Simplified/Same Day(s)-GOLF as First-line Treatment of Metastatic Carcinoma of Unknown Primary (CUP), Suggestive of Pancreatobiliary Tumors.

BACKGROUND: Carcinoma of unknown primary represents a therapeutic challenge in oncological practice. Evidence lacks to support particular chemotherapy selection and empirical therapies are commonly extrapolated from data on patients where primary tumor site is known. Gemcitabine, Oxaliplatin, Leucovorin and 5-Fluorouracil was previously developed to treat pancreatic cancer. These agents have also demonstrated activities in other gastrointestinal malignancies. Considering promising anti-tumor effects of GOLF, we performed a retrospective study to investigate anti-tumor activity and safety of a simplified Gemcitabine, Oxaliplatin, Leucovorin and 5-Fluorouracil in patients with Carcinoma of unknown primary in whom immunohistostaining was suggestive of either upper gastrointestinal cancers or pancreatobiliary cancers. METHODS: This retrospective study included 18 patients recorded to have a diagnosis of Carcinoma of unknown primary between Aug 2010-Dec 2015, who received biweekly G 1000 mg/m2, O 85 mg/m2, L 200 mg/m2 and F 2400 mg/m2 over 46-h on day 1 with pegfilgrastim on day 3 every 14 days. IHC staining pattern favored upper GI origin, including stomach, bile duct or pancreas. Tumor assessments were repeated every 8 weeks. RESULTS: Median age was 67 years (range: 46-76), with ECOG PS<2, and 50% were women. Median number of cycles was 4 (range: 3-14). 7 partial responses were obtained (RR: 39%) and 7 achieved stable disease with overall disease control of 78%. Median time to tumor progression was 4 months (range: 2-9). 8 (44%) patients received liver-directed therapy and 1 underwent HIPEC (5%). Median survival time was 10.5 months (range: 6.7-14.5) and 1-year overall survival rate was 35%. Grade 3-4 toxicities included neutropenia, febrile neutropenia, thrombocytopenia, nausea, diarrhea, mucositis and oxaliplatin-induced neuropathy. CONCLUSION: Simplified Gemcitabine, Oxaliplatin, Leucovorin and 5-Fluorouracil regimen appears to be feasible with promising activity for Carcinoma of unknown primary and deserves to be evaluated in future trials.

Hip Abductor Strengthening Improves Physical Function Following Total Knee Replacement: One-Year Follow-Up of a Randomized Pilot Study.

BACKGROUND: Total knee replacement (TKR) is the commonest surgical procedure for patients with severe pain and impaired physical function following end stage knee osteoarthritis. The hip abductors are well renowned in stabilization of the trunk and hip during walking, maintaining the lower limb position, and transferring the forces from the lower limbs to the pelvis. OBJECTIVE: To assess the efficacy of hip abductor strengthening exercise on functional outcome using performance based outcome measures following total knee replacement. METHODS: An observer blinded randomized pilot trial design was conducted at Manipal hospital, Bangalore, India. Participants designated for elective TKR were randomized to experimental group hip abductor strengthening along with standard rehabilitation (n=10) or control group standard rehabilitation alone (n=10). Participants followed for one year to assess physical function using performance based outcomes, such as timed up and go test, single leg stance test, six minute walk test, knee extensor strength and hip abductor strength. RESULT: Eighteen participants with a mean age of 63.1 ± 5.5 years (8 Males and 10 Females) completed the study. Improvement in hip abduction strength, single leg stand test was superior in hip abductor strengthening group at 3 months and 1 year when compared to standard rehabilitation alone. CONCLUSION: Hip abductor strengthening showed superior improvements in single leg stance test and six minute walk test. Hip abductor strengthening exercises has the potential to improve physical function following total knee replacement.

Successful endoscopic treatment of an intraductal papillary neoplasm of the bile duct.

We present a case of a 76-year-old man with right upper quadrant abdominal pain and weight loss, who was found to have an intraductal papillary neoplasm of the bile duct (IPNB) of the pancreaticobiliary subtype, deemed curatively resectable. The patient declined surgery and opted for endoscopic therapy. He underwent two sessions of endoscopic retrograde cholangiopancreatography (ERCP)-guided radiofrequency ablation (RFA). Ten months later, no evidence of recurrence was identified on repeat ERCP. To our knowledge, this is the first reported case of successful use of RFA as a primary treatment modality for resectable IPNB.

High-flow nasal oxygen availability for sedation decreases the use of general anesthesia during endoscopic retrograde cholangiopancreatography and endoscopic ultrasound.

AIM: To examine whether high-flow nasal oxygen (HFNO) availability influences the use of general anesthesia (GA) in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) and associated outcomes. METHODS: In this retrospective study, patients were stratified into 3 eras between October 1, 2013 and June 30, 2014 based on HFNO availability for deep sedation at the time of their endoscopy. During the first and last 3-mo eras (era 1 and 3), no HFNO was available, whereas it was an option during the second 3-mo era (era 2). The primary outcome was the percent utilization of GA vs deep sedation in each period. Secondary outcomes included oxygen saturation nadir during sedation between periods, as well as procedure duration, and anesthesia-only time between periods and for GA vs sedation cases respectively. RESULTS: During the study period 238 ERCP or EUS cases were identified for analysis. Statistical testing was employed and a P < 0.050 was significant unless the Bonferroni correction for multiple comparisons was used. General anesthesia use was significantly lower in era 2 compared to era 1 with the same trend between era 2 and 3 (P = 0.012 and 0.045 respectively). The oxygen saturation nadir during sedation was significantly higher in era 2 compared to era 3 (P < 0.001) but not between eras 1 and 2 (P = 0.028) or 1 and 3 (P = 0.069). The procedure time within each era was significantly longer under GA compared to deep sedation (P ≤ 0.007) as was the anesthesia-only time (P ≤ 0.001). CONCLUSION: High-flow nasal oxygen availability was associated with decreased GA utilization and improved oxygenation for ERCP and EUS during sedation.

Radiation recall gastritis secondary to erlotinib in a patient with pancreatic cancer.

BACKGROUND: Radiation recall refers to chemotherapy-triggered inflammation in healthy areas previously exposed to irradiation. Chemotherapeutics known to be associated with radiation recall phenomenon include anthracyclines, taxanes and antimetabolites, such as gemcitabine and capecitabine. Case reports detailing radiation recall dermatitis and pneumonitis associated with erlotinib have been previously described in the literature, however, there are no reported cases describing radiation gastritis associated with erlotinib. We report a patient with pancreatic cancer who developed gastrointestinal bleeding secondary to radiation recall gastritis related to erlotinib exposure. CASE REPORT: A 57-year-old Hispanic male with pancreatic cancer initially received 7 cycles of FOLFIRINOX followed by capecitabine with radiation therapy for 28 fractions for a total of 5,040 cGy. Re-staging with computed tomography demonstrated stable disease. The patient was then treated with erlotinib and capecitabine for approximately two months before restaging demonstrated progressive disease. Shortly after discontinuing erlotinib and capecitabine, the patient reported maroon colored stools. Laboratory studies demonstrated a precipitous drop in hemoglobin and hematocrit from pre-treatment baseline, ultimately requiring transfusion with packed red blood cells. Subsequent esophagogastroduodenoscopy demonstrated findings consistent with radiation gastritis, with oozing in the gastric body and antrum, which was treated therapeutically with argon plasma coagulation. The patient's gastrointestinal bleed was difficult to control. Over the course of a two-month period - the patient required multiple admissions, repeat therapeutic esophagogastroduodenoscopies and transfusions. DISCUSSION: Radiation recall from erlotinib is rare but can potentially arise in any site that has been previously irradiated. There may be an association between the pathogenesis of radiation recall and erlotinib's up-regulation of the angiogenic growth factor thymidine phosphorylase. Treating physicians are reminded of the potential toxicity from erlotinib either given concomitantly or followed by radiation. We suggest discontinuing erlotinib if radiation gastritis is observed. We encourage physicians with similar experiences with erlotinib to report their findings. Further studies are warranted to investigate the pathogenesis of this unique phenomenon and its association with erlotinib.

Double-balloon enteroscopy in the elderly: safety, findings, and diagnostic and therapeutic success.

BACKGROUND: Double-balloon enteroscopy (DBE) is an important tool in the evaluation and management of small-bowel disease. Limited data are available on the safety, findings, and outcomes of DBE in elderly patients. OBJECTIVE: To determine the safety and efficacy of DBE in elderly patients. DESIGN: Single-center, retrospective analysis of prospectively collected database. SETTING: Open-access, tertiary care referral center. PATIENTS: A total of 176 patients undergoing DBE (216 procedures) for evaluation of small-bowel disease between August 2007 and August 2008. INTERVENTIONS: Argon plasma coagulation of bleeding small-bowel lesions. MAIN OUTCOME MEASUREMENTS: DBE complication rate, diagnostic/therapeutic success of DBE. METHODS: An age cutoff of 75 years and older was used to designate patients as elderly. Data on complications, indications, findings, and diagnostic and therapeutic success of DBE were compared between age groups. RESULTS: The mean age of patients was 66 +/- 16.4 years (range 20-95 years). DBE was performed in 185 patients, including 60 patients age 75 years and older and 110 patients younger than age 75. An overall complication rate of 0.9% was seen for DBE in this study, with no significant difference between age groups. No major complications were observed in elderly patients. Elderly patients were more likely to have angioectasias (39% vs 23%; P = .01) and were more likely to require endoscopic therapy during DBE (46.8% vs 29.2%; P = .01). LIMITATIONS: Single-center, retrospective study. CONCLUSIONS: DBE is safe in elderly patients. Elderly patients are more likely to have angioectasias and to require endoscopic therapy during DBE.

Transluminal endosurgery: novel use of endoscopic tacks for the closure of access sites in natural orifice transluminal endoscopic surgery (with videos).

BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) is a novel and potentially less-invasive alternative to laparoscopic surgery. Successful reproducible secure closure of the transluminal access site represents one of the largest obstacles in the evolution of this discipline. AIM: To study the feasibility and efficacy of a novel transluminal closure device in a live porcine model. DESIGN: Experimental endoscopic study of transgastric incision and closure with a novel device in a porcine survival model. Six survival experiments were conducted on Yorkshire pigs that weighed 22 to 25 kg. INTERVENTIONS: After general anesthesia was administered, a therapeutic endoscope was inserted into the stomach. Two gastrotomies were made in each pig by using a needle-knife with blended current, a guidewire, and an 18-mm through-the-scope dilating balloon. The peritoneum was easily accessed in all pigs without complications. One gastrotomy was closed with T-tag fasteners and the other one with endoscopic tacks. Two different closure methods were used with the tacks: the anchor-and-loop technique (ALT) and the serosa-to-serosa closure (SSC). All closures were immediately completely sealed, with no carbon dioxide (CO(2)) leak detected at 25 cm of water pressure. After recovery from anesthesia, all the animals resumed feeding and returned to preprocedure activities on the same day as the procedure. The animals were monitored daily for signs of peritonitis and sepsis. Preplanned euthanasia of the animals was performed after 7 to 14 days. The peritoneal cavity was studied at necropsy for evidence of wound dehiscence, abscess formation, and gross adhesions. MAIN OUTCOME MEASUREMENTS: Full-thickness healing of the gastric-wall incisions without intraperitoneal complications on postmortem examination. RESULTS: All animals survived without complications. Transgastric closure was successful in all the animals by using both study techniques (ALT and SSC) and the T-tag closure. The deployment device performed well, and accurate closure was rapid and reproducible. CONCLUSIONS: This prototype closure device holds promise in solving some of the problems of closure for transluminal access for NOTES. Both the ALT and the SSC technique hold promise for threadless closure and for simplifying endoscopic techniques. The SSC technique holds promise to maintain surgical principles of serosa-to-serosa apposition. Further studies are recommended before in vivo human use.

Systemic and targeted therapy for advanced colon cancer.

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer-related death in the USA. Prognosis is best when the disease is detected early; however, nearly two-thirds of newly diagnosed cases of CRC have lymph node involvement or metastatic disease. For years, 5-fluorouracil (FU)-based regimens represented the only viable treatment option for patients with metastatic CRC. However, in recent years several newer agents have been added to the treatment arsenal for this disease. These agents include oxaliplatin, irinotecan and newer monoclonal antibodies targeting the epidermal growth factor receptor (cetuximab and panitumumab) and VEGF (bevacizumab). This review aims to discuss current systemic and targeted therapies for metastatic colon cancer with a focus on mechanism of action, indications, toxicity and efficacy.