Retroperitoneal mass

with possible prostate

involvement or
Lymphoma.
Ashoka Benedict Gomes. 02/21/18
History of present illness:
Our patient PC is a 76 yr old male with PMH significant for BPH, skin cancer, GERD who complains of upper left
side abdominal pain, fatigue and no appetite for the last 3 months with weight loss of 30-35 lbs.
HPI: An Ultrasound followed by CT scan of the abdomen in february showed a large lobulated retroperitoneal mass
at midline to the left compressing the left ureter.
In march, a PET scan showed large retroperitoneal mass compatible with neoplasm with accumulation at
mediastinum, left lung lower lobe, para-aortic nodes, superior mesenteric nodes, tail of the pancreases, peritoneal
implants, left inguinal and iliac nodes. A biopsy is pending.
PMH: In 2010 pt had similar pain and a CT scan showed early small bowel obstruction which was non-malignant. Pt
had laparotomy with mesentery biopsy and biopsy of the axillary lymph nodes.

Current Medical Problem List:

1- GERD. 2- lack of appetite. 3-Hydroneprosis. 4-Retroperitoneal mass.
Family History/Social History:
Health Plan: Medicare part D. Primary Provider: Doctor in puerto rico.
Occupation: Retired. Family History: No family history listed.
Race: Caucasian. Smoking: None
Alcohol: None Illicit drug use: None
Hobbies: Watching TV.
Allergies: NKA.
Immunization: uptodate.
Current Medications:
1- Aspirin 81 mg daily.
2- Famotidine 20 mg daily.
3-Tamsulosin 0.4mg daily.
4- Heparin 5,000 units sc every 12 hours.
5- Acetaminophen as needed.
6-Oxycodone as needed.
7- docusate 100 mg twice daily as needed.
8- Senna daily as needed.
9- Ondansetron as needed.
Review of Symptoms:
General: PC is a 76 year caucasian male; he is 5 feet 6 inches and weighs 150 lb, he reports upper left side
abdominal pain, fatigue and no appetite for the last 3 months with weight loss of 30-35 lbs.
Vital signs: BP 163/89 mmHg. Pulse=101, RR=18. Temp=97.6*F.
Skin: normal skin turgor, no jaundice, some hyperpigmented lesions on chest.
ENT/Mouth/Neck: moist mucous membranes no lesions, neck soft and supple. PERRL, EOMI (eye).
Neuro: moves all extremities, no facial asymmetry.
Psych: Alert and oriented x3, normal mood and affect.
Musculoskeletal: no joint swelling or clubbing.
Abd: BS+, abdomen soft, non-distended, tender at epigastric and diffusely on the left side to palpation.
Cardiovascular: mildly tachycardic regular rhythm, no murmur, no pitting edema.
Respiratory: clear to auscultation with good air flow bilaterally.
Renal: Scr=1.59. BUN=23 mg/dl. Liver: AST=58, ALT=33.
Blood sugar: 75 mg/dL.
Identification of Drug Therapy Problems:
1- Indication for a drug but drug not prescribed. (Imaging shows a retroperitoneal mass but there is no drug treatments
started and a biopsy is pending).
2- Indication for a drug but drug is not effective. (Pt is taking megestrol acetate for lack of appetite but there is risk for
PE and the drug has not been effective for the patient).
3- No indication for a drug (patient is taking Aspirin 81 mg but no indication listed).

Drug Therapy Problem #1:

Indication for a drug but no drug prescribed. Imaging shows a retroperitoneal mass but there is no drug treatments
started and a biopsy is pending.
Pathophysiology of Retroperitoneal mass with possible prostate involvement or Lymphoma:
The retroperitoneal area is behind the peritoneum lining which covers the abdominal space that covers the abdominal
organs (kidneys, pancreas, colon, ureter, bladder). Retroperitoneal Masses are relatively rare and can be benign or
malignant, they are usually diagnosed late at which point the symptoms start.
Disease, cancer, injury or drugs can cause the development of a retroperitoneal mass; the common causes are the
kidneys, pancreas, the colon or adrenal glands.

Treatment of a peritoneum mass depends on its cause; correcting the primary cause of the development of the mass
should shrink the tumor, hence we need to characterize the mass before treatment and verify if it is malignant via CT/MRI
scans, immunohistology, immunophenotyping, flow cytometry for cell surface markers(CD type), PCR for Ig markers and
a biopsy.
Retroperitoneal masses can be malignant tumors like lymphomas, soft tissue sarcomata, neoplasms, neuroblastomas or
can arise from lesions of the organs(kidneys, pancreas, colon, ureter, bladder, prostate).

Lymphomas are further divided into 2 main types Hodgkin and Non-Hodgkin lymphoma and depends on the cell type
involved. Non-hodgkin lymphoma can be further divided into b-cell lymphoma and t-cell lymphoma or other types based
on the cells involved.
It can be treated but might need a stem cell transplant and treatment is decided based on the cells involved. Below is the
usual treatment for diffuse large B-cell (DLBCL) lymphoma the most common non-hodgkin lymphoma.
Intervention to resolve drug therapy problem: for #1
● Per research articles and case studies a starting high dose of prednisolone 60 mg/day tapered by 10 mg/day
within 2 months and stop after 12 months or stop/re-evaluate if confirmed malignancy and start R-CHOP.
Rationale for intervention: Based on research articles and clinical cases.

Pharmacology of prednisolone: Prednisolone suppresses the immune system, decreases inflammation by

suppressing migration of immune cells(leukocytes), decreases capillary permeability.
Pharmacokinetics/dynamics of prednisolone:
Prednisolone is well absorbed, it is hepatically metabolized, it is eliminated in the urine as conjugates.
Preparation/administration/stability/cost of prednisolone: Prednisolone is available as a tablet, solution or syrup. Its
cost is low.
Scientific/Expert opinion: #1
1- Prednisone versus tamoxifen in patients with idiopathic retroperitoneal fibrosis: an open-label randomised controlled trial. Vaglio A, Palmisano A,
Alberici F, Maggiore U, Ferretti S, Cobelli R, Ferrozzi F, Corradi D, Salvarani C, Buzio C. Lancet. 2011 Jul 23;378(9788):338-46.
Objective: The authors evaluated the efficacy of prednisone (corticosteroids(CS) vs tamoxifen in maintenance of remission in
patients with idiopathic retroperitoneal fibrosis (iRPF).
Methods: This was an open label randomized controlled trial of patients with newly diagnosed iRPF who were 1st treated with
1 mg/kg prednisone(cs) and those that achieved remission (36 patients) were randomized to 2 groups of 1- prednisone(cs)
0.5mg/kg for 1 month then 0.25 mg/kg for 2-3 months then, 0.2 mg/kg for 4th month then 0.15 mg/kg for 5th month then 7.5
mg for 6th month then 5 mg for 7th month then 2.5 mg daily for half of the 8th month and 2.5 mg every other day for the rest of
the 8th month. 2- Tamoxifen 0.5 mg/kg daily for months 1-8. Both treatments were stopped on the 8th month and pts followed
for 18 more months.
1* endpoint was relapse rate at month 8 defined by recurrent symptoms, hydroneprosis, mass growth seen on CT/MRI or
combinations. 2* endpoints were change in renal function, ESR, CRP values and size of RPF.
Results: For the primary end point of relapse rate at end of 8th month 1 of 18 patients (6%) in the prednisone group and 7 pts
(39%) in the tamoxifen group relapsed. In the followup 8 to 26 month period 12% of CS and 18% of tamoxifen patients
relapsed showing a lower 26th month cumulative probability for the cs group.
CV, diabetic, HTN, UTIs were similar adverse effects, weight gain was 7 kg (1-10) in the CS group and 2 kg (-3-11) in the
tamoxifen group(p<0.002).
Conclusion: The authors concluded that prednisone is better than tamoxifen in maintenance of remission in pts with iRPF
and causes greater reduction in retroperitoneal mass size, however they note that relapses were frequent and necessitate the
need for other approaches to sustain remission and reduce steroid use.
Scientific/Expert opinion: #2
2- Outcome in patients with idiopathic retroperitoneal fibrosis treated with corticosteroid or tamoxifen monotherapy, Floor E. van der Bilt, Tadek R.
Hendriksz, Wilbert A.G. van der Meijden, Lisette G. Brilman, Eric F.H. van Bommel. Clinical Kidney Journal, Volume 9, Issue 2, 1 April 2016, Pages
184–191.

Objective: The authors evaluated the effectiveness of first use of corticosteroids(CS) vs tamoxifen monotreatment in
patients with idiopathic retroperitoneal fibrosis (iRPF).

Methods: A retrospective study of 118 patients with iRPF was done with treatment success being a composite of 1- relief of
symptoms, 2- CT mass reduction, 3-removal of ureteral stent. Recurrence was reappearance of symptoms/signs and/or CT
mass increase. Mean prednisone/prednisolone(CS) dose was 60 mg/kg and tamoxifen was 20 mg twice daily followed for 2
years.
Results: The time to amelioration of symptoms was shorter 2 weeks in cs group vs 4 weeks in tamoxifen group. Similarly 1st
follow-up CT scan showed mass reduction in cs group vs tamoxifen group. Kaplan-meier analysis for recurrence free survival
was better for tamoxifen group. Recurrence rate was 21.4% for tamoxifen and 67.7% for cs group (p<0.01).

Conclusion: The authors concluded that CS treatment shows more rapid reduction in symptoms and mass reduction but
higher recurrence rates than tamoxifen in iRPF.
Drug Therapy Problem#2:
Indication for a drug but drug is not effective. (Pt is taking megestrol acetate for lack of appetite but there is risk for
PE and the drug has not been effective for the patient).

Rationale for intervention: Based on research articles and clinical cases.

Intervention to resolve drug therapy problem: for #2

discontinuation of megestrol and start 15 mg mirtazapine daily.
Pathophysiology of cancer cachexia:
Cachexia in a cancer patient is a marker of progression of disease and likely poor prognosis. Cachexia should not be looked at
as “STARVATION” as there is research showing that even with supplementation of parenteral nutrition there continues to be
weight loss unlike in starvation. Also mainly skeletal muscle tissues are targeted for wasting v/s fat tissue that are targeted in
starvation suggesting different signalling pathways for cancer cachexia and starvation.

The key mechanism underlying cachexia is thought to be the increased breakdown of self muscle protein, along with
decreased protein synthesis, which leads to overall muscle loss (13) although the signaling between the cells that cause the
increased breakdown / the cancer cells and other cells/proteins are unclear. Suggested causes of cachexia that when targeted
have improved appetite are 1-Immune system cytokines: TNFa has been shown to promote anorexia and muscle wasting
but blockage has not been shown to reverse cachexia hence by itself it is insufficient to reverse wt loss, Similarly IFNg and
IL1. IL6 is also secreted by the tumors directly correlating to cachexia.

2-Skeletal muscle wasting: Changes in the anabolic and catabolic events regulating muscles is disrupted during cancer
cachexia some of the molecular mechanisms are a) decrease in anabolic insulin-like growth factor-1 (IGF-1) (and
increased insulin resistance). b) increase in catabolic factors like myostatin, activin A , Block of activin receptor IIB
(ActRIIB)) and cytokines. c) upregulation in skeletal muscle of ubiquitin-mediated proteasome degradation (UPR) by
increased ubiquitin-ligase MurF1 and Atrogin-1 regulated by NF-κB d) Autophagy by mediators BNIP3 (mRNA)/ LC3B and
transcription factor FOXO1. e) NF-κB induces the activation and expansion of the satellite cells (skeletal stem cells), but they
do not complete differentiation further worsening the wasting (15) due to the deregulation of the regeneration of muscle.
3-Cardiac muscle: cardiac wasting involves proteins of the UPR system (16). (arrhythmias and HF cause death in cancer pts).
4- Liver wasting. liver mass substantially increases during cachexia progression by promoting hypermetabolism and increased
energy expenditure. 5-Lipid wasting and browning: Fat tissue switch from white adipose to brown adipose with mitochondria
and high levels of UCP-1, which directly promotes thermogenesis (heat). 6-Brain and food intake: The hypothalamus plays a
role as it does not respond to peripheral signals in the case of ghrelin (orexigenic), neuropeptide Y. 7-Pancreas. cancer
patients can present with insulin resistance. 8- Gastrointestinal tract.

There is data supporting SARMs (selective androgen receptor modulators) that, bind the androgen receptor like testosterone but with
tissue selectivity. Enobosarm a non FDA approved (SARM) lacks testosterone’s steroid rings and thus cannot convert to
dihydrotestosterone, which promotes prostate growth (and cancer). This moiety went up to phase 3 trials and boosted lean
muscle mass in 2 trials, but stair-climbing power only in 1. It was abandoned due to CV risks, it is sold as a dietary supplement
“ostarine”.

Pharmacokinetics/dynamics of mirtazapine: Mirtazapine is rapidly orally absorbed with 50% bioavailability, its half life is 20-40
hours. 75% is excreted in the urine as metabolites after liver CYP1A2, 2D6, 3A4 metabolism.
Preparation/administration/stability/cost of mirtazapine: Mirtazapine is available as a tablet and orally disintegrating tablet. It is
inexpensive.
Scientific/Expert opinion: #1
11- Phase II trial of mirtazapine for cancer-related cachexia and anorexia. Riechelmann RP, Burman D, Tannock IF, Rodin G, Zimmermann C. Am J Hosp
Palliat Care. 2010;27(2):106.

Objective: The authors analyzed the effectiveness of mirtazapine on weight gain in cancer cachexia patients(wt loss).
METHODS: This was an open label phase 2 trial of mirtazapine 15 daily x3 days then 30 mg daily x 8 weeks.on 17 patients. The 1*
endpoint was gain of >1 kg at week 4.
2* endpoint was improvement in HQOL or appetite at week 4.
Results: For the 1* endpoint 4 of 17 patients (24%) increased weight >1 kg (1 to 3.6kg) and also had better 2* endpoints of improvement
in appetite (ESAS score >2 points improvement) and HQOL. At the end of 8 weeks there was still weight gain and improvement in
appetite and HQOL scores.

CONCLUSION: The authors concluded that mirtazapine induced weight gain, increased appetite and HQOL increases in cancer
cachexia patients are promising and should be further studied.
Scientific/Expert opinion: #2
Intervention of mirtazapine on gemcitabine-induced mild cachexia in nude mice with pancreatic carcinoma xenografts.Jiang SM1, Wu JH,
Jia L. World J Gastroenterol. 2012 Jun 14;18(22):2867-71.

Objective: The authors analyzed the effect of mirtazapine on tumor growth, food intake, weight and nutritional status on
induced cachexia.

Methods: 14 mice were grafted with pancreatic cancer cell line(SW1990) and divided into mirtazapine (10 mg/kg) or saline
groups fed each day. A model of cachexia was established by gemcitabine (50 mg/kg) intraperitoneal injection on days 10, 13,
16.

Results: On day 7 of gemcitabine injection wt loss of 5-7% was seen indicating induction of mild cachexia. At day 21
mirtazapine group ate more food 3.95g vs 3.54g (p<0.004); similarly at day 25 mirtazapine group weighed more 18.05g vs 17g
for control (p<0.014).

Conclusion: The authors concluded that mirtazapine improved gemcitabine induced cachexia in pancreatic tumor bearing
mice.
Alternative Drug Therapy:

For drug problem#1: 1- Tamoxifen 20 mg twice daily. 2- Combination of prednisone 60-120 mg qid with cellcept 1000 mg twice
daily. 3- Combination of prednisolone followed by tamoxifen treatment.

For drug problem#2: 1- Prednisone 15 mg daily for 4 weeks then consider a week off (5,6,7). 2- Marinol 2.5 mg daily. 3-
Dexamethasone 4 mg/day. 4- Medroxyprogesterone 200 mg/day 5- Methylprednisolone 4-48 mg/day.
Monitoring Plan:

Parameter Frequency

Weight daily Goal will be an increase in weight.

Improvement in appetite measured by Every 4 weeks

ESAS score

CT scan to measure mass size monthly Goal will be a reduction.

Patient is in the hospital.

Physical examination daily Goal will be relief of symptoms.

Patient is in the hospital.

Patients hydration status daily Patient might need chemotherapy if

malignancy is detected and needs to be
ready.

Blood Pressure daily JNC 8 guidelines of <150/90

CBC daily Patient is in the hospital.

Adverse effects:
Parameter Frequency

Temperature monitoring for Daily Patient is in the hospital.

development of
fever/infection.

Hyperuricemia Daily Patient is in the hospital.

May need to start allopurinol to reduce uric
acid levels.

Hypercalcemia Daily Patient is in the hospital.

Follow-up evaluation plan:

Patient will be monitored for any adverse events and hydration status. Patient is in the hospital.
References:
3- Retroperitoneal Fibrosis Treatment & Management. Nov 02, 2017, Chandra Shekhar Biyani.
4- Retroperitoneal fibrosis – a report of five cases. Runowska M, Majewski D, Puszczewicz M. Reumatologia. 2017;55(3):140-144.
5- Alshaikh S, Harb Z. Prostate Cancer Presenting as Huge Mediastinal and Retroperitoneal Masses: Case Report and Review of the
Literature. Case Reports in Pathology.;2017:7312740.
6- Health-Related Quality of Life in Men With Metastatic Prostate Cancer Treated With Prednisone Alone or Mitoxantrone and
Prednisone. David Osoba, Ian F. Tannock, D. Scott Ernst, and Alan J. Neville. Journal of Clinical Oncology 1999:17:6, 1654-
1654.
7- Retroperitoneal Diffuse Large B-Cell Lymphoma Presenting As Pseudoachalasia. Danielle M. Pastor, Ashley D. Eggers,
Joseph J. Drabick, Thomas P. Loughran, Michael G. Bayerl, and Timothy R. Shope. Journal of Clinical Oncology 2010 28:12,
e184-e187.
8- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Non-Hodgkin's.Lymphomas.
9- Chen C, He H, Yu Z, Qiu Y, Wang X. Renal and retroperitoneal metastasis from prostate adenocarcinoma: a case report. World Journal of
Surgical Oncology. 2016;14:74.
10- Malignant lymphoma involving the prostate: Report of 62 cases. David G. Bostwick M.D, Kenneth A. Iczkowski M.D, Mahul B.
Amin M.D, Guzel Discigil M.D, Barbara Osborne M. Cancer: Volume 83, Issue 4: 15 August 1998, Pages 732–738.
References (continued):
13- Cachexia: The last illness. Nature: Vol 528: 10 dec 2015, pp 182-183.
14- Understanding cachexia as a cancer metabolism syndrome. PE Porporato. Oncogenesis (22 feb 2016) 5, e200.
15- He WA, Berardi E, Cardillo VM, Acharyya S, Aulino P, Thomas-Ahner J et al. NF-kappaB-mediated Pax7 dysregulation in the
muscle microenvironment promotes cancer cachexia. J Clin Invest 2013; 123: 4821–4835.
16- Willis MS, Bevilacqua A, Pulinilkunnil T, Kienesberger P, Tannu M, Patterson C. The role of ubiquitin ligases in cardiac disease.
J Mol Cell Cardiol 2014; 71: 43–53.
17- Garcia JM, Garcia-Touza M, Hijazi RA, Taffet G, Epner D, Mann D et al. Active ghrelin levels and active to total ghrelin ratio in
cancer-induced cachexia. J Clin Endocrinol Metab 2005; 90: 2920–2926.
18-Laviano A, Russo M, Freda F, Rossi-Fanelli F. Neurochemical mechanisms for cancer anorexia. Nutrition 2002; 18: 100–105.
19- The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy
elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. Journal of Cachexia,
Sarcopenia and Muscle ,Vol 2: 3, Sept 2011. Pp 153–161.
20- The enobosarm saga. Nature Biotechnology 34, 458–461. (6th may 2016).
21-http://dpg-storage.s3.amazonaws.com/ondpg/documents/7efcf017571f4635/Medication_Guide.pdf