Undifferentiated Weight Loss — DCE Clinical Case

The patient scenario

Mr R, a 68-year-old retired carpenter, was referred by his GP for the investigation of the involuntary weight loss. [1]

Over the preceding 3 months he had lost 8 kg (10 per cent of his usual body weight of 80 kg). The loss was documented objectively on the GP record. He had not been trying to lose weight. He described a marked reduction in his appetite — he felt full after a few mouthfuls (the early satiety) — and intermittent nausea. He had the drenching night sweats that soaked the bedsheets. He had noticed increasing fatigue and breathlessness on the exertion (the anaemia). He had no dysphagia, no change in the bowel habit, no rectal bleeding, no abdominal pain, no jaundice, no cough, no haemoptysis, and no urinary symptoms. [1]

His past medical history included the hypertension (on the amlodipine 10 mg daily), the hyperlipidaemia (on the atorvastatin 40 mg daily), and the osteoarthritis. He was a non-smoker and drank 10 standard drinks per week. His father had the colorectal cancer at the age of 72. [1]

His GP bloods showed: the haemoglobin 102 g per litre (MCV 72 fL), the ALP 320 U per litre, the LDH 480 U per litre, the albumin 32 g per litre, the white cell count 14.2, the CRP 48, the normal electrolytes, the normal TFTs, the normal glucose and the HbA1c, the normal LFTs apart from the ALP. His faecal immunochemical test was positive. [1]

The history-taking framework

The structured history for the weight loss patient covers: [1]

The amount and the rate:

• "How much weight have you lost, and over how long?"
• "Were you trying to lose weight?" (the intentional versus the involuntary)
• "Can we check your weight from the records to confirm?" (the objective documentation) [1]

The appetite (the single most important discriminator):

• "Have you lost your appetite, or are you eating normally or more than usual?"
• The preserved appetite with the weight loss points to the hyperthyroidism, the diabetes, the malabsorption.
• The reduced appetite with the weight loss points to the malignancy, the infection, the depression, the obstruction. [1]

The GI symptoms:

• "Do you have any difficulty swallowing?" (the dysphagia — the oesophageal)
• "Do you feel full quickly?" (the early satiety — the gastric outlet obstruction)
• "Any abdominal pain, any change in your bowel habit, any blood in the stool?"
• "Any pale, oily, or foul-smelling stools that are difficult to flush?" (the steatorrhoea — the malabsorption) [1]

The endocrine symptoms:

• "Any excessive thirst or passing a lot of urine?" (the diabetes)
• "Any heat intolerance, palpitations, tremor, or anxiety?" (the hyperthyroidism)
• "Any dizziness when you stand up, any salt craving?" (the Addison disease) [1]

The systemic symptoms:

• "Any fever, night sweats, or itching?" (the malignancy, the lymphoma, the infection)
• "Any fatigue, any weakness, any breathlessness?" (the anaemia, the cachexia) [1]

The mood and the function:

• "How is your mood? Have you lost interest in the things you used to enjoy?" (the depression screen)
• "How is your sleep? Do you wake early?"
• "Can you manage the shopping, the cooking, the cleaning?" [1]

The drug history:

• "What medications do you take? Any recent changes?"
• (The metformin, the SGLT2 inhibitors, the topiramate, the levothyroxine, the chemotherapy) [1]

The social history:

• "Do you live alone? How do you manage the meals?"
• "Are there any financial concerns?" [1]

The presentation (SASPOP)

"Mr R is a 68-year-old retired carpenter presenting with a 3-month history of the involuntary weight loss of 8 kg (10 per cent of his usual body weight), with the anorexia, the early satiety, the drenching night sweats, and the iron deficiency anaemia with the positive faecal immunochemical test." [1]

The problem list: [1]

1. The significant involuntary weight loss (10 per cent in 3 months) with the multiple red flags for the malignancy — the anorexia, the early satiety, the night sweats, the iron deficiency anaemia, the positive FIT, the elevated ALP and LDH.
2. The iron deficiency anaemia — the microcytic anaemia (Hb 102, MCV 72) from the likely chronic GI blood loss.
3. The elevated ALP, the elevated LDH, the low albumin, the elevated white cell count — three of the five Hernandez malignancy prediction score variables.
4. The positive faecal immunochemical test — confirming the GI mucosal abnormality.
5. The nutritional risk — the 10 per cent weight loss and the reduced intake.
6. The family history of the colorectal cancer (the father at 72) — the increased risk. [1]

The integrated management plan

The investigations (the priority — the Tier 2 malignancy workup): [1]

1. The CT chest, abdomen, and pelvis with the intravenous contrast — to identify the primary tumour, the metastatic disease, and the staging.
2. The upper GI endoscopy with the duodenal biopsy — to identify the oesophageal, the gastric, and the duodenal malignancy, to obtain the biopsy, and to screen for the coeliac disease.
3. The colonoscopy — to identify the colorectal malignancy (the family history) and to obtain the biopsy.
4. The iron studies and the ferritin — to confirm the iron deficiency.
5. The tumour markers (the CEA, the CA 19-9) — as the adjuncts. [1]

The nutritional support:

• The oral nutritional supplements (Fortisip 200 mL, 2 to 3 bottles per day).
• The dietitian referral for the individualised plan.
• The food fortification (the small, frequent, energy-dense meals).
• The antiemetic for the nausea and the early satiety (the metoclopramide 10 mg three times daily before the meals).
• The iron replacement (the oral ferrous sulphate 200 mg three times daily, or the intravenous iron if the oral is not tolerated). [1]

The communication and the shared decision-making:

• The honest discussion with the patient and the family about the concern for the malignancy.
• The explanation of the planned investigations and the timeline.
• The support available (the cancer nurse coordinator, the social work, the psychology).
• The advance care planning discussion at the appropriate time. [1]

The discussion questions

Q1: What is the most likely diagnosis and why?

"The most likely diagnosis is the GI malignancy — the gastric, the pancreatic, or the colorectal. The reasoning: the significant involuntary weight loss (10 per cent in 3 months) with the anorexia (not the preserved appetite), the early satiety (the gastric outlet obstruction from the gastric or the pancreatic malignancy), the night sweats (the malignancy or the lymphoma), the iron deficiency anaemia (the chronic GI blood loss), the positive faecal immunochemical test (the GI mucosal abnormality), and the elevated ALP and LDH (the malignancy markers from the Hernandez score). The family history of the colorectal cancer (the father) increases the probability of the colorectal malignancy. The CT CAP and the bidirectional endoscopy will identify the primary." [1]

Q2: What is the Hernandez prediction score and how does it apply?

"The Hernandez score is the clinical prediction tool for the malignancy in the involuntary weight loss, derived from the 2003 cohort of 306 patients [2] [3]. The five variables: the elevated ALP, the elevated LDH, the albumin below 40, the elevated white cell count, the age above 80. Two or more variables increase the malignancy probability. This patient has three: the elevated ALP, the elevated LDH, and the low albumin — placing him in the high-probability group. The score supports the urgent Tier 2 workup."

Q3: How would you manage the cancer cachexia if the malignancy is confirmed?

"The cancer cachexia is the cytokine-mediated syndrome of the skeletal muscle wasting that cannot be fully reversed by the feeding alone (the Fearon 2011 consensus) [5]. The management at each stage: in the precachexia, the nutritional counselling and the early intervention; in the cachexia, the nutritional support (the oral supplements, the enteral feeding if needed), the symptom control, and the treatment of the cancer; in the refractory cachexia, the palliative approach with the symptom control, the corticosteroid or the progestogen for the appetite, and the advance care planning. The forced feeding in the refractory cachexia causes the distress without the benefit."

Q4: What if the CT and the endoscopy are normal?

"If the CT CAP and the bidirectional endoscopy are normal, the probability of the GI malignancy is very low. The next step depends on the clinical picture: if the weight loss continues, the further investigation (the PET scan, the capsule endoscopy for the small bowel) may be considered. If the workup is otherwise normal and the weight loss stabilises, the observation with the re-weigh and the reassessment is appropriate. The Metalidis evidence supports the observation: the completely normal workup has a 99 per cent negative predictive value for the malignancy at one year [4]."

The short-case examination — the cachectic patient

The instruction: "Examine this patient who has lost weight." [1]

The examination routine: [1]

1. General inspection — the cachexia (the temporal wasting, the hollow cheeks), the pallor (the anaemia), the agility. [1]

2. Hands — the clubbing (the malignancy, the IBD, the cirrhosis, the coeliac), the koilonychia (the iron deficiency), the pulse (the AF of the hyperthyroidism), the tremor. [1]

3. Face and neck — the conjunctival pallor (the anaemia), the oral candidiasis (the immunosuppression, the HIV), the angular cheilitis and the glossitis (the iron, the B12, the folate), the dental decay and the dentures, the goitre, the lymph nodes (the cervical, the supraclavicular — the Virchow node). [1]

4. Chest — the heart (the murmurs, the rub), the lungs (the crackles, the wheeze, the apical signs of the TB). [1]

5. Abdomen — the cachexia (the scaphoid abdomen), the hepatomegaly, the splenomegaly, the masses, the ascites, the PR examination (the rectal mass, the prostate, the melaena). [1]

6. Skin — the hyperpigmentation (the Addison), the dermatitis herpetiformis (the coeliac). [1]

7. Functional and cognitive — the gait, the grip strength, the ADLs, the MMSE or the MoCA, the depression screen. [1]

The presentation template: [1]

"On the general inspection, the patient is cachectic with the temporal wasting and the prominent cheekbones. The hands show the clubbing and the conjunctival pallor. The neck reveals a 2-cm firm, non-tender left supraclavicular lymph node. The abdominal examination reveals a hard, irregular mass in the epigastium. These findings — the cachexia, the clubbing, the pallor, the supraclavicular node (the Virchow node), and the epigastric mass — are consistent with the advanced gastric cancer. I would arrange the upper GI endoscopy and the biopsy, the CT chest abdomen and pelvis for the staging, and the referral to the gastroenterology and the oncology team." [1]

References

1. Gaddey HL, Holder K. Unintentional weight loss in older adults. Am Fam Physician 2014;89(9):718-722. PMID 24784334.
2. Hernández JL, Riancho JA, Matorras P, González-Macías J. Clinical evaluation for cancer in patients with involuntary weight loss without specific symptoms. Am J Med 2003;114(8):631-637. PMID 12798450.
3. Hernández JL, Matorras P, Riancho JA, González-Macías J. Involuntary weight loss without specific symptoms: a clinical prediction score for malignant neoplasm. QJM 2003;96(9):649-655. PMID 12925720.
4. Metalidis C, Knockaert DC, Bobbaers H, Vanderschueren S. Involuntary weight loss. Does a negative baseline evaluation provide adequate reassurance? Eur J Intern Med 2008;19(5):355-359. PMID 18549937.
5. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011;12(5):489-495. PMID 21296615.
6. Wallace JI, Schwartz RS, LaCroix AZ, Uhlmann RF, Pearlman RA. Involuntary weight loss in older outpatients: incidence and clinical significance. J Am Geriatr Soc 1995;43(4):329-337. PMID 7706619. [1]