Comparison of Acute Toxicities in Two Primary Chemoradiation Regimens in the Treatment of Advanced Head and Neck Squamous Cell Carcinoma

Purpose

The optimal dosage and frequency of platinum-based chemoradiotherapy (CRT) regimen for treating advanced head and neck squamous cell carcinoma remains unresolved. This study aims to compare the toxicity and efficacy of weekly versus more dose-intensive cisplatin-based CRTs.

Methods

We reviewed 155 stage III/IV head and neck squamous cell carcinoma patients with no evidence of distant metastasis treated with one of two CRT regimens from 2000 to 2010 at Greater Baltimore Medical Center. Twice-daily radiation was provided as a split course over a 45-day period. Regimen A consisted of concomitant cisplatin (30?mg/m²/1?h) weekly for 6 cycles; regimen B consisted of concomitant cisplatin (12?mg/m²/1?h) and 5-fluorouracil (600?mg/m²/20?h) on days 1 through 5 and days 29 through 33. Main outcome measures included acute toxicities (myelosuppression, neurotoxicity, nephrotoxicity, gastrointestinal dysfunction), unplanned hospitalizations, and disease control at 12?months.

Results

Patients on regimen A were much less likely to experience ototoxicity due to their treatment (0% vs. 9.8%, P?=?0.04). They were more likely to experience thrombocytopenia acutely (46% vs. 26%, P?=?0.02), but the toxicity was not limiting (grade 1?C2). No significant differences exist in the incidence of other toxicities or unplanned hospitalizations. At 1?year, 97% of patients on A vs. 86% of patients on regimen B were free of disease (P?=?0.11).

Conclusions

With concurrent radiotherapy, low-dose, single-agent, weekly cisplatin is less likely than higher-dose daily cisplatin plus 5-fluorouracil provided at the beginning and end of treatment to be associated with ototoxicity. The preliminary data suggest at least equivalent efficacy, but longer follow-up is required.     

Induction of a Pathological Complete Response by Four Courses of Neoadjuvant Chemotherapy for Gastric Cancer: Early Results of the Randomized Phase II COMPASS Trial

Background

The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results.

Methods

Patients received S-1 (80 mg/m² for 21 days with 1 week’s rest)/cisplatin (60 mg/m² at day 8) or paclitaxel/cisplatin (80 and 25 mg/m², respectively, on days 1, 8, and 15 with 1 week’s rest) as neoadjuvant chemotherapy.

Results

Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms.

Conclusions

Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.     

Fluorouracil-based Chemoradiation with Either Gemcitabine or Fluorouracil Chemotherapy after Resection of Pancreatic Adenocarcinoma: 5-Year Analysis of the U.S. Intergroup/RTOG 9704 Phase III Trial

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/m²/day, and gemcitabine was provided at 1000 mg/m² 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.     

Significance of docetaxel-based chemotherapy as treatment for metastatic castration-resistant prostate cancer in Japanese men over 75?years old

Objectives

The objective of this study was to evaluate the significance of docetaxel-based chemotherapy in elderly Japanese men with metastatic castration-resistant prostate cancer (CRPC).

Materials and methods

This study included a total of 159 consecutive patients aged ??75?years with mCRPC who were treated with docetaxel-based chemotherapy. The efficacy and tolerability of this therapy were retrospectively analyzed.

Results

In these 159 patients, the median age and prostate-specific antigen (PSA) level before docetaxel-based chemotherapy were 78?years and 44.0?ng/ml, respectively. Of these patients, 42 (26.4?%) and 117 (73.6?%) received docetaxel as a weekly (30?mg/m²) and 3-weekly (70?mg/m²) regimen, respectively, and estramustine was administered combining with docetaxel in 77 (48.4?%). Following docetaxel-based chemotherapy, PSA declined in 118 patients (74.3?%), including 87 (54.6?%) achieving a PSA decline ??50?%, and the median progression-free survival and overall survival (OS) were 2.9 and 23.2?months, respectively. Of several factors examined, univariate analysis identified performance status (PS), significant clinical pain, bone metastasis, schedule of treatment, treatment cycle, and PSA response as significant predictors of OS, of which only PS, treatment cycle, and PSA response appeared to be independently associated with OS on multivariate analysis. The major grade 3?C4 toxicities were myelosuppression, including neutropenia, anemia, and thrombocytopenia in 78 (49.1?%), 22 (13.8?%), and 14 (8.8?%), respectively.

Conclusions

These findings suggest that docetaxel-based chemotherapy is clinically feasible in Japanese men aged ??75?years with mCRPC considering the cancer control as well as safety associated with this therapy.     

Phase II Study of Induction Fixed-Dose Rate Gemcitabine and Bevacizumab Followed by 30 Gy Radiotherapy as Preoperative Treatment for Potentially Resectable Pancreatic Adenocarcinoma

Background

Eighty percent of patients with resected pancreatic ductal carcinoma (PDC) experience treatment failure within 2 years. We hypothesized that preoperative fixed-dose rate (FDR) gemcitabine (GEM) combined with the angiogenesis inhibitor bevacizumab (BEV) and accelerated 30 Gy radiotherapy (RT) would improve outcomes among patients with potentially resectable PDC.

Methods

This phase II trial tested induction FDR GEM (1,500 mg/m²) plus BEV (10 mg/kg IV) every 2 weeks for three cycles followed by accelerated RT (30 Gy in 10 fractions) plus BEV directed at gross tumor volume plus a 1–2 cm vascular margin. Subjects underwent laparoscopy and resection after day 85. Therapy was considered effective if the complete pathologic response rate exceeded 10 % and the margin-negative resection rate exceeded 80 %.

Results

Fifty-nine subjects were enrolled; 29 had potential portal vein involvement. Two grade 4 (3.4 %) and 19 grade 3 toxicities (32.8 %) occurred. Four subjects manifested radiographic progression, and 10 had undetected carcinomatosis. Forty-three pancreatic resections (73 %) were performed, including 19 portal vein resections (44 %). Margin-negative outcomes were observed in 38 (88 %, 95 % confidence interval [CI] 75–96), with one complete pathologic response (2.3 %; 95 % CI 0.1–12). There were seven (6 grade 3; 1 grade 4) wound complications (13 %). Median overall survival for the entire cohort was 16.8 months (95 % CI 14.9–21.3) and 19.7 months (95 % CI 16.5–28.2) after resection.

Conclusions

Induction therapy with FDR GEM and BEV, followed by accelerated BEV/RT to 30 Gy, was well tolerated. Although both effectiveness criteria were achieved, survival outcomes were equivalent to published regimens.     

Phase II Study of Single Intraperitoneal Chemotherapy Followed by Systemic Chemotherapy for Gastric Cancer with Peritoneal Metastasis

Background

We conducted a phase II study involving a single administration of intraperitoneal chemotherapy with paclitaxel followed by sequential systemic chemotherapy with S-1+ paclitaxel for advanced gastric cancer patients with peritoneal metastasis.

Methods

Gastric cancer patients with peritoneal metastasis were enrolled. Paclitaxel (80?mg/m²) was administered intraperitoneally at staging laparoscopy. Within 7?days, patients received systemic chemotherapy with S-1 (80?mg/m²/day on days 1?C14) plus paclitaxel (50?mg/m² on days 1 and 8), followed by 7-days rest. The responders to this chemotherapy underwent second-look laparoscopy, and gastrectomy with D2 lymph node dissection was performed in patients when the disappearance of peritoneal metastasis had been confirmed. The primary endpoint of the study was overall survival rate.

Results

Thirty-five patients were enrolled. All patients were confirmed as having localized peritoneal metastasis by staging laparoscopy. Eventually, gastrectomy was performed in 22 patients. The median survival time of the total patient population and those patients in which gastrectomy was performed was 21.3 and 29.8?months, respectively. The overall response rate was 65.7?% for all patients. The frequent grade 3/4 toxic effects included neutropenia and leukopenia.

Conclusions

Sequential intraperitoneal and intravenous paclitaxel plus S-1 was well tolerated in gastric cancer patients with peritoneal metastasis.     

Phase II Study of Gemcitabine and Erlotinib as Adjuvant Therapy for Patients with Resected Pancreatic Cancer

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.     

Docetaxel, with or without estramustine phosphate, as first-line chemotherapy for hormone-refractory prostate cancer: results of a multicentre, randomized phase II trial

OBJECTIVE

To report the results of a randomized phase II trial of docetaxel with and without estramustine phosphate (EP) in patients with hormone‐refractory prostate cancer (HRPC).

PATIENTS AND METHODS

Patients with progressive HRPC were randomized to receive docetaxel 70 mg/m² on day 1 (arm A), or docetaxel 70 mg/m² on day 2 plus oral EP three times daily, at a total daily dose of 840 mg, on days 1–5 (arm B). The primary objective of the trial was to evaluate the activity of the treatments in terms of the response in prostate‐specific antigen (PSA) level.

RESULTS

Forty‐five of the 49 patients centrally randomized to arm A and 44 of the 46 in arm B were evaluable for activity. The PSA level decreased by ≥50% in 40% of the patients in arm A and in 75% of those in arm B. The median time to PSA progression was 20 weeks in arm A and 30 weeks in arm B. The patients in arm B had an improvement in pain over time.

CONCLUSION

These data support the existence of a possible advantage in combining docetaxel and EP, which should be verified in a specific randomized phase III study.     

Perioperative Intra-Arterial and Systemic Chemotherapy for Pancreatic Cancer

Background

Even after curative resection of pancreatic cancer, there is a high probability of systemic recurrence. This indicates that subclinical metastases are already present at the time of operation. The purpose of this study was to assess the feasibility and outcomes of patients who received a novel multimodality therapy combining pancreatic resection and intraoperative radiation therapy (IORT) with pre- and postoperative chemotherapy for pancreatic cancer.

Methods

For eligible patients with pancreatic cancer, 5-FU was administered at a dose of 125 mg/m²/day on days 1–5 every week as a continuous pancreatic and hepatic arterial infusion, and gemcitabine was infused intravenously at a dose of 800 mg/m² per day once per week for 2 weeks for preoperative chemotherapy. Pancreatic resection combined with IORT was performed 1 week after preoperative chemotherapy. Postoperative chemotherapy was performed in the same way as preoperative chemotherapy. We performed an intention-to-treat analysis for all enrolled patients.

Results

This study enrolled 44 patients. The most common toxicities were hematological and gastrointestinal events. Grade 3/4 hematological toxicities were observed during preoperative chemotherapy, although there were no grade 3/4 nonhematological events. Postoperative chemotherapy-related toxicities were more critical and frequent than preoperative ones. There were no pre- or postoperative chemotherapy-associated deaths. Median overall survival was 36.5 months with 30.5% overall 5-year survival.

Conclusions

This multimodality therapy is feasible and promises to contribute to survival. It should be evaluated in a phase III setting.     

Preoperative Chemotherapy with Cisplatin and Docetaxel Followed by Surgery and Clip-Oriented Postoperative Chemoradiation in Patients with Localized Gastric or Gastroesophageal Junction Adenocarcinoma: Results from a Phase II Feasibility Study

Background

We conducted a phase II feasibility study using preoperative chemotherapy with cisplatin and docetaxel followed by surgical resection and postoperative chemoradiation in patients with gastric or gastroesophageal cancer.

Methods

Preoperative chemotherapy (two or three cycles) consisted of 50 mg/m² docetaxel and 50 mg/m² cisplatin. Surgical resection was planned 4 weeks after the last chemotherapy cycle. Patients underwent postsurgical chemoradiation, receiving a total dose of 39.6 Gy and 5-fluorouracil (5-FU) continuous infusion (350 mg/m²/day). The primary end-points were feasibility, overall response rate and R0 resectability rate after preoperative chemotherapy. The secondary end-points were tolerability, treatment-associated complications, disease-free survival and overall survival.

Results

Between 2002 and 2004, 15 patients were enrolled in this study. After neoadjuvant treatment, two patients (13%) experienced progressive disease, four patients (27%) showed partial remission and nine patients (60%) showed stable disease. In 11 patients (73%) R0 resectability could be achieved. Six of these patients (54%) were able to undergo postoperative chemoradiation. Notably, five (83%) of these patients were disease free and alive at median follow-up of 72 months. Chemotherapy-associated neutropaenia and neutropaenic fever, anastomotic dehiscence, pulmonary embolism and acute pancreatitis were observed.

Conclusions

The combination of preoperative chemotherapy and postoperative chemoradiation is feasible in a significant subset of gastric cancer patients.     

Impact of Sarcopenia on Outcomes Following Resection of Pancreatic Adenocarcinoma

Introduction

Assessing patient-specific risk factors for long-term mortality following resection of pancreatic adenocarcinoma can be difficult. Sarcopenia??the measurement of muscle wasting??may be a more objective and comprehensive patient-specific factor associated with long-term survival.

Methods

Total psoas area (TPA) was measured on preoperative cross-sectional imaging in 557 patients undergoing resection of pancreatic adenocarcinoma between 1996 and 2010. Sarcopenia was defined as the presence of a TPA in the lowest sex-specific quartile. The impact of sarcopenia on 90-day, 1-year, and 3-year mortality was assessed relative to other clinicopathological factors.

Results

Mean patient age was 65.7 years and 53.1?% was male. Mean TPA among men (611?mm²/m²) was greater than among women (454?mm²/m²). Surgery involved pancreaticoduodenectomy (86.0?%) or distal pancreatectomy (14.0?%). Mean tumor size was 3.4?cm; 49.9?% and 88.5?% of patients had vascular and perineural invasion, respectively. Margin status was R0 (59.0?%) and 77.7?% patients had lymph node metastasis. Overall 90-day mortality was 3.1?% and overall 1- and 3-year survival was 67.9?% and 35.7?%, respectively. Sarcopenia was associated with increased risk of 3-year mortality (HR?=?1.68; P?<?0.001). Tumor-specific factors such as poor differentiation on histology (HR?=?1.75), margin status (HR?=?1.66), and lymph node metastasis (HR?=?2.06) were associated with risk of death at 3-years (all P?<?0.001). After controlling for these factors, sarcopenia remained independently associated with an increased risk of death at 3?years (HR?=?1.63; P?<?0.001).

Conclusions

Sarcopenia was a predictor of survival following pancreatic surgery, with sarcopenic patients having a 63?% increased risk of death at 3?years. Sarcopenia was an objective measure of patient frailty that was strongly associated with long-term outcome independent of tumor-specific factors.     

Toxicity Analysis in the ADEBAR Trial: Sequential Anthracycline-Taxane Therapy Compared with FEC120 for the Adjuvant Treatment of High-Risk Breast Cancer

Background

Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer.

Patients and Methods

The ADEBAR trial was a multicenter phase III trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4× epirubicin (90 mg/m²) and cyclophosphamide (600 mg/m²) every 3 weeks (q3w), followed by 4× docetaxel (100 mg/m²) q3w (EC-Doc arm), or 6× epirubicin (60 mg/m²) and 5-fluorouracil (500 mg/m²) on days 1 and 8 and cyclophosphamide (75 mg/m²) on days 1–14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility.

Results

Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009).

Conclusion

The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy.     

Outcomes of Revisional Procedures for Insufficient Weight Loss or Weight Regain After Roux-En-Y Gastric Bypass

Background

The Roux-en-Y gastric bypass (RYGB) performed laparoscopically (LRYGB) is the most frequently performed bariatric procedure in Belgium. However, late results in terms of weight loss or weight regain are inconsistent and may warrant a second procedure. This retrospective study analyzes the laparoscopic options for revisional surgery after LRYGB.

Methods

Between January 1, 2001 and December 31, 2009, 70 patients underwent a new laparoscopic procedure for poor weight loss or weight regain after LRYGB. The revisional procedure was performed a median of 2.6?years after the initial bypass operation. Fifty-eight patients were available for follow-up (82.9?%); 19 underwent distalization; and 39 a new restrictive procedure.

Results

The mean mass index (BMI) before the revisional procedure was 39.1?+?11.3?kg/m² (30.8?C51.8), down from 42.7?+?19.7?kg/m² (33.0?C56.6) initially, which corresponded to a percentage of excess weight loss (EWL) of 12.4?+?9.3?% (?1.0?C29.1). After the corrective procedure, with a follow-up of approximately 4?years, mean BMI was 29.6?+?12.4?kg/m² (18.0?C45.5), for a significant additional percentage of EWL of 53.7?+?9.8?% (2.0?C65.8). The overall complication rate was 20.7?%, and the reoperation rate was 7.3?%. The overall leak rate was 12.1?%. Patients suffering from leaks could consistently be treated conservatively or by stent placement. Two patients needed reconversion after distal bypass. The satisfaction index was good in just over 50?% of the patients.

Conclusion

Revisional laparoscopic surgery after RYGB performed for weight issues provides good additional weight loss but carries significant morbidity. Leaks can usually be handled non-surgically. Patient satisfaction is only fair.     

Laparoscopic surgery for colon cancer in obese patients: a case-matched control study

Purpose

This study compared the results of laparoscopic surgery for colon cancer in obese patients with a body-mass index (BMI) of 25 kg/m² or higher with those in nonobese patients (BMI <25 kg/m²) who were matched for clinicohistopathological factors.

Methods

The oncologic outcomes were compared between 140 patients with a BMI of 25 kg/m² or higher (obese group) and 140 patients with a BMI of <25 kg/m² (nonobese group) that were matched for sex, tumor location, date of operation, and pTNM stage.

Results

The proportion of patients with postoperative complications was significantly higher in the obese group (15 %) than in the nonobese group (6 %). The disease-free survival rate and overall survival rate in patients with stage I or II disease were similar in the obese group (98.6 and 98.8 %, respectively) and the nonobese group (97.8 and 97.8 %, respectively). The disease-free survival rate and overall survival rate in patients with stage III disease also did not differ significantly between the obese group (77.2 and 79.4 %, respectively) and the nonobese group (83.4 and 84.9 %, respectively).

Conclusions

Postoperative complications and long-term oncologic outcomes were similar in obese and nonobese patients who underwent laparoscopic colectomy for colon cancer in this hospital.     

Selective Reoperation for Locally Recurrent or Metastatic Pancreatic Ductal Adenocarcinoma Following Primary Pancreatic Resection

Background

Resection of certain recurrent malignancies can prolong survival, but resection of recurrent pancreatic ductal adenocarcinoma is typically contraindicated because of poor outcomes.

Methods

All patients from 1992 to 2010 with recurrent pancreatic cancer after intended surgical cure were retrospectively evaluated. Clinicopathologic features were compared from patients who did and did not undergo subsequent reoperation with curative intent to identify factors associated with prolonged survival.

Results

Twenty-one of 426 patients (5?%) with recurrent pancreatic cancer underwent potentially curative reoperation for solitary local-regional (n?=?7) or distant (n?=?14) recurrence. The median disease-free interval after initial resection among reoperative patients was longer for those with lung or local-regional recurrence (52.4 and 41.1?months, respectively) than for those with liver recurrence (7.6?months, p?=?0.006). The median interval between reoperation and second recurrence was longer in patients with lung recurrence (median not reached) than with liver or local-regional recurrence (6 and 9?months, respectively, p?=?0.023). Reoperative patients with an initial disease-free interval >20?months had a longer median survival than those who did not (92.3 versus 31.3?months, respectively; p?=?0.033).

Conclusion

Patients with a solitary pulmonary recurrence of pancreatic cancer after a prolonged disease-free interval should be considered for reoperation, as they are more likely to benefit from resection versus other sites of solitary recurrence.     

Neoadjuvant Docetaxel, Capecitabine and Cisplatin (DXP) in Patients with Unresectable Locally Advanced or Metastatic Gastric Cancer

Background

This phase II study was conducted to evaluate the efficacy of neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DXP) in patients with unresectable locally advanced and/or intra-abdominal metastatic gastric cancers.

Methods

Patients with advanced gastric cancer (AGC), clinically unresectable because of local invasion or limited intra-abdominal metastasis in para-aortic lymph nodes and/or the peritoneum based on multidetector row computed tomography, were enrolled. DXP consisted of docetaxel 60 mg/m² i.v. and cisplatin 60 mg/m² i.v. on day 1, and capecitabine 937.5 mg/m² twice daily p.o. on days 1–14 every 21 days. Surgery was performed after 4–6 cycles of DXP.

Results

Thirty-six (74%) of the 49 patients enrolled underwent surgery, and 31 (63%) had an R0 resection. R0 resection was possible in 15 of 21 patients (71%) with unresectable locally advanced lesions, 12 of 17 patients (70%) with para-aortic lymph node metastasis but only 4 of 11 patients (36%) with peritoneal metastasis. Grade 3/4 toxicities included neutropenia (69%), febrile neutropenia (4%) and hand–foot syndrome (8%).

Conclusions

Neoadjuvant DXP may offer a reasonable chance of curative surgery in AGC patients with unresectable locally advanced or para-aortic lymph node metastasis.     

Impact of Obesity on Perioperative Outcomes and Survival Following Pancreaticoduodenectomy for Pancreatic Cancer: A Large Single-Institution Study

Background

To examine the effect of body mass index (BMI) on clinicopathologic factors and long-term survival in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma.

Methods

Data on BMI, weight loss, operative details, surgical pathology, and long-term survival were collected on 795 patients who underwent pancreaticoduodenectomy. Patients were categorized as obese (BMI?>?30 kg/m²), overweight (BMI 25 to <30 kg/m²), or normal weight (BMI?<?25 kg/m²) and compared using univariate and multivariate analyses.

Results

At the time of surgery, 14% of patients were obese, 33% overweight, and 53% normal weight. Overall, 32% of patients had preoperative weight loss of >10%. There were no differences in operative times among the groups; however, higher BMI was associated with increased risk of blood loss (P?<?0.001) and pancreatic fistula (P?=?0.01). On pathologic analysis, BMI was not associated with tumor stage or number of lymph nodes harvested (both P?>?0.05). Higher BMI patients had a lower incidence of a positive retroperitoneal/uncinate margin versus normal weight patients (P?=?0.03). Perioperative morbidity and mortality were similar among the groups. Obese and overweight patients had better 5-year survival (22% and 22%, respectively) versus normal weight patients (15%; P?=?0.02). After adjusting for other prognostic factors, as well as preoperative weight loss, higher BMI remained independently associated with improved cancer-specific survival (overweight: hazard ratio, 0.68; obese: hazard ratio, 0.72; both P?<?0.05).

Conclusion

Obese patients had similar tumor-specific characteristics, as well as perioperative outcomes, compared with normal weight patients. However, obese patients undergoing pancreaticoduodenectomy for pancreatic cancer had an improved long-term survival independent of known clinicopathologic factors.     

Pancreatic Anastomotic Leakage after Pancreaticoduodenectomy. Risk factors, Clinical predictors, and Management (Single Center Experience)

Background

Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) remains a challenge even at high-volume centers.

Methods

This study was designed to analyze perioperative risk factors for POPF after PD and evaluate the factors that predict the extent and severity of leak. Demographic data, preoperative, intraoperative, and postoperative variables were collected.

Results

A total of 471 consecutive patients underwent PD in our center. Fifty-seven patients (12.1 %) developed a POPF of any type; 21 patients (4.5 %) had a fistula type A, 22 patients (4.7 %) had a fistula type B, and the remaining 14 patients (3 %) had a POPF type C. Cirrhotic liver (P = 0.05), BMI > 25 kg/m² (P = 0.0001), soft pancreas (P = 0.04), pancreatic duct diameter <3 mm (0.0001), pancreatic duct located <3 mm from the posterior border (P = 0.02) were significantly associated with POPF. With the multivariate analysis, both BMI and pancreatic duct diameter were demonstrated to be independent factors. The hospital mortality in this series was 11 patients (2.3 %), and the development of POPF type C was associated with a significantly increased mortality (7/14 patients). The following factors were predictors of clinically evident POPF: a postoperative day (POD) 1 and 5 drain amylase level >4,000 IU/L, WBC, pancreatic duct diameter <3 mm, and pancreatic texture.

Conclusions

Cirrhotic liver, BMI, soft pancreas, pancreatic duct diameter <3 mm, pancreatic duct near the posterior border are risk factors for development of POPF. In addition a drain amylase level >4,000 IU/L on POD 1 and 5, WBC, pancreatic duct diameter, pancreatic texture may be predictors of POPF B, C.     

Clinical evaluation of adjuvant chemoradiotherapy with CDDP, 5-Fu, and VP-16 for advanced esophageal cancer

Objectives

The aim of this study was to evaluate the efficacy of adjuvant chemoradiotherapy following surgery in patients with advanced esophageal cancer.

Subjects and Methods

We followed the cases of 57 such patients treated at our hospital, involving 19 who received adjuvant chemoradiotherapy (CR group), 19 who received radiotherapy alone (R group), and 19 who did received neither (N group). In the CR group, chemotherapy, consisting of cis-diaminodichloroplatinum (CDDP), 5-fluorouracil (5-FU), and etoposide (VP-16), was combined with radiotherapy was administered from 4 weeks after surgery. Concurrent radiotherapy was started at 3 weeks after esophagectomy. CDDP at 50 mg/m² was administered on days 1 and 7. 5-FU at 500 mg/m² and VP-16 at 60 mg/m² were administered on days 3, 4, and 5. Thirteen patients (68.4%) were treated with more than 2 cycles of chemotherapy combined with radiation.

Results

Side-effects of severe anorexia (grade 3) and leukocytopenia (<1900/μl) were observed in 47% and 39% of the patients, respectively. However no treatment-related death was observed. The 5-year-survival rate was 25.2%, 18.9%, and 15.8%, in the CR group, R group, and N group, respectively. The recurrence rate was 66.7% in the CR group, which was higher than in the matched control groups (46.2% in the N group and 54.5% in the R group), but with no a significant difference.

Conclusion

These results suggested that adjuvant chemoradiotherapy did not contribute to improvement in prognosis for these patients with advanced esophageal cancer.     

Glomerular filtration rate is related to severity of obstructive coronary artery disease in patients undergoing coronary angiography

Purpose

Chronic kidney disease is independently associated with an increased risk of cardiovascular events; however, the relationship between the glomerular filtration rate (GFR) and coronary artery disease (CAD) in patients undergoing coronary angiography has yet to be fully elucidated.

Methods

This retrospective study enrolled a total of 7968 patients who underwent diagnostic coronary artery catheterization [mean age?=?54.8?±?10.6?years, 74.4% males] and did not have any previous history of coronary revascularization, diabetes mellitus, hypertension, end-stage renal disease treated by dialysis or renal transplantation, and were not taking diuretics or drugs acting on renin angiotensin system. The severity of CAD was defined as the number of coronary arteries with a luminal stenosis ??50% on the angiogram, and the GFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).

Results

There were 2133 (26.8%) patients with GFR????90?ml/min/1.73?m², 4574 (57.4%) patients with 60????GFR?2, 1073 (13.5%) with 45????GFR?2 and 181 (2.3%) with 15?2. After adjustment for traditional cardiovascular risk factors (age, sex, dyslipidemia, low to high-density lipoprotein ratio, smoking status, and family history), the GFR showed a significant association with the severity of CAD and remained a significant predictor of CAD (Odds Ratio raised from 1.1 in patients with 60????GFR?2 to 1.8 in patients with 15?2).

Conclusions

A reduced kidney function, even mildly, is significantly associated with CAD severity, independently of other traditional CAD risk factors.