Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 1796, 1804. ISBN 1-4160-2999-0.

Magnetic resonance appearance of granular cell tumor of the breast.

Daniel D Maki, Donna Horne, Lawrence J Damore, Connie Jones Clin Imaging 33(5):395-7 (2009),

Schrader, KA.; Nelson, TN.; De Luca, A.; Huntsman, DG.; McGillivray, BC. (Feb 2009). “Multiple granular cell tumors are an associated feature of LEOPARD syndrome caused by mutation in PTPN11.”. Clin Genet 75 (2): 1859.

Rejas RA, Campos MS, Cortes AR, Pinto DD, de Sousa SC. The neural histogenetic origin of the oral granular cell tumor: an immunohistochemical evidence. Med Oral Patol Oral Cir Bucal. Jan 1 2011;16(1):e6-10.

25.Narra SL, Tombazzi C, Datta V, et al. Granular cell tumor of the esophagus: report of five cases and review of the literature. Am J Med Sci. May 2008;335(5):338-41

For Lay version see here

NHS says: “Cytotoxic chemotherapy is not regarded as standard treatment in the management of vulvar cancers but can be used in selected patients with metastatic disease. The drugs of choice are 5-Fluorouracil and cisplatin, alone or in combination. Single agent Taxol is considered in patients who progress after first line chemotherapy. The response rate to chemotherapy is low and the duration of response of the order of 3-6months.Some patients particularly those with local vulvar relapse can be salvaged with further surgery. Generally patients with nodal and/or distant failure have poor prognosis and palliative treatments are appropriate. Selected patients may be considered on an individual basis for more aggressive treatment.”

NHS, 2009: http://www.mccn.nhs.uk/userfiles/documents/Vulva%20Clinical%20guidelines%20final.doc#_Toc237233876

National Cancer Institute at the National Institutes of Health
Vulvar Cancer Treatment (PDQ)
Health Professional Version
Last Modified: 11/09/2012

Australian 2009 Best Practice: http://www.aci.health.nsw.gov.au/__data/assets/pdf_file/0010/154549/go_clinical_guidelines.pdf

UpToDate 2013
Vulvar cancer: Staging, treatment, and prognosis
Elkas, J. C., et al.

For Lay Version see here

Small bowel adenocarcinoma (SBA) is a very rare entity accounting for one-fourth of the small intestine neoplasms. Usually accompanied by nonspecific symptoms occurring late in the course of the disease, they are associated with a dismal prognosis. It appears that SBA shares several genetic characteristics with large bowel tumors, but also has unique features. The similarity to large bowel cancers has led to application of colon cancer protocols to small bowel cancer.

Because of its low prevalence, few clinical trials have been performed to assess the efficacy of chemotherapy for treating small-bowel cancer.

The largest published study was in 1984 by Jigyasu et al and involved 14 subjects with metastatic small-bowel adenocarcinoma who were treated with 21 chemotherapy regimens, most containing 5-fluorouracil (5-FU). Two minor responses and one partial response occurred, with a median survival of 9 months.

In their 1984 review of 65 patients with small-bowel adenocarcinoma, Ouriel and Adams reported a mean survival of 10.7 months in 6 patients with metastatic disease treated with 5-FU–based regimens, compared with a mean survival of 4 months in 6 patients with metastatic disease who received no chemotherapy. An additional 6 patients with recurrent disease were also treated with chemotherapy and had a mean survival of 11.5 months, compared with 21 patients with recurrent disease who received no chemotherapy and survived a mean of 7.9 months.

More recently, a 1998 British study by Crawley et al reported 8 patients with advanced small-bowel adenocarcinoma treated with infusional 5-FU–based regimens and found a response rate of 37.5% and a median survival of 13 months.
Newer agents found to be effective for colorectal carcinoma also may be active for small-bowel adenocarcinoma.

As reported by Polyzos and colleagues in 2003, 3 subjects with 5-FU–refractory small-bowel adenocarcinoma were treated with salvage irinotecan therapy. Two patients achieved a minor response and had improvement of their symptoms.

Also in 2003, Bettini and colleagues found that the FOLFOX 4 regimen (ie, combination infusional 5-FU, oxaliplatin, and leucovorin) was safely administered as adjuvant chemotherapy in 3 subjects with resected small-bowel adenocarcinoma associated with celiac disease.

Because these are uncontrolled studies with few patients, drawing conclusions regarding the benefit of chemotherapy for small-bowel adenocarcinoma, either in the metastatic or adjuvant setting, is difficult. In patients with a good performance status, any attempts using the regimens mentioned seem reasonable.
Similarly, few studies have assessed the efficacy of cytotoxic chemotherapy for small-bowel sarcomas. An analysis by Fernandez-Trigo and Sugerbaker from 1993 reported on 7 randomized prospective studies of subjects with nonextremity sarcomas and found no survival benefit with the addition of adjuvant chemotherapy after surgery.
Studies of chemotherapy in patients with metastatic GI soft tissue sarcomas have also yielded disappointing results.

For example, the Southwest Oncology Group, as reported by Zalupski et al in 1991, found that only 3 (7%) of 43 subjects with GI sarcomas responded to a combination of doxorubicin and dacarbazine, whereas 21% of subjects with leiomyosarcomas of other sites responded to the same combination.

A trial reported by Blair et al in 1994 found that a combination of ifosfamide and etoposide produced no responses among 10 patients with GI sarcomas.  In 2006, Fishman reviewed 114 patients for natural history.

Forty-four patients received palliative chemotherapy with an overall response rate (ORR) of 36% during a first or second line regimen (9% complete responses and 27% partial responses). Newer chemotherapy regimens including gemcitabine and irinotecan combinations appeared to have higher ORR, than older fluorouracil-based regimens. Some patients responded to more than one line of chemotherapy. Palliative chemotherapy predicted for overall survival (OS) in a multivariate analysis (HR 0.47, P = 0.035).

She concluded: “Chemotherapy appears to have activity in adenocarcinoma of the small bowel. Prospective trials evaluating patient benefit are required to confirm this activity using newer systemic therapies, until such time retrospective reviews such as this will continue to guide treatment decisions.” A 2010 review staes that  retrospective studies have indicated that chemotherapy prolongs OS in patients with advanced SBA, but there is no agreed frontline regimen owing to a lack of randomized trials.

Evidence indicates that in general, small-bowel sarcomas and GISTs are more resistant to chemotherapy than sarcomas in other sites. A 2000 Dutch study by Plaat et al found greater expression of multidrug-resistance proteins in GISTs compared with non-GI leiomyosarcomas. The use of imatinib for GIST is outside the scope of this brief review.

There is a generally accepted belief that you can treat distal small bowel adenocarcinoma as colon cancer and proximal as gastric cancer, but it is not experimentally confirmed and certainly should not extend into later line treatment.

Overman MJ, Varadhachary GR, Kopetz S, et al. Phase II study of capecitabine and oxaliplatin for advanced adenocarcinoma of the small bowel and ampulla of Vater. J Clin Oncol 2009; 27: 2598–2603.

Fishman PN, Pond GR, Moore MJ, Oza A, Burkes RL, Siu LL, Feld R, Gallinger S, Greig P, Knox JJ.

Natural history and chemotherapy effectiveness for advanced adenocarcinoma of the small bowel: a retrospective review of 113 cases.

Am J Clin Oncol. 2006 Jun;29(3):225-31.

Delaunoit T, Neczyporenko F, Limburg PJ, Erlichman C. Pathogenesis and risk factors of small bowel adenocarcinoma: a colorectal cancer sibling? Am J Gastroenterol. 2005 Mar;100(3):703-10.

Bettini AC, Beretta GD, Sironi P, et al: Chemotherapy in small bowel adenocarcinoma associated with celiac disease: a report of three cases. Tumori 2003 Mar-Apr; 89(2): 193-5

Neugut AI, Marvin MR, Rella VA, Chabot JA: An overview of adenocarcinoma of the small intestine. Oncology (Huntingt) 1997 Apr; 11(4): 529-36; discussion 545, 549-50[Medline].
Neugut AI, Arber N: Epidemiology, molecular epidemiology, and molecular biology of small bowel and appendiceal adenocarcinomas. In: Abbruzzese J, ed. Principles and Practice of Gastrointestinal Oncology. Baltimore, Md: Lippincott Williams & Wilkins; 2001.

Polyzos A, Kouraklis G, Giannopoulos A, et al: Irinotecan as salvage chemotherapy for advanced small bowel adenocarcinoma: a series of three patients. J Chemother 2003 Oct; 15(5): 503-6

Ryder NM, Ko CY, Hines OJ, et al: Primary duodenal adenocarcinoma: a 40-year experience. Arch Surg 2000 Sep; 135(9): 1070-4; discussion 1074-5

He, Yong-Tao (2005) Primary adenosquamous carcinoma of the jejunum. Pathology International 55(9)

A. Zaanan; L. Costes; M. Gauthier; D. Malka; C. Locher; E. Mitry; D. Tougeron; T. Lecomte; J.-M. Gornet; I. Sobhani; V. Moulin; P. Afchain; J. Taïeb; F. Bonnetain; T. Aparicio Chemotherapy of Advanced Small-bowel Adenocarcinoma: A Multicenter AGEO Study

Annals of Oncology. 2010;21(9):1786-1793.

Revised: 3/22/11

Merkel cell carcinoma (MCC) is an aggressive yet uncommon neoplasm that often arises on the head and neck. Because of the rarity of the tumor, however, diagnosis and treatment have previously been based more on anecdotal data than on scientific data. Because of the high degree of local recurrence and early lymph node and distant metastases in patients with NEC, patients should be treated aggressively at the time of initial diagnoses. Although no widely adopted classification system exists, treatment guidelines have been based on three clinical stages of disease: local disease without lymph node or systemic involvement (stage I), regional lymph node development without systemic disease (stage II), and systemic metastases (stage III). Most treatment guidelines include wide excision of the primary tumor, alone or in combination with adjuvant radiation therapy, therapeutic regional lymph node dissection, or elective regional lymph node dissection. This patient has loco-regional disease which is usually treated with wide resection and adjuvant radiation. Some recommend adjuvant chemo and there is little information on which to base firm recommendations. Merkel cell carcinoma is  associated with the Merkel cell polyomavirus in ~80% of patients. The other 20% of patients harbor a heavy ultraviolet-induced mutation load. Until recently, chemotherapy was the only treatment option for unresectable disease. In 2017, avelumab became the first drug ever approved by the U.S. Food and Drug Administration for Merkel cell carcinoma. Pembrolizumab and nivolumab have shown similar efficacy in metastatic disease, and their approval in this setting is pending. Updates of these studies were presented at the ASCO meeting, as were new data for neoadjuvant nivolumab.

Clinical stage III disease usually presents in the bone, abdomen, skin, mediastinum, lung, liver, or basin. The usual time span from diagnosis of stage III disease to death is 8 months. Chemotherapy is the treatment most often employed within this setting. However, as in the case of all other treatment modalities used against this tumor, the rarity of the condition precludes the availability of statistically significant comparisons. No firmly established chemotherapy for MCC exists. Because of the neuroendocrine features of this tumor, it has been treated with etoposide and cisplatin as well as with cisplatin and 5-fluorouracil. More recently, there are anecdotal reports of responses to paclitaxel. Unfortunately, the rarity of this tumor has prevented cooperative efforts to establish a firm basis for a recommended therapy.

NCCN mentions adriamycin, cytoxan AND vincristine  or cisplatin or carboplatin/etoposide for metastatic disease but for first line only. Recently  David et al rep0rted a case of response to Votrient and others who treat this disease anecdotally also reported success. However, there remain no prospective trials of this treatment.

Merkel cell carcinoma is a rare, aggressive, and often fatal skin cancer that is associated with the Merkel cell polyomavirus in ~80% of patients. The other 20% of patients harbor a heavy ultraviolet-induced mutation load. Until recently, chemotherapy was the only treatment option for unresectable disease. In 2017, avelumab became the first drug ever approved by the U.S. Food and Drug Administration for Merkel cell carcinoma. Pembrolizumab and nivolumab have shown similar efficacy in metastatic disease, and their approval in this setting is pending. Updates of these studies were presented at the ASCO meeting, as were new data for neoadjuvant nivolumab.

Radiographic regression by computed tomography was noted for 40% of 25 evaluable patients, in whom target lesions were reduced by more than 30%, she reported. Dr. Topalian added that radiographic response underestimated the impact of nivolumab in this short treatment interval; a better reflection was pathologic tumor response.

In 17 tumors evaluated by central pathologic review, the researchers documented a 47% rate of pathologic complete response by traditional criteria and an 18% major pathologic response rate, defined as up to 10% viable tumor cells remaining. These preliminary data yielded a total major pathologic response rate of 65% by central review. Some responses were striking. There were a significant number of patients in the trial with complete responses who had come off therapy about 1 to 2 years earlier and remained free of disease.

Rationale:

http://www.nccn.org/professionals/physician_gls/PDF/mcc.pdf, p.12, 2019

1.Topalian SL, Bhatia S, Kudchadkar RR, et al: Nivolumab as neoadjuvant therapy in patients with resectable Merkel cell carcinoma in CheckMate 358. 2018 ASCO Annual Meeting. Abstract 9505. Presented June 4, 2018.

2. Nghiem P, Bhatia S, Brohl AS, et al: Two-year efficacy and safety update from JAVELIN Merkel 200 part A: A registrational study of avelumab in metastatic Merkel cell carcinoma progressed on chemotherapy. 2018 ASCO Annual Meeting. Abstract 9507. Presented June 4, 2018.

3. Nghiem P, Bhatia S, Lipson EJ, et al: Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy. 2018 ASCO Annual Meeting. Abstract 9506. Presented June 4, 2018.

4. Nghiem PT, Bhatia S, Lipson EJ, et al: PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med 374:2542-2552, 2016.

The peripheral giant cell granuloma has an unknown etiology, with some dispute as to whether this lesion represents a reactive or neoplastic process. It is often a dental disease. Most authorities believe peripheral giant cell granuloma is a reactive lesion. Surgical management of the CGCG with aggressive curettage is regarded as the treatment of choice. Resection is performed for recurrent or more aggressive variants, which leads to major defects and loss of teeth. This is particularly mutilating in a growing child or young adult. In such cases, extensive reconstructive procedures are required for anatomic restoration and rehabilitation to achieve satisfactory form and function.

Alternative treatmetns have been reported. All of these reports and the literature in general is based on case reports and series. These treatments include calcitonin, intralesional steroids or interferon.

Interferon alfa-2a inhibits angiogenesis and was discovered through a series of laboratory experiments that began in 1980. It was first used in 1989 in the management of a child with pulmonary haemangiomatosis. Interferon alfa A was then subsequently use to treat life threatening haemangiomas and other vascular tumours in various organs. Kaban reported on anti-angiogenic therapy of a recurrent giant cell tumour of the mandible in a 5 year old girl with interferon alfa-2a reasoning that as it was a rapidly proliferating vascular lesion it could be treated as an haemangioma. Since then a number of reports have apeared. Becasue of their rarity, no treatment guidelines are available.

Int J Oral Maxillofac Surg. 2006 Sep;35(9):865-9.
Comment in:

de Lange J, van den Akker HP, van den Berg H, Richel DJ, Gortzak RA.
Limited regression of central giant cell granuloma by interferon alpha after failed calcitonin therapy: a report of 2 cases.Int J Oral Maxillofac Surg. 2006 Nov;35(11):1074-5; author reply 1076.
MICHAEL C. ADORNATO, D.D.S. and KENNETH A. PATICOFF, D.D.S.
Intralesional corticosteroid injection for treatment of central giant-cell granuloma J Am Dent Assoc, Vol 132, No 2, 186-190.

Shohat I, Shoshani Y, Taicher S.
[Medical treatment of central giant cell granuloma of the jaws, Refuat Hapeh Vehashinayim (Treatment of Mouth and teeth). 2002 Oct;19(4):37-44, 70.

Collins A.Experience with anti-angiogenic therapy of giant cell granuloma of the facial bones.
Ann R Australas Coll Dent Surg. 2000 Oct;15:170-5.

In globoid cell leukodystrophy (GCL), the lack of the enzyme ß-galactocerebrosidase results in an accumulation of galactocerebroside, a component of myelin. This disrupts the cells that normally produce myelin, a fatty substance that coats nerve cells, serves as an electrical insulator and is crucial to the normal conduction of nerve impulses. The progressive loss of myelin in the white matter tracts of the nervous system (brain, spinal cord and/or peripheral nerves) causes a variety of clinical signs such as lack of coordination, tremors, and weakness.

With appropriate timing and use of allogeneic stem cells, GCL can be effectively treated in late onset cases with normalization of CSF protein, stabilization of the neurologic examination, neuropsychologic function, and the extent of demyelination on MRI. However, to date, Krabbe disease, if diagnosed antenatally, can only be ameliorated if HCT is performed in the neonatal period.

C Peters et al, Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines BMKT, February (2) 2003, Volume 31, Number 4, Pages 229-239

Kurtzberg J, Richards K, Wenger D et al.. Correction of Krabbe disease with neonatal hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2002; 8: 97 (Abstr. 130).

Hematopoietic stem-cell transplantation in globoid-cell leukodystrophy. N Engl J Med 1998; 338: 1119-1126.

The guidelines support the proposed recommendation. It is reasonable to use temozolomide at a dose of 200 mg/m2 orally for five days every four weeks as initial systemic treatment for patients with unresectable metastatic malignant melanoma. It is listed by NCCN.

Quirt I, Verma S, Petrella T, Bak K, Charette M, Melanoma Disease Site Group. Temozolomide for the treatment of metastatic melanoma: a clinical practice guideline. Toronto (ON): Cancer Care Ontario (CCO); 2006 Mar 20. 25 p. (Evidence-based series; no. 8-4). [38 references]

Highlights of the NCCN 11th Annual Conference: Clinical Practice Guidelines & Quality Cancer Care™, published as a supplement to The Oncology Report by Elsevier Oncology. © 2006 NCCN.

Darkes M.J.M.; Plosker G.L.; Jarvis B. Temozolomide: A Review of its Use in the Treatment of Malignant Gliomas, Malignant Melanoma and Other Advanced Cancers American Journal of Cancer, Volume 1, Number 1, 1 January 2002, pp. 55-80(26)

Oral problems that already exist, such as periodontitis, caries, failing restorative work (such as crowns, or fillings), and dentures may increase the risk of infection. Areas where the gums or tissues are irritated can lead to ulceration in the mouth. Pain and discomfort resulting from teeth and gums may make it difficult for a patient to receive all of his or her cancer treatment. Sometimes treatment must be stopped completely. These patients require urgent dental care before and after cancer treatment.

Because of typical tissue reactions to ionising radiation, radiotherapy in the head and neck region usually results in complex oral complications affecting the salivary glands, oral mucosa, bone, masticatory musculature, and dentition. When the oral cavity and salivary glands are exposed to high doses of radiation, clinical consequences including hyposalivation, mucositis, taste loss, trismus, and osteoradionecrosis should be regarded as the most common side-effects. Mucositis and taste loss are reversible consequences, usually subsiding early post-irradiation, whereas hyposalivation is commonly irreversible. Additionally, the risk of rampant tooth decay with its sudden onset and osteonecrosis is a lifelong threat. Thus, early, active participation of the dental profession in the development of preventive and therapeutic strategies, and in the education and rehabilitation of patients is paramount in consideration of quality-of-life issues during and after radiotherapy.

What can a dentist do? It is generally accepted that teetch at risk for other reasons or those teeth exposed to radiation doses of greater than 5000cGy should be extracted. Most treatment protocols to prevent sequelae are still based on clinical experience, but alternatives based on fundamental basic and clinical research are becoming more and more available. The dentist will also generally create fluoride carriers to protect the teeth from decay during radiation.

There are physicans who advocate removal of all metal fillings to allow better penetration of raditaion tehrapy; however, there is littel evidence to support that and radiation distribution can be managed through computer modeling.

Kielbassa AM, Hinkelbein W, Hellwig E, Meyer-Luckel H. Radiation-related damage to dentition.Lancet Oncol. 2006 Apr;7(4):326-35.

STEPHEN J. MERAW, D.D.S. and CHARLES M. REEVE, D.D.#######.S. DENTAL CONSIDERATIONS AND TREATMENT OF THE ONCOLOGY PATIENT RECEIVING RADIATION THERAPY
J Am Dent Assoc, Vol 129, No 2, 201-205

Vissink A, Burlage FR, Spijkervet FK, Jansma J, Coppes RP. Prevention and treatment of the consequences of head and neck radiotherapy.Crit Rev Oral Biol Med. 2003;14(3):213-25.

http://jada.ada.org/cgi/reprint/129/2/201

The proposed study is: A Phase I Study of Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Avastin for Patients with Advanced Solid Tumors Metastatic to the Liver. The goal of this clinical research study is to find the highest tolerable dose of oxaliplatin used in combination with 5-fluorouracil, leucovorin, and Avastin® (bevacizumab) for patients with advanced cancer that has spread to the liver. The safety and effectiveness of this study drug combination will also be studied. This si celarly experiemntal by any definition.

Oxaliplatin is a platinum derivative without nephrotoxicity with in vitro activity against human melanoma cell lines. A Phase I and II trials suggested activity in melanoma, although a combination of oxaliplatin, docetaxel, and GM-CSF had limited clinical activity in previously treated patients with advanced melanoma. A non-nephrotoxic platinum compound active in melanoma is of interest in the development of combination chemo-or chemoimmunotherapy. This trial is an attempt to begin doing this in a pahse I trial setting, that is, with dose escalation of oxaliplatin.

The proposed study is: A Phase I Study of Hepatic Arterial Infusion of Oxaliplatin in Combination With Systemic Fluorouracil, Leucovorin and Avastin for Patients with Advanced Solid Tumors Metastatic to the Liver. The goal of this clinical research study is to find the highest tolerable dose of oxaliplatin used in combination with 5-fluorouracil, leucovorin, and Avastin® (bevacizumab) for patients with advanced cancer that has spread to the liver. The safety and effectiveness of this study drug combination will also be studied. This is clearly experimental by any definition.