What We Have Learned About Combining a Ketogenic Diet and Chemoimmunotherapy: a Case Report and Review of Literature.

Background: A high-fat, moderate-protein, low-carbohydrate ketogenic diet has been reported in the literature as a treatment option for patients with cancer. Case Presentation: A 69-year-old veteran was initially diagnosed with stage III colorectal cancer and progressed to having liver, pancreatic, and omental lymph node involvement despite completing adjuvant FOLFOX (fluorouracil, leucovorin calcium, and oxaliplatin) after surgery. The patient was treated with FOLFIRI (fluorouracil, leucovorin calcium, and irinotecan hydrochloride) and bevacizumab, followed by encorafenib and cetuximab on progression. Subsequently, he received pembrolizumab but continued to progress. The patient was later placed on trifluridine/tipiracil and bevacizumab concurrent with a ketogenic diet. Positron emission tomography and carcinoembryonic antigen levels indicated disease stabilization for 10 months. On progression, the patient was transitioned to ipilumimab and nivolumab and continued to adhere to the ketogenic diet. The patient's disease has continued to remain stable for the past 1 year. His degree of ketosis was determined using the glucose ketone index. The patient continues to have a good quality of life during concurrent ketogenic diet and therapy. Conclusions: This case supports the tolerability of the ketogenic diet along with chemotherapy and immunotherapy and should be considered as an adjunct to standard cancer treatment. In this report, we reviewed the latest literature about cellular mechanism of the ketogenic diet and the efficacy and relationship with chemotherapy and immunotherapy. We are about to open a ketogenic diet protocol at the Veterans Affairs Central California Health Care System in Fresno.

Immunohistochemical ALK Expression in Granular Cell Atypical Fibroxanthoma: A Diagnostic Pitfall for ALK-Rearranged Non-neural Granular Cell Tumor.

ABSTRACT: Atypical fibroxanthoma (AFX) is a neoplasm that most commonly occurs on sun-damaged skin of the head and neck in elderly patients and that usually exhibits indolent clinical behavior with complete excision. The granular cell variant of AFX demonstrates overlapping histopathologic features with dermal non-neural granular cell tumor (NNGCT), which typically arises on the extremities of young to middle aged adults with rare reports of regional metastasis. A subset of NNGCT harbors ALK rearrangements and expresses ALK by immunohistochemistry. Here, we present 2 cases of granular cell AFX occurring on the scalp of males aged 73 and 87 with ALK expression by immunohistochemistry and no evidence of an ALK rearrangement on fluorescence in situ hybridization, representing a diagnostic pitfall for NNGCT.

A rare case of MGRS with immunotactoid glomerulopathy responding to bortezomib, dexamethasone, and rituximab.

Patients with monoclonal gammopathy of renal significance should be treated with clone-directed therapy against sources of monoclonal proteins in order to prevent progression to more advanced monoclonal gammopathies and renal failure.

The Effect of Radium-223 Therapy in Agent Orange-Related Prostate Carcinoma.

BACKGROUND: Radium-223 (Ra-223) radioisotope has been reported to increase median survival in bone metastatic prostate carcinoma. The addition of Ra-223 to abiraterone was associated with an increased risk of bone fractures. There has been no comprehensive data for using Ra-223 in veterans who were exposed to Agent Orange (AO+). METHODS: We present a retrospective study of veterans with bone metastatic castration-resistant prostate cancer (CRPC) who received standard doses of Ra-223 and other sequential therapies at US Department of Veterans Affairs Pittsburgh Healthcare System in Pennsylvania from January 2014 to January 2019. Veterans were divided into 2 groups: those who were exposed to Agent Orange (AO+) and those who had no exposure (AO-). Time to study was calculated from the initiation of Ra-223. Time to skeletal-related events (SRE), progression of prostate specific antigen (PSA), bone metastasis, and alkaline phosphatase (ALP) were calculated in months using unpaired t test with 2-tailed P values. Median survival was calculated by Kaplan Meier R log-rank test. RESULTS: There were 34 veterans with bone metastatic CRPC: 17 veterans (50%) were AO+ and 17 veterans (50%) were AO-. The mean age of diagnosis of AO+ veterans was 62 years and 69 years (P = .005) for AO- veterans (the mean Gleason score 8.2 and 8.0, respectively [P = .71]). The median number of Ra-223 cycles was 6 (60%). Ten veterans received Ra-223 as first line (29%) and 24 veterans received Ra-223 later (71%). There were 12 SREs with median survival of 15 months. There was no difference in mean time to SRE between AO+ (8 veterans, 10.6 months) and AO- (4 veterans, 10.3 months) (P = .93). The mean time to PSA progression for AO+ was 5.4 months and AO- was 6.8 months (P = .28). Mean time to bone progression for AO+ was 7.6 months and AO- was 10.1 months (P = .16). Mean time to ALP progression for AO+ and AO- was 6.3 months and 8.7 months, respectively (P = .05). Twenty veterans (58%) had died. Median survival for Ra-223 first was 32 months and for Ra-223 later was 15 months (P = .14; hazard ratio [HR] 0.48; 95% CI, 0.17-1.3). Median survival for AO+ and AO- veterans was 12 months and 18 months, respectively (P = .15; HR, 2.0; 95% CI, 0.77-5.0). CONCLUSIONS: There was no statistical difference between AO+ and AO- veterans in terms of time to SRE, PSA, bone and ALP progression, even though there was a trend of shorter duration in AO+ veterans. There was no median survival difference between Ra-223 first vs Ra-223 later as well as between AO+ and AO- but there is a trend of worse survival in AO+ veterans.

A Rare Case of Systemic Mastocytosis With Associated Clonal Hematological Non-Mast Cell Lineage Disease That Transformed to Acute Leukemia With IDH2 Mutation.

An elderly 72-year-old man presented with anemia, thrombocytopenia, monocytosis, splenomegaly and lymphadenopathy. Bone marrow biopsy was consistent with mast cell neoplasm with positive CD117, CD25, CD34 myeloblasts and polymerase chain reaction (PCR) revealed mutation of D816V. He developed bilateral femoral neck fractures and biopsy confirmed that he has systemic mastocytosis (SM). He received cladribine and midostaurin with stable disease for 21 months. His SM with associated clonal hematological non-mast cell lineage disease (SM-AHNMD) transformed to acute myelogenous leukemia with isocitrate dehydrogenase 2 (IDH2) mutation. A trial of enasidenib was given for 5 months but without any response. Patient decided to go with home hospice and died afterwards.

A Rare Case of Sunitinib-Induced Rhabdomyolysis in Renal Cell Carcinoma.

We report a rare case of metastatic renal cell carcinoma (RCC) in a patient who developed rhabdomyolysis while on sunitinib. He was admitted to the hospital due to muscle weakness, fatigue, poor oral intake, and difficulty swallowing in March 2017. He was found to have pancytopenia, liver failure, kidney failure, high uric acid, and increased creatine phosphokinase of more than 5000. He quickly developed lactic acidosis and acute respiratory failure. He was transferred to the ICU, but his condition declined rapidly. He died 3 days later. In this article we discussed about sunitinib-mediated inhibition of adenosine monophosphate kinase (AMPK) as a possible pathophysiology of rhabdomyolysis. Our case is the third sunitinib-induced rhabdomyolysis reported in the literature.

A Case of Metastatic Adamantinoma That Responded Well to Sunitinib.

Adamantinoma is a rare low-grade malignant bone tumor of epithelial origin. Metastatic adamantinoma has been reported to be resistant to chemotherapy. We report a case of metastatic adamantinoma to the lung, 10 years after the initial diagnosis of tibial mass. The patient received radiation therapy to the lung with partial response. A surveillance PET scan revealed progression of the lung mass and biopsy confirmed to be progressive residual metastatic adamantinoma. He received carboplatin and etoposide for 7 months and achieved a partial response. Four months later, PET scan showed disease progression. We started him on sunitinib, a multikinase inhibitor. He achieved a good partial response for 3 years. He died due to pneumonia at the age of 72.

Squamous Cell Carcinoma of the Lung with Metastasis to the GI Tract Associated with EGFR Exon 19 Deletion.

We describe three confirmed cases of squamous cell carcinoma (SCC) of the lung with metastasis to the gastrointestinal (GI) tract, with two having epidermal growth factor receptor (EGFR) exon 19 deletions in all available specimens. One of these patients received EGFR tyrosine kinase directed therapy for a brief period with some symptom relief. Consideration of EGFR exon 19 mutation testing in SCC of the lung, particularly for those with GI tract metastasis, may identify this potentially drug-targetable entity.

Lung cancer with gastrointestinal metastasis - review of theories of metastasis with three rare case descriptions.

Approximately 1 in 14 men and women during their lifetime will be diagnosed with lung cancer, which is the leading cause of cancer-related mortality in the world. As of January 1, 2008, there were about 373,500 men and women living with lung cancer in the United States. Fewer than 60,000 of these are estimated to be alive by January 2013, reflecting a poor overall 5-year relative survival rate of under 16 %. With metastatic cancer, the overall 5-year survival is meager 4 %. On the other hand, the overall five-year survival is over 50 % when the cancer is still in the localized stage. However, unfortunately, more than half of cases of lung cancer are diagnosed at an advanced stage Howlader et al. (2010). Cancer metastasis, the single most critical prognostic factor, is still poorly understood and a highly complex phenomenon. The most common sites of lung cancer metastasis are the lymph nodes, liver, adrenals, brain and bones. The gastrointestinal (GI) tract is an exceptionally rare site of metastasis; with only a handful of cases reported in the literature Centeno et al. (Lung Cancer, 18: 101-105, 1997); Hirasaki et al. (World J Gastroenterol, 14: 5481-5483, 2008); Carr and Boulos (Br J Surg, 83: 647, 1996); Otera et al. (Eur Respir Rev, 19: 248-252, 2010); Antler et al. (Cancer, 49: 170-172, 1982); Fujiwara et al. (Gen Thorac Cardiovasc Surg, 59: 748-752, 2011); Stinchcombe et al. (J Clin Oncol, 24: 4939-4940, 2006); John et al. (J Postgrad Med, 48: 199-200, 2002); Carroll and Rajesh (Eur J Cardiothorac Surg, 19: 719-720, 2001); Brown et al. (Dis Colon Rectum, 23: 343-345, 1980). We report three cases of non-small cell (squamous cell) lung cancer with GI tract metastasis-two in the colon and one in the jejunum. Then we present a review of literature exploring various theories of metastasis, as an attempt to understand the reason of preferential tumor metastasis.

Aggressive digital papillary adenocarcinoma: a report of two diseases and review of the literature.

Aggressive digital papillary adenocarcinoma (ADPAca) is a rare, underreported, and often misdiagnosed malignant tumor of the sweat glands most commonly occurring in males in their fifties to seventies. We report two cases of ADPAca with important clinical implications. A 54-year-old man presented 3 years after digit amputation for ADPAca with new blue nodules on his arm, lymphadenopathy, and a lung nodule; he was diagnosed with and treated for metastatic ADPAca. He underwent chemotherapy, but died 4 months later. A 15-year-old boy presented with an enlarging tumor on his finger occurring after a trauma 3 years earlier. The tumor was suspected to be a deep fungal infection or pyogenic granuloma; however, results of excisional biopsy revealed an ADPAca. The patient underwent amputation and sentinel lymph node examination. No signs of metastases were found, and he is alive and well. These cases highlight both the importance of high clinical suspicion of digital tumors, even in children, enabling prompt diagnosis and treatment and also emphasize the metastatic potential of the tumor and the need for aggressive treatment and close long-term follow-up.

Should women with atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, receive reflex human papillomavirus-DNA testing?

BACKGROUND: The 2001 American Society for Colposcopy and Cervical Pathology Consensus Guidelines recommend that women who have Papanicolaou (Pap) smears diagnosed as atypical squamous cells (ASC), cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) should be referred for immediate colposcopic examination. The objective of this pilot study was to evaluate whether reflex human papillomavirus (HPV)-DNA testing performed on smears diagnosed as ASC-H may obviate the need for immediate colposcopic examination. METHODS: All ThinPrep Pap smears that were diagnosed as ASC-H or atypical squamous metaplastic cells (ASMT) between 2001-2003 and that had HPV-DNA testing and subsequent histologic and/or cytologic follow-up were evaluated. Those smears that were diagnosed as ASMT were reviewed and reclassified under the 2001 Bethesda System as either ASC of undetermined significance (ASCUS) or ASC-H. Smears that were diagnosed as ASCUS were excluded from the study. RESULTS: The study included of 48 smears that were diagnosed as ASC-H. All patients with biopsy-proven HSIL had positive high-risk (HR)-HPV results (100% negative predictive value). Approximately 80% of patients with ASC-H who had biopsy-proven, low-grade intraepithelial lesion on follow-up had positive HR-HPV results. Among the patients who had ASC-H with negative follow-up, 50% had positive HR-HPV results, and 50% had negative HR-HPV results. CONCLUSIONS: Among patients with ASC-H, a negative HR-HPV result was found to be an excellent predictor of the absence of HSIL. The results of this pilot study suggested that HPV-DNA testing may serve as a means to better select which patients with ASC-H on Pap smear should undergo colposcopic examination. This approach potentially may reduce medical costs and eliminate the need for routine colposcopic examination among patients with ASC-H Pap smears.