Complete pathologic response is independent of the timing of esophagectomy following neoadjuvant chemoradiation for esophageal cancer.

BACKGROUND: The relationship of complete pathologic response (cPR) with the timing of esophagectomy after neoadjuvant chemoradiation (nCRT) is not well defined. We sought to determine if a delay in esophagectomy after nCRT would result in increased likelihood of cPR and improved survival. METHODS: This is a retrospective analysis of a prospectively maintained database of all patients treated with nCRT and esophagectomy between 2004 and 2014. Patients were divided into two groups based on timing of esophagectomy (≤50 vs. >50 days) after completion of nCRT. Survival outcomes were compared using standard Kaplan-Meier curves, and multivariable analyses were performed using Cox regression models. RESULTS: This study included 226 patients (males, 211 and median age, 61 years) for analysis. Fifty-two patients (23%) in the early group (≤50 days) were compared to 174 patients (77%) in the delayed group (>50 days). The two groups were similar with respect to age, gender, comorbid conditions, ECOG status, location, grade, and tumor histology. There was no statistically significant difference in cPR rate between the early and late groups (26.9% vs. 19.0%, respectively, P=0.24). On multivariable analysis, lower age, absence of signet cell histology, better ECOG status, shorter length of stay and cPR were independent predictors of improved survival. The median follow-up was 52 months (range, 2-110 months), and there was no difference in the median overall survival (OS) between the early and late groups (48.9 vs. 42.6 months, respectively, P=0.73). CONCLUSIONS: This analysis of a large cohort of patients with esophageal cancer undergoing multi-modality therapy shows that cPR is independent of the timing of esophagectomy. Other considerations for the timing of surgery, including recovery from nCRT and patient performance, may have more relevant roles than cPR when deciding when to perform esophagectomy.

Water lavage as an adjunct to cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC).

BACKGROUND: Water lavage (WL) during gastrointestinal cancer surgery has osmotically mediated lytic effects on tumor cells. We investigated the safety and efficacy of WL with CRS-HIPEC. METHODS: This is a retrospective review, 1/2003-7/2014, of a single institution experience with CRS-HIPEC comparing patients who had WL (WL+) to those who did not (WL-). RESULTS: Of 157 CRS-HIPECs, 16 (10.2%) were WL+. WL+ had more PCI scores >20 compared to WL- (56.3% vs 19.4%, respectively, p = 0.003); however, the completeness of cytoreduction (CC) was similar. There were no differences in hospital length of stay or post-operative complications. The average POD 1 sodium (Na) level was statistically lower in the WL+ group (133.6 ± 2.5 vs 135.5 ± 3.2 mEq/L, p = 0.023); however, the average Na at discharge for each group was 140 mEq/L. There were no differences in 3-year OS (3WL+:0.63 vs WL-:0.68, p = 0.97) or RFS (WL+:0.32 vs WL-:0.39, p = 0.47). A subset analysis for patients with PCI >20 showed no difference between groups. CONCLUSIONS: WL offers a low cost, safe and theoretically efficacious method of tumor cell lysis for peritoneal malignancy.

Ki67 score as a potential predictor in the selection of liver-directed therapies for metastatic neuroendocrine tumors: a single institutional experience.

BACKGROUND: Neuroendocrine tumors (NETs) metastatic to the liver are treated with transarterial radioembolization (TARE) using yttrium-90 (Y-90) microspheres or transarterial chemoembolization (TACE). However the criteria for patient selection are not well defined. We sought to determine if Ki67 score could help select patients for one therapy over the other in the management of hepatic neuroendocrine metastases. METHODS: Single institution analysis of patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 staining. Data were analyzed using multivariate association for survival outcomes. RESULTS: Amongst 72 patients (male: 39, female: 33, median age: 57 years) with metastatic NET, the most common site of origin was small bowel (n=35, 49%), while pancreas constituted 32% (n=23). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) with TACE. Within Y-90 group, there was greater use of Sandostatin (95% vs. 75%, P=0.02) and less number of total treatments completed (89% vs. 46%, P<0.001). There was no significant difference in overall survival (OS) between Y-90 and TACE when used without selection (median, 69 vs. 82 months, P=0.47). When adjusted for Ki67, patients with Ki67 score ≥3% had better OS with Y-90 compared to TACE (HR, 0.1; CI, 0.01-0.9), however for Ki67 <3%, OS was better when treated with TACE compared to Y-90 (HR, 13.5; CI, 1.22-148.87). CONCLUSIONS: There is significant interaction between Ki-67 score and liver-directed treatment benefit in patients with hepatic neuroendocrine metastases. Ki-67 score ≥3% predicts greater benefit with Y-90 and a Ki-67 score <3% predicts greater benefit with TACE.

Pathologic Complete Response Is an Independent Predictor of Improved Survival Following Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma.

INTRODUCTION: Reports of improved survival in patients with pathologic complete response (pCR) to neoadjuvant therapy for esophageal and gastroesophageal junction (GEJ) adenocarcinoma is extrapolated from heterogeneous studies that include squamous cell histology. We sought to determine if pCR is associated with a survival advantage in a homogenous group of patients with esophageal adenocarcinoma. METHODS: This is a single institution analysis of all patients with T2-T4 or node positive esophageal adenocarcinoma treated with neoadjuvant chemoradiotherapy and esophagectomy between 2004 and 2014. Patients were divided into two groups based on pathological response, pCR vs. incomplete pathological response (iPR). Survival outcomes were evaluated using standard Kaplan-Meier methods and multivariable Cox regression models. RESULTS: A total of 205 patients were included in the study: 38 (19 %) patients with pCR and 167 patients (81 %) with iPR. The two groups were similar with respect to clinical stage, age, gender, comorbid conditions, ECOG status, smoking, and alcohol use. Patients in the pCR group had a higher percentage of tumors located in middle third of esophagus (11 vs. 2 %, p = 0.04) while tumor grade was similar in both groups. Median follow-up was 50 months, range 2-109 months. The 3-year overall (OS) and recurrence-free survival (RFS) for iPR was 48 and 39 %, respectively, vs. 86 and 80 % for pCR group, respectively. CONCLUSION: This analysis of a cohort of homogeneous patients with esophageal adenocarcinoma undergoing multimodality therapy showed that pCR is an independent predictor of improved RFS and OS. This data contributes to a growing body of evidence highlighting the benefits of neoadjuvant therapy specific to esophageal adenocarcinoma particularly when pCR is achieved.

Pre-operative unintentional weight loss as a risk factor for surgical outcomes after elective surgery in patients with disseminated cancer.

BACKGROUND: With improvement in survival, elective surgical procedures are being increasingly performed on patients with metastatic disease. We aimed to study the association of pre-operative unintentional weight loss (UWL) with operative outcomes in this patient population. METHODS: We extracted data on all patients with disseminated cancer undergoing elective surgeries between 2005 and 2011 from the National Surgical Quality Improvement Program (NSQIP), along with the Current Procedure Terminology (CPT) codes. Based on the presence of unintentional weight loss of >10% body weight in the 6-month period preceding surgery, patients were divided into 2 cohorts - (1) patients with UWL ('UWL' cohort) and (2) patients without UWL ('No UWL') cohort. Differences in patient characteristics, co-morbid conditions and outcomes were compared. RESULTS: There were 30,669 surgeries recorded under 1,638 CPT codes, with 8,436 surgeries involving the eight most common CPT codes. UWL was present in 11.5% of all patients. UWL patients were more commonly (P < 0.05) male, African-American, of higher ASA (American Society of Anesthesiology) class, and had multiple associated comorbidities. Nearly all complications, including wound infections, prolonged ventilator requirement, unplanned intubation, cardiac arrest, DVT, sepsis and mortality were more common in UWL patients. Multivariate analysis demonstrated that UWL was independently associated with 21%, 22% and 49% higher risk of overall morbidity, serious morbidity and 30-day mortality, respectively. CONCLUSION: UWL is an independent risk factor associated with increased morbidity and mortality following elective surgeries in patients with disseminated cancer.

Evolving ablative therapies for hepatic malignancy.

The liver is a common site for both primary and secondary malignancy. Hepatic resection and transplantation are the two treatment modalities that have been shown to achieve complete cure, but only 10 to 20% of patients are candidates for these treatments. For the remaining patients, tumor ablation has emerged as the most promising alternative modality. In addition to providing local control and improving survival outcomes, tumor ablation also helps to down stage patients for potential curative treatments, both alone as well as in combination with other treatments. While tumor ablation can be achieved in multiple ways, the introduction of newer ablative techniques has shifted the focus from palliation to potentially curative treatment. Because the long-term safety and survival benefits are not substantive at present, it is important that we strive to evaluate the results from these studies using appropriate comparative outcome methodologies.

Challenges in the treatment of angiosarcoma: a single institution experience.

BACKGROUND: Angiosarcomas are rare tumors that carry poor prognosis. Because of insidious growth rate, the diagnosis is often difficult and delayed. METHODS: Between 1990 and 2011, 72 (41 female, 31 male) patients were treated at our institution. Pathologic confirmation was obtained and multiple prognostic factors were evaluated for survival. RESULTS: Forty-four cases were sporadic and 28 cases were secondary. In the sporadic group, 16 (36%) patients had increased sun exposure, while in the secondary group, the majority (n = 23, 82%) of patients had prior exposure to radiation. The latent period between radiation exposure and diagnosis was predictive of survival (P = .037). Presentation was delayed by more than 3 months in 41% of patients. The majority of men developed head and neck angiosarcomas (n = 15, 48.5%), while women developed breast angiosarcomas (n = 21, 51%). Median survival was prolonged in patients treated initially with surgery. CONCLUSIONS: A delay in the diagnosis of angiosarcoma can affect survival. Clinical suspicion and prompt diagnosis are essential for successful multimodal therapy. Initial surgical resection with adjuvant chemotherapy provides survival advantage.

Partial stomach-partitioning gastrojejunostomy and the success of this procedure in terms of palliation.

BACKGROUND: In the 1990s, partial stomach-partitioning gastrojejunostomy (PSPG) was introduced. Benefits of this method are that it preferentially shunts food away from the obstructed duodenum or pylorus, thus reducing reflex emesis. METHODS: A retrospective review of patients undergoing PSPG for malignant obstruction from 1999 to 2011 was performed. Ability to tolerate oral intake in the postoperative period and at last follow-up was the criterion for a successful bypass. RESULTS: Fifty-five patients with locally advanced or metastatic tumors underwent PSPG. The median follow-up period was 8 months. No patient developed signs of gastric outlet obstruction after PSPG. Seventy-five percent of patients had pancreatic or duodenal and 25% had nonpancreatic cancers. Nine patients developed postoperative complications. The perioperative mortality rate was zero. Median overall survival was 9 months. All patients were tolerating an enteral diet on the day of discharge, and as of the last follow-up, 95% were tolerating their enteral diets. CONCLUSIONS: This and a previous study from the authors' institution show that PSPG is a good alternative for palliative bypass in the setting of malignant gastric outlet obstruction over classic gastrojejunostomy.

Dual ErbB1 and ErbB2 receptor tyrosine kinase inhibition exerts synergistic effect with conventional chemotherapy in pancreatic cancer.

Patient survival in pancreatic cancer remains poor with gemcitabine (GEM)-based regimens. The target specific molecular agent lapatinib, a dual ErbB1 and ErbB2 receptor tyrosine kinase inhibitor, has shown significant activity against ErbB1 and ErbB2-expressing tumors. Since pancreatic tumors frequently overexpress these proteins, we investigated its effects, both alone and in conjunction with 5-FU or GEM. The pancreatic cancer cell lines PANC-1 and AsPC were treated with varying doses of lapatinib in vitro. The effects on ErbB1/ErbB2 protein phosphorylation and on the cell survival protein survivin were determined by western blotting. Cytotoxicity was determined by MTT assay and apoptosis was measured using the caspase-3 colorimetric assay. Similar dose-response lapatinib experiments were conducted with varying concentrations of 5-FU or GEM and isobolograms were constructed to evaluate therapeutic synergy. Lapatinib inhibited protein phosphorylation in the range of 4-16 µM, a clinically achievable concentration. The lapatinib-treated cells showed a dose-dependent inhibition of cell proliferation and induction of apoptosis at the same concentrations that blocked ErbB1/ErbB2 phosphorylation. The addition of 5-FU or GEM to these cells resulted in synergistic effects. The lapatinib-treated cells also demonstrated downregulation of survivin. Simultaneous dual ErbB1 and ErbB2 receptor tyrosine kinase inhibition with lapatinib results in significant reduction of pancreatic cancer cell growth and proliferation. These effects occur at clinically achievable concentrations and are synergistic with the effects of 5-FU or GEM. These findings support the potential role of lapatinib in the treatment of pancreatic cancer.

Intussusception after laparoscopic gastric bypass surgery: an underrecognized complication.

Introduction. Intussusception after bariatric surgery is an uncommon complication that is now being frequently reported. Most people consider dysmotility to be the causative mechanism in the absence of obvious etiology. Material and Methods. A worldwide search identified literature describing intussusception after bariatric surgery. We also included our own patients and analyzed information regarding demographic profile, risk factors, presentation, diagnosis, and post treatment course. Results. Seventy one patients were identified between 1991 and 2011. Majority of the affected patients were females (n = 70, 98.6%); median time to presentation after gastric bypass surgery was 36 months. Most patients presented with abdominal pain, nausea and vomiting, but without obvious peritonitis. Sixty eight patients (96%) required surgery; 48 (70.6%) underwent revision of anastomosis, 16 (23.5%) had reduction without resection, while 4 patients (5.9%) had plication only. Amongst these, most patients (n = 51, 75%) were found to have retrograde intussusception. Post-operatively, 9 patients presented with recurrence (range, 0.5-32 months). Five patients, who had earlier been treated without resection, eventually required revision of the anastomosis. There was no mortality noted. Conclusion. Intussusception after bariatric surgery is uncommon and its diagnosis is based on a combination of physicial, radiological and operative findings. An early surgical intervention reduces morbidity and prevents recurrence.

Oriental cholangiohepatitis masquerading as cholangiocarcinoma: A rare presentation that surgeons need to know.

INTRODUCTION: The detection of an abnormal hepatic mass with ductal dilatation is highly concerning for malignancy. However, if such patients happen to be immigrants from endemic parts of Asia or South America, further investigations are necessary to rule out oriental cholangiohepatitis, a rare recurrent disease of the hepatobiliary system that can masquerade as cholangiocarcinoma. PRESENTATION OF CASE: We report a case of a patient of South Asian origin who presented to us with acute cholangitis and moderately dilated left hepatic ducts. The findings were highly suspicious for advanced hepatic malignancy; however the laboratory and pathological investigations remained normal. We suspected an unlikely etiology and proceeded with conservative hepatic resection. The histology revealed cholangiohepatitis without any evidence of malignancy. DISCUSSION: Cholangiohepatitis is a complex hepatobiliary disease that commonly manifests as recurrent cholangitis or overt biliary sepsis and can rarely present as an abnormal hepatic mass. It results from the development of intrahepatic or extrahepatic strictures that causes stone formation and biliary dilation in the absence of gallbladder disease. Although it is endemic in many parts of the world, it is rare in the western world, and therefore it can present as a significant diagnostic enigma. CONCLUSION: Cholangiohepatitis is a rare clinical entity that requires a multi-disciplinary team approach. Surgery plays a dominant role in the management of such patients and therefore surgeons need to be aware of this disease.

Should asymptomatic enlarged thymus glands be resected?

OBJECTIVE: Patients frequently have an "enlarged thymus" incidentally identified on imaging. We sought to determine whether thymectomy is appropriate in patients with diffusely enlarged thymus glands. METHODS: A retrospective review was conducted of patients undergoing thymectomy without myasthenia gravis at 1 institution over 15 years. RESULTS: Of 117 patients undergoing thymectomy, 109 patients had complete data. Thirty-six had a gland judged by the surgeon to be diffusely enlarged, and 73 had a discrete mass. Of the 36 diffusely enlarged thymus glands, 18 (50%) occurred in patients with no symptoms referable to the thymus. No patient (0/18; 0%) with an asymptomatic diffusely enlarged thymus gland had a pathologic diagnosis that would have required resection (8 normal; 10 "hyperplasia"). Of the 18 symptomatic patients with diffusely enlarged glands, 4 (22.2%) harbored lymphoma, but none harbored thymoma or other tumor (P < .05; symptomatic vs asymptomatic). Of the 73 patients with discrete masses, 45 (61.6%) were symptomatic, and both the symptomatic and asymptomatic patients had a high rate of pathologic diagnoses that represented an indication for resection (53.3% and 42.8%, respectively, harbored thymoma or other tumor). Of the 25 (of 109) patients initially having a diagnosis of thymic hyperplasia, only 3 (12%) had true follicular hyperplasia on re-review of the pathologic condition. Interestingly, an autoimmune disorder developed in 2 (67%) of these 3 patients on long-term follow-up. CONCLUSIONS: Asymptomatic patients with diffusely enlarged thymus glands can be followed up expectantly because they have a negligible incidence of significant thymic disease; symptomatic patients with diffusely enlarged thymus glands may have lymphoma, so biopsy is appropriate. Half of patients with a discrete mass have tumors requiring resection; imaging advances would be useful to better differentiate among patients within this group.

Medullary carcinoma of the large intestine: a population based analysis.

Medullary carcinoma (MC) of the colorectum is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and intraepithelial lymphocytic infiltrate. To date, there has been no epidemiological study of this rare tumor type, which has now been incorporated as a separate entity in the World Health Organization (WHO) classification of colorectal cancers. We used the population-based registries of the Surveillance, Epidemiology and End Results (SEER) database to identify all cases of colorectal MC between 1973 and 2006 and compared them to poorly and undifferentiated colonic adenocarcinomas (PDA and UDA, respectively). We observed that MCs were rare tumors, constituting approximately 5-8 cases for every 10,000 colon cancers diagnosed, with a mean annual incidence of 3.47 (+/-0.75) per 10 million population. Mean age at diagnosis was 69.3 (+/-12.5) years, with incidence increasing with age. MCs were twice as common in females, who presented at a later age, with a lower stage and a trend towards favorable prognosis. MCs were extremely rare among African-Americans. MCs were most common in the proximal colon (74%), where they present at a later age than the sigmoid colon. There were no cases reliably identified in the rectum or appendix. Serum carcinoembryonic antigen levels (CEA) were elevated prior to first course of treatment in 40% of the patients. MCs were more commonly poorly differentiated (72%), with 22% being undifferentiated. MCs commonly presented with Stage II disease, with 10% presenting with metastases. Only one patient presented with N2b disease (>7 positive nodes). Early outcome analyses showed that MCs have 1- and 2-year relative survival rates of 92.7 and 73.8% respectively. Although MCs showed a trend towards better early overall survival, undifferentiated MCs present more commonly with Stage III, with comparatively worse early outcomes.