The first case concerns the integrated treatment of a 58-year-old woman affected by PC with metastatic involvement ab initio of peripancreatic lymph nodes and liver parenchyma, with numerous secondary lesions greater than 9.5 cm in size (Figures 1A and 1B) in March 2014. The disease was stage IV. A biopsy of the pancreatic lesion was done to define the histological features of the neoplastic lesion. The outcome was adenocarcinoma of pancreatic origin, moderately differentiated and parenchyma infiltrating. Because of the young age of the patient and her good health, chemotherapy based on 3 drugs was recommended: fluorouracil, irinotecan, and oxaliplatin in a 1-8-21 day regimen (FOLFIRINOX: oxaliplatin 85 mg/m², intravenous [IV]; irinotecan 180 mg/m², IV; 5-fluorouracil 400 mg/m², IV; 5-fluorouracil 2400 mg/m², IV over 46 hours). Side effects, such as severe nausea, vomiting, marked fatigue, and lack of appetite with a net impaired QoL, appeared at the beginning of the treatment. Because of such side effects, the second cycle of chemotherapy was given along with some natural substances known for their antitumor effects: curcumin for its antiangiogenic and antiproliferative properties^18–20; polydatin for proapoptotic properties^22–26; lactoferrin for antiproliferative and antimetastatic properties^24,25; Active Hexose Correlated Compound (AHCC), a derivative of shitake mushroom cultured in rice bran extract, for its immunomodulating properties²⁷; melatonin for immunomodulation²⁸; and mistletoe for QoL and stimulation of bone marrow.^29–31 Treatments were administered during and after chemotherapy, and the dose and daily time of treatment for each natural substance are reported in Table 1. Moreover, the patient underwent acupuncture treatment for nausea, vomiting, and pain, using the standard points (PC6, CV12, SP4, ST36).^16,32,33 During chemotherapy, starting from the second cycle, the patient underwent capacitive regional deep hyperthermia treatment by means of an ONCOTHERM 3000, using the standard frequency of 13.6 MHz with 50-minute sessions. Every cycle of chemotherapy, the patient was monitored with blood counts (white and red blood cells as well as platelets) and tumor markers (CA 125, CA 19-9; CEA, all elevated) every 2 months, with liver function tests every month (alanine aminotransferase, gamma-glutamyltransferase, glutamic–pyruvic transaminase, lactate dehydrogenase, bilirubin total and fractionated, increased at the beginning). Initially, the number of blood cells was reduced, whereas tumor and liver markers were found to be upregulated. Throughout the treatment, all the parameters progressively improved toward normalization. At the end of the fourth cycle, the patient underwent an audit computed tomography (CT) that showed a net reduction of pancreatic injury and secondary liver lesions (Figures 1C and 1D). Although we did not use health-related QoL questionnaires, the patient’s general clinical status during the period of treatment was notable for side effects being almost absent, with only a mild asthenia the day after the administration of chemotherapy. Alopecia became complete only at the end of cycle III. The patient received massage therapy once a week during the entire period of chemotherapy. Once good clinical response and the well-being of the patient were established, we decided to administer 2 more cycles of the same chemotherapy to consolidate the results obtained. Oxaliplatin was withdrawn from the protocol because of minor sensory hand neuropathy referred by the patient.

Table 1. Natural substances administrated during and after chemotherapy.

At the end of the sixth cycle, we observed the complete disappearance of the liver metastases, as evidenced by the diagnostic examination (Figure 1E and 1F). Currently, the patient has no late side effect, and blood tests are good in the absence of residual tumor. At the end of March 2017, 36 months after the diagnosis, the patient is still alive.

The second case concerns the integrated treatment of a patient bearing PC with metastatic involvement of the liver parenchyma with small secondary lesions. She was a 55-year-old woman operated for pancreatic pseudocyst in 2013. Following an abdominal ultrasound and a CT scan in September 2014, she was diagnosed with a lesion of the pancreatic body (Figures 2A and 2B). A biopsy of the lesion demonstrated a pancreatic histology of “moderately differentiated adenocarcinoma, G2, the pancreatic parenchyma.” The patient was characterized by young age and good compliance; thus, a treatment with FOLFIRINOX: fluorouracil + irinotecan + oxaliplatin (in a 1/8/21 regimen) was chosen (oxaliplatin 85 mg/m², IV; irinotecan 180 mg/m², IV; 5-fluorouracil 400 mg/m², IV; 5-fluorouracil 2400 mg/m², IV over 46 hours), with the addition of capacitive regional deep hyperthermia treatments (ONCOTHERM 3000 using the standard frequency of 13.6 MHz, with 50-minute sessions). Simultaneously with chemotherapy, the patient started taking some natural substances (used for their antitumor effects, as reported in case 1), such as curcumin,^18–20 polydatin,^22–26 lactoferrin,^24,25 AHCC,²⁷ melatonin,²⁸mistletoe,^29–31 and artemisinin,³⁴ the last added for its proapoptotic properties. Dose and time of treatment for each natural substance are reported in Table 2. Moreover, the patient underwent acupuncture treatment for nausea, vomiting, and pain, using the points previously mentioned.^16,32,33

Table 2. Natural substances administrated during and after chemotherapy.

The patient was monitored with instrumental examination, and it was observed that tumor markers as well as liver enzymes were normalized. At the end of the third cycle, a CT scan showed a clear reduction (60%) of pancreatic lesions (Figures 2C and 2D). She continued both treatments for 6 cycles. A new TC scan, after the sixth cycle of combined therapy, showed the quite complete disappearance of the pancreatic injury and of all the hepatic lesions (data not shown). Once a week during the period of chemotherapy, the patient received massage therapy and attended a yoga session. At the end of March 2017, 30 months after the diagnosis, the patient is still alive.