Splenectomy in Patients with Visceral Leishmaniasis Resistant to Conventional Therapy and Secondary Prophylaxis: A Retrospective Cohort.

Some patients with visceral leishmaniasis (VL), or kala-azar, suffer relapses and low quality of life despite adequate drug therapy, especially those co-infected with HIV. Occasionally, physicians indicate splenectomy, but the benefit of the procedure needs to be analyzed systematically. Therefore, a retrospective open cohort study was conducted in Teresina, Brazil. Inpatients from a reference hospital with relapsing VL who had a rescue splenectomy between 2012 and 2019 after the nationally recommended drug therapy failed were studied. The procedure's risks and benefits were assessed in a limited-resource setting. The primary outcomes were surgical complications, complete blood count, CD4+ cell count, hospitalizations, survival time, and medical complications preceding death. Thirteen adult patients received medical and surgical indications of splenectomy (12 men and one woman). Eleven had HIV infection. Two had early and two had late complications. Four died, all of whom were infected with HIV. An additional HIV-coinfected patient, apart from the cohort, died just before surgery. The death rate after surgery was 13.3 overall and 22.1 per 100 person-years among HIV-infected patients (31% overall and 36%, respectively). The impressive rise of complete blood counts and reduction of blood transfusions and hospitalizations were observed among all patients. Also, a meaningful increase in CD4+ cells in HIV-infected patients was noted. Splenectomy may benefit patients with relapsing VL. However, before performing splenectomy, available combined drug therapy for VL should be tried.

Serological Markers of Recent Campylobacter jejuni Infection in Patients with Guillain-Barré Syndrome in the State of Piauí, Brazil, 2014-2016.

In countries where poliomyelitis has been eradicated, Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis. The range of infections that precede GBS in Brazil is unknown. Campylobacter jejuni infection is the most frequent trigger of GBS worldwide. Given the lack of systematic surveillance of diarrheal diseases, particularly in adults, the incidence of enteritis caused by C. jejuni in developing countries is unknown. From 2014 to 2016, pretreatment serum samples from 63 GBS patients were tested by immunoglobulin M (IgM) enzyme-linked immunosorbent assay for C. jejuni. Campylobacter jejuni IgM antibodies were detected in 17% (11/63) of the samples. There was no association between serological positivity (IgM) for C. jejuni and the occurrence of diarrhea among the investigated cases (P = 0.36). Hygiene measures, basic sanitation, and precautions during handling and preparation of food of animal origin may help prevent acute flaccid paralysis.

Predictors of overall and recurrence-free survival after neoadjuvant chemotherapy for gastroesophageal adenocarcinoma: Pooled analysis of individual patient data (IPD) from randomized controlled trials (RCTs).

BACKGROUND: Neoadjuvant chemotherapy improves prognosis of patients with locally advanced gastroesophageal adenocarcinoma. The aim of this study was to identify predictors for postoperative survival following neoadjuvant therapy. These could be useful in deciding about postoperative continuation of chemotherapy. METHODS: This meta-analysis used IPD from RCTs comparing neoadjuvant chemotherapy with surgery alone for gastroesophageal adenocarcinoma. Trials providing IPD on age, sex, performance status, pT/N stage, resection status, overall and recurrence-free survival were included. Survival was calculated in the entire study population and subgroups stratified by supposed predictors and compared using the log-rank test. Multivariable Cox models were used to identify independent survival predictors. RESULTS: Four RCTs providing IPD from 553 patients fulfilled the inclusion criteria. (y)pT and (y)pN stage and resection status strongly predicted postoperative survival both after neoadjuvant therapy and surgery alone. Patients with R1 resection after neoadjuvant therapy survived longer than those with R1 resection after surgery alone. Patients with stage pN0 after surgery alone had better prognosis than those with ypN0 after neoadjuvant therapy. Patients with stage ypT3/4 after neoadjuvant therapy survived longer than those with stage pT3/4 after surgery alone. Multivariable regression identified resection status and (y)pN stage as predictors of survival in both groups. (y)pT stage predicted survival only after surgery alone. CONCLUSION: After neoadjuvant therapy for gastroesophageal adenocarcinoma, survival is determined by the same factors as after surgery alone. However, ypT stage is not an independent predictor. These results can facilitate the decision about postoperative continuation of chemotherapy in pretreated patients.

Recommendations for pathologic staging (pTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

We report analytic and consensus processes that produced recommendations for pathologic stage groups (pTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 13,300 without preoperative therapy had pathologic assessment after esophagectomy or endoscopic treatment. Risk-adjusted survival for each patient was developed using random survival forest analysis to identify data-driven pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus pathologic stage groups. For pT1-3N0M0 squamous cell carcinoma (SCC) and pT1-2N0M0 adenocarcinoma, pT was inadequate for grouping; subcategorizing pT1 and adding histologic grade enhanced staging; cancer location improved SCC staging. Consensus eliminated location for pT2N0M0 and pT3N0M0G1 SCC groups, and despite similar survival, restricted stage 0 to pTis, excluding pT1aN0M0G1. Metastases markedly reduced survival; pT, pN, and pM sufficiently grouped advanced cancers. Stage IIA and IIB had different compositions for SCC and adenocarcinoma, but similar survival. Consensus stage IV subgrouping acknowledged pT4N+ and pN3 cancers had poor survival, similar to pM1. Anatomic pathologic stage grouping, based on pTNM only, produced identical consensus stage groups for SCC and adenocarcinoma at the cost of homogeneity in early groups. Pathologic staging can neither direct pre-treatment decisions nor aid in prognostication for treatment other than esophagectomy or endoscopic therapy. However, it provides a clean, single therapy reference point for esophageal cancer.

West Nile Virus Encephalitis: The First Human Case Recorded in Brazil.

A Brazilian ranch worker with encephalitis and flaccid paralysis was evaluated in the regional Acute Encephalitis Syndromic Surveillance Program. This was the first Brazilian patient who met the Centers for Disease Control and Prevention (CDC) confirmation criteria for West Nile virus disease. Owing to the overlapping of neurological manifestations attributable to several viral infections of the central nervous system, this report exemplifies the importance of human acute encephalitis surveillance. The syndromic approach to human encephalitis cases may enable early detection of the introduction of unusual virus or endemic occurrence of potentially alarming diseases within a region.

Outcomes of induction chemotherapy followed by chemoradiation using intensity-modulated radiation therapy for esophageal adenocarcinoma.

This study looks at toxicity and survival data when chemoradiation (CRT) is delivered using intensity-modulated radiation therapy (IMRT) after induction chemotherapy. Forty-one patients with esophageal adenocarcinoma treated with IMRT from March 2007 to May 2009 at Memorial Sloan-Kettering Cancer Center were analyzed. All patients received induction chemotherapy prior to CRT. Thirty-nine percent (n = 16) of patients underwent surgical resection less than 4 months after completing CRT. Patients were predominantly male (78%), with a median age of 68 years (range 32-85 years). The majority of acute treatment-related toxicity was hematologic or gastrointestinal, with 17% of patients having grade 3+ hematologic toxicity and 12% of patients having grade 3+ gastrointestinal toxicity. Only two patients developed grade 2-3 pneumonitis (5%) and 5 patients experienced post-operative pulmonary complications (29%). Eight patients (20%) required a treatment break. With a median follow up of 41 months for surviving patients, 2-year overall survival was 61%, and the cumulative incidences of local failure (LF) and distant metastases were 40% and 51%, respectively. This rate of LF was reduced to 13% in patients who underwent surgical resection. Surgery and younger age were significant predictors of decreased time to LF on univariate analysis. Induction chemotherapy followed by CRT using IMRT in the treatment of esophageal cancer is well tolerated and is not associated with an elevated risk of postoperative pulmonary complications. The use of IMRT may allow for integration of more intensified systemic therapy or radiation dose escalation for esophageal adenocarcinoma, ultimately improving outcomes for patients with this aggressive disease.

Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis.

BACKGROUND: To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma. PATIENTS AND METHODS: Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive. RESULTS: Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194). CONCLUSIONS: Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.

Tobacco use is associated with increased recurrence and death from gastric cancer.

BACKGROUND: Tobacco use increases the risk of developing gastric cancer. We examined the hypothesis that gastric cancer developing in patients with a history of tobacco use may be associated with increased risk of cancer-specific death after curative surgical resection. METHODS: From the Memorial Sloan-Kettering Cancer Center Gastric Cancer prospective surgical database, we collected baseline demographic data and tumor characteristics from all patients who had undergone curative resection for gastric cancer between 1995 and 2009 and who had not received pre- or postoperative chemo- or radiotherapy. A smoking history was defined as >100 cigarettes' lifetime use. The primary end point was gastric cancer disease-specific survival (DSS); secondary end points were 5-year disease-free survival (DFS) and overall survival (OS). Gastric cancer-specific hazard was modeled by Cox regression. RESULTS: A total of 699 eligible patients were identified with a median age of 70 years (range 25-96 years); 410 (59%) were current or previous smokers. Smoking was associated with gastroesophageal junction/cardia tumors and white non-Hispanic ethnicity. Multivariate analysis included the following variables: tumor stage, age, performance status, diabetes mellitus, gender, and tumor location. In this analysis, the hazard ratio for gastric cancer DSS in smokers was 1.43 (95% confidence interval 1.08-1.91, P=0.01). Smoking was also an independent significant risk factor for worse 5-year DFS (hazard ratio 1.46, P=0.007) and OS (hazard ratio 1.48, P=0.003). Among 516 patients for whom tobacco pack-year usage was available, both heavy (≥20 pack-years) and light (<20 pack-years) tobacco use was significantly associated with DSS, DFS, and OS. CONCLUSIONS: Smoking history appears to be an independent risk factor for death from gastric cancer in patients who have undergone curative surgical resection.

Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma.

BACKGROUND: To characterise recurrence patterns and survival following pathologic complete response (pCR) in patients who received preoperative therapy for localised gastric or gastrooesophageal junction (GEJ) adenocarcinoma. METHODS: A retrospective review of a prospective database identified patients with pCR after preoperative chemotherapy for gastric or preoperative chemoradiation for GEJ (Siewert II/III) adenocarcinoma. Recurrence patterns, overall survival, recurrence-free survival, and disease-specific survival were analysed. RESULTS: From 1985 to 2009, 714 patients received preoperative therapy for localised gastric/GEJ adenocarcinoma, and 609 (85%) underwent a subsequent R0 resection. There were 60 patients (8.4%) with a pCR. Median follow-up was 46 months. Recurrence at 5 years was significantly lower for pCR vs non-pCR patients (27% and 51%, respectively, P=0.01). The probability of recurrence for patients with pCR was similar to non-pCR patients with pathologic stage I or II disease. Although the overall pattern of local/regional (LR) vs distant recurrence was comparable (43% LR vs 57% distant) between pCR and non-pCR groups, there was a significantly higher incidence of central nervous system (CNS) first recurrences in pCR patients (36 vs 4%, P=0.01). CONCLUSION: Patients with gastric or GEJ adenocarcinoma who achieve a pCR following preoperative therapy still have a significant risk of recurrence and cancer-specific death following resection. One third of the recurrences in the pCR group were symptomatic CNS recurrences. Increased awareness of the risk of CNS metastases and selective brain imaging in patients who achieve a pCR following preoperative therapy for gastric/GEJ adenocarcinoma is warranted.

Molecular identification of Coccidioides spp. in soil samples from Brazil.

BACKGROUND: Since 1991 several outbreaks of acute coccidioidomycosis (CM) were diagnosed in the semi-arid Northeast of Brazil, mainly related to disturbance of armadillo burrows caused by hunters while digging them for the capture of these animals. This activity causes dust contaminated with arthroconidia of Coccidioides posadasii, which, once inhaled, cause the mycosis. We report on the identification of C. posadasii in soil samples related to outbreaks of CM. RESULTS: Twenty four soil samples had their DNA extracted and subsequently submitted to a semi-nested PCR technique using specific primers. While only 6 (25%) soil samples were positive for C. posadasii by mice inoculation, all (100%) were positive by the molecular tool. CONCLUSION: This methodology represents a simple, sensitive and specific molecular technique to determine the environmental distribution of Coccidioides spp. in endemic areas, but cannot distinguish the species. Moreover, it may be useful to identify culture isolates. Key-words: 1. Coccidioidomycosis. 2. Coccidioides spp. 3. C. posadasii. 4. Semi-arid. 5. Semi-nested PCR.

Risk factors for developing a new venous thromboembolism in ambulatory patients with non-hematologic malignancies and impact on survival for gastroesophageal malignancies.

BACKGROUND: Venous thromboembolism(VTE) is a significant, common comorbidity of cancer patients associated with increased mortality. We evaluated the incidence and risk factors for developing a new VTE in ambulatory cancer patients while they were receiving therapy for advanced cancer. We also examined the affect of developing a new VTE on survival for patients with gastroesophageal malignancies. METHODS: All patients with non-hematologic malignancies who were treated using investigator-initiated therapeutic protocols at Memorial Sloan Kettering Cancer Center (MSKCC) from 2003 through to 2005 were identified for this cohort study. The occurrence of VTE was prospectively recorded in an actively managed clinical research database. Baseline laboratory parameters, treatment details and tumor type were correlated with VTE risk and patient survival. RESULTS: 115 out of 2120 patients being treated for advanced malignancy developed a new VTE (12.8 VTEs/100 person-years). In multivariate analysis, a diagnosis of gastroesophageal cancer (hazard ratio (HR), 2.76 (1.41-5.38); P=0.003), pancreatic cancer (HR, 2.26 (1.06-4.80); P=0.05), use of white cell growth factors (HR 1.69(1.09-2.64); P=0.02) and irinotecan therapy (HR, 1.89 (1.29-3.59); P=0.05) were independently associated with VTE development. Hemoglobin >10 g dL(-1) (HR, 0.52 (0.3-0.91); P=0.02) and albumin ≥ 4 g dL(-1) (HR, 0.61 (0.39-0.94); P=0.024) were associated with reduced VTE risk. The unadjusted HR for death among ambulatory gastroesophageal cancer patients with VTE is 0.89 (0.61-1.3), P=0.53. After adjusting for confounding risk factors associated with survival, the HR for death associated with VTE is 0.78 (0.5-1.2), P=0.25. CONCLUSION: Upper gastrointestinal malignancies are independently associated with the development of a new VTE, implicating tumor biology in VTE development. Even after adjusting for prognostic factors, we were unable to demonstrate an adverse impact on survival due to the new development of VTE amongst patients with active gastroesophageal malignancy receiving therapy.

Small-cell carcinoma of the esophagus and gastroesophageal junction: review of the Memorial Sloan-Kettering experience.

BACKGROUND: Esophageal small-cell carcinoma (SCC) is rare, highly malignant and the optimal treatment approach has not been defined. PATIENTS AND METHODS: We report the largest single-institution retrospective review of patients with esophageal and gastroesophageal (GE) junction SCC. RESULTS: Twenty-five patients were identified, with complete records available for 22. Eighty-two percent were male, 82% had pure SCC histology and 86% of tumors were in the lower esophagus or GE junction. On the basis of the Veterans' Administration Lung Study Group criteria, 14 patients (64%) presented with limited disease (LD). Median survival was 19.8 months (range, 1.5 months to 11.2+ years); for LD patients, 22.3 months (range, 6 months to 11.2+ years); for extensive disease (ED) patients, 8.5 months (range, 1.5 months to 2.2 years, P = 0.02). With a median follow-up of 38 months, six patients (27%) are alive, one with ED and five with LD. Two LD patients are alive and free of disease for >5 years. Four of the five LD patients who are long-term survivors received induction chemotherapy followed by chemoradiotherapy without surgery. CONCLUSIONS: Our data indicate that patients with LD esophageal SCC treated with induction chemotherapy followed by consolidative chemoradiation can achieve long-term survival. The contribution of surgery remains unclear.

A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma.

PURPOSE: To determine the maximum tolerated dose (MTD) of erlotinib when administered concurrently with twice weekly gemcitabine and radiation therapy (RT) for locally advanced pancreatic cancer, assess the safety and toxicity profile of this combination and secondarily evaluate response, time to tumor progression and overall survival. METHODS: Patients with untreated locally advanced pancreas cancer were treated with daily erlotinib in combination with gemcitabine 40 mg/m(2)/30 min twice weekly and RT delivered at 180 cGy/day in 28 fractions over 5.5 weeks for a total of 5040 cGy. Erlotinib was dose escalated in successive cohorts (100 mg, 125 mg). When the MTD was determined, the cohort was expanded to better define toxicity and preliminarily efficacy. All patients were surgically staged. After chemoradiation, patients received maintenance weekly gemcitabine 1000 mg/m(2) on days 1 and 8 of a 21 day cycle and daily erlotinib for four cycles. RESULTS: Three patients were treated at dose level 1 (erlotinib 100 mg) without limiting toxicity. Two of six patients at dose level 2 (erlotinib 125 mg) had dose-limiting toxicities, neutropenia and thrombocytopenia, causing dose delay and elevated liver enzymes. The MTD for erlotinib in combination with twice weekly gemcitabine-based chemoradiation was 100 mg/day. Eleven additional patients were treated at dose level 1. All twenty patients were assessable for toxicity. Seventeen patients were assessable for response. The partial response rate was 35% and 53% had stable disease. The median survival for all patients was 18.7 months. CONCLUSION: In combination with fixed dose gemcitabine at 40 mg/m(2) twice weekly and radiation at 180 cGy/day, the MTD of erlotinib was found to be 100 mg/day. This is a relatively well tolerated, biologically active combination in a poor prognostic cancer.

Phase I dose-finding study of weekly docetaxel followed by flavopiridol for patients with advanced solid tumors.

PURPOSE: Flavopiridol is a cyclin-dependent kinase inhibitor that enhances docetaxel-induced apoptosis in a sequence-specific manner. In vivo, docetaxel must precede flavopiridol by at least 4 h to induce this effect. We conducted a phase I trial of weekly, sequential docetaxel followed 4 h later by flavopiridol in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Docetaxel at a fixed dose of 35 mg/m2 was administered over 30 min, followed 4 h later by escalating doses of flavopiridol, ranging from 20 to 80 mg/m2 in successive cohorts, administered weekly over 1 h. This schedule was repeated for 3 weeks of each 4-week cycle. RESULTS: Twenty-seven evaluable patients were enrolled. The combination was well tolerated, with one dose-limiting toxicity occurring at flavopiridol 70 mg/m2 (grade 3 mucositis) and one dose-limiting toxicity at 80 mg/m2 (grade 4 neutropenia). We observed 1 complete response in a patient with pancreatic carcinoma and 4 partial responses in pancreatic (1), breast (2), and ovarian (1) cancer patients. Stable disease was seen in 10 patients. Pharmacokinetic studies showed Cmax ranging from 1.49 +/- 0.69 micromol/L (flavopiridol 20 mg/m2) to 4.54 +/- 0.08 micromol/L (flavopiridol 60 mg/m2) in cycle 1. CONCLUSIONS: Treatment with weekly, sequential docetaxel followed by flavopiridol is an effective and safe regimen at all flavopiridol dose levels. The pharmacokinetic data indicate that concentrations of flavopiridol that enhance the effects of docetaxel both in vitro and in vivo can be achieved. Clinical activity is encouraging, even in patients who have received a prior taxane and in patients with gemcitabine-refractory metastatic pancreatic cancer.

Systemic chemotherapy does not increase the risk of gastrointestinal perforation.

BACKGROUND: Gastrointestinal perforation is a rare complication of gastric cancer. Although there is the perception of chemotherapy aggravating the perforation risk, the rate of perforation in patients with gastric cancer receiving chemotherapy is unknown. This study describes the incidence and clinical course of patients with gastric or gastroesophageal junction (GEJ) carcinoma who experience a perforation while receiving chemotherapy. PATIENTS AND METHODS: The records of patients with gastric or GEJ adenocarcinoma over a 6-year period who received chemotherapy for locally advanced or metastatic disease were reviewed. Extracted information included demographics, treatment received, and overall survival was calculated. RESULTS: 1032 patients at MSKCC received systemic cytotoxic chemotherapy for locally advanced or metastatic gastric or GEJ carcinoma; 11 patients experienced a perforation (1.1%, 95% CI 0.5-1.9%); 5/11 (45%) patients received further chemotherapy and had a median survival of 5.6 months. CONCLUSIONS: The rate of perforation in patients with advanced GEJ/gastric adenocarcinoma receiving chemotherapy is 1.1%, which is the same rate as in surgical series of patients presenting with perforation. Chemotherapy does not significantly add to the risk of gastrointestinal perforation.

Combined modality chemoradiation in elderly oesophageal cancer patients.

We present a single institution experience with 5-FU, mitomycin-C based chemoradiation for the primary treatment of elderly patients with oesophageal cancer. Twenty-five patients with a median age of 77 years (range 66-88) with a diagnosis of stage II-III squamous cell or adenocarcinoma of the oesophagus were treated at Memorial Sloan Kettering from 1996 to 2001 with two cycles of concurrent 5-FU, mitomycin-C and 50.4 Gy. Owing to age and comorbidity, these patients were not considered surgical candidates. The Charlson comorbidity score was used to evaluate patient comorbidity. Nine patients (36%) experienced grade 3-4 haematologic toxicity. Of the 23 patients evaluable for response, 17 patients (68%) had a negative post-treatment endoscopy and CT scan without evidence of progressive disease. Eleven patients (44%) are alive and 10 (40%) remain without evidence of recurrent or progressive oesophageal cancer at a median follow-up of 35 months. The median overall survival was 35 months and 2-year survival 64%. There was no significant difference in overall survival between Charlson score /=2 (P=0.10). Similar survival was observed for patients with adenocarcinoma or squamous carcinoma. Primary chemoradiation with two cycles of 5-FU, mitomycin-C, and 50.4 Gy in elderly patients is an active regimen with moderate toxicity, despite the advanced age and heavy comorbidity burden of this cohort. Patients with local/regional oesophageal cancer with adequate functional status should not be excluded from potentially curative treatment based on age alone.

Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer.

BACKGROUND: The purpose of the study was to evaluate the efficacy of weekly paclitaxel (Taxol) in advanced esophageal cancer. PATIENTS AND METHODS: One hundred and two patients with advanced esophageal cancer were treated with paclitaxel 80 mg/m2 weekly over a 1-h infusion. One cycle was defined as 4 weeks of therapy. Ninety-five patients were assessable for toxicity and 86 patients who completed at least two cycles of treatment were assessable for response. Sixty-six patients had adenocarcinoma (66%) and 65 patients (68%) had no prior chemotherapy. RESULTS: A median of three cycles was delivered (range 1-11). Partial responses (PRs) were seen in 11 patients [13%, 95% confidence interval (CI) 6% to 20%]. In patients without prior chemotherapy, PRs were seen in 10 patients (15%, 95% CI 6% to 24%), with comparable response in adenocarcinoma (8/50, 16%) and squamous carcinoma (2/15, 13%). Limited response was seen in patients with prior chemotherapy (1/21, 5%). The median duration of response was 172 days. The median survival was 274 days. Therapy was well tolerated with minimal hematologic or grade 3 or 4 toxicity. CONCLUSION: Weekly paclitaxel has limited activity in esophageal cancer. The median survival, modest activity, and tolerance of therapy indicate that weekly paclitaxel may be an option in patients unable to tolerate combination chemotherapy.

A phase II trial of neoadjuvant cisplatin-fluorouracil followed by postoperative intraperitoneal floxuridine-leucovorin in patients with locally advanced gastric cancer.

BACKGROUND: The aim of the study was to evaluate the efficacy and toxicity of neoadjuvant chemotherapy with intravenous (i.v.) cisplatin and fluorouracil (5-FU), surgery and postoperative intraperitoneal (i.p.) floxuridine (FUdR) and leucovorin (LV) in patients with locally advanced gastric cancer. PATIENTS AND METHODS: Preoperative staging was confirmed by laparoscopy (LAP). Two cycles of i.v. cisplatin (20 mg/m(2)/day, rapid infusion) and 5-FU (1000 mg/m(2), continuous 24-h infusion), given on days 1-5 and 29-34, were followed by a radical gastrectomy and a D2 lymphadenectomy. Patients having R0 resections were to receive three cycles of i.p. FUdR (1000 mg/m(2)) and LV (240 mg/m(2)), given on days 1-3, 15-17 and 29-31. Intraperitoneal chemotherapy was begun 5-10 days from surgery. RESULTS: Thirty-eight patients were treated. Both preoperative and postoperative chemotherapy were well tolerated. T stage downstaging (pretreatment LAP versus surgical pathological stage) was seen in 23% of patients. The R0 resection rate was 84%. Neither an increase in postoperative morbidity nor operative mortality was noted. With a median follow-up of 43.0 months, 15 patients (39.5%) are still alive (median survival 30.3 months). Good pathologic response, seen in five patients (15%), was associated with better survival (P = 0.053). Peritoneal and hepatic failures were found in 22% and 9% of patients, respectively. Quality of life seemed to be preserved. CONCLUSIONS: Neoadjuvant cisplatin/5-FU followed by postoperative i.p. FUdR/LV can be safely delivered to patients undergoing radical gastrectomy and D2 lymphadenectomy. The R0 resection and the survival rates are encouraging. An association between pathologic response and patient outcome was suggested.

Small-cell carcinoma of the gastrointestinal tract: a retrospective study of 64 cases.

Small-cell carcinoma (SmCC) of the gastrointestinal tract is a very rare and aggressive malignancy. To better define its clinicopathological features, the records of all patients with this disease seen at Memorial Sloan Kettering Cancer Center between 1980 and 2002 (n=64) were reviewed. The most common primary tumour locations were in the large bowel and oesophagus. Predisposing medical conditions for non-small-cell cancers, positive family cancer history, and metachronous tumours were common. In all, 37% had mixed tumour histology and 48% presented with extensive disease, according to the Veterans' Administration Lung Study group (VALSG) staging system used for small-cell lung cancer. Treatment outcome in limited disease (LD) suggested a role for surgery and chemotherapy. Platinum-based regimens resulted in a 50% response rate. The 2-year survival was 23% and two prognostic factors were identified, the extent of disease according to the VALSG system (P<0.01) and TNM stage (P=0.03). Anatomic location had no clinical impact. In conclusion, SmCC from various gastrointestinal sites can be viewed as one clinical entity. Mixed tumour histology is common and may affect therapy. Surgery, combined with chemotherapy, should be considered for LD. The value of the VALSG system was implied and possible differences from small-cell lung cancer were noted.