Survival of pedicled pectoralis major flap after secondary myectomy of muscle pedicle including transection of thoracoacromial vessels: does the flap remain dependent on its dominant pedicle?

BACKGROUND: The pectoralis major (PM) flap is a frequently used flap for head and neck reconstructions. The muscle is easy to transpose on the dominant thoracoacromial bundle and has relative low morbidity. Some patients complain of pain and restricted neck motion after PM flap transposition. Secondary contraction due to radiotherapy, atrophy or insufficient denervation during transposition can be causes for this function deficit. In a series of ten patients we analysed the causes of this contraction and show the results of secondary myectomy of the PM pedicle with transection of the thoracoacromial bundle. METHODS: Between 2000 and 2008 a total of 12 myectomies were performed in ten patients. Indication, radiation, denervation of the PM, and follow-up before and after myectomy were analysed retrospectively. RESULTS: Indications for PM flap reconstruction were floor of mouth malignancy, covering of neck wound, (osteo)radionecrosis, and larynx fistula. In six cases the PM muscle was denervated primarily. Seven patients received preoperative radiation on the wound bed. The interval between PM flap reconstruction and myectomy ranged from five months to seven years. There was no (partial) necrosis of the PM flaps after myectomy (median follow-up 15 months). All patients were satisfied with the result of myectomy. CONCLUSION: Myectomy of the PM pedicle with transection of the thoracoacromial bundle after muscle transposition is an effective method to treat secondary neck contracture. The procedure is safe, regardless of pre- or postoperative radiotherapy. Our results question the general accepted theory that muscle flaps remain dependent on their dominant pedicle.

The post-surgical inflammatory response provokes enhanced tumour recurrence: a crucial role for neutrophils.

BACKGROUND/AIMS: Peritoneal trauma activates a cascade of peritoneal defence mechanisms responsible for postoperative intra-abdominal tumour recurrence. After peritoneal trauma, inflammatory cells and soluble factors are present in the abdominal cavity and can be captured in lavage fluids. The present study evaluated which component enhances intra-abdominal tumour recurrence. Furthermore, we evaluated which inflammatory cells are present and studied the influence of anti-neutrophil serum (ANS) on peritoneal tumour recurrence. METHODS: In a peritoneal trauma model in rats, postoperative lavage fluids were collected and separated into cellular and supernatant components. Both components were injected in naïve rats together with CC531s colon carcinoma cells. In a second experiment, rats were treated with one or three doses of ANS. RESULTS: Intraperitoneal injection of naïve recipients with inflammatory cells or supernatant resulted in significant tumour recurrence. Severe peritoneal trauma provoked significant intra-abdominal neutrophil influx which could be prevented by ANS. Treatment with one dose did not affect blood cell counts and significantly reduced tumour recurrence. Treatment with three doses of ANS decreased blood lymphocytes, monocytes, and neutrophils and induced tumour load. CONCLUSIONS: Neutrophils play a crucial role in postoperative adhesion and growth of spilled tumour cells after surgical peritoneal trauma. Prevention of peritoneal neutrophil influx reduces local tumour recurrence.

Inflammatory cytokines stimulate the adhesion of colon carcinoma cells to mesothelial monolayers.

Surgical handling of the peritoneum causes an inflammatory reaction, during which a potentially lethal cocktail of active mediators is produced, including cytokines and growth factors. The aim of this study was to investigate the effects of inflammatory cytokines on the interaction between tumor and mesothelial cells. Tumor cell adhesion to a mesothelial monolayer was assessed after preincubation of the mesothelium with interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. Preincubation of the mesothelial monolayer with IL-1beta or TNF-alpha resulted in enhanced tumor cell adhesion of Caco2 and HT29 colon carcinoma cells. The amount of stimulation for the Caco2 cells was between 20% and 40% and for HT29 cells between 30% and 70%. Blocking experiments with anti-IL-1beta and anti-TNF-alpha resulted in significant inhibition of the cytokine-stimulated tumor cell adhesion. The presented results prove that IL-1beta and TNF-alpha are significant stimulating factors in tumor cell adhesion in vitro and may therefore account for tumor recurrence to the peritoneum in vivo.

Glove powder promotes adhesion formation and facilitates tumour cell adhesion and growth.

BACKGROUND: The presence of foreign material in the abdominal cavity irritates the peritoneal surface, leading to an inflammatory response. This defensive mechanism can provoke adhesion formation. The same peritoneal defence cascade is thought to play a role in the process of intra-abdominal tumour recurrence. The aim of this study was to evaluate whether glove powder produced peritoneal adhesions in a rat adhesion model and whether it promoted intra-abdominal tumour recurrence in a rat tumour cell adhesion and growth model. METHODS: A reproducible model that allowed semiquantitative scoring of adhesion formation or tumour load was used in three different groups of rats. One group was treated by intra-abdominal application of powder obtained from starch-powdered gloves, one by application of pure starch and in one group no powder was used. RESULTS: Application of glove powder or pure starch on minimally and severely traumatized peritoneum gave rise to significantly greater adhesion formation and intra-abdominal tumour load than peritoneal trauma alone (both P < 0.001). CONCLUSION: Starch-induced peritoneal trauma leads not only to more adhesion formation but also to increased adhesion and growth of tumour cells. Since good powder-free alternatives are available there is no longer any justification for the use of powdered gloves during intra-abdominal surgery.

Effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum.

In this experimental study, the effect of inflammatory cytokines and growth factors on tumour cell adhesion to the peritoneum was investigated. A reproducible in vitro assay was developed to study the adhesion of CC531 colon carcinoma cells to an autologous monolayer of rat mesothelial cells. Tumour cell adhesion to mesothelium pre-incubated with interleukin-1beta (IL-1beta) and epidermal growth factor (EGF) resulted in at least 60% more tumour cell adhesion at maximal stimulation (p

Scavenging of reactive oxygen species leads to diminished peritoneal tumor recurrence.

Previously, we demonstrated that RBCs inhibit the recurrence of perioperatively spilled tumor cells. The aim of this study was to identify on which RBC component(s) the inhibitory effect is based. By using a cell-seeding model in rats, the effect of RBC-related antioxidant scavengers [hemoglobin, catalase, and superoxide dismutase (SOD)] on peritoneal tumor recurrence was investigated. i.p. injection of hemoglobin caused 45% more tumor load (P < 0.0001). At least 40% inhibition of tumor recurrence was achieved with the use of catalase or SOD (P < 0.05). Combining SOD and catalase did not lead to additional inhibition of tumor recurrence. Inhibition of the overwhelming oxidative potential after surgical peritoneal trauma with the use of scavengers may lead to interesting new approaches for diminishing peritoneal tumor recurrence.

Hyaluronate-based coating solution for prevention of surgical adhesions has no major effect on adhesion and growth of intraperitoneal tumour cells.

OBJECTIVE: To find out whether the perioperative use of a solution containing hyaluronic acid (HA, Sepracoat) might affect the adhesion of tumour cells. DESIGN: Laboratory studies in vitro and in two experiments in rats. SETTING: Teaching hospital, The Netherlands. SUBJECTS: 27 female inbred WAG rats. INTERVENTIONS: Mesothelial cells were cultured in monolayers and the adhesion of CC-531 colonic carcinoma cells was assessed with and without Sepracoat. Uterine horn experiment: after laparotomy Sepracoat 3 ml (n = 5) or phosphate buffered saline (PBS) (n = 4) were instilled in rats; the right uterine horn was abraided with gauze, and the left was left untouched; CC-531 cells were seeded intraperitoneally; and the tumour load at 8 different sites was scored after 3 weeks. Laparotomy model: after laparotomy Sepracoat and PBS were instilled (n = 9 rats in each group), CC-531 cells were seeded, and the wound was closed; the tumour load was scored after 3 weeks. RESULTS: Sepracoat had a small but significant inhibitory effect on the adhesion of CC-531 cells in vitro. However, we were unable to repeat this effect in either rat experiment. CONCLUSION: Sepracoat may inhibit adhesion of tumour cells to the mesothelium but it had no appreciable effect on intra-abdominal tumour growth in this dose in either experiment in rats.

Red blood cells inhibit tumour cell adhesion to the peritoneum.

BACKGROUND: Perioperative blood transfusion has been associated with increased tumour recurrence and poor prognosis in colorectal cancer. Blood loss in the peritoneal cavity might be a tumour-promoting factor for local recurrence. The aim of this study was to investigate whether blood in the peritoneal cavity affects local tumour recurrence. METHODS: In an established in vivo rat model the effect of 1.5 ml syngeneic whole blood on tumour cell adhesion and tumour growth was investigated. In the same model the effect of 1.5 ml pure red blood cell (RBC) concentrate and 1.5 ml RBC-derived substances on tumour cell adhesion was studied. In an established in vitro model the effect of increasing numbers of RBCs (0-250 bx 10(6)) on tumour cell adhesion and tumour growth was assessed. RESULTS: Both the presence of blood and RBC concentrate in the peritoneal cavity prevented tumour cell adhesion in vivo (overall P

Paracrine interactions between mesothelial and colon-carcinoma cells in a rat model.

This study used a co-culture system with Transwell tissue-culture inserts to investigate the role of primary cultures of rat peritoneal mesothelial cells on the proliferation of rat colon-carcinoma cells (CC531 cells). Mesothelial cells significantly inhibited the growth of CC531 cells, while, conversely, CC531 cells stimulated the growth of mesothelial cells. Receptor-binding studies demonstrated the presence of high-affinity IGF-I receptors on the mesothelial and CC531 cells. Both cell types also produced IGF-I, as measured by radioimmunoassay. IGF-I stimulated DNA synthesis in mesothelial cells, but had no effect on the growth of CC531 cells. In co-culture, it was found that IGF-I potentiated the inhibitory effect of mesothelial cells on CC531 cells. The effect of IGF-I on mesothelial-cell proliferation was additive to the stimulatory effect of CC531 cells. TGF-beta had no effect on the growth of the CC531 cells, suggesting that this growth (-inhibitory) factor is not involved in the inhibitory effect of mesothelial cells on CC531 cell growth. The study provides evidence for the existence of a paracrine loop between mesothelial and colon-carcinoma cells, giving more insight into the basic cellular mechanisms that may modulate the growth of intraperitoneal colon carcinoma. Inhibition of CC531-cell proliferation by rat mesothelial cells might explain the earlier finding that tumour cells grow poorly in a surgically uncompromised abdomen.