A 73-year-old woman who had pancreatic head adenocarcinoma underwent pancreatoduodenectomy (PD) at the Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, in July 2005. The patient’s height, body weight, and body mass index were 154 cm, 56 kg, and 23.6 kg/m2, respectively. The patient was discharged 40 days after surgery; however, about a month after discharge, she visited the hospital’s Division of Dentistry and Oral Surgery with a chief complaint of tongue pain with dysgeusia. The first intraoral examination revealed complete atrophy of the lingual papillae, which became erythematous; this is a symptom of glossitis (Fig. 1a). Furthermore, remarkable taste disorder (hypogeusia) and oral pain were reported. The angle of the mouth had stomatitis with erosive changes. The extremities showed acrodermatitis enteropathica-like eruption and abnormal keratinization (Fig. 1b). Blood test results showed hypoproteinemia (total protein (TP) 5.1 g/dL, albumin (ALB) 2.4 g/dL) (Table 1). Examination of trace elements showed remarkably lower serum zinc and copper levels (30 µg/dL, 40 µg/dL, respectively) (Table 1). We diagnosed malnutrition, dysgeusia, glossitis, angular cheilitis, and acrodermatitis enteropathica due to zinc deficiency.
Table 1
Data of blood tests at the time of initial examination
TP
|
5.1 g/dL
|
WBC
|
7030/µL
|
AST
|
45 IU/L
|
ALB
|
2.4 g/dL
|
RBC
|
400×106/µL
|
ALT
|
46 IU/L
|
Zn
|
30 µg/dL
|
Hb
|
12 g/dL
|
ALP
|
368 IU/L
|
Cu
|
40 µg/dL
|
Ht
|
36.2 %
|
CEA
|
18 ng/mL
|
Zn/Cu ratio
|
0.75
|
PLT
|
16.7×106/µL
|
CA 19-9
|
15 U/mL
|
TP: total protein, ALB: albumin, Zn: zinc, Cu: copper, WBC: white blood cell, RBC: red blood cell, Hb: hemoglobin, Ht: hematocrit, PLT: platelets, |
AST: aspartate aminotransferase, ALT: alanine aminotransferase, ALP: alkaline phosphatase, CEA: carcinoembryonic antigen, CA 19-9: colorectal carcinoma antigen 19-9 |
Initially, we orally administered 150 mg of Promac® granules 15% (polaprezinc, ZERIA Pharmaceutical Co., Ltd, Japan) per day (total zinc dose, 34 mg/day) to treat the zinc deficiency. However, due to the insufficient effectiveness of the replacement therapy, we additionally administered multi-trace elements (MTEs) for high-calorie infusions. Elemenmic® (Ajinomoto Co Inc, Japan) was administered intravenously, 1 ampule of which included ferric chloride 9.460 mg, manganese chloride 0.1979 mg, zinc sulfate hydrate 17.25 mg, copper sulfate 1.248 mg, potassium iodide 0.1660 mg, elemental iron (Fe) 35 µmol, manganese (Mn) 1 µmol, zinc (Zn) 60 µmol (= 4 mg), copper (Cu) 5 µmol, and iodine (I) 1 µmol; this was administered twice a week for two weeks as an outpatient treatment. However, the intravenous replacement therapy was similarly inadequate at this dosing interval and did not provide sufficient improvement in the serum copper and zinc values. The blood test results four months after PD were as follows: TP, 4.4 g/dL; ALB, 2.0 g/dL; Zn, 34 µg/dL; and Cu, 28 µg/dL; the patient required nutritional management during hospitalization with total parenteral nutrition (TPN). An improvement was observed in the zinc level (99 µg/dL) and copper level (204 µg/dL) after 20 days of administering 1 ampule of Elemenmic® per day. Concurrently, her tongue pain and dysgeusia gradually improved. Because of a similar improvement in her nutritional status, she completed TPN (TP 5.1 g / dL, ALB 2.5 g/dL, Zn 99 µg/dL, Cu 204 µg/dL). A central venous catheter (CVC) inserted after admission was removed and she was discharged 20 days after admission.
Intravenous zinc replacement therapy was discontinued simultaneously with the second discharge. One month after discharge, the serum zinc level decreased sharply, her oral pain increased again, and she had reduced food intake (Zn 35 µg/dL, Cu 44 µg/dL). We administered Promac® 150 mg per day; however, no improvement was observed in her symptoms, and the patient was readmitted at the end of December 2005. To improve malnutrition, a CVC was re-inserted through the external jugular vein and injected with the MTE formulation and high-calorie infusions on consecutive days for 4 weeks (TP 5.9 g/dL, ALB 3.4 g/dL, Zn 75 µg/dL, Cu 47 µg/dL). In January 2006, since her oral pain and diet had improved, she was discharged from the hospital after receiving an implant of a central venous port, and she continued home self-injection of MTEs to maintain zinc levels. In February 2006, her taste function tended to improve, and in April 2006, the taste almost improved. When MTEs were self-injected daily, the serum zinc level gradually exceeded the normal range and reached 167 µg/dL in August 2006; therefore, the administration was switched to every other day. Subsequently, we had to confirm the blood test data repeatedly to monitor serum zinc levels to ensure that they were within the normal range (Fig. 2). Despite continuing intravenous zinc replacement therapy, serum zinc levels decreased when additional oral zinc was discontinued in May 2007. After resuming the oral administration of Promac® due to the recurrence of dysgeusia, both the serum zinc level and dysgeusia improved. Since 2008, Pancreatin® (pancreatic enzyme, Mylan Co Inc, USA) 3 g/day had been administered alongside conventional zinc administration for this patient.
As of January 2012, she continued using Elemenmic® intermittently while her serum zinc values were monitored; however, slight angular cheilitis was observed, and she exhibited no signs of glossitis and dysgeusia (Fig. 1c). Moreover, recurrence and metastasis of the primary tumor were not observed. She subsequently died of lung cancer in May 2020.