ABSTRACT
BACKGROUND: Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown. OBJECTIVE: The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC. METHODS: All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS). RESULTS: Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (-SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with -SM compared with +SM in both groups (p = 0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p < 0.001). On multivariable analysis, +SM in the upfront surgery group (hazard ratio [HR] 2.94, 95% confidence interval [CI] 2.04-4.24; p < 0.001) and older age (HR 1.01, 95% CI 1.00-1.03, per year; p = 0.007) predicted worse OS. +SM in the NACRT group was not associated with worse OS (HR 1.09, 95% CI 0.72-1.65; p = 0.70). CONCLUSION: Patients with a positive margin after NACRT and surgery had longer survival compared with patients with a positive margin after upfront surgery. NACRT should be strongly considered for patients at high risk of R1 resections.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Adenocarcinoma/therapy , Aged , Humans , Margins of Excision , Neoadjuvant Therapy , Pancreatic Neoplasms/therapy , PrognosisABSTRACT
BACKGROUND: Several registry-based analyses suggested a survival advantage for married versus single patients with pancreatic cancer. The mechanisms underlying the association of marital status and survival are likely multiple and complex and, therefore, may be obscured in analyses generated from large population-based databases. The goal of this research was to characterize this potential association of marital status with outcomes in patients with resected pancreatic cancer who underwent combined modality adjuvant therapy on a prospective clinical trial. MATERIALS AND METHODS: This is an ancillary analysis of 367 patients with known marital status treated on NRG Oncology/RTOG 97-04. Survival analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: Of 367 patients, 271 (74%) were married or partnered and 96 (26%) were single. Married or partnered patients were more likely to be male. There was no association between marital status and overall survival (OS) or disease-free survival (DFS) on univariate (hazard ratio [HR], 1.09 and 1.01, respectively) or multivariate analyses (HR, 1.05 and 0.98, respectively). Married or partnered male patients did not have improved survival compared with female or single patients. CONCLUSION: Ancillary analysis of data from NRG Oncology/RTOG 97-04 demonstrated no association between marital and/or partner status and OS or DFS in patients with resected pancreatic cancer who received adjuvant postoperative chemotherapy followed by concurrent external beam radiation therapy and chemotherapy. Clinical trial identification number. NCT00003216. IMPLICATIONS FOR PRACTICE: Several population-based studies have shown an epidemiological link between marital status and survival in patients with pancreatic cancer. A better understanding of this association could offer an opportunity to improve outcomes through psychosocial interventions designed to mitigate the negative effects of not being married. Based on the results of this analysis, patients who have undergone a resection and are receiving adjuvant therapy on a clinical trial are unlikely to benefit from such interventions. Further efforts to study the association between marital status and survival should be focused on less selected subgroups of patients with pancreatic cancer.
Subject(s)
Pancreatic Neoplasms , Female , Humans , Male , Marital Status , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Proportional Hazards Models , Prospective Studies , Survival AnalysisABSTRACT
BACKGROUND: Neoadjuvant therapy for pancreatic cancer is being employed more commonly. Most of these patients undergo biliary stenting which results in bacterial colonization and more surgical site infections (SSIs). However, the influence of neoadjuvant therapy on the biliary microbiome has not been studied. METHODS: From 2007 to 2017, patients at our institution who underwent pancreatoduodenectomy (PD) and had operative bile cultures were studied. Patient demographics, stent placement, bile cultures, bacterial sensitivities, SSIs and clinically-relevant postoperative pancreatic fistulas (CR-POPF) were analyzed. Patients who underwent neoadjuvant therapy were compared to those who went directly to surgery. Standard statistical analyses were performed. RESULTS: Eighty-three patients received neoadjuvant therapy while 89 underwent surgery alone. Patients who received neoadjuvant therapy were more likely to have enterococci (45 vs 22%, p < 0.01), and Klebsiella (37 vs 19%, p < 0.01) in their bile. Resistance to cephalosporins was more common in those who received neoadjuvant therapy (76 vs 60%, p < 0.05). Neoadjuvant therapy did not affect the incidence of SSIs or CR-POPFs. CONCLUSION: The biliary microbiome is altered in patients undergoing pancreatoduodenectomy (PD) after neoadjuvant therapy. Most patients undergoing PD with a biliary stent have microorganisms resistant to cephalosporins. Antibiotic prophylaxis in these patients should cover enterococci and gram-negative bacteria.
Subject(s)
Biliary Tract/microbiology , Carcinoma, Pancreatic Ductal/therapy , Microbiota , Neoadjuvant Therapy , Pancreatic Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Bile/microbiology , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Drug Resistance, Bacterial , Enterococcus/isolation & purification , Female , Humans , Klebsiella/isolation & purification , Male , Middle Aged , Pancreatectomy , Pancreaticoduodenectomy , Retrospective Studies , Stents , Surgical Wound Infection/epidemiologyABSTRACT
BACKGROUND: Because pancreatoduodenectomy for pancreatic adenocarcinoma is focused on disease-free and overall survival, morbidity among long-term survivors is not well described. This study sought to evaluate outcomes for long-term survivors of pancreatic cancer after pancreatoduodenectomy. METHODS: The authors identified 29 patients from their prospectively collected database of patients with pancreatic adenocarcinoma who had undergone pancreatoduodenectomy and were without evidence of disease during at least 3 years of follow-up evaluation. Demographics, treatment, and pathologic characteristics were collected for review. Data with regard to long-term sequelae also were collected, focusing on those complications requiring additional procedures and on the development of metachronous cancers. RESULTS: The median follow-up period was 83 months, with 62 % of patients still alive. All patients received an R0 resection, and 34 % of the patients had N1 disease. For 42 % of the patients, no significant subsequent sequelae occurred. In the four remaining patients (14 %), ascites developed, requiring repeated paracentesis or Denver shunt, with a median time to development (MTD) of 63 months. Six patients (21 %) experienced a biliary stricture requiring stent placement (MTD, 56 months). One patient experienced portal venous thrombosis requiring a venous stent (MTD, 52 months), and four patients (14 %) experienced clinically significant ulcers (MTD, 52 months). With regard to metachronous cancers, two patients experienced subsequent lymphomas (MTD, 92 months). CONCLUSIONS: Long-term survivors among patients who undergo pancreatoduodenectomy for pancreatic adenocarcinoma can experience significant late sequelae, which often manifest more than 3 years after surgery. As such, continued follow-up evaluation and counseling are warranted.
Subject(s)
Adenocarcinoma/surgery , Morbidity , Neoplasm Recurrence, Local/surgery , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy/mortality , Postoperative Complications , Survivors , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , Female , Follow-Up Studies , Humans , Male , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Prognosis , Prospective Studies , Survival RateABSTRACT
New combinations of cytotoxic chemotherapy have been proven to increase response rates and survival times compared with single-agent gemcitabine for patients with metastatic pancreatic cancer. These responses have been dramatic for a subset of patients, therefore raising questions about the management of limited metastatic disease with surgery or other ablative methods. Similarly, for patients having a complete radiographic response to chemotherapy in the metastatic compartment, whether to consider local therapy in the form of radiation or surgery for the primary tumor is now an appropriate question. Therefore, collaboration among experts in surgery, medical oncology, and radiation oncology has led to the development of guiding principles for local therapies to the primary intact pancreatic tumor for patients with limited metastatic disease and those who have had a significant response after systemic therapy.
Subject(s)
Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/therapy , Combined Modality Therapy , Disease Management , Humans , Neoplasm Metastasis , Treatment OutcomeABSTRACT
BACKGROUND: Neoadjuvant chemoradiation and chemotherapy provided for borderline or locally advanced, potentially resectable pancreatic adenocarcinoma improves resectability rates. Response to therapy is also an important prognostic factor. There are no data in the literature regarding optimal time interval or duration of chemotherapy after chemoradiation before surgery, and pathologic response rates. Using our database, we evaluated these relationships and the effect on overall and progression-free survival. METHODS: We retrospectively analyzed the records of 83 patients who underwent neoadjuvant chemoradiation for locally advanced, potentially resectable, and borderline resectable pancreatic cancers before definitive resection. We divided patients into three groups according to time interval between completion of chemoradiation and resection: group A (0-10 weeks), group B (11-20 weeks), and group C (>20 weeks). After chemoradiation, patients underwent ongoing chemotherapy before resection. Pathologic response was defined as major (>95% fibrosis), partial (50-94% fibrosis), or minor (<50% fibrosis). RESULTS: There were 56 patients in group A, 17 patients in group B, and 10 patients in group C. Patients in groups B and C were significantly more likely to experience a major response than group A (p < 0.013). Patients in group C had significantly increased median progression-free and overall survival (p < 0.05). Multivariable classification and regression tree analysis demonstrated pathologic response to be the only significant factor in overall survival. CONCLUSIONS: Patients who underwent a prolonged time interval after neoadjuvant chemoradiation with ongoing chemotherapy were more likely to have an improved pathologic response at time of surgical resection, which was associated with improved median overall survival.
Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Neoadjuvant Therapy , Pancreatic Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Capecitabine , Chemotherapy, Adjuvant , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Preoperative Care , Prognosis , Radiotherapy, Adjuvant , Retrospective Studies , Survival Rate , Time Factors , GemcitabineABSTRACT
The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings.
Subject(s)
Adenocarcinoma/drug therapy , Neoadjuvant Therapy , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Guidelines as Topic , Humans , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgeryABSTRACT
BACKGROUND: A theoretical advantage of preoperative therapy in pancreatic adenocarcinoma is that it facilitates the early treatment of micrometastases and reduces postoperative systemic recurrence. METHODS: Medical records of 309 consecutive patients undergoing resection of adenocarcinoma in the head of the pancreas were reviewed. Survival was calculated using the Kaplan-Meier method. Associations between preoperative therapy and patterns of recurrence were determined using chi-squared analysis. RESULTS: Preoperative therapy was administered to 108 patients and upfront surgery was performed in 201 patients. Preoperative therapy was associated with a significantly longer median disease-free survival of 14 months compared with 12 months in patients submitted to upfront surgery (P = 0.035). The rate of local disease as a component of first site of recurrence was significantly lower with preoperative therapy (11.3%) than with upfront surgery (22.9%) (P = 0.016). Preoperative therapy was associated with a lower rate of hepatic metastasis (21.7%) than upfront surgery (34.3%) (P = 0.026). Preoperative therapy did not affect rates of peritoneal or pulmonary metastasis. CONCLUSIONS: Preoperative therapy for pancreatic cancer was associated with longer disease-free survival and lower rates of local and hepatic recurrences. These data support the use of preoperative therapy to reduce systemic and local failures after resection.
Subject(s)
Adenocarcinoma/therapy , Neoadjuvant Therapy , Neoplasm Recurrence, Local , Pancreatectomy , Pancreatic Neoplasms/therapy , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Chi-Square Distribution , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/prevention & control , Liver Neoplasms/secondary , Lung Neoplasms/prevention & control , Lung Neoplasms/secondary , Male , Middle Aged , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/mortality , Neoplasm Micrometastasis , Pancreatectomy/adverse effects , Pancreatectomy/mortality , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Peritoneal Neoplasms/prevention & control , Peritoneal Neoplasms/secondary , Retrospective Studies , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Imatinib inhibits the KIT and PDGFR tyrosine kinases, resulting in its notable antitumor activity in gastrointestinal stromal tumor (GIST). We previously reported the early results of a multi-institutional prospective trial (RTOG 0132) using neoadjuvant/adjuvant imatinib either in primary resectable GIST or as a planned preoperative cytoreduction agent for metastatic/recurrent GIST. METHODS.: Patients with primary GIST (≥5 cm, group A) or resectable metastatic/recurrent GIST (≥2 cm, group B) received neoadjuvant imatinib (600 mg/day) for approximately 2 months and maintenance postoperative imatinib for 2 years. We have now updated the clinical outcomes including progression-free survival, disease-specific survival, and overall survival at a median follow-up of 5.1 years, and we correlate these end points with duration of imatinib therapy. RESULTS: Sixty-three patients were originally entered (53 analyzable: 31 in group A and 22 in group B). Estimated 5-year progression-free survival and overall survival were 57% in group A, 30% in group B; and 77% in group A, 68% in group B, respectively. Median time to progression has not been reached for group A and was 4.4 years for group B. In group A, in 7 of 11 patients, disease progressed >2 years from registration; 6 of 7 patients with progression had stopped imatinib before progression. In group B, disease progressed in 10 of 13 patients>2 years from registration; 6 of 10 patients with progressing disease had stopped imatinib before progression. There was no significant increase in toxicity compared with our previous short-term analysis. CONCLUSIONS: This long-term analysis suggests a high percentage of patients experienced disease progression after discontinuation of 2-year maintenance imatinib therapy after surgery. Consideration should be given to studying longer treatment durations in intermediate- to high-risk GIST patients.
Subject(s)
Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/secondary , Neoplasm Recurrence, Local/drug therapy , Piperazines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Adult , Aged , Aged, 80 and over , Benzamides , Chemotherapy, Adjuvant , Disease Progression , Disease-Free Survival , Female , Follow-Up Studies , Gastrointestinal Stromal Tumors/mortality , Humans , Imatinib Mesylate , Male , Middle Aged , Piperazines/adverse effects , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Survival Rate , Treatment Outcome , Young AdultABSTRACT
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.
Subject(s)
Adenocarcinoma/diagnosis , Adenocarcinoma/therapy , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Diagnostic Imaging/methods , Humans , Neoplasm Staging , Pancreatic Neoplasms/pathologyABSTRACT
BACKGROUND: Over the past few years, surgeons have been able to obtain training in advanced minimally invasive surgery (MIS) for hepatic, pancreatic, and biliary (HPB) cases instead of having to teach themselves these complex techniques. As a result, the initial experience of a surgeon with advanced MIS HPB training at a national cancer center was reviewed. METHODS: The experience of a surgeon with the first 50 laparoscopic hepatectomies for cancer was reviewed retrospectively. All cases begun with the intention to complete the hepatectomy laparoscopically were included in the laparoscopic group. RESULTS: From November 2008 to October 2010, a total of 57 hepatectomies were performed, with 53 attempted laparoscopically. Of these 57 hepatectomies, 46 (87%) were completed laparoscopically, 4 (7%) required hand assistance, and 3 (6%) were converted to an open approach. Laparoscopic minor hepatectomies were performed for 28 patients and laparoscopic major hepatectomies for 25 patients. The mean operative time was 265 min, and the mean estimated blood loss was 300 ml. The mean hospital stay was 7 days. Complications occurred for six patients (11%) (2 bile leaks, 2 hemorrhages requiring conversion, 1 hernia requiring a hernia repair on postoperative day 7, and 1 ileus managed nonoperatively). CONCLUSIONS: Surgeons with advanced MIS HPB training may be able to perform a higher percentage of their hepatectomies laparoscopically. Training in both open and laparoscopic HPB surgery is advisable before these techniques are performed.
Subject(s)
Hepatectomy/methods , Laparoscopy/methods , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Hepatectomy/education , Humans , Laparoscopy/education , Length of Stay , Middle Aged , Postoperative Complications/etiology , Preoperative Care , Reoperation/statistics & numerical data , Retrospective StudiesABSTRACT
BACKGROUND: Given the difficulty level of minimally invasive pancreatoduodenectomy (MIPD), limited data exist for a comparison to open pancreatoduodenectomies. As the technique becomes more diffuse, issues regarding the adequacy of oncologic margins and lymph node retrieval need to be addressed. METHODS: All published cases of MIPD were examined. Variables analyzed included conversion rates, operating room time, estimated blood loss, length of stay, follow-up, complications, mortality, lymph node retrieval, and margins. RESULTS: Twenty-seven articles describing outcomes after MIPD were found, and a total of 285 cases were described. Main malignancy treated was pancreatic adenocarcinoma, accounting for 32% of all cases. Eighty-seven percent were performed totally laparoscopically, and 13% were performed with a hand-assisted approach to facilitate the reconstruction step of the procedure. The rate of conversion to an open procedure was 9%. Estimated blood loss had a weighted average (WA) of 189 mL. Average length of stay had a WA of 12 days, and average follow-up had a WA of 14 months. The overall complication rate was 48%, and the overall mortality rate was 2%. Average lymph nodes retrieved ranged from 7 to 36 nodes, with a WA of 15 nodes, and positive margins of resection were reported to be positive in 0.4% of patients with malignant disease. CONCLUSIONS: This review found similar outcomes with respect to perioperative morbidity and mortality rates compared to open pancreatoduodenectomies. The oncologic goals of pancreatic resection may be able to be achieved by MIPD, but longer follow-up and larger series are still needed.
Subject(s)
Laparoscopy , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Humans , Treatment OutcomeABSTRACT
BACKGROUND: The impact of the addition of gemcitabine to 5-fluorouracil (5-FU) chemoradiation (CRT) on 5-year overall survival (OS) in resected pancreatic adenocarcinoma are presented with updated results of a phase III trial. METHODS: After resection of pancreatic adenocarcinoma, patients were randomized to pre- and post-CRT 5-FU versus pre- and post-CRT gemcitabine. 5-FU was provided continuously at 250 mg/m(2)/day, and gemcitabine was provided at 1000 mg/m(2) weekly. Both were provided over 3 weeks before and 12 weeks after CRT. CRT was provided at 50.4 Gy with continuously provided 5-FU. The primary end point was survival for all patients and for patients with tumor of the pancreatic head. RESULTS: Four hundred fifty-one patients were eligible. Univariate analysis showed no difference in OS. Pancreatic head tumor patients (n = 388) had a median survival and 5-year OS of 20.5 months and 22% with gemcitabine versus 17.1 months and 18% with 5-FU. On multivariate analysis, patients on the gemcitabine arm with pancreatic head tumors experienced a trend toward improved OS (P = 0.08). First site of relapse local recurrence in 28% of patients versus distant relapse in 73%. CONCLUSIONS: The sequencing of 5-FU CRT with gemcitabine as done in this trial is not associated with a statistically significant improvement in OS. Despite local recurrence being approximately half of that reported in previous adjuvant trials, distant disease relapse still occurs in ≥ 70% of patients. These findings serve as the basis for the recently activated EORTC/U.S. Intergroup RTOG 0848 phase III adjuvant trial evaluating the impact of CRT after completion of a full course of gemcitabine.
Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/therapy , Pancreatic Neoplasms/therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Adult , Aged , Aged, 80 and over , Cohort Studies , Combined Modality Therapy , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Fluorouracil/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/surgery , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/surgery , Prospective Studies , Survival Rate , Treatment Outcome , GemcitabineABSTRACT
BACKGROUND: Pathologic response to preoperative therapy is increasingly recognized as an important prognostic factor in solid tumors. The impact of pathologic response on survival in pancreatic adenocarcinoma is not well established. METHODS: Data on 135 consecutive patients treated with chemoradiation followed by pancreatectomy for adenocarcinoma of the pancreatic head and/or body between July 1987 and May 2009 were reviewed. Histopathologic examination was performed in 107 patients to determine pathologic response, defined as minor (<50% fibrosis relative to residual neoplastic cells), partial (50-94% fibrosis), or major (95-100% fibrosis). RESULTS: Minor, partial, and major pathologic response rates were 17% (n = 18), 64% (n = 68), and 19% (n = 21), including a 7% (n = 8) complete pathologic response rate. Pathologic response correlated with R0 resection (P = 0.019), negative lymph nodes (P = 0.006), and smaller tumor size (P = 0.001). Median survival rates by pathologic response were as follows: 17 months [95% confidence interval (CI), 0-36 months] for minor response, 20 months (95% CI, 17-23 months) for partial response, and 66 months (95% CI, 8-124 months) for major response (minor versus partial response, P = not significant; partial versus major response, P < 0.001). On multivariate analysis, major pathologic response was the only factor significantly associated with improved survival (P = 0.025; hazard ratio, 2.26). CONCLUSIONS: Major pathologic response to preoperative therapy occurs in a minority of patients with pancreatic adenocarcinoma and is independently associated with prolonged survival.
Subject(s)
Adenocarcinoma/mortality , Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatectomy , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Pancreatic Neoplasms/therapy , Prognosis , Radiotherapy Dosage , Survival RateABSTRACT
BACKGROUND: Indications for minimally invasive major hepatectomies have been increasing as experience with these techniques grows. Invasion into the diaphragm is considered a contraindication to the laparoscopic approach. At their institution, the authors have begun approaching all tumors laparoscopically. This report presents the techniques necessary to perform right hepatectomy, partial diaphragm resection, and repair using totally laparoscopic techniques. METHODS: Five trocars are placed in a semilunar fashion approximately one handbreadth apart along a line one handbreadth below the right subcostal margin. The hepatic inflow is taken extraparenchymally before transection of the hepatic parenchyma in an anterior-to-posterior fashion. The hepatic inflow then is transected, and the involved portion of diaphragm is transected with ultrasonic shears. Next, the diaphragm is repaired primarily and buttressed with an absorbable material to decrease the incidence of recurrent diaphragmatic hernia. RESULTS: Laparoscopic treatment was attempted for ten patients and successfully completed for nine of these patients (90%). All 10 patients had secondary liver tumors. Three patients required concomitant partial diaphragm resection. The median estimated blood loss (EBL) was 500 ml (range, 300-3,000 ml). All margins were negative, and the average hospital stay was 8 days (range, 5-17 days). Two patients (20%) experienced complications, which consisted of biliary leaks, which were treated with percutaneous drainage. One of these patients underwent conversion to an open procedure due to an inferior vena cava injury. No mortality occurred at 30 or 90 days of follow-up evaluation. CONCLUSION: The minimally invasive approach to secondary tumors requiring right hepatectomy is feasible and safe even when there is diaphragmatic involvement. Larger series with long-term follow-up evaluation are needed to determine whether these short-term results translate into durable benefits.
Subject(s)
Diaphragm/surgery , Hepatectomy/methods , Laparoscopy/methods , Liver Neoplasms/surgery , Blood Loss, Surgical/statistics & numerical data , Humans , Length of Stay/statistics & numerical data , Liver Neoplasms/secondary , Postoperative Complications , Treatment OutcomeABSTRACT
PURPOSE: Diabetes mellitus (DM) has been proposed to be tumorigenic; however, prior studies of the association between DM and survival are conflicting. The goal of this ancillary analysis of RTOG 9704, a randomized controlled trial of adjuvant chemotherapy in pancreatic cancer, was to determine the prognostic effects of DM and insulin use on survival. METHODS AND MATERIALS: Eligible patients from RTOG 9704 with available data on DM and insulin use were included. Overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and variable levels were compared using log-rank test. Cox proportional hazards models were created to assess the associations among DM, insulin use, and body mass index phenotypes on outcomes. RESULTS: Of 538 patients enrolled from 1998 to 2002, 238 patients were eligible with analyzable DM and insulin use data. Overall 34% of patients had DM and 66% did not. Of patients with DM, 64% had insulin-dependent DM, and 36% had non-insulin-dependent DM. On univariable analysis, neither DM nor insulin dependence were associated with OS or DFS (P > .05 for all). On multivariable analysis, neither DM, insulin use, nor body mass index were independently associated with OS or DFS. Nonwhite race (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.35-3.50; P = .0014), nodal involvement (HR, 1.74; 95% CI, 1.24-2.45; P = .0015), and carbohydrate antigen 19-9 (CA19-9) ≥90 U/mL (HR, 3.61; 95% CI, 2.32-5.63; P < .001) were associated with decreased OS. Nonwhite race (HR, 1.67; 95% CI, 1.05-2.63; P = .029) and CA19-9 ≥90 U/mL (HR, 2.86; 95% CI, 1.85-4.40; P < .001) were associated with decreased DFS. CONCLUSIONS: DM and insulin use were not associated with OS or DFS in patients with pancreatic cancer in this study. Race, nodal involvement, and increased CA19-9 were significant predictors of outcomes. These data might apply to the more modern use of neoadjuvant therapies for potentially resectable pancreatic cancer.
Subject(s)
Diabetes Mellitus/drug therapy , Insulins/therapeutic use , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/diagnosis , Aged , Female , Humans , Male , Middle Aged , Prognosis , Proportional Hazards ModelsABSTRACT
BACKGROUND: Pancreatic adenocarcinoma impinging the portal and/or superior mesenteric vein (PV-SMV) is classified as borderline resectable, and preoperative chemoradiation is recommended to increase the margin-negative resection rate. There is no consensus about what degree of venous impingement constitutes borderline resectability. METHODS: All patients undergoing potentially curative pancreatectomy for pancreatic adenocarcinoma were reviewed. Venous involvement was classified by preoperative computed tomography according to Ishikawa types: (I) normal, (II) smooth shift without narrowing, (III) unilateral narrowing, (IV) bilateral narrowing, (V) bilateral narrowing with collateral veins. RESULTS: From 1990-2009, 109 patients underwent resection of pancreatic adenocarcinoma involving the PV-SMV. Seventy-four patients received preoperative chemoradiation, whereas 35 did not. Patients who received preoperative therapy had a significantly longer median overall survival rate of 23 months compared with 15 months for patients without preoperative therapy (P = 0.001). Preoperative chemoradiation was associated with higher R0 resection rate and negative lymph nodes (both P < 0.0001) but did not affect the need for vein resection. When stratified by Ishikawa types, preoperative therapy was associated with improved overall survival among patients with types II and III but not types IV and V. Similarly, the correlation between preoperative therapy and R0 resection rate was observed only among patients with Ishikawa types II and III. CONCLUSIONS: Preoperative therapy for borderline resectable pancreatic adenocarcinoma is associated with higher margin-negative resection and survival rates in patients with Ishikawa type II and III tumors, defined as a smooth shift or unilateral narrowing of the PV-SMV. Patients with bilateral venous narrowing were less likely to benefit from preoperative treatment.
Subject(s)
Adenocarcinoma/pathology , Pancreas/blood supply , Pancreatic Neoplasms/pathology , Adenocarcinoma/surgery , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Male , Mesenteric Veins/pathology , Mesenteric Veins/surgery , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Pancreas/pathology , Pancreatectomy , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/therapy , Portal Vein/pathology , Portal Vein/surgery , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Although laparoscopic cholecystectomy was one of the first laparoscopic procedures, gallbladder cancer has been one of the last malignancies tackled with minimally invasive techniques. This video reviews the minimally invasive approaches to preoperatively suspected gallbladder cancer. METHODS: Like the standard laparoscopic cholecystectomy, the minimally invasive procedure is performed with four trocars. The surgeon operates with the patient in the French position. A totally laparoscopic radical cholecystectomy including wedge resections of segments IVB and V is undertaken with hepatoduodenal lymphadenectomy and common bile duct excision. The biliary system is reconstructed via a laparoscopic choledochojejunostomy. RESULTS: Six patients have undergone laparoscopic radical cholecystectomy. Three of these patients were found to have gallbladder cancer according to the final pathology. All the final surgical margins were negative, and the average lymph node retrieval was 3 (range, 1-6). CONCLUSION: The minimally invasive approach to gallbladder cancer is feasible and safe. It should currently be performed in high-volume centers with expertise in both hepatobiliary and minimally invasive surgery. Larger trials are needed to determine whether either the open or laparoscopic approach offers any advantage.