Laparoscopy in the management of gastric adenocarcinoma.

OBJECTIVE: The authors determined the accuracy of laparoscopy in detecting metastatic disease in patients with gastric adenocarcinoma. SUMMARY BACKGROUND DATA: The majority of patients with gastric adenocarcinoma in the United States present with advanced disease. They are at high risk for intraabdominal metastatic spread. METHODS: One hundred eleven patients with gastric adenocarcinoma underwent laparoscopy at Memorial-Sloan Kettering Cancer Center from December 1991 to December 1995. All were judged to be free of intra-abdominal metastatic disease on preoperative computed tomographic scan imaging. RESULTS: Laparoscopic exploration was successful in 110 of 111 patients and accurately staged 94% of the patients with respect to metastatic disease with a sensitivity of 84% and a specificity of 100%. The prevalence rate of metastatic disease was 37%. Twenty-four patients underwent laparoscopy only and were discharged in an average 1.4 days versus 6.5 days in patients undergoing exploratory laparotomy without resection (p < 0.05). No patients undergoing laparoscopy only have returned for palliative surgery. CONCLUSIONS: Laparoscopy should be performed in nonobstructed, nonbleeding patients with advanced gastric cancer in the United States. More than one third of these patients have unsuspected metastatic disease at time of operation. Laparoscopy is highly accurate in detecting occult metastases and identifies a unique population of stage IV patients who may benefit from newer induction chemotherapeutic approaches while avoiding unnecessary laparotomy.     

Nerve-sparing retroperitoneal lymph node dissection for advanced testicular cancer after chemotherapy

BACKGROUND: Nerve-sparing techniques are commonly used in retroperitoneal lymph node dissection (RPLND) in patients with early stage testicular germ cell tumors to preserve postoperative ejaculation. The indications for nerve-sparing procedures have been extended to patients who have residual retroperitoneal tumor postchemotherapy with an increase in the incidence of local recurrence. Here, we report on 26 Japanese men with advanced testicular cancer who underwent nerve-sparing RPLND after partially successful chemotherapy. METHODS: Between January 1995 and December 2000, 26 patients with metastatic or recurrent testicular cancer underwent nerve-sparing RPLND after chemotherapy. Eight patients had seminoma and 18 had non-seminoma. Three patients received high-dose chemotherapy with carboplatin (250 mg/m2 per day x 5 days), etoposide (300 mg/m2 per day x 5 days) and ifosfamide (1.5 g/m2 per day x 5 days) in combination with peripheral blood stem cell transplantation. RESULTS: In all cases, lumbar splanchnic nerves were preserved macroscopically during the operation, at least unilaterally. Twenty-two patients (84.6%) achieved antegrade ejaculation during a mean follow-up at 3.9 months (range: 1-7 months). Three patients have fathered children. Only one patient suffered a retroperitoneal recurrence during a median follow-up at 25.8 months (range: 6-76 months). CONCLUSION: Nerve-sparing procedures for RPLND are appropriate for patients with metastatic testicular cancer, even after chemotherapy. The procedure preserves ejaculatory function in the majority of the patients without increasing the risk of local recurrence. Nerve-sparing RPLND improves the quality of life in patients who require postchemotherapy RPLND to treat residual tumor.     

High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.     

Patients with pancreatic adenocarcinoma benefit from staging laparoscopy

Background: Unnecessary laparotomy in patients with advanced pancreatic cancer may both compromise the quality of life and delay the initiation of more appropriate therapy. Very often, peritoneal small liver metastases and true local status cannot be fully determined without surgery. Laparoscopy may spare laparotomy and decrease morbidity for patients with nonresectable advanced disease. The aim of this study was to determine the impact of laparoscopy in patients with potentially resectable adenocarcinoma of the pancreas. Materials and Methods: We reviewed the records of patients undergoing pancreatic surgery at the University of Nebraska Medical Center from October 2001 to April 2005. A total of 59 patients were included in the study. All patients were staged radiographically with a high resolution helical computed tomography scan and their tumors were considered resectable. Thirty-seven patients underwent staging laparoscopy while 22 proceeded directly to laparotomy. Results: Of the 37 patients who underwent laparoscopic staging, 9 (24.3%) were detected to have metastatic disease or advanced tumor; the remaining 28 (75.7%) patients with negative laparoscopy proceeded to laparotomy. Of those, 24 patients (85.7%) underwent pancreatic resection with curative intent, while 4 patients had metastatic or locally advanced disease at subsequent laparotomy which was missed on staging laparoscopy (false negative rate of 14.3%). Of the 22 patients who proceeded directly to laparotomy, 16 (72.7%) received curative Whipple resection and 6 (27.3%) were found to have advanced disease and received bypass procedures or biopsy alone. Conclusion: These findings suggest that staging laparoscopy is beneficial in a significant proportion of patients deemed resectable by routine noninvasive preoperative studies. We plan to add intraoperative laparoscopic ultrasound to our staging protocol in order to decrease the false negative rate.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

The significance of resections for residual masses after chemotherapy in metastatic testicular tumors

BACKGROUND: After chemotherapy for metastatic testicular tumors, masses may remain, often in the metastatic sites. This study analyses the role of resections for the residual masses. METHODS: Seventy-seven patients with advanced (stage II, III) testicular tumors were treated. Of these, 38 patients, including eight with seminoma and 30 patients with non-seminomatous germ cell tumors, underwent resection of residual masses after chemotherapy and have been followed for a median of 41.5 months (range 2-138) after the resection. RESULTS: Residual masses were necrosis/fibrosis in 19 patients, mature teratoma in 11 and cancer in eight. The ratio of cancer in stage III (41.2%) was significantly higher than that in stage II (4.8%). Ten of 38 (26.3%) patients experienced recurrences in sites other than the resected sites, and five of 10 patients have died of cancer. Most recurrences (80%) occurred within two years. Recurrences after resection were detected in 4.8% of stage II patients, 52.9% of stage III, 16.7% of necrosis/fibrosis and mature teratoma, and 62.5% of cancer. The survival rate of patients with cancer was significantly lower in spite of adjuvant chemotherapy after surgery. CONCLUSIONS: Resection for residual masses after chemotherapy in metastatic testicular tumors was useful in confirming the tissue and in controlling the metastatic sites. Recurrences were often found in patients with cancer in the residual mass and the prognosis of patients with cancer was poor, therefore the development of more effective therapy for patients with cancer is required to improve the prognosis.     

Staging of pancreatic cancer before and after neoadjuvant chemoradiation

Neoadjuvant chemoradiation therapy is used at many institutions for treatment of localized adenocarcinoma of the pancreas. Accurate staging before neoadjuvant therapy identifies patients with distant metastatic disease, and restaging after neoadjuvant therapy selects patients for laparotomy and attempted resection. The aims of this study were to (1) determine theutilityof staging laparoscopy in candidates for neoadjuvant therapy and (2) evaluate the accuracy of restaging CT following chemoradiation. Staging laparoscopy was performed in 98 patients with radiographically potentially resectable (no evidence of arterial abutment or venous occlusion) or locally advanced (arterial abutment or venous occlusion) adenocarcinoma of the pancreas. Unsuspected distant metastasis was identified in 8 (18%) of 45 patients with potentially resectable tumors and 13 (24%) of 55 patients with locally advanced tumors by CT Neoadjuvant chemoradiation therapy and restaging CT were completed in a total of 103 patients. Thirty-three patients with potentially resectable tumors by restaging CT underwent surgical exploration and resections were performed in 27 (82%). Eleven (22%) of 49 patients with locally advanced tumors by restaging CT were resected, with negative margins in 55%; the tumors in these 11 patients had been considered locally advanced because of arterial involvement on restaging CT Staging laparoscopy is useful for the exclusion of patients with unsuspected metastatic disease from aggressive neoadjuvant chemoradiation protocols. Following neoadjuvant chemoradiation, restaging CT guides the selection of patients for laparotomy but may overestimate unresectability to a greater extent than does prechemoradiation CT. Presented at the 2001 Americas Congress of the American Hepatopancreatobiliary Association, Miami, Fla., February 25, 200l.     

Guideline discordant care in patients with metastatic germ cell tumors

IntroductionDespite high curability, patients with metastatic germ cell tumors (GCT) in the United States general population persistently face inferior outcomes compared with those treated in specialty referral centers. We characterized guideline discordant management in patients with metastatic GCT who experienced relapse after first-line chemotherapy and compared those who were initially treated in community practices vs. academic referral centers.Patients/MethodsRetrospective analysis of 53 patients with relapsed GCT between 2005 and 2018. First-line GCT management was assessed against the National Comprehensive Cancer Network guidelines. Guideline discordant management, predictors of discordance, and associations with outcomes were assessed.ResultsOf 53 patients with relapsed GCT, 34% received guideline discordant care in the first-line setting. Guideline discordant care was more prevalent in patients initially treated in community practices (12/30, 40%) vs. those initially treated in academic centers (3/22, 14%), though in multivariate logistic regression, this difference was not statistically significant (odds ratio: 4.07, P = 0.08). Most patients in community settings who received guideline discordant care were undertreated (10/12, 83%). There were 3 major reasons for guideline discordant care: (1) failure to resect residual masses after chemotherapy (27%, 4/15), (2) mismanagement of chemotherapy-related adverse events (27%, 4/15), and (3) under staging at diagnosis, resulting either insufficient chemotherapy regimen intensity (13%, 2/15) and/or inappropriately receiving primary surgical resection for metastatic disease (20%, 3/15).ConclusionUnder treatment was identified in nearly half of patients initially treated in a community setting who later developed relapsed GCT. Referral to specialized centers for a second opinion should be considered for all metastatic GCT patients in the first-line setting and all patients with post-chemotherapy residual disease. More effective methods should be developed to facilitate second opinions from expert centers in the United States.     

Surgical treatment of gastrointestinal stromal tumors in the imatinib (STI-571) era

BACKGROUND: Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors that are characterized by constitutive overexpression of the tyrosine kinase receptor KIT (CD117). Imatinib mesylate is a selective inhibitor of tyrosine kinase-mediated activity. This study reports a single-institution experience of surgical resection and the use of imatinib in the treatment of GIST. METHODS: A retrospective review from 1995 to 2002 identified 57 patients (M:F, 29:28; median age, 61 years) with GIST who were treated at the University of Chicago. Twenty-eight patients underwent exploratory surgery with curative intent; 29 patients were referred for treatment of metastatic disease after surgery at outside institutions. Twenty-nine patients were treated with oral imatinib for either metastatic disease (n=26 patients) or in the adjuvant setting after complete resection (n=3 patients). RESULTS: Resections were performed in 53 patients, and metastatic disease was identified in 17 patients at the time of exploratory surgery. Immunohistochemical staining for CD117 was positive in 96% of patients. A size larger than 5 cm, a mitotic rate larger than 1/10 high-power field, and tumor necrosis predicted recurrence in patients after resection. The median follow-up period was 18 months (range, 4-81 months). Twenty-three patients (40%) are alive without disease; 22 patients (39%) are alive with disease; 7 patients died, and 5 patients are lost to follow-up. Among the 26 patients with metastatic disease who were treated with imatinib, 5 deaths have occurred, and disease stabilization or tumor regression was observed initially in 22 patients, with a median duration of response of 19 months. CONCLUSIONS: Complete surgical extirpation remains the only curative treatment of GIST. Imatinib-targeted therapy of metastatic disease yields encouraging clinical responses. The true efficacy of imatinib in this setting, as induction therapy or as an adjuvant treatment in patients with GIST, is unknown pending the completion of ongoing prospective trials.     

Pancreaticoduodenectomy for locally advanced stomach cancer: preliminary results

Background: Pancreaticoduodenectomy (PD) for locally advanced stomach cancer involving duodenum or/and pancreatic head was controversial and rarely carried out. It was mainly reported from the Japanese institutions. Methods: A review of prospective database from January 2003 to December 2006 of patients who had locally advanced stomach cancer involving duodenum or/and head of pancreas that precluded curative subtotal gastrectomy who underwent diagnostic laparoscopy or exploratory laparotomy to exclude peritoneal metastatic disease. Patients were advised to undergo neoadjuvant chemotherapy before PD. Results: Seven patients underwent PD during the above‐mentioned period. Only four patients had neoadjuvant chemotherapy before PD. The median operative time was 8 h (range 6–9 h). Five patients had combined tranverse colectomy done. There was no 30‐day operative mortality or re‐operation. Three patients developed controlled pancreatic leaks and fistulas that were successfully treated with conservative measures. The length of hospital stay was 10–53 days (median 15 days). Median survival was 13 months and 2‐year survival rate was 60%. Patients who received neoadjuvant chemotherapy seemed to have better survival rate (P = 0.039). Conclusion: Our initial experience has shown that with careful and stringent patients selection, PD for locally advanced stomach cancer can be carried out with acceptable morbidity and mortality. Early results for patients who received neoadjuvant chemotherapy showed trend towards prolonged survival. However, longer follow up and further patient recruitment are needed to confirm our initial optimistic findings.     

Dynamic CT in the Preoperative Evaluation of Patients With Gastric Cancer: Correlation With Surgical Findings and Pathology

Background: The use of diagnostic techniques in the preoperative staging of patients with gastric cancer must be better defined. To further clarify which technique is indicated, we applied a new modality of computed tomography (CT) scanning for patients with gastric cancer.Methods: Dynamic CT of the abdomen using water as oral contrast agent was performed in 30 patients with gastric adenocarcinoma. Patients without evidence of metastatic disease underwent exploratory laparotomy and intraoperative staging. Resectable patients had surgical excision and definitive pathologic staging.Results: Two patients (7%) had metastatic disease by CT and were considered inoperable. The remaining 28 underwent laparotomy. Of these, six (21%) were unresectable and 22 (79%) had surgical resection. Dynamic CT adequately suggested advanced stage disease in four (67%) of the 6 unresectable patients. Wall thickness in dynamic CT correlated with the risk of serosal involvement (P < .001). Both CT and surgery had an accuracy of 64% (P > .05) in predicting pathologic staging. CT overstaged only 4% of cases.Conclusions: Dynamic CT is a useful modality that can indicate inoperable disease, obviating the need for laparotomy in patients with gastric adenocarcinoma. CT can modify the surgical approach by suggesting unresectable or advanced disease. The low percentage of patients that are overstaged by CT, combined with its similar staging accuracy when compared with laparotomy, support its preoperative use in these patients.     

Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas.

Chemoradiation prior to pancreaticoduodenectomy ensures that all patients who undergo resection complete multimodality therapy, avoids resection in patients with rapidly progressive disease, and allows radiation therapy to be delivered to well-oxygenated cells before surgical devascularization. Twenty-eight patients with cytologic or histologic proof of localized adenocarcinoma of the pancreatic head received preoperative chemoradiation (fluorouracil, 300 mg/m2 per day, and 50.4 Gy) with the intent of proceeding to resection; all 28 completed this preoperative therapy. Hospital admission because of gastrointestinal toxic effects was required in nine patients, yet no patient experienced a delay in operation. Restaging was performed 4 to 5 weeks after completion of chemoradiation, and five patients were found to have metastatic disease; the 23 patients without evidence of progressive disease underwent laparotomy. At laparotomy, three patients were found to have unsuspected metastatic disease, three patients had unresectable locally advanced disease, and 17 patients were able to undergo pancreaticoduodenectomy. One perioperative death resulted from myocardial infarction, and perioperative complications occurred in three patients. Histologic evidence of tumor cell injury was present in all resected specimens. Our results suggest that pancreaticoduodenectomy can be performed with a low incidence of complications after chemoradiation for localized adenocarcinoma of the pancreas.     

Influence of laparoscopy on postoperative recurrence and survival in patients with ruptured hepatocellular carcinoma undergoing hepatic resection

BACKGROUND: Use of laparoscopy in patients with gastrointestinal cancer has been associated with port-site and peritoneal tumour metastases. The effect of laparoscopy on tumour recurrence and long-term survival in patients undergoing resection of ruptured hepatocellular carcinoma (HCC) remains unknown. METHODS: Between June 1994 and December 2001, 59 patients with ruptured HCC underwent surgical exploration with a view to hepatic resection. Laparoscopy with laparoscopic ultrasonography was performed in 33 patients; the other 26 patients underwent exploratory laparotomy without laparoscopy. Perioperative and long-term outcomes were compared between the two groups. RESULTS: Exploratory laparotomy was avoided in 12 of 13 patients with irresectable HCC who had a laparoscopy. The hospital stay of these 12 patients was significantly shorter than that of eight patients found to have irresectable HCC at exploratory laparotomy (median 11 versus 15 days; P = 0.043). Twenty patients had a laparoscopy followed by open resection of HCC, whereas 18 patients underwent laparotomy and resection without laparoscopy. There were no significant differences in disease-free (16 versus 19 per cent; P = 0.525) and overall (32 versus 48 per cent; P = 0.176) survival at 3 years between the two groups. The tumour recurrence pattern was similar between the two groups, and there were no port-site or wound metastases. CONCLUSION: Use of diagnostic laparoscopy in patients with ruptured HCC helps avoid unnecessary exploratory laparotomy. The present data suggest that laparoscopy does not have an adverse effect on tumour recurrence or survival in patients who undergo resection.     

Gemcitabine and cisplatin therapy in advanced or metastatic urothelial cancer: comparison of side effect with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin)

OBJECTIVE: Cisplatin-based combination chemotherapy has been considered as standard therapy for advanced or metastatic urothelial carcinoma. A recent study has, however, revealed that gemcitabine may have the potential to act synergistically with cisplatin. Therefore, the side effects of gemcitabine plus cisplatin (GC) therapy were compared with those of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) therapy in patients with advanced or metastatic urothelial carcinoma. PATIENTS AND METHODS: Twenty-two patients received GC therapy. Gemcitabine (1000 mg/m2) was administered on days 1, 8 and 15 of each 28-day cycle. Cisplatin (70 mg/m2) was administered on day 2 of each cycle. As a control group, 24 patients received MVAC therapy (methotrexate at 30 mg/m2 on days 1, 15, 22, vinblastine at 3 mg/m2 on days 2, 15, 22, doxorubicin at 30 mg/m2 on day 2, and cisplatin at 70 mg/m2 on day 2 of each 28-day cycle. RESULTS: In the group of patients which received GC therapy, the overall response rates based on independent radiologic reviews of the 20 patients with measurable disease were 55%, with 20% CR and 35% PR. Fewer GC patients as compared with MVAC patients had grade 3/4 anorexia (4.5% vs. 75%, respectively), stomatitis (9.0% vs. 66.7%, respectively), and alopecia (27.3% vs. 100%, respectively). On the other hand, there were no significant differences in the incidence or pattern of hematologic toxicities between the group receiving GC therapy and that receiving MVAC therapy. Fatal neutropenic sepsis occurred in one patient receiving MVAC therapy. CONCLUSION: GC therapy is effective for the treatment of advanced or metastatic urothelial carcinoma, with an acceptable clinical safety profile. This study also indicates that GC therapy may be better tolerated and safer than MVAC therapy.     

Post-chemotherapy nerve-sparing retroperitoneal lymph node dissection for advanced germ cell tumor

Objective:   To report our experience with post-chemotherapy nerve-sparing retroperitoneal lymph node dissection (RPLND) for advanced germ cell tumor (GCT).
Methods:   Between 1994 and 2008, 92 patients with advanced GCT underwent RPLND after multiple treatments with systemic chemotherapy at our institution. A nerve-sparing RPLND was carried out in 78 patients (84.8%; median age 32 years). Of them, 19 had a seminoma and 59 had a non-seminoma.
Results:   Lumbar splanchnic nerves controlling ejaculatory function were macroscopically preserved during RPLND. Bilateral and unilateral lumbar splanchnic nerves were preserved in 40 patients and 38 patients, respectively. Sixty-five patients could be evaluated for ejaculation. Fifty-four patients (83.1%) achieved antegrade ejaculation with a median postoperative interval of 3 months (range: 1–10 months). Twenty-eight patients (28/30: 93.3%) and 26 patients (26/35: 74.3%) undergoing bilateral and unilateral nerve-sparing RPLND had antegrade ejaculation, respectively ( P  = 0.041). Only two patients (2.6%) had mediastinal and retroperitoneal recurrences during a median follow-up of 42 months (range: 1–138 months), respectively. However, these patients were cured by chemotherapy and surgery.
Conclusions:   Post-chemotherapy nerve-sparing RPLND preserves ejaculatory function in the majority of patients with advanced GCT without increasing the risk of local recurrence.     

Late relapse of metastatic testicular nonseminomatous germ cell cancer: surgery is needed for cure

OBJECTIVE: To identify patients with late relapse of metastatic, nonseminomatous germ cell tumour (NSGCT) and to evaluate the patterns of relapse, treatment and outcome, as such relapse at >2 years after complete remission to treatment for metastatic disease (late relapse) is uncommon, but with prolonged follow-up is becoming increasingly recognized. PATIENTS AND METHODS: Between 1980 and 2004, 1405 patients with testicular GCTs were identified who presented to Southampton University Hospital; 742 had NSGCTs or combined testicular GCTs, of whom 405 received primary chemotherapy for metastatic disease. In all, 329 (81%) patients achieved a complete response (CR) to initial treatment, with 101 of them (31%) requiring surgical resection of residual masses after chemotherapy. Any patient relapsing at >2 years after a CR to initial treatment (late relapse) was assessed in detail. RESULTS: In all, 20 patients had a late relapse, 17 of whom received initial treatment locally and three of whom were initially treated elsewhere. Most (65%) late relapses were asymptomatic and detected by routine cross-sectional imaging or rising levels of tumour markers. Late relapse occurred at a median (range) of 108 (26-217) months (approximately 9 years) after CR. Fifteen (75%) patients underwent only surgery for late relapse, including five who had invasive malignant germ cell cancer within the resected specimens. Fourteen of 15 surgically treated patients remained alive at a median of 44 (9-184) months from initial treatment for late relapse; one had died with progressive recurrent germ cell/epithelial malignancy. Five (25%) patients were initially treated with chemotherapy for late relapse; three of them died from progressive germ cell cancer and the two survivors both had surgical excision of residual abnormalities after salvage chemotherapy. Overall, 15 of 20 (75%) men remain alive with no evidence of disease; one further patient is currently undergoing salvage treatment for his third relapse. CONCLUSION: Late relapse is uncommon after modern therapy for metastatic GCTs. Surgical treatment for localized disease, where possible, is associated with prolonged disease-free and overall survival. By contrast, chemotherapy is associated with a low response rate and a poor outcome.     

High-dose chemotherapy with haematopoietic stem-cell support in patients with poor prognosis, relapsed or refractory germ cell tumours

OBJECTIVE: To report our experience of high-dose chemotherapy (HDC) with haematopoietic stem-cell support (HSC) in patients with poor risk, relapsed or refractory germ cell tumours (GCTs), as this treatment might offer effective salvage for patients with disseminated GCTs. PATIENTS AND METHODS: We retrospectively reviewed the medical records and database for 33 patients with GCT who were treated with HDC with HSC in our centres. RESULTS: Thirty-three patients were treated with either one or two cycles of carboplatin and etoposide-based HDC with HSC support, between March 1990 and October 2003. Twenty-six patients (79%) had nonseminomatous GCT, six seminoma (18%), and one (3%) a combined seminoma and teratoma. Twenty patients (60%) had previously had a clinical complete response after previous chemotherapy +/- surgery for residual disease. Most patients were treated with HDC for relapsing (49%) or relative refractory disease (30%), but seven (21%) had HDC in the first partial remission. The complete response rate to HDC was 58%. There were two treatment-related deaths (6%). As of April 2005, 18 patients were alive and disease-free with a median (range) follow-up of 72 (0.5-174) months. The 5-year overall and progression-free survival probabilities were 57% and 56%, respectively. The median (range) times to absolute neutrophil count recovery (> or = 500/microL) were 13 (9-24) and 12 (10-15) days, and for platelet count recovery ( > or = 20,000/microL) were 16 (7-50) and 13 (11-17) days, in the first and second cycles, respectively. CONCLUSION: The role of HDC with HSC support in metastatic GCTs remains controversial, and data from randomized controlled trials are needed. Our experience suggests that, in selected patients, this approach might be a useful form of salvage therapy.     

Intraoperative interstitial radiation therapy for hepatic metastases from colorectal carcinomas

Liver metastases from colorectal carcinomas occur frequently. While surgical resection offers the only hope for long-term cure, unsuspected bilobar metastases or extrahepatic metastatic disease may be found at laparotomy, precluding hepatic resection for cure. In this setting intraoperative interstitial hepatic irradiation using the Gamma Med II (Mick Radio-Nuclear Instruments, Bronx, New York) remote afterloading irradiator and an Iridium-192 source permits delivery of a tumoricidal dose to liver tumor(s) with a limited radiation dose to adjacent normal liver. Six patients underwent laparotomy for potential resection of hepatic metastases in a shielded operating room equipped with remote anesthesia monitoring capability and were found to be unresectable. An upper hand retractor facilitated liver exposure during the exploratory and subsequent radiation phases of the procedure. Intraoperative interstitial radiation therapy was performed in each patient. No significant complications occurred on follow-up from 2 to 9 months. Hepatic tumor regression or stabilization occurred on sonography and/or CT scan in each case with a median follow-up of 5 months. The technique offers the potential to ablate discrete tumor nodules within the liver. Ongoing clinical trials will determine the role of intraoperative interstitial radiation in the treatment of hepatic metastases.     

Surgical treatment of pulmonary metastases from colon and rectal cancer

We retrospectively studied the surgical treatment for pulmonary metastases from colon and rectal cancer. A total of 24 patients (9 males and 15 females; mean age 61 years) underwent 29 thoracotomies for metastatic colon carcinoma, while 22 patients (16 males and 6 females; mean age 63 years) underwent 29 thoracotomies for metastatic rectal cancer. The median interval between the primary procedure and lung resection for metastases was 26 months in the patients with colon carcinoma and 32 months in the patients with rectal cancer. In the patients with colon carcinoma, 16 underwent wedge resection or segmentectomy (including 4 video-assisted procedures) and 13 (54%) underwent lobectomy or pneumonectomy. In the patients with rectal cancer, 15 underwent wedge or segmentectomy (including 1 video-assisted procedure), 13 (59%) underwent lobectomy or pneumonectomy, and 1 underwent exploratory thoracotomy. All procedures except exploratory thoracotomy were curative operations. There was no mortality. Overall 5-year survival was 56% (n=46). Five-year survival was 65% for patients with colon metastases (n=24) and 45% for patients with rectal metastases (n=22), and there was no significant difference. Recurrent sites were 4 lungs (36%), 4 livers (36%), 1 bone, 1 uterus, and 1 peritoneum in patients with colon carcimoma, and 10 lungs (43%), 5 brains (22%), 3 livers (13%), 1 bone, and 1 vagina in patients with rectal cancer. Pulmonary resection for metastases from colon carcinoma may have better prognosis than that from rectal cancer. However, further investigation may be required to obtain convincing conclusions.