Cancer Treatment

Laparascopic liver resection for benign lesions.

It is a fairly rare for benign liver lesions causing pain and there are no specific guidelines for thist. However, the literature contains many reports of this procedure being performed for non-cancer diagnosis(2,4). In experienced hands, laparoscopic liver resection is a favorable alternative to open resection. Perioperative morbidity and mortality and long-term survival after laparoscopic resection  appear to be comparable to those after open resections.

1.http://www.hpblondon.com/assets/Laparoscopic%20liver%20re%20EC5A1.pdf

2.Simillis C, Constantinides V, Tekkis P, et al. Laparoscopic versus open hepatic resections for benign and malignant neoplasms- a meta-analysis. Surgery. 2007;141:203–211.

3.Vibert E, Perniceni T, Levard C, et al. Laparoscopic liver resection. Br J Surg. 2006;93:67–72.

4.Laparoscopic Liver Resection for Malignant and Benign Lesions Ten-Year Norwegian Single-Center Experience Airazat M. Kazaryan,Arch Surg. 2010;145(1):34-40

Treatment of sclerosing mesenteritis

 

Sclerosing mesenteritis, also called mesenteric panniculitis, is a rare non-neoplastic disease that affects the small bowel mesentery with chronic fibrosing inflammation. Although a relatively benign condition, sclerosing mesenteritis can have a prolonged debilitating course with a fatal outcomeThere are few data on the natural history and therapeutic options for this condition. Tamoxifen in combination with prednisone is teh most common treatment, and most patients respond. I did not find any reports of the use of Rituxan.

 

Savvas Hiridis et al, Sclerosing mesenteritis affecting the small and the large intestine in a male patient with non-Hodgkin lymphoma: a case presentation and review of the literature

Journal of Medical Case Reports 2008, 2:388 

 

Akram S, Pardi DS, Schaffner JA, Smyrk TC.

Sclerosing mesenteritis: clinical features, treatment, and outcome in ninety-two patients.

Clin Gastroenterol Hepatol. 2007 May;5(5):589-96.

Pemberton, John D, Idiopathic Sclerosing Orbital Inflammation: A Review of Demographics, Clinical Presentation, Imaging, Pathology, Treatment, and Outcome Ophthalmic Plastic & Reconstructive Surgery: January/February 2012 - Volume 28 - Issue 1 - p 79–83

 

Treatment of Langherhan's Hystiocytosis

Histiocytosis is a rare  disease that involves hystiocytes. The disease can range from limited involvement that spontaneously regresses to progressive multiorgan involvement that can be chronic and debilitating. In some cases, the disease can be life-threatening.It is approximated that histiocytosis affects 1 in 200,000 children born each year in the United States. The disease us rare and not much is known securely about how to treat it. Because of its rarity, prospective studies are not possible.

In 2009, a guideline was published by the Hystiocytosis Soceity It recommens an initial 6-week course of therapy with vinblastine and prednisone  for all patients with MS-LCH; regardless of risk organ involvement.It is also recommended that all patients who have complete disease resolution (NAD)
after 6-12 weeks of initial therapy continue with maintenance therapy. Maintenance therapy consists of pulses of vinblastine and prednisone every 3 weeks and daily continuous 6-mercaptopurine (6MP) for a total treatment duration of 12 months. Currently, there is insufficient evidence to support an optimal course of treatment for use with patients suffering from severe progressive MS-LCH who do not respond to standard therapy. Recently, promising results have been reported for patients treated with a combined regimen of 2-chlorodeoxyadenosine (2-CdA, Cladribin, Leustatin) and cytarabine (Ara-C) (12); as well as stem cell transplantation after reduced intensity conditioning regimen (RIC-SCT). However, the results generated by both reports are based on limited observations and must be validated by the prospective clinical trials.

LANGERHANS CELL HISTIOCYTOSIS Histiocyte Society Evaluation and Treatment Guidelines April 2009

Histiocyte Society 26th Annual Meeting Abstracts, Boston, Massachusetts
Article first published online: 4 FEB 2011
Pediatric Blood & Cancer Volume 56, Issue 4, pages 689–703, April 2011

Bernard F, Thomas C, Bertrand Y, Munzer M, Landman Parker J, Ouache M,
et al. Multi-centre pilot study of 2-chlorodeoxyadenosine and cytosine arabinoside
combined chemotherapy in refractory Langerhans cell histiocytosis with
haematological dysfunction. Eur J Cancer 2005;41(17):2682-9.

Steiner M, Matthes-Martin S, Attarbaschi A, Minkov M, Grois N, Unger E, et al.
Improved outcome of treatment-resistant high-risk Langerhans cell histiocytosis after
allogeneic stem cell transplantation with reduced-intensity conditioning. Bone Marrow
Transplant 2005;36(3):215-25.

Erbitux for squamous cell cancer of unknown primary site

When the primary site is not identified and when it does not fall neatly into certain specific clinical patterns, empiric broad-spectrum chemotherapy is recommended by NCCN and is generally acceptable. The issue remains second line chemotherapy. Erbitux is approved for squamous cell cacner of head and neck and is an attractive candidate for unknown primary.  Unfortunately, these patients have a dismal prognosis despite management with a variety of chemotherapeutic combinations in small clinical studies. A recent meta-analysis showed no evidence of superior efficacy of any of the administered regimens incorporating platinum salts, taxanes or new generation cytotoxic compounds (gemcitabine, vinca alkaloids, irinotecan). Modest if any survival prolongation and symptom palliation with preservation of quality of life are the only realistic aims of therapy for these patients. Consequently, low-toxicity patient-convenient chemotherapy regimens should be administered to reasonably fit poor-risk patients. Currently neither ESMO nor NCCN recommend Erbitux even in first line. NCCN recommendations do nto include Erbitux(OCC-B, 1) and enitehr recommends second line chemotherapy.

N. Pavlidis1, E. Briasoulis, G. Pentheroudakis and On behalf of the ESMOCancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Ann Oncol (2010) 21 (suppl 5): v228-v231.

K. Hemminki et al, Power and limits of modern cancer diagnostics: cancer of unknown primary
Ann Oncol (2012) 23(3): 760-764

Greco, F. Anthony , Rodriguez, Gladys I. , Shaffer, Don W. , Hermann, Robert , Litchy, Sharlene , Yardley, Denise A. , Burris, Howard A., III , Morrissey, Lisa H. , Erland, Joan B. , Hainsworth, John D. Carcinoma of Unknown Primary Site: Sequential Treatment with Paclitaxel/Carboplatin/Etoposide and Gemcitabine/Irinotecan: A Minnie Pearl Cancer Research Network Phase II Trial Oncologist 2004 9: 644-652;

F. Anthony Greco et al, Carcinoma of Unknown Primary Site: Sequential Treatment with Paclitaxel/Carboplatin/Etoposide and Gemcitabine/Irinotecan: A Minnie Pearl Cancer Research Network Phase II Trial The Oncologist, Vol. 9, No. 6, 644-652, November 2004; 

nccn.org, occult primary,2012

 

Sorafenib for FLT3+ AML

Sorafenib (Nexavar,) has been approved for the treatment of metastatic renal cancer and advanced hepatocellular carcinoma. It inhibits the serine threonine kinase RAF-1, but also the FLT3-RTK and FLT3-ITD, suggesting that it may have a role in treating AML with FLT3 mutations.Sorafenib in a phase 1 clinical trial on 16 patients with AML was found to be active in 6 of the 7 Flt3-ITD–positive patients.11 However, treatment duration was short (21-70 days), and no durable responses were reported. Notably, a complete molecular remission has recently been reported in a patient relapsing after stem cell transplantation (SCT).

There is a high degree of interest in the use of sorefenib with other drugs or alone for FLT+ AML but corroborating literaure is still very preliminary and at the level of case reports. For this reason, it is still experimental at this time.

Delmonte J, Jr, Kantarjian HM, Andreeff M, Faderl S, Wright JJ, Zhang W, et al. Update of a Phase I Study of Sorafenib in Patients with Refractory/Relapsed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome. ASH Annual Meeting Abstracts. 2007 November 16;110(11):893. 2007.

Zhang W, Konopleva M, Shi YX, et al. Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia. J Natl Cancer Inst 2008;100:184-198

Mori S, Cortes J, Kantarjian H, Zhang W, Andreef M, Ravandi F. Potential role of sorafenib in thetreatment of acute myeloid leukemia. Leuk Lymphoma 2008;49:2246-2255.

Safaian NN, Czibere A, Bruns I, et al. Sorafenib (Nexavar[registered]) induces molecular remission and regression of extramedullary disease in a patient with FLT3-ITD(+) acute myeloid leukemia. Leuk Res 2009;33:348-350.

Stephan Metzelder et al, Compassionate use of sorafenib in FLT3-ITD–positive acute myeloid leukemia: sustained regression before and after allogeneic stem cell transplantation Blood June 25, 2009 vol. 113 no. 26 6567-6571

Hu S, Niu H, Inaba H, Orwick S, Rose C, Panetta JC, Yang S, Pounds S, Fan Y, Calabrese C, Rehg JE, Campana D, Rubnitz JE, Baker SD. Activity of the multikinase inhibitor sorafenib in combination with cytarabine in acute myeloid leukemia.J Natl Cancer Inst. 2011 Jun 8;103(11):893-905.

Inaba H, Rubnitz JE, Coustan-Smith E, Li L, Furmanski BD, Mascara GP, Heym KM, Christensen R, Onciu M, Shurtleff SA, et al.
Phase I pharmacokinetic and pharmacodynamic study of the multikinase inhibitor sorafenib in combination with clofarabine and cytarabine in pediatric relapsed/refractory leukemia. J Clin Oncol. 2011 Aug 20; 29(24):3293-300

Allogeneic stem cell transplantation for medulloblastoma

Medulloblastoma is treated primarily with surgical excision followed by radiation therapy and chemotherapy. When there is spinal extension, craniospinal radiation is standard.

Inoperable medulloblastomas are often treated iwth chemotherapy but there is no randomized prospective evidence to support this. This is especially so in adults, in whom this disease is much less common and in whom it appears to behave distinctly differently. 30% of cases occur in adults.

Autologous transplantation of relapsed disease ahs support from case reports, series and small prospective trials. There are but a few case reports of allogeneic transplantation for medulloblastoma, some of them from the older literature. I am not aware of any cases of allogeneic being used after failure of autologous stem cell transpalntation that have been reported.

David D Eisenstat Clinical management of medulloblastoma in adults
Expert Review of Anticancer Therapy October 2004, Vol. 4, No. 5, Pages 795-802

S Secondino Antitumor effect of allogeneic hematopoietic SCT in metastatic medulloblastoma
Bone Marrow Transplantation (2008) 42, 131–133;

Lundberg JH, Weissman DE, Beatty PA, Ash RC. Treatment of recurrent metastatic medulloblastoma with intensive chemotherapy and allogeneic bone marrow transplantation. J Neurooncol 1992; 13: 151–155.

Matsuda Y, Hara J, Osugi Y, Fujisaki H, Takai K, Ohta H et al. Allogeneic peripheral stem cell transplantation using positively selected CD34+ cells from HLA-mismatched donors. Bone Marrow Transplant 1998; 21: 355–360. J Korean Med Sci. 2010 Aug;25(8):1160-1166.
 
Jun Eun Park et al, Efficacy of High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with Relapsed Medulloblastoma: A Report on The Korean Society for Pediatric Neuro-Oncology (KSPNO)-S-053 Study 
 Korean Med Sci. 2010 Aug;25(8):1160-1166.

 

Temodar for small cell lung cancer

Several phase II trials have been reported using Temodar(TEM) for patients with brain metastases from solid tumors, including
SCLC. In one study, two out of five patients with SCLC pretreated with whole brain radiation therapy showed disease stabilization with TEM. A second study explored the use of whole-brain radiation therapy with concurrent and adjuvant TEM in patients with metastatic cancer and three patients with SCLC were included in this study, two of whom demonstrated a complete response in the brain. Anecdotally, single-agent TEM has been used in patients with SCLC with response. Memorial Sloan-Kettering Cancer Center has an ongoing phase II study using TEM in second- or third-line treatment of SCLC: Temozolomide for Relapsed Sensitive or Refractory Small Cell Lung Cancer,  NCT00740636. Most of this work appears to have been done by one investigator in a single institution, Dr. Pietanza in Memorial, who is also the author on the two reported phase II trials, which seem based on the same body of experience.

For second line, NCCN recommends many single agents on SCL-B,1, including paclitaxel, etoposide, irinotecan, topotecan, ifosfamide and others.

Lee M. Krug, MD, and Maria C. Pietanza, MD Emerging Therapies in Small Cell Lung Cancer
http://www.spom.com.py/Content/Manuscripts/C15_S60_M75.pdf, 2009

M. Catherine Pietanza Et aL, Phase II Trial of Temozolomide in Patients with Relapsed Sensitive or Refractory Small Cell Lung Cancer, with Assessment of Methylguanine-DNA Methyltransferase as a Potential Biomarker Clin Cancer Res February 15, 2012 18; 1138

 

 

Post-mastectomy radiation

Post-mastectomy radiation tends to be overused in the USA. For example, women who have stage I or II disease with spread to no more than three lymph nodes and who did not undergo radiation therapy,  have the overall locoregional recurrence rate of just 2.3% at 10 years. A 2005 meta-analysis looked at randomized trials conducted between 1964 and 1984. The analysis determined that postmastectomy radiation in these women resulted not only in about a 66% reduction in locoregional recurrence compared with no radiation, but also about a 5% survival advantage. However, the overall recurrence rate in those studies ranged from 20% to 25%, much higher than observed in the present.

Certainly, locoregional PMRT is recommended for women with an advanced primary tumour (tumour size 5 cm or greater, or tumour invasion of the skin, pectoral muscle or chest wall) or with 4 or more positive axillary lymph nodes. However, the role of PMRT in women with 1 to 3 positive axillary lymph nodes is unclear. Locoregional PMRT is generally not recommended for women who have tumours that are less than 5 cm in diameter and who have negative axillary nodes. Other patient, tumour and treatment characteristics, including age, histologic grade, lymphovascular invasion, hormone receptor status, number of axillary nodes removed, axillary extracapsular extension and surgical margin status, may affect locoregional control, but their use in specifying additional indications for PMRT is currently unclear.

Pauline T. Truong,Clinical practice guidelines for the care and treatment of breast cancer: 16. Locoregional post-mastectomy radiotherapy CMAJ April 13, 2004 vol. 170 no. 8

Sharma R, et al "Present day locoregional recurrence rates (LRR) in patients with T1 and T2 breast cancer (BC) with zero and one to three lymph node (LN) metastases following mastectomy without radiation" SSO 2010; Abstract 47

Taylor ME, Haffty BG, Rabinovitch R, Arthur DW, Halberg FE, Strom EA, White JR, Cobleigh MA, Edge SB, Expert Panel on Radiation Oncology-Breast. ACR Appropriateness Criteria® postmastectomy radiotherapy. [online publication]. Reston (VA): American College of Radiology (ACR); 2008. 17 p. [96 references]

Postmastectomy Radiotherapy: Clinical Practice Guidelines of the American Society of Clinical Oncology Journal of Clinical Oncology, Vol 19, Issue 5 (March), 2001: 1539-1569

Narcotics for cancer pain: Legal standards

Safe and effective chronic opioid therapy for chronic cancer related pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic cancer pain, several guidelines provide recommendations developed by multidisciplinary expert panel after a systematic review of the evidence.

Generally, narcotics are not the only modality that can be used to treat pain. Adjuvant therapies together with narcotics can be very helpful. For example, steroids and non-steroidal anti-inflammatory drugs, such as ibuprofen(Advil) can reduce the inflammation associated with tumors pressing on tissues, and certain anti-depressants and anti-seizure drugs can modify how the brain perceived pain and lessen it. There are also procedures, such as nerve blocks, that can be helpful  when pain is localized.

Cancer pain can require very high doses of narcotics. Guidelines provide guidance and in some case, recommend a specialty pain management consultation. A diagnostic re-evaluation is often indicated to exclude cancer progression. If there is progression, the best pain management is successful treatment of the underlying disease. It may sometimes be possible to switch to a different narcotic, which reduces tolerance and allows a lower dose, or decrease  total narcotic dose by using adjuvant analgesics, steroids or neuro-modifiyng drugs discussed above, but there remain situations in which very high doses are required despite all efforts. Intravenous patient controlled analgesia(PCA) with outpatient medication via a pump, or intrathecal catheters present other options.

Risk of addiction in cancer patients is very low, around 2% (Friedman et al), but several instruments can reduce it even farther:  CAGE questionnaire, Cyr-Wartman Screen, Skinner Trauma Screen, Screener and Opioid Assessment for Patients. It is important to understand the distinction between addiction, a psychological syndrome, and habituation, which is the body getting used to  narotics and requring higher doses. Habituation can be easily treated; addiction is much more difficult to treat. Unfortunately, overrated fear of addiction or unwarranted anxiety about attracting the attention of the DEA, sometimes leaves patients with inadequate pain control. 

Failure to provide adequate pain control to cancer patients is a deviation from the standard of care and can be  grounds for a malpractice suite, or it can play a role in increasing recovery. The use of national guidelines or local state policies can be helpful to both plaintiff and defense. State pain policies can shield  practitioners who have complied with the state policy, or a damn physician who have not. Some state policies are so restrictive that they automatically put the defendant at a disadvantage. An expert who is familiar with the use of guidelines and local policies can prove invaluable in the litigation of cases the involve standards of pain management.

REFERENCES:

Davis MP, Weissman DE, Arnold RM, Opioid dose titration for severe cancer pain: a systematic evidence-based review.J Palliat Med. 2004 Jun;7(3):462-8.

Washington State Agency Medical Directors' Group. Interagency guideline on opioid dosing for chronic non-cancer pain: an educational aid to improve care and safety with opioid treatment. Olympia (WA): Washington State Department of Labor and Industries; 2010. 55 p. [123 references].

Friedman DP. Perspectives on the medical use of drugs of abuse. J Pain Symptom Manage 1990; 5: S2-S5.

Joranson DE, Gilson AM, Dahl JL, Haddox JD. Pain management, controlled substances, and state medical board policy: A decade of change. J Pain Symptom Manage. 2002;23:138-147.

Furrow BR. Pain management and provider liability: No more excuses. J Law Med Ethics. 2001;29:28-51.

Ziegler SJ, Lovrich NP Jr. Pain relief, prescription drugs, and prosecution: A four-state survey of chief prosecutors. J Law Med Ethics. 2003;31:75-100.

Procrit for anemia of Thalassemia Minor

Individuals with thalassemia minor have only one copy of the beta thalassemia gene (together with one perfectly normal beta-chain gene). They are heterozygous for beta thalassemia.

Persons with thalassemia minor have (at most) mild anemia. This situation can very closely resemble that with mild iron-deficiency anemia. However, persons with thalassemia minor have a normal blood iron level (unless they have are iron deficient for other reasons). No treatment is necessary for thalassemia minor.

Not much is known about using erythropoietin in these patients. Case reports suggest that it is only useful when there are concomittant indication, such as renal failure or cardiac conditions or symptoms.

Biagio Di Iorioa et al,
Efficacy of Erythropoietin on Dialysis in Patients with Beta Thalassemia Minor Blood Purification Vol. 22, No. 5, 2004 

Pérez Ferrer A, Ferrazza V, Gredilla E, de Vicente J, de la Rua A, Larrea A. Bloodless surgery in a patient with thalassemia minor. Usefulness of erythropoietin, preoperative blood donation and intraoperative blood salvage.Minerva Anestesiol. 2007 May;73(5):323-6.