Anatomy and Embryology Department University of Medicine and Pharmacy Iuliu Haåieganu, Clinicilor street Peritoneal cancer final stages Napoca, Romania Received: Accepted: Rezumat Introducere: Carcinomatoza peritoneală reprezintă un stadiu avansat al cancerelor abdominale în general şi a cancerului colorectal în particular. Singurele metode de tratament disponibile la momentul actual pentru această patologie sunt chimioterapia sistemică caracter paliativ şi chirurgia citoreductivă CR asociată cu chimioterapie intraperitoneală hipertermică HIPEC.
Material şi metodă: În lucrarea de faţă am analizat prospectiv rezultatele imediate postoperatorii obţinutede către echipa noastră la primii 50 de pacienţi operaţi pentru carcinomatoză peritoneală de diferite origini. În ceea ce priveşte originea histopatologică, 30 de paciente au avut cancer ovarian; 19 pacienţi au avut carcinomatoză cu peritoneal cancer final stages colorectală sau pseudomixom peritoneal de origine apendiculară.
Nu a existat mortalitate la 30 de zile. Concluzii: Chirurgia citoreductivă urmată de chimioterapie intraperitoneală hipertermică este o procedură complexă însoţită de o incidenţă acceptabilă a complicaţiilor şi a deceselor postoperatorii, rezultatele putând fi optimizate prin management perioperator standardizat şi selecţia atentă a pacienţilor.
Rezultatele iniţiale obţinute de echipa noastră subliniază fezabilitatea acestei proceduri, cu rezultate imediate bune, obţinute ca rezultat a respectării unui protocol standardizat de selecţie a pacienţilor şi a managementului perioperator. Cuvinte cheie: carcinomatoză peritoneală, cancer colorectal, cancer ovarian, pseudomixom peritoneal, chimioterapie intraperitoneală hipertermică, rezecţii multiorgan. Abstract Introduction: Peritoneal carcinomatosis represents an advanced stage of tumor dissemination peritoneal cancer final stages abdominal cancers in general and colorectal cancer in particular.
The only therapeutic methods currently available for the treatment of this pathology are systemic chemotherapy palliative character and cytoreductive surgery CR with intraperitoneal chemotherapy.
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Material and method: In the present study we prospectively analyzed the immediate postoperative results obtained in the first 50 patients that were treated by our team for peritoneal carcinomatosis of different origin. Results: From January till Dec we evaluated 98 patients with peritoneal carcinomatosis.
In regard with the histopathological diagnosis, 30 peritoneal cancer final stages had ovarian cancer and 19 had colorectal cancer or peritoneal pseudomixoma of appendicular origin.
There was no 30 days postoperative mortality. Conclusions: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy is a complex technique accompanied by an acceptable rate of complications and postoperative deaths, the results being optimized by a standardized perioperative management and patient selection.
The initial results obtained by our team emphasize the feasibility of this procedure, with peritoneal cancer final stages good results, as a result of a standardization protocol of patient selection and perioperative care. Bartoæ et al of the cases, the recurrence will be limited to the peritoneum 1,2. For these patients, if the treatment involves only palliative systemic chemotherapy, the median survival rate will not exceed 15 months 2.
Cytoreductive surgery CR caracteristicas del virus del papiloma humano (vph) hyperthermic intraperitoneal chemotherapy HIPEC have proven their feasibility sinceperiod in which Sugarbaker has repeatedly reported favorable outcomes for patients with peritoneal pseudomixoma 3,4.
Since then, the technique has been applied with promising results for patients diagnosed with peritoneal carcinomatosis of ovarian, gastric and appendicular origin as well as for malignant peritoneal mesothelioma 2.
Starting from yearinternational guidelines recommends applying this treatment in experienced centers, on selected cases but only when a complete cytoreduction R0 can be obtained Taking into account the favorable results reported in the literature and the high incidence of advanced colorectal pathology diagnosed and treated in the "Professor Dr. Octavian Fodor" Institute of Gastroenterology and Hepatology, starting we began a selection and treatment program for patients with peritoneal carcinomatosis; all these in order to implement CR surgery and HIPEC as standard treatment in our institution 8.
Principles The Peritoneal Carcinomatosis Index PCI represents a quantification score for the extent of peritoneal neoplastic lesions, described for the first time by Sugarbaker 9. It involves the evaluation of 13 abdomino-pelvic regions central, right hypochondrium, epigastrium, left hypochondrium, left flank, right flank, right iliac fossa, pelvis, left iliac fossa, proximal jejunum, distal jejunum, proximal ileum, distal ileum and peritoneal cancer final stages scoring, depending on peritoneal cancer final stages size of the peritoneal neoplastic deposits.
Thus, the PCI can be between 0 and 39, this score being designed to predict the likelihood of a complete cytoreduction The success of cytoreduction is evaluated and graded at the end of the surgical procedure by establishing the "completeness of cytoreduction" CC score 11, Thus, we are talking about a CC-0 score in cases where there are no macroscopically visible tumoral deposits after cytoreduction.
A CC-1 peritoneal cancer final stages is given peritoneal cancer final stages nodules smaller then 2. After Kitayama et al. A CC-3 score is given in cases when the remnant tumors are bigger then 2. In the case of colorectal cancer with peritoneal carcinomatosis, a complete CR CC-0 achieved with the cost of multiorgan resections and extended peritonectomies is the only option able to provide optimal results, the CC score being the main prognostic factor Intraperitoneal chemotherapy consists of an extended lavage of the peritoneal cavity with cytotoxic drugs.
The main advantage of intraperitoneal administration of chemotherapeutic agents is the low systemic toxicity that allows prolonged exposure in higher doses of the intra-abdominal tumors with antineoplastic agents.
Regarding the temperature of intraperitoneal administration of cytotoxic agents, it has been shown that above 41 C they have selective cytotoxicity on tumor cells, activating protein degradation, inhibiting the oxidative metabolism, increasing the ph, activating the lysosomes and the cellular apoptosis. Moreover, temperatures above 41 C lead to augmentation of the cytotoxic effect of cytotoxic agents as well as increased absorption and penetration of the tumor tissue 2, The role of hyperthermia was highlighted in studies indicating the superiority of HIPEC versus early postoperative intraperitoneal chemotherapy EPIC or sequential postoperative intraperitoneal chemotherapy SPICboth normothermic lavage methods.
The peritoneal cancer final stages of Peritoneal cancer final stages have been translated through prolonged peritoneal cancer final stages with a lower rate of recurrence and postoperative complications Achieving the optimal temperature C and maintaining it are conditioned by the presence of an increased flow of the intraperitoneal lavage, which is peritoneal cancer final stages thanks to peritoneal cancer final stages devices The role of systemic chemotherapy remains particularly important, essentially contributing in papillomavirus humain remboursement the correct treatment peritoneal cancer final stages its neoadjuvant or adjuvant character, case depending.
This study was performed to evaluate the clinical risk profile of patients with ovarian tumors who were surgically treated, measuring the survival rate at 5 years. Furthermore, the surgical treatment by TNM stages was achieved, measuring the survival rate after five years of follow-up. Most of the patients with malignant disease were multiparous Moreover, from menopausal patients, the higher prevalence was seen at the group between 45 and 55 years old, not being dependent on the earlier appearance. The highest incidence of gynecological pathology was seen in women with polycystic ovaries i.
Furthermore, concomitant intraoperative administration of systemic cytotoxic agents leads to an enhancement of the cytotoxic intraperitoneal effect by reaching a bidirectional diffusion gradient. Typically, minutes before HIPEC, intravenous 5-fluorouracil and folinic acid are administrated 19, Material and Method Starting Januarywe began using this treatment on patients histopathological diagnosed with peritoneal carcinomatosis from colorectal adenocarcinoma, appendicular mucoceles, ovarian adenocarcinoma and gastric adenocarcinoma.
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To establish the opportunity for surgery, we followed a standard protocol with routine multidisciplinary meetings: surgeon, anesthesiologist, oncologist. All patients who were referred to our team were clinically and imagistically evaluated.
The investigations used to assess the extent of the neoplastic disease were thoraco-abdominal CT scan with intravenous contrast agent and PET-CT when appropriate - suspicion of distant dissemination with inconclusive CT scan result. Except for patients with peritoneal pseudomyxoma, a PCI greater peritoneal cancer final stages 20 contraindicated the surgery. The surgical procedure has also been standardized. The resection time meant the excision of all tumor deposits in block with the invaded organs multiorgan resections - MOR 12,24the goal being to obtain a CC-0 score for all patients Fig.
For this purpose, when needed, vascular or urogenital resections with consecutive reconstructions were performed.
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In order to minimize the septic risks, the sectioning of the digestive tract was done Chirurgia, 25 A. Bartoæ et al A B Figure 1. En block multiorgan resection during cytoreductive surgery from the personal archive of the authors using mechanical suture devices staplers. HIPEC time was performed using the open approach with the abdominal wall suspended by Thompson autostatic retractor: the Colosseum technique Fig.
The cytostatic drug was chosen according to the anatomopathological diagnosis and the literature recommendations. In patients with extensive digestive resections, those with gastric resections or those with poor nutritional status, jejunostomy was routinely performed. Surgeries involving recto-sigmoid resection were completed with terminal colostomy. The discharge of the patients was done Figure 2. Figure 3. Postoperative follow-up required 1-month follow-up and then from 3 to 3-month periodical examinations, including clinical examination, blood count, blood biochemistry, tumor markers CEA, CA, as appropriatequality of life questionnaires EuroQol 5-D Considering that the surgical procedure CR and the intraperitoneal chemotherapy HIPEC are similar for all of the abovementioned diagnoses the procedure generally being applied on patients with peritoneal carcinomatosiswe included in our study all the patients with this diagnosis, regardless of the origin of peritoneal cancer final stages primary tumor.
Внезапно частота вибрации под ногами явно изменилась. Движение замедлялось - в этом не было сомнения.
Thus, we included in our analysis the first 50 consecutive patients diagnosed with peritoneal carcinomatosis, following immediate postoperative outcomes.
Postoperative complications were classified using the Clavien- Dindo classification and were quantified up to 60 days postoperatively The quality of life form was completed at routine post-operative checks, according to the protocol. Peritoneal cancer final stages 15 patients, surgery was limited to exploratory laparotomy, intraoperative exploration indicating an extension of neoplastic disease that was not suitable for cytoreduction. CR and HIPEC technique have been successfully applied to 50 patients: 14 with peritoneal carcinomatosis of colorectal etiology, 5 with peritoneal pseudomyxoma of appendicular origin, 30 of ovarian origin and 1 of gastric origin.
The median age was Median testicular cancer warning signs mass index ICM was. All patients had comorbidities Table 2. The carcinomatosis index peritoneal cancer final stages between 1 and The median operating time was minutes min max Blood loss was between 0 and ml with a median peritoneal cancer final stages ml.
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Перед ним простирался весь город Диаспар, причем самые высокие здания едва доходили ему до плеча.
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Complete cytoreduction CC0 was obtained in all patients. Taking in account the Clavien-Dindo classification, 3 of the patients experienced grade IIIb complications ischemic digestive perforations and intestinal occlusion requiring surgical reintervention. One of these died 51 days postoperatively developing grade V complication. One patient developed a grade IV complication adverse effects of intraperitoneal and systemic Chirurgia, 27 A.
Требовалось постоянное умственное усилие, чтобы помнить: законы жизни и смерти были отменены создателями Диаспара. Временами Хилвару казалось, что несмотря на все окружающее оживление город наполовину пуст, ибо в нем не Он раздумывал над тем, что произойдет peritoneal cancer final stages Диаспаром теперь, по окончании долгой изоляции.
Самое лучшее, что, с точки зрения Хилвара, мог предпринять город - это уничтожить Банки Памяти, столько тысячелетий удерживавшие его в зачарованном состоянии.
Bartoæ et al Table 2. Associated diseases. No 30 days postoperative wart removal on foot surgery was recorded. One patient died 51 days after surgery, after developing late postoperative necrosis of the aponeurosis and 2 intestinal ischemic perforations, complications that led to septic and multiple organ failure.
Thus, the day mortality was 1. The median stay in the intensive care unit was of 5 days min 2 - max Median hospitalization was The median follow-up was of days. Table 3. The selection of patients who can benefit from this treatment is essential.
The patient's biological status must be acceptable, with a proper performance status. Thus, according to the Karnofski score, ideal patients should have a score between 60 and Also, patient age should be an important selection criterion. The Canadian guidelines indicate 65 years peritoneal cancer final stages 'cut off'.
Over this age, surgery is recommended only for carefully selected patients without co-morbidity, low IC and less aggressive histopathology Knowing the extent of neoplastic disease is essential in the selection of cases.
Intraoperative assessment laparoscopy or laparotomy of the extension of peritoneal carcinomatosis is the only procedure that can ultimately evaluate the opportunity and the peritoneal cancer final stages of performing a surgical procedure with a radical, oncological intend.
Thus, PCI can estimate the extent to which complete cytoreduction can be performed, with a direct impact on survival. The final assessment of PCI can be done only by laparotomy In the same idea, HIPEC prophylaxis is also under discussion in patients considered at risk T3-T4 tumorsespecially when peritoneal peritoneal cancer final stages with histopathological extemporaneous examination is positive.
This topic is highly discussed in the literature; the ongoing studies will determine whether this attitude is justified or not 38, Tumor invasion at the level of vital, unresectable structures aorta, vena cava contraindicate the surgery.
Clinical risk profile associated with ovarian cancer
The presence of hepatic metastases is a relative contraindication, segmental resections being accepted. The need for major liver resections, duodenopancrea- Chirurgia, 29 A. Bartoæ et al tectomy or pelvic exenteration will contraindicate the intervention, with rare exceptions limited disease, very good biological status, well differentiated histopathological forms 32, The histopathological origin of the tumor must be known before surgery; the biopsy can be taken by endoscopy, percutaneous ultrasound guided or laparoscopic approach.
As a guide line, the indication of CR and HIPEC in patients with poorly differentiated or undifferentiated tumors should be established with caution, in these cases the benefits being poor. By modest results, presence of signet ring cell, associated with other relative contraindications, limits the applicability of this technique Analyzing our data, we also noticed a much peritoneal cancer final stages modest outcome in relation to the presence of signet cell adenocarcinoma, the only patient that we had with this histopathology developing lymph node metastases at 6 months and died at 14 months after surgery.
Because of peritoneal cancer final stages small number of patients with this histopathological origin in our studywe were not able to draw statistical conclusions. In general, the surgery will not be performed in case of bowel occlusion, although there are reports that indicate CR and HIPEC under emergency conditions as feasible 32, The surgeon must have a good expertise in oncologic surgery, most of the time tumorresections leading to MOR, required in order to achieve R0 resection margins.
Among the postoperative complications, the infectious type ranges first Intraperitoneal chemotherapy per se can cause systemic toxicity with consecutive side effects 51, Two of the patients operated by our team developed such a complication.
As a result, the analysis of our initial experience the first 50 cases indicates a morbidity and mortality that falls within the limits reported by centers with high experience in the field.
Of course, the final validation of the results will also come with the analysis of the survival curves and the factors that influence the long outcomes, a project that is progress in our service Chirurgia, 210 Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for the Treatment of Peritoneal Carcinomatosis: Our Initial Experience Although the literature indicates the peritoneal cancer final stages of reintervention with repeated CR and HIPEC procedure for intraperitoneal tumor recurrence 54in the two cancer renal macroscopia with intraabdominal tumor recurrence, we failed to repeat the procedure due to the intense adhesion syndrome and extent of neoplastic disease.
Although highly complex procedures, indicated for a very advanced stage of neoplastic disease, postoperative controls at months have shown a surprisingly good quality of life, most patients succeeding in reintegrating themselves rapidly into the family-social environment. Future research in the field are dedicated to the improvement of the cytostatic drugs with the help of nanotechnology 55as peritoneal cancer final stages as research in the field of hyperthermia, the standardization of temperature curves and chemotherapeutic concentrations being essential 56, Stoian Raluca has the same contribution as the first author, therefore being considered main author as well.
Adrian Bartoş, Dana Bartoş, Raluca Stoian, Caius Breazu equally contributed to this article see below the contributions so for that, they are all main authors: - conception and design of the article and the acquisition of data; - drafting the article; - final approval of the version to be published. Ioana Iancu, Cristian Cioltean, Cornel Peritoneal cancer final stages had substantial contributions to conception, design of the review and acquisition of data.
Mitre Călin, Peritoneal cancer final stages Hadade, Părău Angela and Claudia Militaru had substantial contributions in regard with drafting the article and revising it critically. Conclusions The good initial results obtained after the implementation of the CR and HIPEC technique in our institution emphasize the feasibility of this procedure as a standard treatment for patients diagnosed with peritoneal peritoneal cancer final stages of colorectal, peritoneal cancer final stages and ovarian origin.
Furthermore, we consider that these results underline the fact that applying a standardized protocol in case selection, operative technique and perioperative care and working with dedicated multidisciplinary teams surgeons, ATI physician, oncologist, nursespecialized in abdominopelvic oncological surgery will lead to optimal immediate results, even before the completeness of the literature stated learning curve of CR and HIPEC.
Part of the data presented in this article is part of the first author's PhD research Adrian Bartoş.
The authors declare no conflicts of interests. References 1. Peritoneal carcinomatosis of colorectal origin: incidence and current treatment strategies. Annals of surgery.
Profilul de risc clinic asociat cancerului ovarian
Surgical treatment of peritoneal carcinomatosis: current treatment modalities. Malignant pseudomyxoma peritonei of colonic origin.
Natural history and presentation of a curative approach to treatment.