levoleucovorin and Carcinoid-Tumor

A rare appendiceal malignancy is characterized by both glandular and neuroendocrine histology. It often presents with dissemination of the perforated tumor to peritoneal surfaces. Current treatments involve systemic chemotherapy, cytoreductive surgery and perioperative intraperitoneal chemotherapy.. The impact of clinical, histological and treatment-related characteristics on survival were evaluated and subjected to univariate statistical analyses. All patients had stage IV disease and were treated by a uniform treatment strategy. Survival was determined from onset of disease until death or most recent follow-up.. There were 47 patients available for study of whom 17 were male. Median age was 48 with a range of 27-65. None or a single symptom vs. 2 or more symptoms had a significant effect on survival. Median survival of the entire cohort was 45 months and 34.88% and 8.72% of patients survived 5 and 10 years, respectively. The use of neoadjuvant chemotherapy showed no impact on survival. Patients with a peritoneal cancer index (PCI) of 0-20 as compared to PCI > 20 survived longer (p = 0.012). The survival of patients able to have a complete resection as compared to an incomplete resection of disease was significant (p = 0.0087). The type of perioperative chemotherapy did not alter survival.. These data show that patients with a lesser extent of disease with a complete cytoreduction had an improved prognosis. No benefit from systemic or perioperative regional chemotherapy was apparent. With long-term follow-up, patients with the combined glandular and neuroendocrine histology exhibiting peritoneal metastases have a guarded prognosis.

Topics: Adenocarcinoma; Administration, Intravenous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Carcinoid Tumor; Cytoreduction Surgical Procedures; Doxorubicin; Female; Fluorouracil; Humans; Hyperthermic Intraperitoneal Chemotherapy; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Mitomycin; Neoadjuvant Therapy; Neoplasm Staging; Neoplasm, Residual; Neoplasms, Complex and Mixed; Neuroendocrine Tumors; Perioperative Period; Peritoneal Neoplasms; Prognosis; Survival Rate; Symptom Assessment

Chemotherapy of neuroendocrine tumors must be improved. The most widely used regimen, which combines streptozotocin with fluorouracil, commonly obtains poor results. The best response rate that has been reported for carcinoid tumors is 33%. From July 1991 through September 1994, 18 patients who had advanced neuroendocrine tumors-including nine carcinoid tumors, seven neuroendocrine tumors of unknown primary site, one insulinoma, and one paraganglioma-were treated with a regimen of dacarbazine, 400 mg/m2/day, plus fluorouracil, 1 g/m2/day, with leucovorin, 200 mg/m2/day, for 2 days every 21 days (DTIC-LVFU2 protocol). The results were assessed according to the World Health Organization criteria of toxicity and response. Toxicity was moderate. The most severe side effects were grade 3 vomiting in two patients, grade 3 leukopenia in three patients, and grade 3 mucositis in one patient. The overall response rate was 27%, with only one partial response for carcinoid tumors but one complete and three partial responses for the other tumor types. Efficacy was insufficient in patients who had carcinoid tumors but the combination of dacarbazine with fluorouracil and leucovorin could be an effective regimen for the treatment of neuroendocrine tumors of unknown primary site.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Dacarbazine; Female; Fluorouracil; Humans; Leucovorin; Leukopenia; Male; Middle Aged; Nausea; Neoplasms, Unknown Primary; Neuroendocrine Tumors; Survival Rate

A 67-year-old man presented with abdominal distention and vomiting.Computed tomography revealed bowel obstruction due to a cecal tumor.We performed laparoscopic ileocecal resection after decompression with an ileus tube. Intraoperative findings included multiple disseminated nodules on the mesenterium surrounding the cecal tumor.The histopathologic diagnosis was poorly differentiated adenocarcinoma, which consisted of glandular proliferation of atypical epithelial cells and dispersed infiltration of goblet cells. Immunohistochemistry showed positively stained neuroendocrine markers, such as CD56, chromogranin, and synaptophysin.The patient was diagnosed with goblet cell carcinoid of the appendix and treated with combination chemotherapy of bevacizumab, fluorouracil, folinic acid, and oxaliplatin.He remained free from progression for over 1 and half years with this treatment.Subsequent chemotherapy was ineffective, and he passed away.There is no established chemotherapy regimen for goblet cell carcinoid, which has the aspects of both adenocarcinoma and neuroendocrine tumors.However, the present case suggested the efficacy of the mFOLFOX6 regimen in combination with bevacizumab for appendiceal goblet cell carcinoid.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Appendix; Bevacizumab; Carcinoid Tumor; Fluorouracil; Humans; Leucovorin; Male; Organoplatinum Compounds

Adenocarcinoma ex-goblet cell carcinoids (AGCCs) are rare appendiceal tumors with mixed neuroendocrine and glandular features. They tend to behave more aggressively than typical carcinoid tumors, affect younger patients, and have a greater predilection for spreading to the peritoneum. Outcomes of AGCC patients treated with chemotherapy, extrapolated from colon cancer regimens, in the adjuvant or metastatic setting have not been explicitly reported. We sought to explore outcomes of AGCC patients with either local disease treated with adjuvant FOLFOX or metastatic disease treated with FOLFOX/FOLFIRI post-cytoreductive debulking (or CRS plus HIPEC in the peritoneal-limited setting).. We performed a single-institution retrospective analysis of 23 pathologically identified AGCC patients from Vanderbilt University Medical Center treated with chemotherapy in either the adjuvant or metastatic settings. Each patient's tumor was categorized as group B or group C based on the criteria from Tang et al. Median progression-free survival (PFS) or disease-free survival (DFS) (in the curative setting) and overall survival (OS) were determined for each patient and specified patient subgroup.. AGCC patients who were treated with FOLFOX chemotherapy in the adjuvant setting or FOLFOX/FOLFIRI in the metastatic setting experienced prolonged PFS, DFS, and OS. Five patients with peritoneal-limited disease treated with CRS plus HIPEC have not yet reached median PFS or OS. While small sample size, patient selection, and retrospective nature limit the generalizability of findings from our analysis, the efficacy signals we observed suggest prospective evaluation with chemotherapy and CRS plus HIPEC is warranted in AGCC patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Camptothecin; Carcinoid Tumor; Chemotherapy, Adjuvant; Cytoreduction Surgical Procedures; Disease-Free Survival; Female; Fluorouracil; Follow-Up Studies; Goblet Cells; Humans; Hyperthermia, Induced; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Peritoneal Neoplasms; Progression-Free Survival; Retrospective Studies

The aim of this retrospective study was to analyse the efficacy of gemcitabine-oxaliplatin (gemox) or 5-fluorouracil-oxaliplatin (folfox) in the treatment of metastatic pulmonary carcinoid tumors.. 45 patients were included in two tertiary referral centers between January 1999 and January 2013. Typical, atypical carcinoids or not otherwise specified carcinoids were diagnosed according to WHO criteria in 19%, 57%, and 24% of cases by two expert pathologists. Patients had synchronous (38%) or metachronous (62%) metastastic disease (median of 2 (1-5) metastatic sites). Seventy-nine percent had progressive disease before start of chemotherapy. Treatment consisted of: gemcitabine 1000mg/m(2) and oxaliplatin 100mg/m(2) every 2 weeks (gemox regimen, n=24) or 5-fluorouracil (5-FU) (400mg/m(2) in bolus injection and 5-FU 2400mg/m(2) in 46h-infusion) and oxaliplatin 85mg/m(2) (folfox regimen, n=21) every 2 weeks. Tumor response was assessed according to RECIST criteria every 8-12 weeks. Progression free survival and overall survival were assessed using Kaplan Meier curves.. Patients received oxaliplatin-based chemotherapy in first-line (20%), second-line (33%), or post-second-line (47%) systemic treatment. The median number of cycles was 8 (1-12). Nine (20%) stopped oxaliplatin before 8 cycles because of toxicity. Nine patients (20%) had a partial response and 29 (64%) had stable disease. Median progression free survival (PFS) was 15 (6-25) months. Median overall survival (OS) was 34 (21-49) months. No significant difference was observed in response and PFS between either regimens.. Our results suggest that either gemcitabine-oxaliplatin or 5-fluorouracil-oxaliplatin combinations are attractive chemotherapy regimen in metastatic pulmonary carcinoid tumors.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Deoxycytidine; Disease-Free Survival; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Male; Middle Aged; Organoplatinum Compounds; Retrospective Studies; Treatment Outcome

The role of SC before CRS/HIPEC for patients with PMCA is unclear. This study explores the effect of SC prior to CRS/HIPEC on overall survival (OS) in patients with PMCA.. 72 patients with recently diagnosed PMCA who underwent CRS/HIPEC were identified from a prospective database. Thirty patients had SC before CRS/HIPEC (Group 1) and 42 did not (Group 2). Patients who were referred to our center after multiple lines of SC were excluded from this analysis. OS was estimated.. Median follow-up was 3.2 years. Groups were similar regarding lymph node positivity, postoperative SC and rate of complete cytoreduction. Twenty-four (80%) patients in Group 1 and 21 (50%) in Group 2 had high grade histology (HG) (p = 0.01). OS from CRS/HIPEC at 1, 2, and 3 years was 93, 68, 51% in Group 1 and 82, 64, 60% in Group 2, respectively (p = 0.74). Among HG patients 3-year survival was 36% in the SC group vs. 35% in the group without SC (p = 0.67). The 3-year OS for patients with low grade (LG) tumors was 100% in the SC group vs. 79% in the group with no prior SC (p = 0.26). Among patients with signet ring cell (SRC) histology, 1, 2 and 3-year survival was 94, 67 and 22% in the SC group vs. 43, 14, 14% in the group with no SC, respectively (p = 0.028). There were only 6 patients with LG PMCA who received prior SC.. Preoperative SC could improve the prognosis of patients with high-grade PMCA with SRC histology.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Bevacizumab; Camptothecin; Capecitabine; Carcinoid Tumor; Carcinoma, Signet Ring Cell; Cytoreduction Surgical Procedures; Deoxycytidine; Female; Fluorouracil; Humans; Hyperthermia, Induced; Infusions, Parenteral; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms; Peritoneum; Prospective Studies; Retrospective Studies

Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located in ascending colon and rectum. A 60-year-old male patient underwent surgery after the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with a diameter of 1 cm at the site of the previously performed gastroenterostomy and dilatation of the right colic flexure, secondary to a solid obstructive mass located in the mid-portion of transverse colon. Histopathological investigation of the biopsies, taken from the gastroenterostomy site and the tumor, revealed mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and subsequently died in the fourth postoperative month. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Colon, Transverse; Colonic Neoplasms; Combined Modality Therapy; Fluorouracil; Gastroenterostomy; Humans; Intestinal Perforation; Laparotomy; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Prognosis

We report on a remarkable diagnostic work up of suspect rectal palpation results in a 54-year-old patient. According to a transrectal ultrasound-guided punch biopsy the patient was suspected of having a carcinoma of the seminal vesicles and an aggressive operational approach was considered. After a median laparotomy a generalized peritoneal carcinomatosis was found. A goblet cell carcinoid of the vermiform appendix was identified as the primary tumor. This case report deals with metastazation of a primary goblet cell carcinoma into the seminal vesicles on both sides as an extremely rare reason for suspicious rectal palpation results. The tumor valency, diagnostic work up, therapy and further differential diagnoses are described.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendectomy; Appendiceal Neoplasms; Appendix; Biomarkers, Tumor; Biopsy; Carcinoid Tumor; Combined Modality Therapy; Diagnosis, Differential; Digital Rectal Examination; Fluorouracil; Genital Neoplasms, Male; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Organoplatinum Compounds; Palliative Care; Patient Care Team; Peritoneal Neoplasms; Seminal Vesicles; Synaptophysin

Goblet cell carcinoids appear less frequently in the appendix than do other carcinoids. In the presented work a case with a goblet cell carcinoid of the appendix is described.. Routine histological and histochemical methods were employed, with a combination of histochemistry and immunohistochemistry on one section and light and electron microscopical immunohistochemisty on paraffin-embedded material, were applied to identify the type of the carcinoid and to reveal the fine structure of cell types in the tumour nests of the appendix.. During the biopsy of a patient who had undergone appendectomy, an infiltration with clusters of goblet cells in the submucosa of the appendix was found. After a second operation of right-sided hemicolectomy, similar clusters of goblet cells were detected in the muscle layers of the caecum. After 18 months the patient died from cirrhosis and had not developed metastases or any recurrence. Immunohistochemically the serotonin-, somatostatin-, chromogranin A- and synaptophysin-positive endocrine cells were basally attached to mucin-secreting cells. The combined staining revealed simultaneously present endocrine cells (chromogranin-A-positive) and mucin-secreting cells (PAS- or alcian blue-positive). The ultrastructural immunohistochemistry showed that chromogranin A-positive cells had discoid and pleomorphic granules and were located in tumour nests or as single cells in the appendiceal wall.. The combined histochemical and immunohistochemical procedure and the ultrastructural immunohistochemistry on archival material could contribute in clarifying the diagnosis of goblet cell carcinoid.

Topics: Antineoplastic Combined Chemotherapy Protocols; Appendiceal Neoplasms; Carcinoid Tumor; Fluorouracil; Humans; Immunohistochemistry; Leucovorin; Male; Microscopy; Middle Aged

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoid Tumor; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Fluorouracil; Humans; Irinotecan; Leucovorin; Middle Aged; Rectal Neoplasms; Rectum; Remission Induction; Soft Tissue Neoplasms; Time Factors; Treatment Outcome

Goblet cell carcinoid (GCC) is a rare malignant tumor with distinct histological and clinical features. Our goals were to review the surgical and chemotherapy outcomes of patients with GCC.. We performed a retrospective review of the Mayo Clinic database from 1984 to 2004 with a prospective follow-up of 57 patients with GCC.. The age at diagnosis (mean +/- SE) was 55 +/- 13 years. The most common presentations were right lower quadrant pain mimicking appendicitis (70%) and right lower quadrant or pelvic mass (25%). Only patients with T4 lesions had positive mesenteric nodes, with a frequency of 28%. Fifty percent of female patients had metastasis to the ovaries. The disease-specific 5-year survivals for stages I, II, III, and IV were 100%, 76%, 22%, and 14%, respectively; the overall mean survival was 47 +/- 3 months. All stage I patients had simple appendectomy. The overall 5-year survival rates for patients with combined stages II to IV who underwent appendectomy versus right hemicolectomy were 43% and 34%, respectively (P = .604). The corresponding survival rates for adjuvant chemotherapy versus no chemotherapy were 32% and 27%, respectively (P = .151).. The prognosis for patients with GCC tumors correlates well with the American Joint Committee on Cancer stage at initial presentation. Appendectomy alone seems adequate for stage I disease. For staging purposes, right hemicolectomy is appropriate for T4 tumors or stage II to III disease provided that it can be performed with minimal risk. Surgical debulking is a consideration but is controversial. Adjuvant chemotherapy with 5-fluorouracil and leucovorin regimen is minimally effective against GCC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Appendectomy; Appendiceal Neoplasms; Carcinoid Tumor; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Neoplasm Staging; Prognosis; Prospective Studies; Retrospective Studies; Survival Analysis; Treatment Outcome

Intersphincteric resection of low rectal tumors is a surgical technique extending rectal resection into the intersphincteric space. This procedure is performed by a synchronous abdominoperineal approach with mesorectal excision and excision of the entire or part of the internal sphincter. This study was designed to evaluate the long-term results of this method focused on continence function and oncologic results.. From 1984 to 2000, a total of 121 patients were operated on. The patients were evaluated prospectively according to a detailed preoperative and postoperative program.. One hundred seventeen patients had rectal cancers, two had dysplastic villous adenomas, and two had carcinoid tumors. Cancers were staged according to the Dukes classification (Stage A in 41 percent, Stage B in 28 percent, and Stage C in 31 percent; median distance from the anal margin, 3 (range, 1-5) cm). Postoperative complications were: one death because of pulmonary embolism, 5.1 percent developed an anastomotic fistula, one patient had a fistula to the bladder requiring reoperation, one patient with ileus needed relaparotomy as well as one for intra-abdominal hemorrhage and a small-bowel fistula. One patient developed a fistula after closing the protective colostomy. Five patients developed late strictures of the coloanal anastomosis. After a median follow-up of 72.86 months, 5.3 percent of patients developed local recurrence. The continence status was satisfactory with 16 patients (13.7 percent) showing continence for solid stool only, and 1 patient (0.8 percent) showing episodes of incontinence. A transient problem was a high stool frequency after closure of the protective stoma.. Intersphincteric resection is a valuable procedure for sphincter-saving rectal surgery. We showed that this technique has satisfactory long-term results in functional and oncologic respects. An important prerequisite is a careful preoperative evaluation of local tumor spread with rectal magnetic resonance imaging excluding infiltration of the external sphincter.

Topics: Adenocarcinoma; Adenoma, Villous; Aged; Anal Canal; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Colectomy; Fecal Incontinence; Female; Fluorouracil; Humans; Leucovorin; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Recovery of Function; Rectal Neoplasms; Treatment Outcome

Although 5-fluorouracil (5-FU)-related cardiotoxicity is well known, atrial arrhythmia, as a potentially serious complication has not been studied in detail. The aim of this study was to determine the P max and Pd in the electrocardiograms (ECG) of patients receiving 5-FU treatment.. Twenty-five patients (mean age: 62 years) receiving a 5-FU bolus plus continuous infusion with calcium leucovorin over 48 h and with normal pre-treatment cardiac physical examinations, ECG and echocardiography were enrolled. P maximum (P max), P minimum (P min) and P dispersion (Pd) (maximum minus minimum P wave duration) were measured from the 12-lead ECG at the 0th and 48th hour of the first chemotherapy cycle. Echocardiography was also obtained in all patients at the same times.. Clinical cardiotoxicity was observed in two patients. P max and Pd were both significantly longer after 5-FU treatment at the 48th hour (P < 0.001). P min did not change (P > 0.05).. Treatment with 5-FU based regimens may increase Pd and prolong the P max in cancer patients. These alterations may be predictive of patients at risk of atrial arrhythmias during 5-FU treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Carcinoma; Colorectal Neoplasms; Coronary Artery Disease; Coronary Vasospasm; Coronary Vessels; Dose-Response Relationship, Drug; Drug Administration Schedule; Echocardiography; Electrocardiography; Female; Fluorouracil; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin; Male; Stomach Neoplasms; Time Factors

Gastrointestinal carcinoid tumors are often associated with other tumors, particularly colon adenocarcinomas; but the association between carcinoid tumors and hereditary nonpolyposis colorectal cancer (HNPCC) syndrome has not yet been explored. We report an unusual case of a 28-year-old woman with HNPCC who underwent surgery for a transverse colon adenocarcinoma in whom an appendix carcinoid tumor was incidentally found. To assess whether the carcinoid tumor displayed the characteristic molecular features of HNPCC tumors, we investigated the expression of mismatch-repair (MMR) proteins and microsatellite instability (MSI) status in both tumors. Both tumors demonstrated normal expression of the MMR proteins hMLH1, hMSH2, hMSH6, and hPMS2. Interestingly, the adenocarcinoma exhibited an MSI phenotype but the carcinoid tumor did not, indicating that these 2 tumors arose through different molecular pathways.

Topics: Adult; Antimetabolites, Antineoplastic; Appendiceal Neoplasms; Carcinoid Tumor; Chemotherapy, Adjuvant; Colonic Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; DNA-Binding Proteins; DNA, Neoplasm; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Microsatellite Repeats; MutS Homolog 3 Protein; Treatment Outcome

A 60-year-old female presented with a one-year history of multiple enlarging tender subcutaneous nodules. Initial biopsy demonstrated a poorly differentiated adenocarcinoma. Mammography showed multiple nodular breast lesions. After the patient failed to respond to tamoxifen, a second biopsy demonstrated a metastatic carcinoid tumor. Further search revealed a single small pulmonary nodule, which on aspiration biopsy proved to be a carcinoid tumor. The patient failed to respond to treatment with streptozotocin and 5'-fluorouracil. Therapy with leucovorin calcium and 5'-fluorouracil then produced a partial response.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoid Tumor; Female; Fluorouracil; Humans; Leucovorin; Lung Neoplasms; Middle Aged; Skin Neoplasms