic points of view. We present a case of pulmonary sarcoidosis; it is the first without skin involvement and initially only with lung presentation, diagnosed during treatment with BRAFi and MEKi for metastatic cutaneous melanoma. After about 2 years of treatment, with an oncological complete response, a histologically confirmed form of pulmonary sarcoidosis was diagnosed and initially interpreted as tumor progression. Sarcoidosis has always remained asymptomatic. After progression in the thorax and supraclavicular lymph nodes, steroid therapy with prednisone was instituted with total remission of the signs of disease. The targeted therapy has never been interrupted, and the patient still shows a complete response. This clinical case suggests that rare immune-mediated events, such as pulmonary sarcoidosis, should be considered during targeted therapy for metastatic melanoma and not only during treatment with immune checkpoint inhibitors. It also suggests that the interruption of targeted treatment should be accurately considered based on the expected risks or benefits since such immune-mediated events may have low clinical impact.

Quality of life and patient satisfaction in outpatient thyroid surgery.

In the last three decades surgeons have begun to perform outpatient thyroid surgery (OTS). Important outcome measures of a day-hospital procedure are the patient's quality of life (QoL) and satisfaction, but information on these issues in the OTS setting is scanty. The aim of this pilot study was to explore how early discharge after thyroidectomy affects patients' QoL and satisfaction. Postoperative QoL and satisfaction were assessed retrospectively by giving each patient a self-report questionnaire specifically created in our center for OTS and derived from the post-discharge surgical recovery (PSR) scale to assess physical and mental well-being. Twenty-three of 24 patients (96%), 16 women and 7 men with a median age of 48 years (range 16-72), completed the questionnaire, answering 92% of the questions. QoL based on this scale gave a median score of 81.8% (range 62-98.8%). No major or minor complications occurred in the study group. Regarding QoL eight patients (35%) reported feeling "tired all the time" and six patients (26%) reported mild pain, which in two cases resolved spontaneously. Regarding patient satisfaction two-thirds of patients judged OTS positively while the remaining one-third would not recommend it. Our study showed very good uptake by patients of a new questionnaire dedicated to OTS as a possible aid in the identification of areas for improvement of OTS management. However, to be considered a safe procedure with maximum patient compliance and satisfaction, OTS was found to require considerable effort by hospital staff and patients' caregivers compared to inpatient thyroid surgery.

Event-free survival in Desmoid-Type fibromatosis (DTF): A pre-post comparison of upfront surgery versus wait-and-see approach.

BACKGROUND: Desmoid-Type Fibromatosis (DTF) is a rare mesenchymal neoplasm with a locally invasive pattern and high risk of local recurrence after surgery. Historically, the standard treatment for DTF was surgical resection. However, considering the difficulty of achieving surgical eradication, the possible unnecessary morbidity and the unpredictability of the natural history, a wait-and-see approach has been proposed for asymptomatic DTF. METHODS: We analyzed 87 consecutive patients with histologically-proven sporadic primary DTF, first recurrence or residual disease managed at our institution between 2000 and 2018. Patients and tumor-related variables were reviewed and analyzed. Two different treatment strategies were adopted according to different time periods: in the "early period" (2000-2010) patients underwent surgical treatment irrespective of the clinical presentation, whereas in the "late period" (2012-2018) asymptomatic patients used to undergo a wait-and-see strategy. The event-free survival (EFS) was compared trough a pre-post comparison. RESULTS: In the early period, surgery was performed in 51 (94.4%) patients and watchful waiting in 3 (5.6%). In the late period, the watchful waiting group accounted for 24 (72.7%) patients and the surgical group for 9 (27.3%). No statistically independent prognostic factors were found. EFS did not show statistically significant differences between early and late period groups. CONCLUSION: Wait-and-see policy has shown to be equivalent to upfront surgery in terms of EFS; therefore, a conservative approach is recommended in asymptomatic patients diagnosed with DTF that can be followed through watchful waiting.

Adoption of a Newly Introduced Dermal Matrix: Preliminary Experience and Future Directions.

INTRODUCTION: Acellular dermal matrix (ADM) products are adopted in the management of injuries to soft tissues. ADMs have been increasingly employed for their clinical advantages, and they are acquiring relevance in the future of plastic surgery. The aim of our study is to evaluate the application of ADMs in our patients who could not undergo fast reconstruction. MATERIALS AND METHODS: We performed a retrospective study on 12 patients who underwent ADM placement for scalp and limb surgical reconstructions at the Humanitas Research Hospital, Rozzano (Milano), Italy. Wounds resulted from 9 tumor resections and 3 chronic ulcers. The ADM substrate used to treat these lesions was PELNAC™ (Gunze, Japan), a double-layered matrix composed of atelocollagen porcine tendon and silicon reinforcement. All patients underwent a second surgical operation to complete the treatment with a full-thickness skin graft to cover the lesion. RESULTS: In this study, 12 patients were treated with PELNAC™: 11 out of 12 patients showed a good attachment over a median time of 21.3 days (range 14-27). After almost 23 days, all patients were ready to undergo a full-thickness skin grafting. CONCLUSION: This study assesses the benefits of PELNAC™ and proposes this method as an alternative to traditional approaches, especially in situations where the latter techniques cannot be applied.

Short-term outcomes after duodenal surgery for mesenchymal tumors: a retrospective analysis from a single tertiary referral center.

Duodenal resections are sometimes necessary for radical surgery. We analyzed technical aspects and post-operative outcomes in patients with RPS and GIST involving duodenum. We identified patients who underwent duodenal resection for RPS and GIST at our Institute between 2000 and 2016. Clinical, pathological and treatment variables were analyzed. Thirty patients were treated: 15 for GIST, 15 for RPS. Sixteen duodenal wedge resections (WR) and 14 segmental resections (SR) were performed. Multi-organ resection was frequently performed (63.4%). Median time to flatus was 3 days (range 1-6), to oral refeeding 4.5 (range 2-15). Overall postoperative morbidity rate was 53% (16/30): Clavien Dindo grade ≤ II: 10; duodenum-related complication rate was 33% (10/30), Clavien Dindo grade ≤ II: 9. Morbidity rates were higher in SR than WR. Duodenal resections for RPS and GIST have significant morbidity rate and whenever it is possible, WR is preferable to SR because of the lower morbidity rate.

Minimally-invasive treatments for benign thyroid nodules: a Delphi-based consensus statement from the Italian minimally-invasive treatments of the thyroid (MITT) group.

Benign thyroid nodules are a common clinical occurrence and usually do not require treatment unless symptomatic. During the last years, ultrasound-guided minimally invasive treatments (MIT) gained an increasing role in the management of nodules causing local symptoms. In February 2018, the Italian MIT Thyroid Group was founded to create a permanent cooperation between Italian and international physicians dedicated to clinical research and assistance on MIT for thyroid nodules. The group drafted this list of statements based on literature review and consensus opinion of interdisciplinary experts to facilitate the diffusion and the appropriate use of MIT of thyroid nodules in clinical practice. (#1) Predominantly cystic/cystic symptomatic nodules should first undergo US-guided aspiration; ethanol injection should be performed if relapsing (level of evidence [LoE]: ethanol is superior to simple aspiration = 2); (#2) In symptomatic cystic nodules, thermal ablation is an option when symptoms persist after ethanol ablation (LoE = 4); (#3) Double cytological benignity confirmation is needed before thermal ablation (LoE = 2); (#4) Single cytological sample is adequate in ultrasound low risk (EU-TIRADS ≤3) and in autonomously functioning nodules (LoE = 2); (#5) Thermal ablation may be proposed as first-line treatment for solid, symptomatic, nonfunctioning, benign nodules (LoE = 2); (#6) Thermal ablation may be used for dominant lesions in nonfunctioning multinodular goiter in patients refusing/not eligible for surgery (LoE = 5); (#7) Clinical and ultrasound follow-up is appropriate after thermal ablation (LoE = 2); (#8) Nodule re-treatment can be considered when symptoms relapse or partially resolve (LoE = 2); (#9) In case of nodule regrowth, a new cytological assessment is suggested before second ablation (LoE = 5); (#10) Thermal ablation is an option for autonomously functioning nodules in patients refusing/not eligible for radioiodine or surgery (LoE = 2); (#11) Small autonomously functioning nodules can be treated with thermal ablation when thyroid tissue sparing is a priority and ≥80% nodule volume ablation is expected (LoE = 3).

Complications after gastrectomy for cancer: Italian perspective.

Surgery for gastric cancer is associated with significant major morbidity and an estimated mortality rate of about 5%. A reliable comparison of post-operative outcomes is hampered by the lack of a clear, universally recognized, definition of the most frequent complications. This paper reports the final results of a project launched by the Italian Research Group for Gastric Cancer in September 2015, whose goal was to propose a comprehensive list of surgical-related, gastric cancer-specific complications, with their definitions. The project was carried out through a multicentric, mainly web-based, consensus of experts. The proposed list, following assessment and validation by a group of experts of the European Chapter of the International Gastric Cancer Association, will form the basis for implementing a "Complications Recording Sheet" that can be disseminated worldwide for proper and reliable post-operative assessment.

Krukenberg Tumors of Gastric Origin: The Rationale of Surgical Resection and Perioperative Treatments in a Multicenter Western Experience.

BACKGROUND: In case of Krukenberg tumor (KT) of gastric origin it is controversial and debated whether radical surgery in case of synchronous KT or metastasectomy in case of metachronous ones is associated with additional benefits. Role of perioperative treatments is unclear. METHODS: Among 2515 female patients who were diagnosed with gastric cancer between January 1990 and December 2012 from 9 Italian centers, 63 presented simultaneously or developed KT as recurrence. RESULTS: Thirty patients presented with synchronous KT, while 33 developed metachronous ovarian metastases during follow-up. The differences between the two groups were analyzed and compared. The median age of 63 patients was 48.0 years (range 31-71). Resection was possible in 53 patients (20 synchronous and 33 metachronous). Twelve patients in the synchronous group and 15 patients of the metachronous group underwent hyperthermic intraperitoneal chemotherapy after resection of KT. All of them underwent adjuvant chemotherapy after KT resection. The median survival for all population was 23 months (95 % confidence interval, 7-39 months). The median survival time in the metachronous group was 36 months, which was significantly longer than that in the synchronous group, 17 months, p < 0.0001. CONCLUSIONS: KT remains a clinical challenge for gastric cancer therapy. The extent of disease and feasibility of removal of the metastatic lesion must be carefully evaluated prior to surgery to define the patients group who could benefit most from a resection associated with perioperative treatments.

Surgical management of duodenal stump fistula after elective gastrectomy for malignancy: an Italian retrospective multicenter study.

BACKGROUND: Duodenal stump fistula (DSF) is a severe complication of gastrectomy. Although nonsurgical therapy is preferred, surgery is still mandatory in one third of DSF patients. The aim of this article is to analyze the surgical management of DSF and factors related to its outcome. METHODS: We performed a retrospective multicenter study using data from January 1990 to November 2011 in 16 Italian surgery centers. We collected 8,268 elective gastrectomies for malignancies, 7,987 by the laparotomic and 281 by the laparoscopic approach. Two hundred five patients developed a DSF, 75 of whom underwent surgery for DSF. We analyzed mortality and DSF healing time as well as the impact of clinical, oncological, and surgical characteristics. RESULTS: The laparoscopic approach increased the risk of DSF development (odds ratio 5.6, 95% confidence interval 2.7-10.6, P < 0.001). The indication for first DSF surgery was intra-abdominal sepsis; the failure rate was over 30%, associated with the appearance of fistulas of neighboring organs, bleeding, and the need for reoperations. The mortality rate was 28% and was related to the presence of vascular disease (P = 0.04), more than one reoperation (P = 0.05), sepsis (P < 0.001), and renal failure (P < 0.001). Fifty-four patients recovered after a median of 39 days (interquartile range 22-68 days); the need to perform more reoperations (P < 0.01) and the presence of an abdominal abscess (P < 0.01) led to an increase in healing time. CONCLUSIONS: Surgery for DSF has a poor prognosis. Our data will help to identify patients at risk of death, but unfortunately could not establish the best surgical procedure applicable to all cases of DSF.

Atypical lipomatous tumors: should they be treated like other sarcoma or not? Surgical consideration from a bi-institutional experience.

BACKGROUND: To identify the best surgical approach to atypical lipomatous tumors we reviewed 171 patients who underwent surgery at two sarcoma referral centers with different surgical policies. METHODS: Of the 151 patients (88 %) with primary tumors, 95 were treated at Institution A and 76 were treated at Institution B. At Institution A, a wide surgical resection, including a slight cuff of soft tissue around the mass, was adopted, which was defined as marginal resection (MR) according to the Enneking classification. At Institution B, a simple tumor resection (SR), according to the Enneking classification, was employed. En bloc surgical resection was the goal in both centers. The primary outcomes of the study were local recurrence-free survival (LRFS), incidence of secondary dedifferentiation at recurrence, and presence of residual tumor after re-excision. RESULTS: Sixteen patients (9 %) had local recurrence. The 10-year LRFS was 82 %. No cases of secondary dedifferentiation were observed. Residual tumor after re-excision was found in 46 % of cases. In univariate analysis, sclerosing subtype, tumor rupture, and SR were unfavorable prognostic factors for LRFS. Sclerosing subtype and tumor rupture were independent prognostic factors for LRFS in multivariate analysis. SR was significantly associated with tumor rupture. CONCLUSIONS: Sclerosing subtype and tumor rupture are unfavorable prognostic factors for local recurrence. MR is associated with a lower risk of tumor rupture than SR. Neurovascular and major muscle resections are not necessary in principle. Re-excision after unplanned surgery is not always mandatory. A preoperative core needle biopsy could be useful in identifying the sclerosing subtype.

Gastric stump cancer after distal gastrectomy for benign disease: clinicopathological features and surgical outcomes.

PURPOSE: The purpose of the present study was to analyze clinicopathologic features and long-term prognosis of gastric stump cancer (GSC) arising in the remnant stomach 5 years or later after partial gastrectomy for benign disease. METHODS: We reviewed the results of 176 patients resected with curative intent for GSC at 8 Italian centers belonging to the Italian Research Group for Gastric Cancer (GIRCG). The median (range) follow-up time for surviving patients was 71.2 (6-207) months. RESULTS: One hundred forty-six patients were men, the mean age at the time of diagnosis was 69.2 years, and the great majority (167 cases) underwent Billroth II reconstruction. R0 resection was achieved in 158 (90 %) patients, and in 94 (53 %) lymph node dissection was ≥D2. Postoperative mortality and complication rates were 6.2 and 43.2 %, respectively. T1 tumor was diagnosed in 45 (25 %) cases. Lymph node metastases were evident in 86 patients (49 %). Thirteen patients had involvement of the jejunal mesentery nodes (pJN+); five cases were T2-T3 and eight cases were T4. Overall 5-year survival rate was 53.1 %. Five-year survival rates were 68.1, 37.8, and 33.1 % for pT1, pT2-3, and pT4 tumors, respectively (P = 0.001). Five-year survival rate was 56.5 % for node-negative tumors (pN0), 32.3 % for tumors with nodal metastases without involvement of jejunal mesentery nodes (pN+), and 17.1 % for tumors with involvement of jejunal mesentery nodes (pJN+) (P = 0.002). CONCLUSIONS: Our study suggests that an aggressive surgical approach can achieve a satisfactory outcome in GSC.

Naso-gastric or naso-jejunal decompression after partial distal gastrectomy for gastric cancer. Final results of a multicenter prospective randomized trial.

BACKGROUND: Only a few, small, monocentric randomized controlled trials (RCTs) have compared routine vs. no placement of a nasogastric or nasojejunal tube decompression (NG/NJT) in patients undergoing partial distal gastrectomy (PDG) for gastric cancer. However, to our knowledge, no multicenter prospective RCT has analyzed the role of decompression after both the Billroth II (BII) procedure and Roux-en-Y (RY) gastrojejunostomy. The aim of this study was to determine whether NG/NJT prevents the consequences of postoperative ileus after PDG for gastric cancer after both BII reconstruction and RY. METHODS: Two hundred seventy patients undergoing PDG for gastric cancer were randomly assigned NG/NJT placement (NG/NJT group) or not (no-NG/NJT group) with either Billroth II gastrojejunostomy or Roux-en-Y gastrojejunostomy. The patients were monitored for postoperative complications, mortality, and postoperative course. RESULTS: By January 2010 to June 2012, among 270 patients undergoing PDG for gastric cancer, 134 were randomly assigned to NG/NJT placement (NG/NJT group) and 136 to no decompression (no-NG/NJT group). Time to passage of flatus was significantly shorter in the NG/NJT group than in the no-NG/NJT group, but only after RY reconstruction (3.3 ± 1.5 vs. 4.3 ± 1.6 days, P < 0.001, respectively). Postoperative abdominal distention was significantly lower in the NG/NJT group than in the no-NG/NJT group after both BII and the RY procedure (P < 0.001). No significant differences in postoperative mortality or morbidity, especially anastomotic leakage or intra-abdominal sepsis, were observed between the groups. CONCLUSION: Routine placement of an NG/NJT after BII and RY PDG is not necessary in elective surgery for gastric cancer.

The Cholegas Study: safety of prophylactic cholecystectomy during gastrectomy for cancer: preliminary results of a multicentric randomized clinical trial.

BACKGROUND: Cholelithiasis is more frequent in patients after gastrectomy, due to dissection of vagal branches and gastrointestinal reconstruction. METHODS: A randomized controlled trial was conducted from November 2008 to March 2012. Patients were randomized into two groups: prophylactic cholecystectomy (PC) and standard gastric surgery only (SS) for curable cancers. We planned three end points: evaluation of the number of patients who developed symptoms and needed further surgery for cholelithiasis after standard gastric cancer surgery, evaluation of the incidence of cholelithiasis overall after standard gastric cancer surgery and perioperative complications or costs of prophylactic cholecystectomy. The present study answers to the last end point only. RESULTS: After 40 months from the beginning of study, 172 patients were eligible from 9 Centers. Ten patients refused consent and 32 were excluded due to flawing of inclusion criteria (not confirmed adenocarcinomas and no R0 surgery). Therefore, final analysis included 130 patients: 65 in PC group and 65 in SS. Among PC group, 12 patients had surgical complications during the perioperative period; only 1 biliary leakage, conservatively treated, might have been caused by prophylactic cholecystectomy. 6 patients had surgical complications in SS group. One postoperative death occurred in PC group due to pulmonary embolism. Differences were not statistically significant. Similarly, no differences were significant in duration of surgery, blood loss, hospital stay. CONCLUSIONS: Concomitant cholecystectomy during standard surgery for gastric malignancies seemed to add no extra perioperative morbidity, mortality and costs to the sample included in the study.

The nutritional risk in oncology: a study of 1,453 cancer outpatients.

PURPOSE: There is little information about the nutritional status of cancer outpatients because the practice of nutritional screening is rarely performed. This study aims to define the pattern of scores of nutritional risk in 1,453 outpatients and factors associated with a high nutrition risk score, to facilitate the identification of such patients by the oncologists. METHODS: We prospectively screened the nutritional status of cancer outpatients according to the NRS-2002 score which combines indicators of malnutrition and of severity of the disease (1-3 points, respectively). A score ≥ 3 indicates "nutritional risk". The association of the nutritional scores with some patient/tumour/therapy-related variables was investigated through univariable and multivariable linear regression models. RESULTS: Thirty-two percent of outpatients were at nutritional risk. Primary tumour site, Eastern Cooperative Oncology Group score and presence of anorexia or fatigue were significantly associated with the nutrition risk score. Depending on the combination of these variables, it was possible to estimate different probabilities of nutritional risk. CONCLUSIONS: The frequency of a relevant nutritional risk was higher than expected considering the favourably selected population. The nutritional risk was associated with common clinical variables which are usually recorded in the charts and could easily alert the oncologist on the need of a further nutritional assessment or a nutritional support.

Metastatic melanoma in a young woman treated with TNF-α inhibitor for psoriatic arthritis: a case report.

INTRODUCTION: The risk of cancer with the use of biologic agents in rheumatic diseases is still a matter of debate. Published data suggest that the extent of cancer risk might differ according to the type of cancer, and there is recent clinical evidence for a significant increased risk for skin cancer, including melanoma. In contrast with the extensive literature on cancer risk in rheumatoid arthritis, little has been reported on the development of malignancies in spondyloarthroparthies. CASE PRESENTATION: We report the case of an otherwise healthy 31-year-old Italian woman with psoriasic arthritis who developed a melanoma of left third toe with metastatic involvement of regional lymphnodes after a 3-year treatment with the TNF-alpha inhibitor adalimumab. CONCLUSION: This case illustrates the possibility of a causal relationship between TNF-alpha inhibitors and melanoma. We believe that vigilance should continue in patients treated with TNF-alpha blocking agents, until the question on the increased incidence of cancers, including skin cancers, associated with these drugs will be defined.