R. Thota

Effect of palliative care services on the aggressiveness of end-of-life care in the Veteran's Affairs cancer population.

BACKGROUND Cancer care near the end of life (EOL) has become more aggressive over the years. Palliative care services (PCS) may decrease this aggressive cancer care in terminally ill cancer patients. Our objective was to observe the aggressiveness of cancer care near the EOL among Veterans Affairs cancer patients before and after the institution of a PCS team. We also assessed the time taken prior to death to initiate a PCS consultation and its effect on the aggressiveness of cancer care near the EOL. METHODS This is a retrospective chart review analysis performed at the local Veterans Affairs hospital looking at the last 100 patients in each of the years, 2002 and 2008, who died with active cancer. Only patients in 2008 had access to a PCS team. RESULTS In the last 30 days of life, compared to 2002, patients in 2008 had a higher incidence of: chemotherapy administration, more than one hospital admission, more than 14 days of hospital stay, intensive care unit admissions, and in-hospital deaths. Patients with timely PCS consults in 2008 appeared to have a lower incidence of: chemotherapy administration, more than one emergency department visit, more than one hospital admission, more than 14-day hospital stays, intensive care unit admissions, and deaths in the hospital. Timely PCS consults were associated with earlier and more frequent hospice referral. CONCLUSIONS Cancer care near the EOL has become more aggressive with time at one of the hospitals in the Veterans Affairs healthcare system (VAHS). Institution of a PCS service was unable to completely decrease this trend of increasing aggressiveness of cancer care near the EOL. However, timely PCS consults may help attenuate this aggressiveness.

Clinicopathological features and survival outcomes of primary signet ring cell and mucinous adenocarcinoma of colon: retrospective analysis of VACCR database.

BACKGROUND Signet ring cell carcinoma (SRCC) accounts for less than 1% of all colon cancers. We examined the clinicopathological features and prognosis of signet ring cell and mucinous adenocarcinoma (MCC) of colon. METHODS A total of 206 patients diagnosed with SRCC from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. Age, race, histology, grade, lymph node status, stage and type of treatment received data were collected. RESULTS Out of 206 patients, 173 (84%) were white, 31 (15%) were black, and 2 patients were listed as unknown. Median age of diagnosis was 67 years as compared to 70 years for both mucinous cell (MCC) and non-mucinous adenocarcinoma (NMCC) of colon. Pathological T-stages were as follows: T1 =3%, T2 =5%, T3 =34%, T4 =26%, and unknown 32%. Of the total, 22.3% were located in cecum, 7.7% in appendix, 21.8% in ascending colon, 7.7% in hepatic flexure of colon, 11% in transverse colon, 2.9% in splenic flexure 4.4% in descending colon, and 15.5% in sigmoid colon. 46.5% were lymph node positive, 21% were lymph node negative, and 32.5% were unknown. SRCC were in general poorly differentiated tumors (57%), small proportion of patients included were well-differentiated tumors with focal signet ring cell pathology (10%) and in 33% grade was unknown. Among stage 3 patients, 34% patients received only surgery while 64% received surgery with adjuvant chemotherapy and 2% received chemotherapy alone. The stage specific 5-year survivals for SRCC, MCC and NMCC were--Stage I: 100%, 61%, and 41% respectively (P<0.0001); Stage II: 42%, 58% and 32% respectively (P<0.0001); Stage III: 19%, 41% and 47% respectively (P=0.0002); Stage IV: 1.5%, 7% and 31% respectively (P<0.0001). Median survival of SRCC compared to NMCC was 18.6 vs. 46 months (P<0.0001) and mucinous cell adenocarcinoma versus NMCC was 47.8 and 46 months (P=0.63) respectively. CONCLUSIONS SRCC of colon has poor survival rates compared to other histological subtypes. SRCC presents at an earlier age, has higher tumor grade and advanced stage at diagnosis when compared to mucinous and NMCC of colon. Due to rarity of this disease further prospective multi-institute studies are required for in-depth understanding of this disease.

Clinicopathologic factors associated with lymph node retrieval in resectable colon cancer: A veterans' affairs central cancer registry (VACCR) database analysis

A long‐term determinant of survival in resectable colon cancer is the involvement of regional lymph nodes. We evaluated the clinicopathologic factors associated with lymph node retrieval.

Apparent heparin resistance in a patient with infective endocarditis secondary to elevated factor VIII levels.

Heparin resistance (HR) is defined as increasing requirements of heparin to maintain a therapeutic activated partial thromboplastin time (aPTT). It is commonly associated with antithrombin deficiency, increased heparin clearance and elevations in heparin binding proteins. Elevated factor VIII levels can cause decrease the aPTT levels (anticoagulant effect) without disturbing heparin activity measured by anti-Xa assay (antithrombotic effect) leading to an apparent heparin resistant state rather than a true heparin resistance. We highlight the importance of increasing awareness of apparent HR and early distinction from true resistance to avoid major life threatening hemorrhagic complications. We hereby report an unusual case of heparin resistance due to increased factor VIII levels in an elderly male with infective endocarditis.

Hemodynamic collapse following bilateral knee arthroplasty: a mysterious case

Severe hemodynamic collapse after knee surgery from bilateral adrenal hemorrhages is rare. Even rarer is it occurring from adrenal hemorrhage as a complication of heparin induced thrombocytopenia. Due to lack of awareness of this rare complication and associated complex scenario in critically ill patients, diagnosis is often made post mortem. A diagnosis of bilateral adrenal hemorrhage should be considered in any patient presenting with non-specific symptoms of fever, abdominal pain, confusion and rapid hemodynamic collapse not responding to standard therapy. This is crucial especially in the setting of heparin induced thrombocytopenia as thrombosis and not hemorrhage is often the most feared complication of this syndrome.

Systemic amyloidosis masquerading as iron deficiency anemia

Amyloidosis is characterized by deposition of amyloid fibrils in tissues causing progressive dysfunction of the affected organs. There are six types: primary (AL), secondary (AA), hemodialysis-related, hereditary, senile, and localized. Primary (AL) amyloidosis is associated with monoclonal light chains in serum and/or urine with 15 % of patients having multiple myeloma. Although internists and gastroenterologists encounter malabsorption syndrome frequently, primary amyloidosis is often overlooked. We report a case of primary amyloidosis presenting as iron deficiency anemia and review the literature related to this disorder. A 44-year-old healthy male presented with intermittent rectal bleeding, watery diarrhea, steatorrhea, dizziness and 13.6 kg weight loss over a year. On admission he was afebrile, tachycardic and hypotensive. Physical examination was unremarkable except for mild epigastric tenderness and reduced bowel sounds. Laboratory data include hemoglobin level of 6.8 g/dL, mean corpuscular volume of 76 fL, serum iron of 11 μg/dL, and ferritin of 6 ng/mL suggestive of iron deficiency anemia. Peripheral smear revealed hypochromia, anisopoikilocytosis and microcytosis. Coagulation studies and other routine biochemical tests were within normal ranges. Esophagogastroduodenoscopy and colonoscopy showed mild gastritis along with small internal and external hemorrhoids. He received 1,000-mg intravenous iron sucrose therapy and was discharged on oral iron supplements. Then on he had several admissions over a year with hypotension, dehydration and severe anemia requiring blood transfusions. Despite extensive investigations including repeat colonoscopy with biopsy, capsule endoscopy, stool studies, urine 5-hydroxyindoleacetic acid levels (5-HIAA), fecal fat, hydrogen breath tests (X2), serum and urine protein electrophoresis (SPEP, UPEP), no obvious cause for blood loss was evident except that on one of the admissions he had hematuria and further evaluation revealed hemorrhagic cystitis. Subsequently he underwent bone marrow biopsy, which showed increased plasma cells with lambda staining being predominant. Since the patient had features of malabsorption associated with increased plasma cells in the bone marrow a review of his pathology from small intestine, colon and urinary bladder was done. It showed amyloid deposition confirmed by a positive Congo red stain in the tissue samples as shown in Figs. 1, 2. The patient was diagnosed with primary AL amyloidosis and was treated with thalidomide and dexamethasone. Amyloidosis encompasses a group of disorders characterized by extracellular deposition of insoluble small molecular weight fibrillary, proteinaceous material in various tissues of the body [1]. Gastrointestinal (GI) involvement is common in reactive amyloidosis (60 %) while it is less common in primary amyloidosis [2]. The most frequent sites of infiltration are the descending duodenum (100 %), the stomach and colorectum (more than 90 %), and the esophagus (about 70 %) [3]. Clinical diagnosis of gut amyloidosis has been difficult as most of the symptoms mimic other common diseases, like gastroparesis, gastric or duodenal ulcers, perforation, malabsorption, GI bleeding and intestinal pseudo-obstruction [4]. Histological examination is required for an accurate diagnosis, irrespective of the organ(s) involved. Apple-green birefringence (when viewed with crossed polarized light) and red staining (under white R. Thota (*) :W. Gonsalves : T. Tashi Department of Internal Medicine, Creighton University School of Medicine, Omaha, NE 68131, USA e-mail: ramyathota1@gmail.com

Clinicopathologic features and survival outcomes of primary signet ring cell carcinoma of colon: Retrospective analysis of VACCR database.

e14097 Background: Signet ring cell carcinoma accounts for less than 1% of all colon cancers. We examined the clinical pathological features and prognosis of signet ring cell carcinoma of colon Methods: A total of 206 patients diagnosed with signet ring cell carcinoma from 1995 to 2009 were identified from the VA Central Cancer Registry (VACCR) database. Age, race, histology, grade, lymph node status, stage and type of treatment received data were collected. RESULTS Out of 206 patients, 173 (83.9%) were white, 31 (15%) were black, and 2 patients were listed as unknown. Median age of diagnosis was 67 years as compared to 70 years for both mucinous and non-mucinous adenocarcinoma of colon. Pathological T-stages were as follows: T1 = 2.9%, T2=5.3%, T3=33.9%, T4= 25.7%, and unknown 32%. Of the total, 22.3% were located in caecum, 21.8% in ascending colon, 15.5% in sigmoid colon, 7.7% in appendix and hepatic flexure of colon, 11.1% in transverse colon, 2.9% in splenic flexure and 4.4% in descending colon. 33.5% were lymph node positive, 34.6% were lymph node negative, and 31.8% were unknown. Histological grade 3-(55.4%) was most commonly reported followed by grade 2 (7.3%), grade1 (2.5%), grade 4 (1.9%) and in 33% grade was unknown. 41.3% patients received only surgery while 34% received surgery with adjuvant chemotherapy, 7.3% received chemotherapy alone, 7.8% received radiation alone and 9% did not receive any therapy. 1 yr, 3 yr and 5 yr survivals for signet ring cell cancer compared to adeno carcinoma was 60% vs 80%, 33% vs 60%, and 24% vs 47% respectively. Median survival of signet ring cell carcinoma compared to mucinous and non mucinous adenocarcinoma was 19 mos, 48 mos and 67 mos respectively. CONCLUSIONS Signet ring cell carcinoma of colon has poor survival rates than other histological subtypes. Signet ring cell carcinoma presents at an earlier age, has higher tumor grade and advanced stage at diagnosis when compared to mucinous and non-mucinous adeno carcinoma of colon. Due to rarity of this disease further multi-institute studies are required for in-depth understanding of this disease.

Surgical outcomes of colorectal cancer in octogenarians: Survival analysis of the Veteran's Affairs population.

e14024 Background: Surgical resection of the primary tumor in the absence of metastatic disease is the treatment of choice for colorectal cancer. There is limited data evaluating surgical outcomes in the very elderly patients (≥80years). The purpose of this study was to evaluate surgical practice patterns and their effects on survival for patients ≥80 years of age. METHODS Retrospective analysis of 36,260 patients with colon cancer in the Veterans Affairs Central Cancer Registry between 1995 and 2009 was done. Demographic data, location of tumor, grade, stage, co-morbidities, therapy and survival data were extracted. RESULTS A total of 36,260 patients were identified with colon cancer and 5473 (15%) were octogenarians. Of the entire population, 97.3% were males, 82% were white and 16% were black. Among octogenarians, 4,111 (75%) received surgery while in the younger population, 25,166 (82%) received surgery. Median survival of patients who had surgery among the elderly compared to the younger population was 48 vs 99 mos (P<0.0001). Median survival was significantly higher among octogenarians who received surgery (50 vs 25 mos, P<0.001). The stage specific median survival with surgery among elderly compared to the younger population are stage 1-62 vs 143 mos (P<0.001), stage 2-53 vs 102 mos (P<0.001), stage 3-34 vs 63 mos (P<0.001). Elderly patients who received adjuvant chemotherapy had significantly better survival outcomes compared to those who did not receive adjuvant therapy (23 versus 64 mos). CONCLUSIONS Surgical resection rates and median overall survival are lower in octogenarians compared to their younger counterparts; however fit elderly patients do benefit from surgery and adjuvant therapy.

Hodgkin lymphoma of the elderly veterans: Veterans Affairs Cancer Registry analysis.

9138 Background: Hodgkin lymphoma (HL) is a very treatable disease that is known to have a bimodal age distribution. Unlike the younger patients,elderly patients with HL have a prognosis which is still unsatisfactory. Prospective studies selected for elderly patients are rare and randomized trials are missing. We studied the clinical and pathological characteristics, treatment received and survival outcomes of patients ≥60yrs and <60 yrs using the Veterans Affair Cancer Registry database. METHODS Retrospective analysis of 947 patients diagnosed with Hodgkin disease from 1995-2003 was obtained.Demographics, histology, tobacco use, agent orange exposure, stage at presentation, presence of B symptoms and type of treatment received data was extracted.Variables were analyzed with Kaplan-Meier and Cox models. RESULTS Of the 947 patients 38.8% were >60yrs and 61.2% were <60. Racial distribution among the elderly and the younger HL patients were similiar. In histological subtypes there was an increased prevelance of lymphocyte depleted and nodular lymphocyte predominant subtypes among older patients. Older patients also had higher incidence of stage IV disease compared to their younger counterparts. Overall survival was significantly higher in the <60 years age group (17.83 mos vs 3.23mos). Median survival was better in the <60 years age group when compared for stage at presentation, type of histology, treatment received and absence of B symptoms (P <0.0001) .Multivariate analysis revealed Stage 1(HR=0.68; 0.48-0.95; p=0.024), age <60 years (HR=0.31; 0.26-0.38; p<0.0001) was associated with improved outcomes whereas Lymphocyte depleted (HR=1.44; 1.07-1.93; p=0.015) subtype correlated with poor outcome. CONCLUSIONS HL of the elderly has a dismal prognosis compared to the younger patients.Older age, lymphocyte depleted subtype and advanced stage at presentation are negative prognostic factors in HL patients.Co-morbid illnesses, delay in diagnosis,incomplete staging, inadequate adherence to treatment protocols and failure to maintain dose intensity are other potential factors which needs to be investigated in multi-centre randomized controlled trials.

Primary genitourinary small cell carcinoma: Clinicopathologic and survival outcomes from SEER database.

200 Background: Small cell carcinoma of genitourinary system (SCC) is a highly aggressive and rare entity. The aim of the study is to characterize the clinicopathologic characteristics and evaluate the treatment outcomes of SCC in adult patients. METHODS Retrospective analysis of 732 patents diagnosed with small cell carcinoma of bladder from 1973 to 2007 was done via SEER database. Demographics, stage, type of treatment received and cancer-specific mortality were examined. RESULTS 732 patients were identified with SCC of genitourinary tract of which 341 were small cell bladder cancer, 336 were small cell prostate cancer and 55 were small cell renal cancer. Of these 644 patients were males and 88 were females. Median age of diagnosis is 73 years for bladder, 72 years for prostate and 70 years for renal cancer. Majority of the patients were Caucasians (89%) followed by African Americans (6%) and other races (4.98%). Grading of the tumor revealed that 12 patients had well differentiated tumor, 18 patients had moderately differentiated tumor, 191 patients had poorly differentiated, 292 patients had undifferentiated tumor and 219 patients had unknown grade. Pathological T-stages were as follows: T1= 34 (4.6%), T2= 102 (14%), T3= 43 (9%), T4= 41 (5.6%), 38.4% unknown T stage and 67 (9%) patients had metastatic disease. In majority of the patients the treatment received was unknown (565), 90 patients received external beam radiation, and 76 patients received surgery. Cancer-specific mortality was 54% in bladder cancer, 71% in prostate cancer and 78.6% in renal cancer. Median overall survival for all stages was 15.8 months in bladder cancer, 11.3 months in prostate cancer and 8 months in renal cancer. CONCLUSIONS Results show that SCC is a highly aggressive tumor with poor prognosis. Clinical trials involving multiple institutes are needed to accrue enough patients so that treatment paradigms for this uncommon disease can be developed. No significant financial relationships to disclose.