As discussed, I am submitting two current hospital cases for discussions. The tilt is not in the diagnoses or management, but in the 'red herring' flavor inherent in both cases, which should allow for generous clinical discussions.
However, before you post these cases for discussion, I believe that the discussion on Lynne's patient with HIV should continue. As a smaller city, Sue's observation and prediction that similar cases will crop up, is important. I believe the SPECIFIC management for the patient with HIV should be discussed fully as a learning baseline:
* determination of the patient's current immune status
* specific chemotherapeutic options [combination therapy]
* adjuvant therapies
* follow-up parameters: management algorithm
* the HIV status of her child
* contact/cohort mapping
* support systems
RED HERRING CASE #1:
A 48-year old lady slipped on ice and fractured her left hip. She was transferred from a local hospital to an orthopedic surgeon in Timmins for further management. Left hip pinning and concomitant repair of the left patella were undertaken successfully. Intraoperative blood loss = 400 ml.. The surgery was uneventful.
She has a functioning ventriculo-peritoneal shunt in place [ 2 previous vehicular accidents --> HP hydrocephalus + post-traumatic seizure]
36 hours later, she became suddenly dyspneic and hypotensive. Respiratory rate was 38/minute. Oxygen saturation on room air was 80%. ABGs: pH - 7.43: pCO2 - 23: pO2 - 45: HCO3 - 23 02 saturation - 85%.
Initial assessment by the ERP:
* afebrile, cyanotic
* pulse rate = 112/minute BP = 75/45
* dullness to percussion, right mid-lung: correlating reduced air entry: bibasilar rhonci
* surgical sites = normal: little blood in the drain tube
* normal abdominal examination: no ascites.
Initial laboratory results:
* white cells: 2x: marked neutrophilia, left shift; * CXR:
* hemoglobin: 68, normal MCV normal hematocrit - a triangular dense infiltrate in the right middle lobe
* thrombocytopenia: 62 - perihilar edema
* mildly elevated D-dimer: elevated fibrinogen - mild pulmonary and interstitial edema
* urinalysis: 4+ blood, minimal proteinuria, hyaline casts
* elevated liver transaminases 3x: LDH 2x: severe hypoalbuminemia
normal globulin.
The patient did not respond to 100% oxygen administered via the rebreather mask. She was transferred to the ICU. She became obtunded, severely hypotensive, peripherally shut down and went into ARDS. Resuscitative measures were started.
What are the differential diagnoses at this stage?
The clinical history and findings are of
1. Pulmonary Embolism (High Probability): now whether Thromboembolic or Fat embolism - both are possible. Did this patient had hematuria before surgery? otherwise a systemic embolic process is a possibility. PE would be massive PE as there is significant hypotension.
2. ARDS: is secondary to process #1. Although ARDS can occur following a massive PE but fat embolism will be high in view of recent HIP Pinning. Was this patient Obese?
3. DIC is also going on with elevated D-Dimer and thrombocytopenia.
4. Sepsis with ARDS and Septic shock is another possibility but as the events occurred so fast, I think #1 is high on the list.
RED HERRING CASE #2:
A 72-year old man was transferred from a local hospital for localization of the primary for metastatic adenocarcinoma, and management.
Over the last one month, he noted a rapidly-enlarging mass on the abdominal wall in the right lower quadrant. It ws associated with a 39-pound weight loss, night sweats, annorexia nad malaise. He had a left lower lung lobectomy in 1968. The indication is not clear. Histology = fibrosis: no granuloma, silicotic nodules or malignancy. He has smoked 2 pckets of cigarettes/day x 40 years. He was exposed to high load of dust, and perhaps to some asbestos. He has no pain. He feels full after eating. Bowel movements are normal, 'but he does not look at his stools'. He has difficulty initiating micturition. Urinary stream is markedly reduced. He has significant terminal dribbling. He drank alcohol heavily from ages 28 to 35, and then moderately since then.
There is no relevant family history.  On examination:  * cachexia: anicteric, no peripheral lymph nodes.  * reduced air entry left lung base: normal thoracotomy scar  * normal cardiovascular examination: reduced peripheral pulses  * abdomen: recurrent tumor at the RLQ scar: no intrabdominal masses  * 2x prostamegaly, no nodules.
A 5 cm mass was excised from the anterior abdominal wall at the local hospital: histology = poorly-diferentiated adenocarcinoma. PSA -negative by immunoperoxidase
Laboratory results at transfer:   * chest x-ray: reactive fibrotic and pleural changes only at the site of previous surgery
* wbc = normal. Hemoglobin = 105. ESR = 104  * liver enzymes = normal.  * urinalysis: 4+ hematuria: wbc = 80 - 100 cells/HPF, minimal proteinuria  * normal BUN, creatinine * abdominal C/T scan: raective changes to previous surgery at L hemidiaphragm, otherwise normal.
Further relevant clinical data in Timmins: - no breast masses - no scrotal lesions
* small bowel follow through: normal  * gastroscopy: minimal gastritis: histology = focal severe dysplasia. H. pylori negative
* colonoscopy: hyperplastic polyps: an ulcerated but benign-appearing polypoid mass at sigmoid colon [final histology pending]
* terminal ileum endoscopy + biopsies: normal  * serum alpha feto-protein: normal   * serum PSA: normal  * sputum: many dust cells, bacteria: negative cytology
The recurrent tumor at the anastomosis was increasing by a size of 0.4cm/day during his admission.
Where is his primary?
Interesting case! A simple answer is GOK (God Only Knows).
This is likely a case of "Tumor of Unknown Primary site" and may represent a tumor of various lineages: Lymphoma, melanoma, Sarcoma. There are various possibilities are there including germ cell tumor or neuroendocrine tumor.
The important questions in these type of cases is how much evaluation be done to find the primary site.
Investigations in these patients should be focused to the symptoms or signs suggesting a system involved. Exhaustive evaluation in this group of patient's is expensive, often misleading, and only rarely leads to detection of primary tumor or to an effective management plan.
I think that the pathologist should do electron microscopy, that at times may help to establish a definitive diagnosis in some poorly differentiated tumors and distingush carcinoma from lymphoma.
The pathologist should consider special staining techniques to give a clue to the origin of tumor rather than labelling it as "poorly differentiated Adenocarcinoma". After special stains gives a clue then may consider evaluation to look for primary. Special stains that could be considered are: leukocyte common antigen, Stains for cytokeratins, PSA staining, HCG, Alpha-fetoprotein (not serum levels but staing of tissue), neuron-specific enolase and chromogranin, S-100 protein, HMB-45, vimentin, desmin, factor VIII antigen. Also chromosomal changes - chromosome 12 [i(12p)] abnormality is diagnostic of germ cell tumnor.
1. ARDS:
Dr. Parmar touched on all the differentials. It was very difficult to mechanically ventilate the patient. Along with ancillary measures, maximally-tolerated positive airway pressures combined with 100% oxygen were employed for 36 hours.
She was put on low-molecular weight heparin, assuming massive [saddle] thromboembolism, and surgery to hip and knee less than 48 hours before. A V/Q scan was deemed useless and wasteful since the CXR showed 'white out', and heparinazation would have commenced irrespective of the lab results. There was no local hematoma or systemic bleeding.
She was put on full-spectrum antibiotic coverage. She had no allergies, and the cheapest combination: penicillin. gentamycin and metronidazole, was employed pending further bacteriologic differentiaition.
The thrombocytopenia was felt to represent systemic suppresion: the elevated fibrinogen product was felt to make the likelihood of significant DIC unlikely.
Fat embolism was indeed a contributory factor. Large amounts of fat globules were recovered from the tracheal aspirate.
Further interim reports:
Day 1:
1. CXR: deterioration in bilateral alveolar edema + interstitial edema: cannot exclude underlying pneumonia.
2. preliminary blood, urine cultures- negative
3. Hemoglobin down to 58 despite transfusion with 6 units of blood. Platelet count - down to 54. worsening liver enzymes [mixed pattern]: serum albumin down to 21 [1+ proteinuria] Total parenteral nutrition without intralipids and 25% albumin transfusion statrted.
4. CPK now elevated 5-fold. AST, LDH elevated 3-fold. ECG: diffuse non-specific ST changes: change in LV transitional zone.
CASE OF METASTATIC ADENOCARCINOMA:
Again, Dr. Parmar was accurate in the need to streamline investigations in the most cost-effective way. Such primaries are usually gastrointestinal, pancreatic, lung, prostatic, renal, testicular [breast, ovarian]. Dr. Parmar listed less common sites. The list is quite exhaustive. Yet the primary is never found in 40 to 50% of such cases.  The polypoid lesion in the sigmoid colon was indeed a benign ulcerated polyp, felt to be secondary to focal ischemia or autoischemia within the polyp.  It was really felt unnecessary to go on to further investigations given the absence of a reasonable-sized [resectable] primary, obvious progresive systemic symptoms and the ultimate commitment to palliative chemotherapy. Arrangements were initiated for chemotherapy assesment for metastatic adenocarcinoma of undetermined primary.  The patient was re-evaluated clinically on day 3. Significant differential breath sounds were found in the right lung.  A thoracic C/T scan was then ordered
RED HERRING CASE #1:  Fat embolism syndrome contributes to the development of the Adult Respiratory Distress Sydrome and is life-threatening. Mortality remains very high. Its letal punch is in the ability of the fat to microembolize. In addition, fat emboli can deform and PASS THROUGH the lungs ending in systemic embolization, especially to the brain, liver and kidneys. Marrow fat is deposited within the pulmonary capillaries. In the systemic circulation, increases in circulating free fatty acids, increases in fibrin split products and increases in platelet adhesiveness occur. Fat embolism occurs in more than 90% of patients with traumatic injury, yet only 0.3 to 4% of patients develop the Fat Embolism Syndrome.
The diagnosis is based on the history, and suported by pulmonary edema and signs of cerebral [CNS depression], renal and cutaneous dysfunction. Fever, hypoxemia, tachypnea, petechiae, retinal fat emboli, altered sensorium and an ARDS-type chest X-ray are seen in all patients. Respiratory alkalosis, anemia and hypocalcemia are seen commonly
It is confirmed by arterial hypoxemia and the demonstration of fat globules within pulmonary macrophages.
Treatment consists of general supportive measures, correction of the severe fluid, electrolye, mineral and acid base imbalances, and graduated oxygen therapy. Aggressive, mechanical ventilatory modalities are required. The use of steroids and heparin is controversial. Recovery does not result in any residual lung injury.
Early diagnosis:  trauma with fractures

• young males under the age of 30, with early hypoxemia are at highest risk
  

• the initial fever, dyspnea, leucocytosis and a classic initial right lung lesion suggesting aspiration pneumonia
  
• massive pulmonary embolism was considere initially, and could not be excluded. It was not the primary problem however, because of the overload of other systemic features. Low-grade PTE could not be excluded and the low-molecular weight heparin was used.