A 65-year-old male; was a heavy smoker from 15 or 16 to 42 years old and did not have relevant co-morbidities. When he was 58 years old, he underwent a left nephrectomy for the occasional detection of the absence of the left urinary duct. On 5 May 2010, he underwent subtotal esophagectomy with intra-thoracic esophago-plastic surgery; post-operative histology showed adeno-carcinoma of the esophageal–gastric junction, intestinal type by Lauren’s classification. pT2 N0 M0 was the post-operative TNM classification, and cells were HER2 negative. He did not receive any adjuvant therapy. This patient remained disease-free until September 2016, when he went to an emergency department because of heavy abdominal cramps. On this occasion, no pathological signs were ascertained by clinical-radiological assessment, and the patient was discharged without symptoms following anti-inflammatory and anti-spastic therapy. Two months later (in November), the same signs and sialorrhoea occurred; again, he went to the same emergency department, where WB CT showed pelvic ascites and mesenteric fat thickness with small nodules suspected for peritoneal metastases. This diagnosis was confirmed at the National Institute of Cancer in Milan, where the patient was sent for consultation. From 24 November 2016 to 1 February 2017, he received four cycles of 2000/sqm/day capecitabine given orally plus 130 mg/sqm oxaliplatin by i.v. infusion (the Xelox regimen) with complete response (CR); after that, on 1 April 2017, he started maintenance cyclic IT. This patient was disease-free at the last clinical-radiological assessment on 20 May 2019. To date, 35 months from the diagnosis of metastases, he is doing well.\nThe median OS of gastrointestinal cancer patients with moderate metastatic peritoneal ascites was reported to be 9.6 and 13.5 months [,].\nDuring IT in all four cases, the mean basal values of IL-2 increased. In patients 4 and 2, the difference was significant (** p = 0.046 and * p = 0.049, respectively) or close to significant (** p = 0.083). In patient 1, it was close to significant (* p = 0.061 and ** p = 0.083). The mean total number of lymphocytes decreased in two of the four cases. The difference was close to significant in patients 1 (* p = 0.076, ** p = 0.083) and 4 (* p = 0.079, ** p = 0.083). Accordingly, CD3+, CD4+, and NK basal values decreased during IT in three (75%) of the four examined patients. In particular, in contrast to NK, for which no significant difference occurred, the difference in CD3+ was significant (* p = 0.040) or close to significant (* p = 0.083) in patient 1 and close to significant (** p = 0.088) in patient 4. The difference in CD4+ was close to significant in both patients 1 (* p = 0.053, ** p = 0.083) and 3 (** p = 0.083). Basal VEGF, IL-12, and CD19+ values decreased in three (75%) patients. The difference in VEFG was close to significant (** p = 0.083) in patients 1 and 3. IL-12 was significant (* p = 0.040) or close to significant (** p = 0.083) in patient 2 and it was close to significant (** p = 0.083) in patient 1. In patients 1 (p = 0.063, ** p = 0.083) and 4 (* p = 0.071, ** p = 0.077), the difference in CD19+ was close to significant (). No significance was found for IL-6. An increase in three patients with only one close to significant was found for IL-10 and IL-2R. Conflicting results were obtained for CD8+; Treg; CD4+45RO; IL-1R; TNF alpha; TGF beta1; FGF; EGF; IGF1; and IL-1, IL-8, and CMP1 inflammatory cytokines (see ).
A 39-year-old female, in her 31st week of pregnancy, presented with a 5 cm breast nodule with inflammatory signs. From ultrasound, it was suspected to be invasive cancer; subsequent biopsy confirmed a diagnosis of invasive adeno-carcinoma. From 14 October 2015 to 18 February 2016, she received neo-adjuvant chemotherapy with four cycles of 90 mg/sqm epirubicin and 600 mg/sqm cyclophosphamide by i.v. infusion, with each cycle occurring every four weeks, followed by weekly 80 mg/sqm paclitaxel by i.v. infusion. This treatment was interrupted on 18 February 2016 because of disease progression. On 3 March 2016, she underwent a radical left mastectomy; post-operative histology showed infiltrating ductal carcinoma without lympho-vascular invasion. pT2 No Mo was the post-operative TNM classification, G3, ER+ (30%) Pr+ (10%), Ki67 90%, and HER2 negative. From 28 April 2016 to 04 July 2016, she received adjuvant chemotherapy with three cycles of CMF (600/40/600 mg/sqm on days 1, 8, and 28, by i.v. infusion) and, from 31 May 2016 to 08 July 2016, she received conventional radiotherapy on the chest wall and lymph-nodes at II–III–IV levels. From 29 July 2016 to 1 February 2017, 25 mg of exemestane daily plus an LHRH agonist every 28 days were administered. On 2 February 2017, exemestane was replaced by tamoxifen because a hormonal assessment showed the recovery of ovarian functionality. On 22 May 2017, diffusion whole body magnetic resonance imaging (MRI) was carried out at the European Institute of Oncology, in Milan, and it signaled an 8 mm nodule of the middle lung lobe, which was suspected for relapse. A 13 mm nodule in the same site of the suspected relapse was confirmed on 30 May 2017 by WB CT. The subsequent biopsy showed that the nodule had malignant characteristics. On 13 June 2017, the metastatic lung nodule was removed by atypical lung resection. The immunophenotype from post-operative histology confirmed that the primary breast cancer was the probable origin; ER, PR, and Ki67 were 30%, negative, and 50%, respectively. From 18 July 2017 to 24 August 2017, the patient received four cycles of liposomal doxorubicin. From 18 September 2017 to date, this patient received four consecutive cycles of IT twice, and the last cycle was followed by one month of rest and then four successive cycles of oral ChT with vinorelbine and capecitabine. In contrast to previous reports on the metronomic use of vinorelbine and capecitabine [,,] in breast cancer patients with detectable metastatic disease, one week of ChT interruption was planned because our patient did not show clinical-radiological evidence of metastatic disease. Vinorelbine at 30 mg was given every other day, and 500 mg of capecitabine was given three times a day continuously, on days 1–14 every 21 days. On 8 October 2018 and 16 October 2019, bone scanning (BS) and WB CT, respectively, were negative for relapse and circulating CEA-TPA-CA.15.3 levels were in the normal range on 14 October 2019.\nA study [] evaluated 103 breast cancer patients who underwent surgery for suspected pulmonary metastases. In this study, the median survival time (ST) was 29 months and the three-year survival was 43% in 14 patients with a disease-free interval (DFI) of less than 24 months. All patients had received complete resections of their lung metastases. Another study [] reported that, in 37 recruited breast cancer patients with completely resected pulmonary metastases (27 with a single pulmonary nodule (SPN) and 10 with two or more pulmonary nodules), the actuarial five-year survival was 59%. However, in five of them with a DFI of one year or less, the mean survival was only 15 ± 3.6 months, and all patients were dead at 26 months. Before, after, or both before and after thoracotomy, all 37 patients received ChT, tamoxifen, or both. Similarly, in another series [] of 40 patients (most of them with one or two pulmonary metastases) who had undergone complete pulmonary resection, the five-year survival rate was 35.6%, while the median DFI following complete pulmonary resection was 1.6 years. Most breast oncologists, even in SPN cases, prefer systemic medical treatment to surgery. In fact, pulmonary metastasis is considered a systemic disease, and poor survival rates have been reported for those with a DFI of <3 years or with discordance in the hormone receptor status between the primary cancer and the SPN [,].