History Of Renal Cell Cancer Research Articles

8813 Nivolumab-Induced Diabetes: A Hidden Danger

Abstract Disclosure: J. Case: None. R.V. Chemitiganti: None. D. Suravajjala: None. Immunomodulating therapy as utilized in chemotherapy for malignancy may lead to potential adverse events including immune-related adverse events(IRAEs). One such pathway by which this may occur is through alteration of the programmed cell death as affected by drugs such as nivolumab which inhibits appropriate matching of PD-1 and PD-L1 and may lead to a robust immune response with collateral damage to nontumor tissue. Multiple downstream effects may be seen leading to other pathologies including development of autoimmune diabetes as noted in the patient described herein. A 61 year old female presented to establish care for suspected type one diabetes mellitus. She had a history of renal cell cancer diagnosed about one year prior for which she was treated with nivolumab. She was found to have hyperglycemia on routine labwork with further labwork revealing inappropriately low c-peptide as measured at less than 0.10 ng/mL (0.8-3.85ng/mL) with a coincident glucose of 566mg/dL (74-106mg/dL). Further workup revealed no measurable presence of GAD65, antipancreatic islet cell or ZNT8 antibodies. Diagnosis was made of insulinopenic diabetes or otherwise autoimmune diabetes induced as an IRAE subsequent nivolumab use. She was subsequently started on a basal bolus regimen with insulin achieving blood glucose control. IRAEs are an unfortunate, albeit rare consequence of immune checkpoint inhibitors including nivolumab. Depending on the toxicity grade and prognosis the offending agent may be discontinued and steroids initiated to mitigate adverse effects. However sometimes the occurrence of an IRAE may go undetected until too late as noted in the above patient. Her presentation was atypical considering many present with DKA and as well IRAEs are less likely in monotherapy. Education of IRAEs as well as appropriate screening would aid in recognition of potential IRAEs at which time appropriate measures may be taken to alleviate collateral damage. Further elucidation of the mechanism by which this autoimmune response is activated against nontumor tissue may also lead to better understanding of autoimmune diabetes caused by other etiologies. Presentation: 6/2/2024

S1766 Metastatic Renal Cell Cancer with Pancreatic Mass

Introduction: Pancreas is an uncommon site of metastatic disease. Almost 63% of pancreatic metastasis arise from renal cell cancer. We report a case of metastatic renal cell cancer to pancreas, with contralateral adrenal metastasis 15 years after a radical nephrectomy. Case Description/Methods: 61 years old man with past medical history of renal cell cancer, status post left radical nephrectomy fifteen years ago, presented with dull pain in right lower abdominal for one day. He denied any other abdominal symptoms or weight loss. He smokes up to half a pack of cigarettes daily. His examination was unremarkable but he was noted to have elevated lipase (213U/L) and a bilirubin of 1.1 mg%. On computer tomography abdomen he had bulky, enhancing, soft tissue mass (∼6.7 cm), with dilated pancreatic duct of 1.5 cm with right adrenal mass (Figure). On EUS, the lesion appeared well circumscribed and previously known pancreatic duct dilation was seen. Fine needle biopsy of the mass, which showed numerous atypical cells with round irregular nuclei with prominent nucleoli with clear cytoplasm suggestive of clear cell renal cell carcinoma (Figure). On immune -histochemistry, the tumor was positive for CD10, renal cell carcinoma antigen and PAX 8( Figure) Discussion: Metachronous renal cell cancer to pancreas fifteen years after radial nephrectomy is rare. Our patient had pancreatic metastasis with adrenal involvement and presented with vague abdominal symptoms. .He was noted to have elevated lipase and dilation of main pancreatic duct. Due to a remote history of nephrectomy and the presenting complaints, pancreatic primary was suspected. However, on endoscopic ultrasound the patient was noted to have a well circumscribed lesion in the head of pancreas with dilated pancreatic duct(Figure). Regular borders and absence of pancreatic duct dilation suggested metastatic disease. Our patient had well circumscribed lesion but with a dilated duct. Most pancreatic metastasis are reported to occur within 10 years after treatment of the primary disease but our patient had metastasis fifteen years later without any loco-regional recurrence. Endoscopic ultrasound is extremely important and allows to evaluate the extent of the disease, involvement of portal vein/ superior mesenteric artery, presence of enlarged lymph nodes, which are a must for evaluating the surgical candidature besides providing tissue diagnosis which helped us establish the diagnosis of metastasis.Figure 1.: CT(A,B,C) and EUS(D,E) findings. Image A shows the mass in the Pancreatic head(arrow with red head) with a dilated pancreatic duct seen in imageB( arrow with red head). Adrenal metastasis is seen in image C marked with a red arrow. On EUS, the mass appears well circumscribed( blue arrow, image D) with dilated pancreatic duct seen ( green arrow) in the head of pancreas in E.

The Yorkshire Kidney Screening Trial (YKST): protocol for a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal pathology within a trial of community-based CT screening for lung cancer

IntroductionKidney cancer (renal cell cancer (RCC)) is the seventh most common cancer in the UK. As RCC is largely curable if detected at an early stage and most patients have...

Secondary Tumors of the Ampulla of Vater: A Tale of Two Cases.

We report two cases of women with metastatic cancers to ampulla of Vater. The first was 91 years old and presented with severe anemia, due to upper gastrointestinal bleeding. She had history of renal cell cancer treated with nephrectomy 8 years ago and diagnosis confirmed to be metastasis of renal cell cancer to ampulla of Vater. The second patient was 54 years old with breast cancer, metastasis and developed obstructive jaundice; diagnosis confirmed to be breast metastasis in the ampulla of Vater. Secondary tumors of the ampulla of Vater due to breast cancer and renal cell cancer are rare findings and prognosis can be poor.

3128 A Rare Case of a Gastroduodenal Ulcer Arising From Checkpoint Inhibitors

INTRODUCTION: Ipilimumab and Nivolimuab are in a class of immune checkpoint inhibitors that are widely used in the treatment of advanced malignancies. 1 Immunotherapy with monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4) and the programmed death-1 receptor (PD-1) and its ligand PD-L1 has become the standard of care for cancer treatment today. 1 Gastrointestinal (GI) toxicity from cancer immunotherapy is well described for anti-CTLA4 Abs, but less well studied in combination of anti-CTLA4 and anti-PD-1Abs. GI effects of these immunotherapies range from enterocolitis, pancreatitis, diarrhea, and ulcerations involving the sigmoid colon and rectum. 1 CASE DESCRIPTION/METHODS: Here, we present the case of an 80 year old male with past medical history of renal cell cancer (RCC) that was diagnosed 3 months prior to admission, who presented with melenic stool for one day. The patient had been initiated on a chemotherapy regimen of Ipilimumab and Nivolimuab of which he received three rounds, the last dose one week prior to hospitalization. He had not been on any anticoagulation nor had he endorsed NSAID use. Patient's hemoglobin was closely trended. One day into admission, patient had a large melenic bowel movement with Hb change from 9.0 to 8.7 mg/dL with significant hypotension and tachycardia. Patient was emergently intubated for airway protection for an EGD. EGD revealed a large 4-5 cm ulcer in the second portion of the duodenum and found to have a large artery protruding from the ulcer base, likely the gastroduodenal artery. Endoscopic intervention was performed by placing 5 clips at the ulcer base in an effort to further prevent bleeding. Hemoglobin was trended closely following the procedure, however post-EGD bleeding continued and patient became acutely hypotensive, requiring vasopressor support. As further EGD intervention was considered to be high risk, Interventional Radiology was consulted for embolization with empiric embolization of gastroduodenal artery using a microcoil, which was successful. Hemoglobin continued to trend downwards despite control of bleeding and vasopressor support increased at which point patient was transitioned to comfort measures. DISCUSSION: This case outlines a rare case of immune checkpoint inhibitors as a cause of a gastroduodenal ulcer and the adverse outcomes with checkpoint inhibitors as treatment for malignancies.

Isolated pancreatic metastases from renal cell carcinoma: an outcome of a special metastatic pathway or of specific tumor cell selection?

Isolated pancreatic metastases (isPM) are a rare metastasizing pattern in the natural history of renal cell cancer. Their clinical hallmark is that they are confined to a single organ, the pancreas, while all other organs are unaffected for a long time. Almost all workers in the field suggested that mechanical tumor cell propagation to the pancreas may be the mechanism underlying this metastasizing pattern. In 2006 our group, by contrast, proposed an alternative mechanism, i.e. a special affinity of the tumor cells for the pancreas. In the present study an attempt was made to shed more light on the settlement of isPM by reviewing recent literature data. 666 observations of isPM reported in the literature were reviewed. The analyses showed that local lymphatic spread does not play a major role because the lymphatic system is, in general, rarely involved in isPM. This also applies to a local venous spread, because the site of pancreatic metastases is independent of the side affected by the primary renal cancer. But the results are compatible with a systemic metastatic pathway. That metastases in other organs, which would be expected given a systemic spread, are absent can plausibly be explained by a seed and soil mechanism: only the pancreas offers the tumor cell emboli an environment which is conducive to the growth of clinically manifest metastases, while settlement of metastatic tumor cells is prevented in all other organs.

Uveal melanoma and renal cell carcinoma both metastatic to the liver

PurposeGermline mutations in the BRCA1‐associated protein‐1 gene (BAP1) predispose carriers to several types of cancer, including uveal and cutaneous melanoma, mesothelioma, renal cell cancer, and possibly other diverse tumor types. Approximately 2% of consecutive Finnish uveal melanoma patients harbor a germline mutation in BAP1.MethodsCase report.ResultsA 53‐year‐old man was diagnosed with renal cancer in 2006. No metastasis was detected during a 5‐year follow‐up after surgery. In 2011, he noted decreased vision in his left eye. Ophthalmological examination revealed a suspicious choroidal mass and the patient was referred to the ocular Oncology service, Helsinki University Eye Clinic. A choroidal melanoma with a largest basal dimension of 15.5 mm and thickness of 11.1 mm and no metastases was detected (T3aN0M0, stage IIB). He received brachytherapy with an iodine plaque. Three years later he had liver metastases, and biopsies indicated the presence of both uveal melanoma and renal carcinoma metastases. Further, a sister of his father also has had uveal melanoma. Given that the patient was a candidate to harbor a germline BAP1 mutation we sequenced the gene. No mutation was found in the coding regions or adjacent intronic sequences. Further, we carried out whole exome sequencing, and no mutations or mosaicism were found in BAP1, BRCA1, SF3B1, or EIF1AX.ConclusionsNot all familial uveal melanoma patients even with history of renal cell cancer harbor an obvious BAP1 germline mutation. Currently, we are analyzing histological samples to further investigate the possible role of BAP1 in tumor tissue and genetic data to find or exclude indirect effect on BAP1 function.

750O - Early Detection of Hereditary Renal Cell Cancer By Improved Evaluation of Spontaneous Pneumothorax Patients

ABSTRACT Aim: Birt-Hogg-Dube syndrome (BHD) is an autosomal dominant condition due to germline mutations in the folliculin (FLCN) gene, clinically characterized by skin fibrofolliculomas, lung cysts, (recurrent) spontaneous pneumothorax (SP) and an increased risk of renal cell cancer (RCC). Families with BHD are most often identified through recognition of fibrofolliculomas A less common way to identify a BHD family is through (recurrent) SP. The characteristic pulmonary cystsare generally not visible on standard chest X-ray, and therefore will be missed in the standard – according to British Thoracic Society guidelines - diagnostic work-up for SP cases. We hypothesize that supplementing the diagnostic work-up of SP patients with CT imaging will result in the identification of BHD patients presenting with SP. This provides the opportunity of the identification of (asymptomatic) RCC at an early stage by screening of identified FLCN mutation carriers. Methods: We retrospectively collected clinical and radiological data of 55 families, including 200 BHD patients with a proven pathogenic FLCN mutation. Our database started in 2004; the mean follow-up time of mutation carriers is 5 years (1-10 years). Results: Sixty patients in 33 families had (recurrent) SP. In 14 out of 30 families we detected one or more patients with RCC. In total 19 patients had a history of RCC, 7 of them had a history of (recurrent) SP and 15 patients had a positive familial history for SP. We found in 14 cases RCC at an early stage, 5 patients died due metastases. Histological diagnosis were mainly (a combination of) clear cell carcinoma and chromophobe carcinoma. Conclusions: Based on these results, we suggest that including (low dose) thoracic CT in the standard SP work up should result in the identification of BHD families. In these families annual screening for RCC should be offered to affected relatives, which was shown to result in early detection of BHD associated RCC. We show that a limited period of observation of these families has resulted in detection of 14 patients with RCC at an early stage. Disclosure: All authors have declared no conflicts of interest.

Renal cancer paradox

To compare temporal trends in the incidence and mortality of renal cell cancer among blacks and whites for clues to etiologic differences. We examined trends in age-adjusted and age-specific Surveillance Epidemiology and End Results incidence and US mortality rates for renal cancer for 1973 through 2007, as well as nephrectomy rates from surgery codes for kidney cancer for 2000 through 2007. For nearly four decades, incidence rates for renal cell cancer have been rising more rapidly among blacks than whites, leading to a shift in excess from among whites to among blacks, almost entirely accounted for by an excess of localized disease. The incidence patterns are puzzling, as localized renal cell cancer is primarily detected incidentally by imaging, to which blacks have historically had less access. In contrast to the incidence patterns, there has been an unexpected convergence of renal cancer mortality rates, which have been virtually identical among blacks and whites since the early 1990 s. Nephrectomy rates, regardless of stage, were lower among blacks than among whites, despite almost identical cause-specific survival rates in both races. The identical mortality patterns, combined with higher and more rapidly increasing incidence and lower rates of nephrectomies among blacks, suggest that renal cell cancer may tend to be a less aggressive tumor in blacks. This hypothesis is supported by the favorable stage distribution among blacks and their higher survival for distant and unstaged cancer. Further research into the enigmatic descriptive epidemiology and the biology and natural history of renal cell cancer may shed light on the etiology of this malignancy and its more frequent occurrence among black Americans.

Abstract C228: Renal insufficiency secondary to Erlotinib: Is it real?

Abstract Objective: We conducted a retrospective chart review to assess the extent of renal insufficiency noted in patients receiving Erlotinib for refractory/relapsed non small cell lung cancer at our Institute. Methods: We reviewed the charts of 285 patients at Roswell Park Cancer Institute, who received Erlotinib for varying durations of time during 2004 and 2009. Baseline and post-erlotinib serum creatinine (SCr) and serum creatinine clearance (SCrCl) levels were noted. Cases with worsening of serum creatinine levels during treatment with erlotinib were isolated. Extent of worsening, associated co-morbidities and medications and other factors possibly contributing to renal dysfunction were noted along with improvement in renal status after discontinuation of erlotinib. Results: Of the 175 patients with data available for evaluation, 21(12%) had worsening of their baseline SCr level while on erlotinib. 13(62%) of the patients with renal insufficiency had documented hypertension as co morbidity and were on anti-hypertensives including diuretics and ACE inhibitors. 8(38%) were diagnosed with diabetes mellitus and 6(28%) had coronary artery disease. 6(28%) patients had established chronic renal insufficiency (CRI) at baseline and had worsening after initiation of erlotinib. 1 patient had CRI secondary to prior history of renal cell cancer and was post nephrectomy. 1 patient had evidence of autoimmune disorder with Reynaud's phenomenon and polycystic kidneys. Another patient had history of lupus without evidence of CRI at baseline. 6(28%) concomitantly had diarrhea as a side-effect with erlotinib and in at least 3(14%) patients was the reason for discontinuation of further drug administration. In the remainder of the patients, the cause of discontinuation of erlotinib was progression in 13(52%), severe rash in 2(9%) and 3(14%) were still on the drug at the time of this analysis. Overall 5(21%) of patients with renal insufficiency after initiation of erlotinib did not have any other confounding factors identified. The onset of worsening renal status ranged from 14 days up to 333 days with a mean of 60 days. Baseline SCrCl of patients ranged from 26.2 to 100.5 ml/min with a mean of 49.8 and baseline SCr levels ranged from 0.9 to 2.4 mg/dl. Post therapy SCrCl in patients with worsening ranged from 18.5 to 59.8 with a mean of 35.9 and SCr levels from 1.3 to 3.4. Hence mean decline in SCrCl in these patients was by approximately 14 ml/min and serum creatinine of 0.5mg/dl. Of the 19 patients not currently on erlotinib any more, 12(63%) were noted to have improvement in SCrCl in mean of 33 days. Conclusion: The incidence of isolated renal insufficiency due to erlotinib is rare but does exist. Most often it is confounded with preexisting hypertension and diabetes mellitus leading to baseline chronic renal dysfunction and multiple other medications or concomitant diarrhea as a side effect of erlotinib leading to pre-renal worsening of kidney function. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C228.

Metastatic Renal Cell Carcinoma Mimicking Colon Cancer

Purpose: Renal cell carcinoma frequently metastasizes to lungs, lymph nodes, bones and liver. Large intestinal metastasis is uncommon. We report a case of metastatic renal cell carcinoma to the cecum three years after radical nephrectomy. Methods: N/A Results: An 84-year-old male with right renal cell carcinoma required radical nephrectomy three years ago, presented with a few episodes of hematochezia. He denied abdominal pain, nausea, vomiting or diarrhea. Past medical history was significant for diabetes mellitus, hypertension and atrial fibrillation. Physical examination was unremarkable other than severely pale conjunctivae and systolic murmurs. Laboratory data revealed a hemoglobin of 5.5 g/dL. A Colonoscopy was performed and demonstrated a large, protruding, partially obstructing cecal mass with surrounding ischemic colitis and a small ischemic ulcer at the proximal transverse colon. A biopsy was taken from the mass; however the pathological findings were consistent with tissue necrosis but no malignancy. CT chest and abdomen demonstrated a 1.3 cm. right lower lobe pulmonary mass, multiple hypodense hepatic lesions and a pericecal mass with mesenteric lymphadenopathy. CEA level was within normal limits. Primary colon cancer with distant metastasis was suspected. He underwent laparotomy. During the operation it was noticed that the tumor which was located above the cecum, was densely adherent posteriorly into the retroperitoneum at the area of previous nephrectomy, as well as laterally into the lateral peritoneal reflection. Right hemicolectomy was performed. Pathological examination demonstrated high grade, clear cell type tumor in the cecum with extension through serosal surface and pericolonic fat. The diagnosis of metastatic renal cell carcinoma similar to the tumor resected 3 years earlier was made. The patient was given Temsirolimus as single agent chemotherapy for metastatic renal cell carcinoma. Conclusion: Recurrence of renal cell carcinoma is sometimes found after radical nephrectomy and has been noted up to 24 years after diagnosis. The recurrence period is unpredictable; therefore lifelong follow up is need in patients with history of renal cell cancer even when curative nephrectomy was achieved. Additionally, endoscopists should consider intestinal metastasis of this unusual tumor in patients with history of renal cell cancer.

A 62-year-old woman with 3 episodes of anaphylaxis

HISTORY OF PRESENT ILLNESS A 62-year-old Hispanic woman with a history of renal cell cancer experienced her first episode of anaphylaxis during surgery in May 2002. Her systolic blood pressure dropped to 60 mm Hg several minutes after the initial incision was made in an attempted nephrectomy for her localized renal cell cancer. No hives were noted. Surgery was stopped, and the patient recovered in the intensive care unit after several doses of epinephrine and dexamethasone. She had received rocuronium and ciprofloxacin during the surgery, which were thought to be the most likely causes of the anaphylaxis. A second attempt at surgery 1 week later resulted in her second episode of anaphylaxis, again marked by a decrease in her blood pressure. This time she was not given ciprofloxacin, and the rocuronium was replaced with cisatracurium. The surgeons completed the procedure with the aid of epinephrine and dexamethasone, and the patient recovered without further incident. Three months later the patient had a third episode of anaphylaxis unrelated to surgery and was sent to the Northwestern University Allergy-Immunology Division for evaluation.

EUS-guided FNA of pancreatic metastasis from renal cell carcinoma

Background The prognosis for patients with renal cell carcinoma metastatic to the pancreas is better than that for patients with primary pancreatic adenocarcinoma. In patients with a history of renal cell cancer, it would, therefore, appear necessary to obtain cytologic or histopathologic evidence of the tumor type. EUS-guided FNA is considered the technique of choice for this purpose. This study retrospectively assessed the efficacy of EUS-guided FNA and specific technical considerations when the procedure is performed for this indication. Methods Over 2 years, EUS-guided FNA was performed in 11 consecutive patients with a history of renal cell carcinoma and a solid mass within the pancreas. Observations After EUS-guided FNA yielded a negative result in two patients, the sampling technique was modified, namely short aspiration with low negative vacuum pressure. This resulted in the detection of metastases of renal cell cancer in the remaining 9 patients. There was no procedure-related complication. Conclusions EUS-guided FNA is safe and accurate for the diagnosis of pancreatic metastases of renal cell carcinoma. However, effective sampling requires techniques that differ from those used for solid pancreatic masses.

Disseminated Brown Tumors from Hyperparathyroidism Masquerading as Metastatic Cancer: A Complication of Parathyroid Carcinoma

Osteitis fibrosa cystica (brown tumors) can be a skeletal manifestation of advanced hyperparathyroidism, including parathyroid cancer. Severe osteitis fibrosa cystica can mimic metastatic bone diseases especially in patients with a history of cancer. Because the treatment and prognosis of these two problems differ greatly considering hyperparathyroidism in the differential diagnosis of patients found to have osteolytic lesions is critical for the appropriate management of these patients. In this case report we describe a patient with a history of renal cell cancer and presumed osteolytic bone metastases. During prophylactic intramedullary rodding to prevent pathologic fracture of her femur she was found to have a benign lesion related to her previously undiagnosed hyperparathyroidism caused by an underlying parathyroid cancer. A detailed review of this disease and the associated bone changes is also included to underscore the importance of an adequate differential diagnosis as well as optimal management. Patients with hypercalcemia or bony lesions should not automatically be treated palliatively for metastatic disease just because of a past medical history of cancer. Hyperparathyroidism is a readily curable problem if properly diagnosed.

Fluorine-18 fluorodeoxyglucose uptake in tubovillous adenoma of the colon.

The authors report intense uptake of fluorine-18 fluorodeoxygluclose in benign tubovillous adenoma of the sigmoid colon in a patient with a history of renal cell cancer who was being evaluated for metastatic disease.