Phospholipase D activation mediates growth and migration of colon cancer cells interacting with cancer-associated fibroblasts.

Cancer-associated fibroblasts of the stroma play a major role in tumor promoting processes. In this study we evaluated the significance of Phospholipase D (PLD) enzyme activity in promoting human colon cancer malignant potency when interacting with proximal colonic fibroblasts. Human colon cancer cell lines SW480 and HCT116, and colonic fibroblasts CCD-18Co were used as an in vitro model. PLD's activity was measured in resting cancer cells and after culturing with fibroblasts and cancer-associated fibroblasts (CAFs) conditioned medium. The viability and migration level of the cancer cells alone and after co-culturing with fibroblast or CAFs conditioned medium were evaluated, with and without adding a PLD inhibitor. Exposure of colon cancer cells to CAFs conditioned medium significantly increased the level of PLD activity in the cancer cells (p<0.0001). Exposure of colon cancer to resting and activated fibroblast conditioned medium significantly enhanced the number of viable cancer cells as well as its migration level measured following 24 and 48 hours. Adding a PLD inhibitor significantly reduced the elevation of cell viability and migration of the colon cancer cells exposed to fibroblasts conditioned medium (p<0.005). In this in vitro model, inhibition of PLD significantly decreased proliferation and migration levels of colon cancer cells generated by stromal fibroblasts. This provides evidence that the PLD signaling pathway is directly involved in stroma-cancer interactions in the colon, thereby promoting cancer progression. Further research is needed in order to evaluate PLD as a target in colon cancer prevention or therapy.

Doppler-guided haemorrhoidal artery ligation in patients with Crohn's disease.

AIM: The outcome of Doppler-guided haemorrhoidal artery ligation (DGHAL) was assessed in patients with Crohn's disease (CD) suffering from grade III haemorrhoids. METHOD: A retrospective study was carried out of patients with CD and symptomatic Grade III haemorrhoids treated by DGHAL. Perioperative and follow-up data were retrieved from our database of patients undergoing DGHAL. RESULTS: The study included seven men and six women. The mean age was 34 years old. All had CD without anorectal involvement. The median duration of haemorrhoidal symptoms was 6.3 years. There was no mortality, new incontinence, faecal impaction, urinary retention, abscess formation or persistent pain following the procedure. Mean pain score based on a visual analogue scale (VAS) decreased from 2.4 at 24 h postoperatively to 1.6 on the seventh postoperative day. All patients had completely recovered by the third postoperative day. At 18 months, three (77%) of the patients were asymptomatic and three had recurrent symptoms. CONCLUSION: Doppler-guided haemorrhoidal artery ligation is safe and effective in treating Grade III haemorrhoids in patients with CD without rectal involvement.

Effects of 5-FU on DNA synthesis and cytotoxicity of human lymphocytes induced by IL-2, TGF-beta3 and PGE2.

BACKGROUND: Low 5-fluorouracil (5-FU) concentrations cause a significant increase in DNA synthesis in mitogen-activated human lymphocytes. MATERIALS AND METHODS: We explored 2.5 microM 5-FU-induced DNA synthesis by testing 5-FU activity in hypoxanthine-aminopterin-thymidine (HAT)-containing medium, and its effect on thymidylate synthase (TS) activity and CD25 expression in interleukin (IL)-2-activated human peripheral blood mononuclear cells (PBMCs) and the combined effects with prostaglandin E(2) (PGE(2)) and transforming growth factor (TGF)-beta3. RESULTS: The co-stimulatory effect of 2.5 microM 5-FU on DNA synthesis was abrogated in HAT-cultured medium. 5-FU substantially reduced TS activity by 50% in IL-2-activated PBMCs. 5-FU combined with TGF-beta3 and PGE(2) did not alter their inhibitory effects on IL-2-activated natural killer cell cytotoxicity, but substantially affected increased DNA synthesis of cells cultured in IL-2 and co-cultured with 10 ng/ml TGF-beta3 and 10 microM PGE(2). CONCLUSION: Low 5-FU concentrations increase DNA synthesis in lymphocytes and exert a co-stimulatory activity on TGF-beta3 and PGE(2) modulation of IL-2-activated lymphocytes.

Effects of intravenous patient-controlled analgesia with buprenorphine and morphine alone and in combination during the first 12 postoperative hours: a randomized, double-blind, four-arm trial in adults undergoing abdominal surgery.

BACKGROUND: Intense pain in the first 12 hours after major abdominal surgery requires the use of large amounts of analgesics, mainly opioids, which may produce undesirable effects. Buprenorphine (BUP) is not typically used intravenously in this setting, particularly in combination with morphine (MO), due to concerns that BUP might inhibit the analgesic effect of MO. OBJECTIVE: This study compared the analgesic effect of BUP and MO separately and in combination for postoperative pain control in patients undergoing abdominal surgery. METHODS: In this double-blind study, adult patients were randomized to receive 1 of 4 regimens for 12 hours: a basal BUP infusion (BUP-i) of 0.4 microg/kg/h + BUP boluses (BUP-b) of 0.15 microg/kg each; a basal MO infusion (MO-i) of 10 microg/kg/h + MO boluses (MO-b) of 5 microg/kg each; a basal BUP-i of 0.4 microg/kg/h + MO-b of 5 microg/kg each; or a basal MO-i of 10 microg/kg/h + BUP-b of 0.15 microg/kg each. Bolus doses were delivered by intravenous patient-controlled anesthesia, with a bolus lockout time of 7 minutes. Diclofenac 75 mg IM q6h was available as rescue pain medication. Every 15 minutes during the first 2 postoperative hours and hourly thereafter, patients used visual analog scales to rate their pain (from 0 = totally free of pain to 10 = unbearable pain), level of sedation (from 1 = totally awake to 10 = heavily sedated), and satisfaction with treatment (from 1 = totally unsatisfied to 10 = fully satisfied). Blood pressure, heart rate, respiration rate, and arterial blood oxygen saturation (SpO(2)) were monitored, and adverse effects reported by patients or noted by clinicians were recorded at the same times. Study end points included total opioid consumption (infusion + boluses), demand:delivery ratio, and use of rescue medication. RESULTS: One hundred twenty patients (63 men, 57 women; age range, 21-80 years; weight range, 40-120 kg) were included in the study. Seventy-four percent had other mild, treated diseases (American Society of Anesthesiologists physical class 2). Pain visual analog scale ratings were comparably high in all groups during the first 2 postoperative hours. Pain intensity ratings at 3 to 12 hours were significantly lower in those who received BUP-i + BUP-b compared with the other treatment groups (P = 0.018). The drug requirement during the postoperative period decreased significantly in all groups (P = 0.01); however, there was a significant difference between groups in the demand:delivery ratio at 3 to 12 hours (group * psydrug interaction, P = 0.026). The numerically lowest demand:delivery ratio was seen with BUP-i + BUP-b. BUP-i was associated with a significantly lower heart rate compared with the other groups (P = 0.027); there were no drug-related differences in respiration rate, SpO(2), or sedation. Patients' level of satisfaction with treatment was significantly higher in the group that received BUP-i + BUP-b compared with the other 3 groups (P < 0.001). Postoperative nausea and vomiting were mild and occurred at a similar incidence in all groups, as did rescue diclofenac use. CONCLUSIONS: In these patients undergoing abdominal surgery, the BUP-i + BUP-b regimen controlled postoperative pain as well as did MO-i + MO-b or the combinations of BUP and MO. BUP neither inhibited the analgesia provided by MO nor induced undesired sedation or hemodynamic or respiratory effects.

Laparoscopic surgery for colorectal polyps.

BACKGROUND: Size, location, and type of colonic polyps may prevent colonoscopic polypectomy. Laparoscopic colectomy may serve as an optimal alternative in these patients. We assessed the perioperative outcome and the risk for cancer in patients operated on laparoscopically for colonic polyps not amenable to colonoscopic resection. METHODS: An evaluation was conducted of our prospective accumulated data of a consecutive series of patients operated on for colonic polyps. RESULTS: Sixty-four patients underwent laparoscopic resection for colonic polyps during a 6-year period. This group comprised 18% of all our laparoscopic colorectal procedures. Forty-six percent were males, mean age was 71. Most of the polyps (66%) were located on the right side. No deaths occurred. Conversion was necessary in 3 patients (4.6%). Significant complications occurred in 3 patients (4.6%). Nine patients (14%) were found to have malignancy. Three of them had lymph-node involvement. No difference existed in polyp size between malignant and nonmalignant lesions. CONCLUSIONS: Laparoscopic colectomy for endoscopic nonresectable colonic polyps is a safe, simple procedure as reflected by the low rate of conversions and complications. However, invasive cancer may be found in the final pathology following surgery. This mandates a strict adherence to surgical oncological principles. Polyp size cannot predict the risk of malignancy.

Extraluminal appendicolith: an indication for interval appendectomy with intraoperative localization and removal of that potential cause of intra-abdominal abscess.

Appendicoliths are formed by calcium salts and fecal debris layered and lodged within the appendix. They are detected on unenhanced X-rays in <10% of patients with appendicitis. When an appendicolith is found extraluminally, it is pathognomonic for perforation of the appendix. Moreover, retained appendicoliths are likely to be infected and to be the source of a postoperative intraperitoneal abscess, whereupon the only definitive treatment is surgical excision. In this paper, we describe an asymptomatic patient with evidence of an extraluminal appendicolith on computed tomography following successful conservative treatment for a periappendicular abscess. She underwent a laparoscopic interval appendectomy that included the removal of an extraluminal appendicolith and was released home on the following day. We advocate this approach in order to prevent the possible formation of an intra-abdominal abscess caused by an infected nidus.

[Anal mucinous adenocarcinoma arising in long standing fistula-in-ano].

Perianal mucinous adenocarcinoma is an unusual but well described malignancy constituting approximately 3 to 11% of all anal carcinoma. The pathology is thought to develop from one of three types, the distal part of the rectum, the mucin-secreting columnar epithelium of the anal glands, and from chronic fistula-in-ano. The association of carcinoma with anal fistula may manifest itself in several ways: a fistula may be associated with cancer elsewhere in the colon; cancer may present as a fistula; or cancer may develop in anal fistula. Mucinous adenocarcinoma of the anus supervening on a long-standing chronic anal fistula is an extremely rare disease with less then 150 cases reported in the literature, mainly single patient reports. The key to long-term survival seems to be a high index of suspicion in those patients with longstanding perianal fistula. Chemotherapy in combination with external beam radiation followed by abdomino-perineal resection seems to be the most appropriate therapy.

Effects of 5-fluorouracil on human mitogen-activated peripheral blood lymphocytes from healthy individuals.

BACKGROUND: The effect of 5-fluorouracil (5-FU) on activated lymphocytes was explored. MATERIALS AND METHODS: The in vitro effects of 5-FU on DNA synthesis in mitogen-activated lymphocytes from healthy volunteers were compared to those of the antimetabolites doxorubicin, cyclophosphamide and 6-mercaptopurine. These effects were assessed by alterations in the phenotypic profile and the percentage of cells in various phases of the cell cycle, as well as by the secretion of T helper (Th)1 and Th2 cytokines (ELISA). RESULTS: Unlike 5-FU, the other antimetabolites failed to augment DNA synthesis in activated lymphocytes. The effect of 5-FU correlated with an increase in the percentage of cells in the S-phase and caused an increased in CD4+ cells, a decrease in CD56+ cells and a shift of the cytokine secretion pattern from Th2 to Th1. CONCLUSION: 5-FU exhibited a unique effect on DNA synthesis in activated lymphocytes which was accompanied by selective effects on various lymphocyte subpopulations.

Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy in peritoneal carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis is an advanced form of cancer with poor prognosis that in the past was treated mainly palliatively. Today, the definitive approach to peritoneal surface malignancy involves peritonectomy, visceral resection and perioperative intra-abdominal hyperthermic chemotherapy. The anticipated results range from at least palliative to as far as intent to cure. Proper patient selection is mandatory. OBJECTIVES: To determine whether cytoreductive surgery and intraperitoneal hyperthermic chemotherapy can extend survival, and with minor complications only, in patients with peritoneal carcinomatosis. METHODS: Twenty-two IPHP procedures were performed in 17 patients with peritoneal carcinomatosis in our institution between 1998 and 2007: 6 had pseudomyxoma peritonei, 5 had colorectal carcinoma, 3 had ovarian cancer and 3 had mesotheliomas. All patients underwent cytoreductive surgery, leaving only residual metastasis < 1 cm in size. Intraperitoneal chemotherapy was administered through four large catheters (2F) using a closed system of two pumps, a heat exchanger and two filters. After the patient's abdominal temperature reached 41 degrees C, 30-60 mg mitomycin C was circulated intraperitoneally for 1 hour. RESULTS: The patients had a variety of anastomoses. None demonstrated anastomotic leak and none experienced major complications. Six patients had minor complications (pleural effusion, leukopenia, fever, prolonged paralytic ileus, sepsis), two of which may be attributed to chemotherapy toxicity (leukopenia). There was no perioperative mortality. Some patients have survived more than 5 years. CONCLUSIONS: IPHP is a safe treatment modality for patients with peritoneal carcinomatosis. It has an acceptable complications rate and ensures a marked improvement in survival and in the quality of life in selected patients.

Learning curve in laparoscopic colorectal surgery: our first 100 patients.

BACKGROUND: Recent data confirming the oncologic safety of laparoscopic colectomy for cancer as well as its potential benefits will likely motivate more surgeons to perform laparoscopic colorectal surgery. OBJECTIVES: To assess factors related to the learning curve of laparoscopic colorectal surgery, such as the number of operations performed, the type of procedures, major complications, and oncologic resections. METHODS: We evaluated the data of our first 100 elective laparoscopic colorectal operations performed during a 2 year period and compared the first 50 cases with the following 50. RESULTS: The mean age of the study population was 66 years and 49% were males. Indications included cancer, polyps, diverticular disease, Crohn's disease, and others, in 50%, 23%, 13%, 7% and 7% respectively. Mean operative time was 170 minutes. One patient died (massive pulmonary embolism). Significant surgical complications occurred in 10 patients (10%). Hospital stay averaged 8 days. Comparison of the first 50 procedures with the next 50 revealed a significant decrease in major surgical complications (20% vs. 0%). Mean operative time decreased from 180 to 160 minutes and hospital stay from 8.6 to 7.2 days. There was no difference in conversion rate and mean number of harvested nodes in both groups. Residents performed 8% of the operations in the first 50 cases compared with 20% in the second 50 cases. Right colectomies had shorter operative times and fewer conversions. CONCLUSIONS: There was a significant decrease in major complications after the first 50 laparoscopic colorectal procedures. Adequate oncologic resections may be achieved early in the learning curve. Right colectomies are less difficult to perform and are recommended as initial procedures.

Multilocular flank abscess due to stone migration following laparoscopic cholecystectomy with spillage of gallstones.

We report a case of a patient who presented with a large flank abscess 18 months after laparoscopic cholecystectomy. The patient underwent repeated percutaneous drainage but the abscess recurred. Further evaluation with ultrasound revealed subcutaneous tracks from the flank leading to the abdominal cavity and suspected stones in one of the tracks. Laparoscopy revealed dense adhesions at the level of the right gutter leading to a retroperitoneal track heading over to the flank. The tracks were partially opened, debrided, and two gallstones were retrieved from one of the retroperitoneal tracks. The patient's recovery was uneventful. This case demonstrates the potential migration of dropped gallstones to extraperitoneal sites leading to infectious complications. Careful dissection of the gallbladder with an attempt not to rupture it is important in order to prevent this complication. Once rupture does occur, efforts should be made to retrieve dropped stones from the peritoneal cavity. Patients presenting with intra- or extraperitoneal abscesses following laparoscopic cholecystectomy and no obvious source of infection should be evaluated for dropped stones.

First 100 cases with Doppler-guided hemorrhoidal artery ligation.

PURPOSE: This study was designed to examine the benefits of a Doppler-guided hemorrhoidal artery ligation technique in terms of surgical outcome, functional recovery, and postoperative pain. METHODS: Using local, regional, or general anesthesia, 100 patients with symptomatic Grades II or III hemorrhoids underwent sonographic identification and suture ligation of six to eight terminal branches of the superior rectal artery above the dentate line. Visual Analog Scales were used for postoperative pain scoring. Surgical and functional outcomes were assessed at 6 weeks and 3, 6, and 12 months after surgery. RESULTS: There were 42 (42 percent) males and 58 (58 percent) females (mean age, 42 years; median duration of symptoms, 6.3 years). The mean operative time was 19 minutes. Local anal block combined with intravenous sedation (n = 93) or general or spinal (n = 7) anesthesia was used. Only five were hospitalized overnight. There was no urinary retention, bleeding, or mortality in the immediate postoperative course. The mean pain score decreased from 2.1 at two hours postoperative to 1.3 on the first postoperative day. All patients had a complete functional recovery by the third postoperative day. Ninety-four patients remained asymptomatic after a mean follow-up of six months: four patients required additional surgical excision, and two required rubber band ligations for persistent bleeding. On follow-up, there was no report of incontinence to gas or feces, fecal impaction, or persistent pain. CONCLUSIONS: Our experience indicates that Doppler-guided hemorrhoidal artery ligation is safe and effective and can be performed as an outpatient procedure with local or regional anesthesia and with minimal postoperative pain and early recovery.

[Proctalgia Fugax--what's new over the last 100 years?].

Proctalgia Fugax is a benign, self-limiting disease characterized by episodes of intense pain in the anorectal area occurring at infrequent intervals. It is common, but most suffers do not seek medical advice. Although its classical symptomatology was describe more than a century ago, the etiology is unclear. Theories regarding the etiology have centered on alteration in the internal anal sphincter function and morphology. For most patients after gathering a detailed history, reassurance and warm baths will suffice. In persistent cases therapies that induce internal anal sphincter relaxation are the main treatment modalities.

Photodynamic therapy for Bowen's disease and squamous cell carcinoma of the skin.

BACKGROUND: Photodynamic therapy involves the activation by visible light of a previously administered photosensitizing agent in order to cause tumor necrosis. Skin tumors can be treated with topical photosensitizers and thus avoiding systemic side effects. In this study we evaluate the immediate and long-term effects of photodynamic therapy (PDT), using aminolevulinic acid (ALA) as a photosensitizer and a non-laser light source, on Bowen's disease (intra-epithelial squamous cell carcinoma) and on frank squamous cell carcinoma (SCC) of the skin. METHODS: ALA in cream form (20%) was topically applied on biopsy-proven Bowen's disease or SCC of the skin. The lesions were covered with occlusive and light-shielding dressing. Sixteen hours later, they were submitted to a 10-min light session using Versa-Light™, a non-laser light source (spectral output of 580-720nm and 1250-1600nm, 100J/cm(2)). The initial evaluation was done 21 days post-treatment and every 3m thereafter. Patients that did not respond to treatment after two to three sessions were referred to surgery. RESULTS: Forty Bowen's disease lesions (24 patients) and 43 SCC lesions (18 patients) underwent treatment. Median follow-up was 21±8m. No patient had any remarkable side effects. Thirty-four Bowen's disease (85%) lesions completely responded as did 32 SCC lesions (74%). CONCLUSIONS: Our findings showed that PDT is highly effective in treating Bowen's disease and SCC lesions and can be used as a first treatment modality in so far as its use does not preclude the subsequent surgery recommended for the small percentage of failures.

Lymphoscintigraphy for sentinel node mapping using a hybrid SPECT/CT system.

UNLABELLED: Lymphoscintigraphy is performed before sentinel node (SN) biopsy for SN mapping. It is of clinical importance mainly if the tumor is located in body parts with ambiguous lymph node drainage. The purpose of this study was to assess the clinical benefit of fused SPECT/CT images to planar images for SN mapping. METHODS: Thirty-four consecutive patients with cutaneous malignant melanoma (n = 28) and squamous cell carcinoma (n = 6) and scheduled for SN biopsy were enrolled. Primary tumors were located in the trunk (n = 12), in the extremities (n = 12), in the head and neck (n = 9), and in the penis (n = 1). Scintigraphy was performed using a hybrid gamma-camera/low-dose CT system. Planar images and fused SPECT/CT images were interpreted separately. RESULTS: SPECT/CT identified multiple draining basins in 6 of 12 patients (50%) with trunk melanoma and in 3 of 9 patients (33%) with head and neck melanoma or mucosal tumor. In 9 of 21 patients (43%) with a primary tumor located in the head and neck or trunk region, SPECT/CT-fused images identified SNs that were missed on planar images, 2 of which were involved with tumor. Three of the 9 nodes were located close to the injection site and were hidden by its scattered radiation, and 2 were in-transit nodes. Another 4 nodes, identified on fused images only, were located in an additional basin to those identified on planar images. Fused images were of no added value either in patients with limb melanoma or in a patient with a penile melanoma. CONCLUSION: SPECT/CT SN mapping provides additional data that are of clinical relevance to SN biopsy in patients with trunk or head and neck melanoma and in patients with mucosal head and neck tumor.

Detection of hepatocyte growth factor/scatter factor receptor (c-Met) in axillary drainage after operations for breast cancer using reverse transcriptase-polymerase chain reaction.

BACKGROUND: The diverse biological effects of hepatocyte growth factor/scatter factor (HGF/SF) are mediated by c-Met, which is preferentially expressed on epithelial cells. Met signaling has a role in normal cellular activities, and may be associated with the development and progression of malignant processes. In this study we examined whether Met can be detected in the axillary drainage from patients who underwent conservative operations for breast cancer, and its prognostic significance. METHODS: Thirty-one consecutive patients with invasive ductal carcinoma of the breast suitable for breast-conserving treatment were studied. The output of the drain that had been placed in the axilla during the operation was collected, and the presence of Met and beta-actin were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) assays. The data were compared with the pathological features of the tumor and the axillary lymph nodes, and with the estrogen receptor and progesterone receptor status. RESULTS: RT-PCR of the axillary lymphatic drainage was positive for Met in 23 (74.2%) of the patients. Positive assays were correlated with increasing tumor size and grade, with capillary and lymphatic invasion, and with lymph node metastasis (P < 0.02, for all comparisons). All 12 patients with axillary lymph node metastases had positive assays for Met, compared with 57.9% of patients without lymph node metastases. All five patients with tumor involvement in the margins of the resection had positive assays for Met in their lymphatic fluid, compared with 18 of 26 positive assays (69.2%) for patients without involved margins (P < 0.04). Finally, Met showed negative correlations with positivity for estrogen receptor and progesterone receptor (P < 0.02). CONCLUSION: Met can be detected in the axillary fluids of patients with breast cancer and its expression in the axillary drainage may have potential as a prognostic factor. This finding might be relevant to therapeutic considerations, because a positive assay for Met in histologically node-negative patients might point to the need to search for node microinvasion or involvement of the excision margins with tumor.

Free perforation in Crohn's disease.

BACKGROUND: Free bowel perforation is one of the indications for emergency surgery in Crohn's disease. It is generally accepted that 1-3% of patients with Crohn's disease will present with a free perforation initially or eventually in their disease course. OBJECTIVES: To evaluate the incidence and treatment results of free perforation in patients with Crohn's disease and, based on our experience, to suggest recommendations. METHODS: Between 1987 and 1996, 160 patients with Crohn's disease were treated in our department and were followed for a mean period of 5 years. RESULTS: Of the 83 patients (52%) requiring surgical intervention, 13 (15.6%) were operated due to free perforation. The mean age of the perforated CD was 33 +/- 12 years and the mean duration of symptoms prior to surgery was 6 years. The location of the free perforation was the terminal ileum in 10 patients, the mid-ileum in 2 patients, and the left colon in 1 patient. Surgical treatment included 10 ileocecectomies, 2 segmental resections of small bowel, and resection of left colon with transverse colostomy and mucus fistula in one patient. There was no operative mortality. Postoperative hospital stay was 21 +/- 12 days (range 8-55 days). All patients were followed for 10-120 months (mean 58.0 +/- 36.7). Six patients (42%) required a second operation during the follow-up period. CONCLUSION: The incidence of free perforation in Crohn's disease in our experience was 15.6%. We raise the question whether surgery should be offered earlier to Crohn's disease patients in order to lower the incidence of free perforation.

Isolated rib fractures in elderly patients: mortality and morbidity.

OBJECTIVES: To describe the management, morbidity and mortality seen with isolated rib fractures in elderly patients and assess the need for hospitalization. DESIGN: A case series. SETTING: A tertiary care centre in Tel Aviv. METHODS: Hospital records of 77 elderly patients (age 65 yr and older) admitted with isolated rib fractures were reviewed over a 9-year period. MAIN OUTCOME MEASURES: Demographic, medical and hospitalization data, blood hemoglobin and oxygen saturation levels. RESULTS: The number of fractured ribs was found to correlate with the morbidity (p = 0.027) and mortality (p = 0.006). There were no significant differences in these rates with respect to comorbidity except for diabetes (higher morbidity) and congestive heart failure (higher mortality). Twenty-eight patients (36%) had pulmonary complications and 1 had cardiac complications. Pulmonary complications were fatal in 6 patients (7.8%). Multivariate analysis of the factors related to morbidity demonstrated that only oxygen saturation (p = 0.0009) and diabetes (p = 0.03) correlated significantly. CONCLUSIONS: In spite of significant morbidity and mortality in elderly patients with isolated rib fractures, prediction of the prognosis for these patients is presently not possible. Admission for observation and treatment is therefore justified and beneficial.

Human colon adenocarcinoma in the SCID/CB6 radiation chimera is susceptible to adoptive transfer of allogeneic human peripheral blood mononuclear cells.

The aim of this study was to develop a murine model of human colon carcinoma (hCC) and to ascertain the potential of cellular immunotherapy in this model. Fragments of hCC obtained at surgery from 6 patients were transplanted under the kidney capsule of lethally irradiated CB6 mice radioprotected with severe combined immunodeficient (SCID) mice bone marrow. Tumor xenografts conserved their malignant behavior in the new environment, invading the mouse kidney parenchyma and expanding into the peritoneal cavity and adjacent tissues. Their growth was typically exponential, and they expanded to dimensions that allowed their subsequent fragmentation and passage to further preconditioned mice. Human carcinoembryonic antigen (hCEA) was detected on the implanted tumor and at occasionally spontaneous lung metastases. Most significantly, high levels of this tumor marker were detected in the sera of tumor-bearing mice, providing a useful tool, which allowed long-term experiments, monitoring of tumor progression, and its response to some treatment modalities. For instance, complete resection of the transplanted tumors, by means of nephrectomy, resulted in the disappearance of hCEA from mice sera within 2 weeks. Similarly, adoptive transfer of allogeneic human peripheral blood mononuclear cells (PBMC) into the peritoneum of tumor-bearing mice, resulted in their rapid engraftment, infiltration of tumor mass, and a significant drop of hCEA levels in mice serum, accounting for inhibition of tumor growth. We suggest that this novel model of human colon carcinoma affords the opportunity for in vivo evaluation of different preclinical treatment modalities, particularly, those involving manipulation with immune effector cells.

A non-laser light source for photodynamic therapy: in vitro effects on normal and malignant cells.

AIM: Photodynamic therapy (PDT) involves the use of photosensitizing drugs combined with light to treat tumors. Laser systems, the current source of light for PDT, have several inherent drawbacks: the spectrum is essentially monochromatic which may be problematic for second generation photosensitizers, the systems are bulky and nearly impossible to move between hospital locations and require complicated electrical and cooling installations, the cost of a typical system is enormous, and its maintenance and operation require highly trained personnel. We now introduce a new non-laser light system, Versa-Light, which appears to work as effectively and has none of the above drawbacks. METHODS: A series of in vitro studies were performed using various murine and human normal and cancer cells which underwent PDT using aluminum phthalocyanine (AlPcS4) as a photosensitizer and Versa-Light as the light source. RESULTS: PDT of cancer cells at light energy levels of 50, 100 and 200 j/cm2 significantly decreased cell viability. PDT also decreased cell viability of normal murine splenocytes and normal human lymphocytes, but to a lesser extent. The observed significant hyperthermia was light dose-dependent. CONCLUSIONS: We believe that Versa-Light can replace laser systems as an enhanced light source for PDT. Further in vitro and pre-clinical studies are in progress.