Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Fourty-eight patients with MCC were observed at the Rare Hormonal Tumors Group of Cremona Hospital, 15 of these with unknown primary site. Due to rarity of Merkel cell carcinoma, clinical experience is generally limited. Data from our series confirm the current recommendations. Wide surgical excision must be associated with radiotherapy also in early stages in order to avoid local relapse and the rapid progression of disease. In advanced stages chemotherapy is the standard despite the short duration of responses and poor quality of life. The data of our series, characterized by a high demand for second opinion, offer some insight about the real rarity of the tumor, the difficulty of managing of disease in our country secondary to a wrong cultural approach to the problem, the indiscriminate use of molecules unnecessary and often expensive, the lack of protocols, and the presence of guidelines often ignored. This results in very poor survival associated with a very low quality of life, requiring to find the right direction towards a correct management of disease.

IMPORTANCE Data about the optimal timing for the initiation of peptide receptor radionuclide therapy (PRRT) for advanced, well-differentiated enteropancreatic neuroendocrine tumors are lacking. OBJECTIVETo evaluate the association of upfront PRRT vs upfront chemotherapy or targeted therapy with progression-free survival (PFS) among patients with advanced enteropancreatic neuroendocrine tumors who experienced disease progression after treatment with somatostatin analogues (SSAs). DESIGN, SETTING, AND PARTICIPANTSThis retrospective, multicenter cohort study analyzed the clinical records from 25 Italian oncology centers for patients aged 18 years or older who had unresectable, locally advanced or metastatic, well-differentiated, grades 1 to 3 enteropancreatic neuroendocrine tumors and received either PRRT or chemotherapy or targeted therapy after experiencing disease progression after treatment with SSAs between January 24, 2000, and July 1, 2020. Propensity score matching was done to minimize the selection bias. EXPOSURES Upfront PRRT or upfront chemotherapy or targeted therapy. MAIN OUTCOMES AND MEASURES The main outcome was the difference in PFS among patients who received upfront PRRT vs among those who received upfront chemotherapy or targeted therapy. A secondary outcome was the difference in overall survival between these groups. Hazard ratios (HRs) were fitted in a multivariable Cox proportional hazards regression model to adjust for relevant factors associated with PFS and were corrected for interaction with these factors. RESULTS Of 508 evaluated patients (mean ([SD] age, 55.7 [0.5] years; 278 [54.7%] were male), 329 (64.8%) received upfront PRRT and 179 (35.2%) received upfront chemotherapy or targeted therapy. The matched group included 222 patients (124 [55.9%] male; mean [SD] age, 56.1 [0.8] years), with 111 in each treatment group. Median PFS was longer in the PRRT group than in the chemotherapy or targeted therapy group in the unmatched (2.5 years [95% CI, 2.3-3.0 years] vs 0.7 years [95% CI, 0.5-1.0 years]; HR, 0.35 [95% CI, 0.28-0.44; P < .001]) and matched (2.2 years [95% CI, 1.8-2.8 years] vs 0.6 years [95% CI, 0.4-1.0 years]; HR, 0.37 [95% CI, 0.27-0.51; P < .001]) populations. No significant differences were shown in median overall survival between the PRRT and (continued)

Medullary carcinoma (MC) of the large intestine is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and an intraepithelial lymphocytic infiltrate. MC can be associated to a defective mechanism for DNA mismatch repair, caused by the so-called microsatellite instability (MSI). We present the case of a 44 years old Caucasian woman, who referred to the Emergency Room with symptoms mimicking an acute appendicitis. Computed tomography and colonoscopy demonstrated an ulcerated and stenotic lesion of the caecum without signs of metastasis and peritoneal carcinosis. Patient underwent a laparoscopic right colectomy. The final pathologic findings provided the diagnosis of medullary carcinoma with MSI. Patient then underwent adjuvant chemotherapy according to the FOLFOX-4 protocol (association of 5-Fluorouracil, Leucovorin, and Oxaliplatin) for twelve cycles. At two-years follow-up, patient is disease free. MC in association with MSI is a non-frequent tumor of the colon characterized by a better prognosis compared to other types of poorly differentiated adenocarcinoma. In the observed case, 24 months after the surgical operation, the patient is in good health and there is no evidence of metastasis or relapse.

Merkel cell carcinoma is a rare neuroendocrine neoplasm of the skin. The tumor most frequently affects elderly patients, with a preference for the head and neck. Eight patients affected by Merkel cell carcinoma have been observed at the General Surgery Unit II of the "Istituti Ospitalieri" hospital in Cremona, each in different stages of the disease; 75% of the cases involved the extremities, and in nearly all of the cases the tumor was nodular in appearance, with an average diameter of 2.2 cm. In 2 cases, the tumor was associated with rheumatoid arthritis, suggesting a dependency on the part of the neoplasm on the immune disorder and on steroid treatment. The available data confirm that in stage I of the disease, surgical treatment should be associated with radiotherapy in order to control the development of local relapses or metastases over time. In this stage, we observed a survival of 34 months (range, 24-48). In stages II and III, survival time falls, with very short duration of responses and poor quality of life as a result of the administration of cytotoxic molecules. Bearing in mind that any local relapse tends to appear within 12 months of the removal of the primitive tumor, that lymph node metastases appear in almost half of the patients, and that metastases over time are manifested in over a third of patients, it is essential to adopt a treatment capable of balancing the demand for longer remissions with a better quality of life. In this situation, we observed that treatment with somatostatin analogues achieves interesting responses without side effects, which suggests a close biological relationship between the tumor and somatostatin and that making a careful assessment of the prognostic factors of the disease can guarantee a correct therapeutic choice.

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