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1.

Background

Surgical resection is the only method for curative treatment of biliary tract cancer (BTC). Recently, an improved efficacy has been revealed in patients with initially unresectable locally advanced BTC to improve the prognosis by the advent of useful cancer chemotherapy. The aim of this study was to evaluate the effect of downsizing chemotherapy in patients with initially unresectable locally advanced BTC.

Methods

Initially unresectable locally advanced cases were defined as those in which therapeutic resection could not be achieved even by proactive surgical resection. Gemcitabine was administered intravenously once a week for 3 weeks followed by 1 week’s respite. Patients whose disease responded to chemotherapy were reevaluated to determine whether their tumor was resectable.

Results

Chemotherapy with gemcitabine was provided to 22 patients with initially unresectable locally advanced BTC. Tumor was significantly downsized in nine patients, and surgical resection was performed in 8 (36.4%) of 22 patients. Surgical resection resulted in R0 resection in four patients and R1 resection in four patients. Patients who underwent surgical resection had a significantly longer survival compared with those unable to undergo surgery.

Conclusions

Preoperative chemotherapy enables the downsizing of initially unresectable locally advanced BTC, with radical resection made possible in a certain proportion of patients. Downsizing chemotherapy should be proactively carried out as a multidisciplinary treatment strategy for patients with initially unresectable locally advanced BTC with the aim of expanding the surgical indication.  相似文献   

2.

Background  

Pancreatic cancer accounts for approximately 3% of cancer deaths in Europe. Locally advanced pancreatic cancer (LAPC) involves vascular structures, and resectability is low, with a median survival time of 6 to 11 months. We conducted a prospective, nonrandomized study of patients with LAPC to assess the effect of stereotactic body radiotherapy (SBRT) on local response, pain control, and quality of life (QOL).  相似文献   

3.
This prospective randomized trial was undertaken to determine the added efficacy of (32)P in treating locally advanced unresectable pancreatic cancer. Thirty patients with biopsy proven locally advanced unresectable adenocarcinoma of the pancreas were assessable after receiving 5-fluorouracil and radiation therapy with or without (32)P, followed by gemcitabine. Intratumoral (32)P dose was determined by tumor size and volume and was administered at months 0, 1, 2, 6, 7, and 8. Tumor cross-sectional area and liquefaction were determined at intervals by computed tomography scan. Tumor liquefaction occurred in 78% of patients receiving (32)P and in 8% of patients not receiving (32)P, although tumor cross-sectional area did not decrease. Serious adverse events occurred more often per patient for patients receiving (32)P (4.2 +/- 3.1 vs. 1.8 +/- 1.9; p = 0.03) leading to more hospitalizations. Death was because of disease progression (23 patients), gastrointenstinal hemorrhage (4 patients), and stroke (1 patient). One patient not receiving (32)P and one receiving (32)P are alive at 28 and 13 months, respectively. (32)P did not prolong survival (7.4 +/- 5.5 months with (32)P vs. 11.5 +/- 8.0 months without (32)P, p = 0.16). (32)P promoted tumor liquefaction, but did not decrease tumor size. Intratumoral (32)P was associated with more serious adverse events and did not improve survival for locally advanced unresectable pancreatic cancer.  相似文献   

4.
Background The purpose of this study was to evaluate the significance of pathologic nodal assessment and extent of nodal metastases on patient outcome in patients with pancreatic adenocarcinoma. Materials and Methods A prospectively maintained pancreatic cancer database was reviewed, and 696 consecutive patients were identified who underwent resection for pancreatic adenocarcinoma between 1995 and 2005. Overall survival was compared to lymph node (LN) status, absolute number of pathologically assessed LN, and LN ratio expressed as the number of positive LN to the total LN assessed. Results Of the 696 patients, 598 (86%) had pancreaticoduodenectomy (PD), and 96 (14%) had distal pancreatectomy (DP). For all patients, median follow-up was 13 months (range, 0–122 months), and estimated 5-year survival was 16%. A total of 243 (35%) patients were LN-negative (N0) and had a median survival of 27 months. When assessed as a continuous variable, the number of pathologically assessed LN did not correlate with survival for N0 patients undergoing either PD or DP. The median survival for the 453 patients with node-positive (N1) disease was 16 months. When analyzed as a continuous variable, the absolute number of positive LNs was a significant predictor of survival for N1 patients with a linear relationship up to eight positive LNs. LN ratio, as a continuous variable, also predicted survival with a linear relationship up to a ratio of 0.35. A ratio of 0.18 was associated with a 19-month median survival and served as the best cutoff, p < 0.01. Conclusions The absolute number of positive LNs and LN ratio are strong predictors of survival for patients with node-positive pancreatic adenocarcinoma. Inadequate surgical lymphadenectomy or pathologic LN assessment understages node-negative patients. Presented in part at the 48th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 22, 2007, Washington, DC.  相似文献   

5.

Background

Survival with long-term follow-up following liver resection for unresectable colorectal liver metastases (CRLM) downsized by chemotherapy has rarely been reported. The aim of this study was to determine the chance of cure following liver resection for initially unresectable CRLM.

Methods

Between January 2000 and December 2009, 61 patients underwent hepatectomy for unresectable liver-only CRLM downsized after chemotherapy. Cure was defined as a recurrence-free interval of at least 5 years after primary hepatectomy.

Results

Resectability of CRLM was achieved after a mean number of 11 courses, and 42.6 % of patients underwent liver resection after ≥10 courses. Postoperative mortality was nil, and morbidity rate was 19.7 %. The 5- and 10-year actuarial overall survival rates were 42.6 and 16.0 %. Of 30 patients with a follow-up ≥5 years, 11 were alive, yielding a 5-year actual overall survival rate of 36.7 %, and 7 (23.3 %) were considered cured because they are alive without recurrence. On multivariate analysis, response to chemotherapy was the only independent predictor of both overall and disease-free survival.

Conclusions

Cure can be achieved in about 23 % of patients resected for initially unresectable CRLM downsized by chemotherapy. Liver resection can be safely performed in selected patients even after multiple courses of chemotherapy.  相似文献   

6.
Abstract Background We evaluated the feasibility and efficacy of neoadjuvant chemotherapy and radiation for patients with locally unresectable pancreatic cancer. Materials and Methods From October 2000 to August 2006, 245 patients with pancreatic adenocarcinoma underwent surgical exploration at our institution. Of these, 78 patients (32%) had undergone neoadjuvant therapy for initially unresectable disease, whereas the remaining patients (serving as the control group) were explored at presentation (n = 167). All neoadjuvant patients received gemcitabine-based chemotherapy, often in conjunction with docetaxal and capecitabine in a regimen called GTX (81%). Seventy-five percent of neoadjuvant patients also received preoperative abdominal radiation (5,040 rad). Results Neoadjuvant patients were younger than control-group patients (60.8 vs 66.2 years, respectively, p < 0.002). Seventy-six percent of neoadjuvant patients were resected as compared to 83% of control patients (NS). Concomitant vascular resection was required in 76% of neoadjuvant patients but only 20% of NS (p < 0.01). Complications were more frequent in the neoadjuvant group (44.1 vs 30.9%, p < 0.05), and mortality was higher (10.2 vs 2.9%, p < 0.03). Among the neoadjuvant patients, all but one of the deaths were in patients that underwent arterial reconstruction. Mortality for patients undergoing a standard pancreatectomy without vascular resection was 0.8% in this series. Of patients resected, negative margins were achieved in 84.7% of neoadjuvant patients and 72.7% of NS. Within the cohort of neoadjuvant patients, radiation significantly increased the complication rate (13.3 vs 54.6%, p < 0.006), but did not affect median survival (512 vs 729 days, NS). Median survival for patients who received neoadjuvant therapy (503 days) was longer than NS that were found to be unresectable at surgery (192 days, p < 0.001) and equivalent to NS that were resected (498 days). Conclusions Resection rate, margin status, and median survivals were equivalent when neoadjuvant patients were compared to patients considered resectable by traditional criteria, demonstrating equal efficacy. Surgical resection with venous reconstruction following neoadjuvant therapy for patients with locally advanced pancreatic cancer can be performed with acceptable morbidity and mortality. This approach extended the boundaries of surgical resection and greatly increased median survival for the “inoperable” patient with advanced pancreatic cancer. This work was presented at the American Hepato-Pancreato-Biliary Association Conference in Las Vegas, NV, April 2007.  相似文献   

7.
《The Journal of arthroplasty》2022,37(9):1822-1826
BackgroundPatients with postpolio syndrome (PPS) may be afflicted by hip arthritis in either the paralytic or contralateral limb. Total hip arthroplasty (THA) may be considered in these patients. However, short-term and long-term outcomes following THA in PPS patients remain poorly characterized.MethodsThe PearlDiver MHip administrative database was queried for patients undergoing THA. Patients with a diagnosis of PPS were matched 1:4 with control patients on the basis of age, gender, and comorbidity burden. Incidence of postoperative adverse events and readmission in the 90 days following surgery and occurrence of revision arthroplasty in the five-year postoperative period were assessed between the two cohorts.ResultsIn total, 1,519 PPS patients were matched to 6,076 control patients without PPS. After controlling for patient demographics and comorbidities, PPS patients demonstrated higher 90-day odds of urinary tract infection (odds ratio [OR] = 1.34, P = .016), pneumonia (OR = 2.07, P < .001), prosthetic dislocation (OR = 1.63, P = .018), and readmission (OR = 1.49, P = .002). Five years following surgery, 94.7% of the PPS cohort remained revision-free, compared to 96.7% of the control cohort (P = .001).ConclusionCompared to patients without PPS, patients with PPS demonstrated a higher incidence of urinary tract infection, pneumonia, prosthetic dislocation, and hospital readmission. In addition, five-year incidence of revision arthroplasty was significantly higher among the PPS cohort. In light of these increased risks, special considerations should be made in both preoperative planning and postoperative surveillance of PPS patients undergoing THA.Level of EvidenceLevel III.  相似文献   

8.

Background

Margin status is one of the strongest prognosticators after resection of pancreatic ductal adenocarcinoma (PDAC). The clinical significance of pancreatic intraepithelial neoplasia (PanIN) at a surgical margin has not been established.

Methods

A total of 208 patients who underwent R0 resection for PDAC between 2004 and 2008 were selected. Intraoperative frozen section slides containing the final pancreatic parenchymal transection margin were evaluated for presence or absence, number, and grade of PanINs. Data were compared to clinicopathologic factors, including patient survival.

Results

PanIN lesions were present in margins in 107 of 208 patients (51.4%). Median number of PanINs per pancreatic resection margin was 1 (range, 1–11). A total of 72 patients had PanIN-1 (34.6%), 44 had PanIN-2 (21.1%), and 16 had PanIN-3 (7.2%) at their margin. Overall median survival was 17.9 (95% confidence interval, 14–21.9) months. Neither the presence nor absence of PanIN nor histological grade had any significant correlation with important clinicopathologic characteristics. There were no significant survival differences between patients with or without PanIN lesions at the resection margin or among patients with PanIN-3 (carcinoma in situ) versus lower PanIN grades. However, patients with R1 resection had a significantly worse outcome compared with patients without invasive cancer at a margin irrespective of the presence of PanIN (P = 0.02).

Conclusions

The presence of PanINs at a resection margin does not affect survival in patients who undergo R0 resection for PDAC. These results have significant clinical implications for surgeons, because no additional resection seems to be indicated when intraoperative frozen sections reveal even high-grade PanIN lesions.  相似文献   

9.
10.
Pancreatic cancer remains one of the greatest challenges within oncology. Among resected patients, 5-year survival is typically only 10–25%. Among eight major randomized trials for resected pancreas cancer, five (GITSG, EORTC, ESPAC-1, RTOG 9704, and CONKO-1), containing a total of over 1,200 patients, have shaped world opinion on this subject. These trials have many significant methodological differences. Major conclusions that can be drawn from these trials in composite are (1) adjuvant chemotherapy is superior to observation following pancreaticoduodenectomy for pancreatic cancer, (2) gemcitabine is superior to 5-FU as adjuvant chemotherapy, and (3) the benefit of adjuvant chemoradiation is uncertain. Additional randomized trials are needed to address significant areas of controversy within available data. Presented at the Postgraduate Course of the 48th Annual Meeting of the Society for Surgery of the Alimentary Tract, May 20, 2007, Washington, DC.  相似文献   

11.

Background  

Patients with unresectable pancreatic cancer (PDAC) or endocrine tumors (PET) often develop splenic vein thrombosis, hypersplenism, and thrombocytopenia which limits the administration of chemotherapy.  相似文献   

12.

Background  

About 30% of patients with pancreatic cancer suffer from locally advanced nonmetastatic carcinoma at the time of diagnosis. We conducted a prospective phase II clinical trial using neoadjuvant chemotherapy, consisting of gemcitabine and docetaxel, to assess the rate of complete radical resection and overall survival.  相似文献   

13.

Background  

Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable after systemic chemotherapy. We reviewed the evidence of downsizing systemic chemotherapy followed by rescue liver surgery in patients with initially unresectable CLM.  相似文献   

14.
Background The prognosis of unresectable metastatic colorectal cancer might be improved if a radical surgical resection of metastases could be performed after a response to chemotherapy. Methods We treated 74 patients with unresectable metastatic colorectal cancer (not selected for a neoadjuvant approach) with irinotecan, oxaliplatin, and 5-fluorouracil/leucovorin (FOLFOXIRI and simplified FOLFOXIRI). Because of the high activity of these regimens (response rate, 72%), a secondary curative operation could be performed in 19 patients (26%). Results Four patients underwent an extended hepatectomy, nine patients underwent a right hepatectomy, three patients underwent a left hepatectomy, and three patients had a segmental resection. In five patients, surgical removal of extrahepatic disease was also performed. In seven patients, surgical resection was combined with intraoperative radiofrequency ablation. The median overall survival of the 19 patients who underwent operation is 36.8 months, and the 4-year survival rate is 37%. The median overall survival of the 34 patients who were responsive to chemotherapy, but who did not undergo operation, is 22.2 months (P = .0114). Conclusions The FOLFOXIRI regimens we studied have significant antitumor activity and allow a radical surgical resection of metastases in patients with initially unresectable metastatic colorectal cancer not selected for a neoadjuvant approach and also those with extrahepatic disease. The median survival of patients with resected disease is promising.  相似文献   

15.

Background

Compared to the widely adopted 2–4 months of pre-operative therapy for patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC), our institution tends to administer a longer duration before considering surgical resection. Using this unique approach, the aim of this study was to determine pre-operative variables associated with survival.

Methods

Records from patients with BR/LA PDAC who underwent attempt at surgical resection from 1992–2014 were reviewed.

Results

After a median duration of 6 months of pre-operative treatment, 109 patients with BR/LA PDAC (BR 63, LA 46) were explored; 93 (85.3 %) underwent pancreatectomy. Those who received at least 6 months of pre-operative treatment had longer median overall survival (OS) than those who received less (52.8 vs. 32.1 months, P?=?0.044). On multivariate analysis, pre-operative treatment duration was the strongest predictor of survival (hazard ratio (HR) 4.79, P?=?0.043). However, OS was similar in those whose CA19-9 normalized regardless of whether they received more or less than 6 months of chemotherapy (71.4 vs. 101.8 months, P?=?0.930).

Conclusions

Pre-operative CA19-9 decline can guide treatment duration in patients with BR/LA PDAC. We endorse 6 months of therapy except in those patients whose values normalize, where surgery can be considered after a shorter course.
  相似文献   

16.
Background There is ongoing debate on how variations in surgical technique affect outcomes in pancreatic cancer. This population-based study examines current surgical practice and outcomes for cancer of the pancreatic head. Methods All patients 18 to 85 years old diagnosed with nonmetastatic adenocarcinoma of the pancreatic head from 1998 through 2003 were identified from the Surveillance, Epidemiology and End Results (SEER) Program registry. Multivariable regression was used to elucidate factors associated with the type of pancreaticoduodenectomy performed, extent of lymph node (LN) assessment, early mortality, and late survival. Results Overall, 2111 patients were included in the study, with 83.7% treated with a standard Whipple pancreaticoduodenectomy (PD). However, there was marked regional variation in the use of pylorus-preserving pancreaticoduodenectomy (PPPD; range, .03%–32.0%; P < .0001) and total pancreatectomy (TP; range, .04%–19.5%; P < .0001). TP was associated with significantly higher early mortality (odds ratio, 2.6; 95% confidence interval, 1.6 to 4.1; P < .0001), but late survival did not differ significantly between TP, PPPD, and PD (P = .69). Significant variation was also seen in the number of LN assessed (range across SEER regions, 7.3–13.5; P < .0001). Decreased LN assessment reduced the odds of diagnosing a patient as node positive and was associated with worse late survival. Conclusions In this population-based study, we found marked clinically important variability in the surgical treatment of adenocarcinoma of the pancreatic head, with respect to the use of TP, PPPD, or PD, and the extent of LN assessment. Further research is warranted to elucidate the underlying reasons, and to clarify the role of adequate lymphadenectomy.  相似文献   

17.

Background

The prognosis of unresectable locally advanced gastric cancer is poor. We applied preoperative chemotherapy via intra-arterial and intravenous administration to convert an initially unresectable gastric cancer to a resectable cancer.

Methods

From January 2005 to December 2010, 105 patients with unresectable locally advanced gastric cancer (T3-4N1-3M0) were selected for preoperative chemotherapy with 5-FU + leucovorin + etoposide + oxaliplatin + epirubicin (FLEEOX) regimen. 5-Fu (370 mg/m2) and leucovorin (200 mg/m2) were administered by intravenous infusion on days 1–5. Intra-arterial administration of etoposide (80 mg/m2), oxaliplatin (80 mg/m2), and epirubicin (30 mg/m2) was performed by Seldinger method on days 6 and 20, repeated two cycles. Patients who achieved partial response (PR) or complete response (CR) underwent D2 dissection, followed by four to six cycles of XELOX chemotherapy. The response rate, 1- and 3-year survival rate, and R0 resection rate were evaluated.

Results

The response rate of preoperative chemotherapy was 78.1 % (82 of 105 patients), with 7 cases of CR and 75 cases of PR, respectively. After chemotherapy, a total of 78 patients (74.3 %) underwent surgery, and 67 cases achieved R0 resection (85.9 %). The 1- and 3-year overall survival (OS) rate of all 105 patients was 71.9 and 31.7 % (median survival time, 18 months). The 1- and 3-year OS rate among the 78 patients treated with chemotherapy plus surgery was 84.5 and 40 % (median survival time, 30 months). Patients treated with chemotherapy plus surgery had significantly longer OS times than patients who underwent chemotherapy alone (P?<?0.01).

Conclusions

Patients with unresectable gastric cancer may obtain a survival benefit from preoperative chemotherapy via intra-arterial and intravenous administration and subsequent surgery.
  相似文献   

18.

Background

There is currently no consensus about the most effective adjuvant therapy for adenocarcinoma of the pancreas. Both gemcitabine and erlotinib have been demonstrated to improve survival in patients with metastatic disease. This study was designed to evaluate the efficacy of gemcitabine and erlotinib as adjuvant therapy, and to explore potential biomarkers associated with response.

Methods

An institutional review board–approved single-center phase II trial of adjuvant biweekly fixed-dose rate gemcitabine (1500 mg/m2) and daily erlotinib (150 mg/day) for 4 months followed by maintenance erlotinib (150 mg/day) over 8 months was initiated. Primary end point was recurrence-free survival (RFS). Epidermal growth factor receptor (EGFR) expression in the resected tumors was assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC).

Results

The study completed planned accrual of 25 patients. Median follow-up was 18.2 (range 11.6–23.5) months. Recurrences were observed in 17 subjects (68%). Median RFS was 14.0 months (95% confidence interval [95% CI], 8.2–24.5) with 1-year and 2-year RFS of 56% (95% CI, 35–73) and 26% (95% CI, 6–52), respectively. Median overall survival was not reached. Estimated 1-year and 2-year overall survival was 84% (95% CI, 63–94) and 53% (95% CI, 22–76), respectively. Nine patients (36%) had a grade 3 event and only 1 (4%) had a grade 4 (neutropenia). Most toxicities were dermatologic, gastrointestinal, and constitutional. There were nonsignificant trends to longer RFS and lower recurrence rates while receiving therapy in subjects with fluorescence in situ hybridization-positive tumors and greater immunohistochemistry expression.

Conclusions

Our phase II results suggest that adjuvant gemcitabine and erlotinib is a promising regimen that merits further investigation.  相似文献   

19.

Purpose

This study was designed to evaluate neoadjuvant intensified chemotherapy in potentially resectable or unresectable liver metastases (LM) from colorectal cancer (CRC).

Methods

Criteria for potentially resectable LM were complex hepatectomy and/or risky procedure, close contact with major vascular structures, and for unresectable LM, a future liver remnant predicted to be less than 25–30 % of total liver volume. Between October 2004 and August 2007, 125 patients were randomized to either standard (FOLFIRI/FOLFOX4) or intensified chemotherapy (FOLFIRI-HD/FOLFOX7/FOLFIRINOX). Primary endpoint was objective response rate (ORR) after 4 cycles of chemotherapy. Secondary endpoints included safety, R0 surgical resection, best ORR, progression-free survival (PFS), and overall survival (OS).

Results

A total of 122 patients were treated; 45 % of patients had less than 30 % of remaining liver tissue, 20 % had major vascular contact, and 35 % were potentially resectable. Grade 3/4 toxicities were neutropenia (24, 19, 10, 23 %) diarrhoea (0, 6, 3, 23 %), mucositis (0, 3, 0, 7 %), vomiting (7, 9, 0, 3 %), and neurotoxicity (0, 0, 10, 3 %) in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. ORR was 33, 47, 43, and 57 % after the first 4 cycles in arms (FOLFIRI + FOLFOX4)/FOLFIRI-HD/FOLFOX7/FOLFIRINOX, respectively. FOLFIRINOX offered the best conversion rate to resectability (67 %). Disease-free status after chemotherapy and surgery (R0, R1, Rx) was achieved in 54 of 64 operated patients. Median PFS was 9.2 months in control arms versus 11.9 months in experimental arms (hazards ratio [HR] = 0.76, p = 0.115), and the median OS was 17.7 versus 33.4 months (HR = 0.73, p = 0.297), respectively.

Conclusions

FOLFIRINOX showed promising activity in CRC patients with LM compared with standard or intensified bi-chemotherapy regimens.  相似文献   

20.

Purpose

The objective of this study was to determine the effect on resection rate and survival of neoadjuvant chemoradiotherapy for primarily unresectable locally advanced pancreatic carcinoma.

Methods

A systematic review of recently published literature was performed. Resection rates and survival data were derived from reports published from 2000 onwards. Only recent studies, based on radiotherapy with standard dose and fractionation, have been analyzed.

Results

Thirteen studies with a total of 510 patients met selection criteria. A resection rate of 8.3–64.2% was reported (median, 26.5%). Of the operated patients, 57.1–100% (median, 87.5%) had R0 tumor resection. Most papers reported occasional pathological complete responses (CR, 3.0–8.8%). When outcome in all patients was considered, median survival ranged from 9 to 23 (median, 13.3) months, comparing favorably with literature data based on concurrent chemoradiation alone (range, 8.6–13 months). Surprisingly, in patients with unresectable tumor at presentation, median survival after surgery ranged from 16.4 to 32.3 (median, 23.6) months.

Conclusions

The finding of a high proportion of R0 resection among all resections performed confirms the activity of neoadjuvant radiochemotherapy and should not be neglected. Based on these data, patients with unresectable pancreatic cancer without disease progression after chemoradiotherapy should be considered for radical surgery.  相似文献   

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