Hyperthermic Chemotherapy Research Articles

Influence of Simultaneous Liver and Peritoneal Resection on Postoperative Morbi-Mortality and Survival in Patients With Colon Cancer Treated With Surgical Cytoreduction and Intraperitoneal Hyperthermic Chemotherapy

IntroductionCytoreductive surgery plus intraperitoneal hyperthermic chemotherapy (HIPEC) has recently been established as the treatment of choice for selected patients with peritoneal carcinomatosis of colonic origin. Until recently, the simultaneous presence of peritoneal and hepatic dissemination has been considered a contraindication for surgery. The aim of this paper is to analyze the morbidity, mortality and survival of patients with simultaneous peritoneal and hepatic resection with HIPEC for peritoneal carcinomatosis secondary to colon cancer. MethodsBetween January 2010 and January 2015, 61 patients were operated on, 16 had simultaneous peritoneal and hepatic dissemination (group RH+), and 45 presented only peritoneal dissemination (group RH−). ResultsThere were no differences between the groups in terms of demographic data, length of surgery and extension of peritoneal disease. Postoperative grade III–V complications were significantly higher in the RH+ group (56.3 vs 26.6%; P=0.032). For the whole group, mortality rate was 3.2% (two patients in group RH−, and none in group RH+). Patients with liver resection had a longer postoperative stay (14.4 vs 23.1 days) (P=.027). Median overall survival was 33 months for RH−, and 36 for RH+ group. Median disease-free survival was 16 months for RH−, and 24 months for RH+ group. ConclusionsSimultaneous peritoneal cytoreduction and hepatic resection resulted in a significantly higher Clavien grade III–V morbidity and a longer hospital stay, although the results are similar to other major abdominal interventions. The application of multimodal oncological and surgical treatment may obtain similar long-term survival results in both groups.

Haemodynamic changes during hyperthermic intra-thoracic chemotherapy for pseudomyxoma peritonei

Purpose: Hyperthermic intra-thoracic chemotherapy (HITOC) combined with cytoreductive surgery (CRS) is a novel approach in the management of pseuodmyxoma peritonei with thoracic extension. The haemodynamic effects of hyperthermic chemotherapy present an anaesthetic challenge. Here, we describe the haemodynamic changes seen during HITOC.Materials and methods: A retrospective case note review of adult patients undergoing CRS with HITOC from 2009 to 2016. Intra-operative haemodynamics were measured using the LIDCOrapidTM brand of invasive cardiac output (CO) monitor. Intravenous fluids, vasopressor requirements and urine output (UO) were recorded.Results: Four patients were included in the study. Mean heart rate (HR) peaked at 20 min following commencement of HITOC. The difference between HR at time 0 and at peak was minimal. There was minimal change in CO, and stroke volume variation (SVV) remained stable. Vasopressor dose was minimally changed throughout surgery. Average UO during HITOC was 142.5 ± 109.6 mls at 60 min. Mean fluid requirements during HITOC was 586.2 ± 441.2 mls. No significant change occurred in pH or base excess (BE).Conclusions: Significant haemodynamic instability including cardiac asystole has been reported during HITOC. The application of hyperthermic agents to the thorax results in vasodilatation, cardiac warming and compression of mediastinal vessels. Measurement of haemodynamic variables allowed careful titration of intravenous fluid therapy to CO and stroke volume, allowing for haemodynamic stability. This has not been described elsewhere.

Impact of Laparotomy and Intraperitoneal Hyperthermic Instillation (LIHI) on the oxaliplatin pharmacokinetics after intravenous administration in Wistar rats

In peritoneal metastasis condition, the fact that most of the disease is limited to the peritoneal cavity laid the foundations for a surgical treatment, including intraperitoneal hyperthermic chemotherapy (HIPEC). The aim of this study was to evaluate the impact of the surgical procedures implied in open HIPEC technique, referred to laparotomy procedures followed by an intraperitoneal hyperthermic instillation (LIHI) on oxaliplatin tissue distribution and elimination. To delimit the influence of this procedure alone, oxaliplatin was administered as an intravenous (iv) bolus in both groups. An experimental model in Wistar rats was employed, and LIHI was evaluated as a dichotomous covariate by using a population pharmacokinetic (PK) approach. Rats were randomized in two groups receiving 1.5mg iv oxaliplatin alone or 1.5mg iv oxaliplatin under LIHI conditions, carrying out a hyperthermic 5% dextrose instillation. The oxaliplatin plasma concentrations were characterized by an open two-compartment PK model. Results concluded that surgical conditions affect the oxaliplatin elimination and distribution from blood to peripheral tissues, increasing the systemic drug exposure. Concretely, oxaliplatin peripheral volume of distribution, and clearance decreased by 48.6% and 55.3%, respectively, compared to the control group that resulted in a two-fold increase of the area under the concentration time curve. Comparison in clinical practice of oxaliplatin PK parameters obtained after iv administrations with those obtained after HIPEC interventions must be done carefully. This would limit the use of iv PK parameters to simulate new scenarios for oxaliplatin in HIPEC.

Radical appendectomy as an alternative to right colon resection in patients with epithelial appendiceal neoplasms

ObjectiveAppendectomy is an extremely common surgical procedure usually performed for an inflammatory process within this organ. Upon occasion, the pathology within the appendix is a neoplastic process which requires definitive oncologic management. MethodsThe optimal management strategies for appendiceal neoplasms were reviewed and pertinent literature critically evaluated. The technology for appendectomy for an inflammatory process and an appendectomy for a neoplastic process were compared and contrasted. ResultsA new surgical procedure called “radical appendectomy” was described and its merits for optimizing the management of an appendiceal neoplasm enumerated. The technology of radical appendectomy was described. The possible shortcomings that may be encountered in performing a new surgical methodology for appendectomy was presented and the results of a technically perfect radical appendectomy enumerated. The integration of a radical appendectomy with perioperative hyperthermic chemotherapy was described. ConclusionsWhen a malignancy exists as the cause of appendiceal pathology, the radical appendectomy will provide the maximal amount of information required for optimal decisions regarding patient management.

Management of an inguinal hernia in patients with pseudomyxoma peritonei

BackgroundPseudomyxoma peritonei is a disease that results from a perforated mucinous neoplasm of the appendix so that mucinous ascites and mucin-producing tumor cells are widely disseminated in a characteristic pattern throughout the abdomen and pelvis. The intraabdominal mucus can accumulate in the inguinal canal and by physical examination be indistinguishable from the usual inguinal hernia. MethodsA database of patients with pseudomyxoma peritonei was used to identify patients who had an inguinal hernia prior to or at the time of cytoreductive surgery (CRS) and perioperative hyperthermic chemotherapy (HIPEC). At the time of CRS, care was taken in all patients to remove the peritoneal lining of the inguinal canal. Patients who had the inguinal hernia repaired prior to definitive treatment with CRS and HIPEC had all tissue and mesh associated with prior herniorrhaphy resected. ResultsIn 178 pseudomyxoma peritonei patients, 17 had a new onset or previously repaired inguinal hernia that required extraction of mucus and mucinous tumor from the hernia site. No repair of the open inguinal canal was attempted at the time of CRS. No recurrent inguinal hernias were recorded and no patients required an inguinal incision at a later time to resect progressive disease within the inguinal canal. ConclusionsInguinal hernias caused by mucinous ascites and tumor were definitively treated by cytoreductive surgery plus HIPEC. Extraction of tumor and peritoneum from the inguinal canal facilitates fibrous closure of the hernia defect so that hernia recurrence was not observed.

Upregulated Heat Shock Proteins After Hyperthermic Chemotherapy Point to Induced Cell Survival Mechanisms in Affected Tumor Cells From Peritoneal Carcinomatosis.

In patients with peritoneal carcinomatosis cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment strategy. Here, we studied the role of hyperthermic chemotherapy on heat shock protein (HSP) expression and induction of tumor cell death and survival. HSP27, HSP70, and HSP90 combined with effects on tumor cell proliferation and chemosensitivity were analyzed in human colon cancer. Hyperthermic chemotherapy resulted in significant HSP27/HSP70 and HSP90 gene/protein overexpression in analyzed HT-29/SW480/SW620 colon cancer cells and peritoneal metastases from patients displaying amplified expression of proliferation markers, proliferating cell nuclear antigen and antiapoptotic protein Bcl-xL. Moreover, functionally increased chemoresistance against 5-fluorouracil/mitomycin C and oxaliplatin after hyperthermic chemotherapy points to induced survival mechanisms in cancer cells. In conclusion, the results indicate that intracellular HSP-associated antiapoptotic and proliferative effects after hyperthermic chemotherapy negatively influence beneficial effects of hyperthermic chemotherapy-induced cell death. Therefore, blocking HSPs could be a promising strategy to further improve the rate of tumor cell death and outcome of patients undergoing HIPEC therapy.

Hyperthermic chemotherapy inhibits respiration, glutamate dehydrogenase and increases susceptibility to cisplatin of ovarian cancer cells

P.4.1-086. Abstracts of special issue: 42nd FEBS Congress, From Molecules to Cells and Back, Jerusalem, Israel, September 10‐14, 2017. Leidinio DOI: 10.1111/febs.14174

P1.08-074 Effect of Intrapleural Perfusion Hyperthermic Chemotherapy in Non-Small Cell Lung Cancer with Pleural Seeding

Pleural seeding is generally associated with poor prognosis in advanced non-small cell lung cancer (NSCLC). Although palliative chemotherapy is the mainstay modality for these patients, intrapleural perfusion hyperthermic chemotherapy (IPHC) may be a good alternative. The aim of this study was to evaluate the efficacy of IPHC and predictive factors for longer survival in NSCLC with pleural seeding. From 2003 to 2014, 51 patients who underwent IPHC for NSCLC with pleural seeding at the first operation in 36 or after postoperative recurrence in 16 patients were enrolled. IPHC was performed with cisplatin (dose:150mg/m2) for 90 minutes. For patients with pleural seeding at first operation, parenchymal resection was performed and mediastinal LN was evaluated. We included some procedures other than pre-IPHC pleural biopsy, pre-IPHC lavage cytology, post-IPHC lavage cytology, and post-IPHC pleural biopsy. Subjects were divided into two groups: group I is shorter survivor of less than 36 months and group II is longer survivor of more than 36 months of overall survival duration. There were 22 male patients and the mean age was 59.6 years. There were 7 patients in pathologic stage T1, 28 in T2, 13 in T3, and 3 in T4. With respect to N stage, 18 patients in N0, 9 in N1, 17 in N2, and 8 in Nx. Major post-IPHC complication was acute renal insufficiency (n=4). All patients, except 3, received systemic chemotherapy after IPHC. Pleural seeding aggravation was seen in 28 patients, and the development of pleural effusion was observed in 5 patients after IPHC. EGFR mutation was examined in 38 patients after 2007; of which, 20 patients showed to have EGFR mutation. Targeted agents were used in 32 out of 51 patients. The mean overall survival was 36.4 months (5.9-98.0); 28 patients died during the follow-up period. The 2-year and 5-year survival rates were 75.7% and 39.8%, respectively. The prognostic factors for patients with overall survival of more than 36 months, seen in 19 patients, were old age, negative post-IPHC pleural biopsy, and presence of EGFR mutation. IPHC appears to be a safe procedure for advanced lung cancer patients with pleural seeding, and IPHC may provide better survival to only a highly selective group of patients. Old age, negative post-IPHC pleural biopsy, and presence of EGFR mutation are the predictive factors for longer survivor.

Liver Metastases and Peritoneal Carcinomatosis in A Sigmoid Adenocarcinoma Should We Perform Colectomy in A Stage IV Colorectal Cancer?

Colorectal cancer is the second cause of death in Spain (20% diagnosed in stage IV), improving survival in recent years thanks to chemotherapy and metastatic surgeries. With regard to a patient diagnosed with native stage IV KRAS colon adenocarcinoma (peritoneal, hepatic), the subject of cytoreduction with HIPEC (intraperitoneal hyperthermic chemotherapy) and the factors that influence the tumor response are reviewed.

Pharmacokinetic evaluation of intrapleural perfusion with hyperthermic chemotherapy using cisplatin in patients with malignant pleural effusion

ObjectivesMalignant pleural effusion (MPE) has a poor prognosis. Most patients are treated with tube thoracostomy and sclerotherapy, although its success rate is around 64%. We have investigated intrapleural perfusion with hyperthermic chemotherapy (IPHC) using cisplatin in a study with a pharmacokinetic evaluation. MethodsPatients with MPE, performance status of 0–1, possibility of good lung expansion and Cr<1.2mg/dL were treated with IPHC. The circuit was filled with 2000mL of normal saline containing cisplatin at a dose of 80mg/m2. Under video-assisted thoracoscopic surgery, the thoracic cavity was filled and perfused at a speed of approximately 1L/min at a temperature of 43°C for 1h. Perfusion solution and plasma samples were periodically collected, and concentrations of protein-unbound (free) platinum, which was the active derivative of cisplatin, and total platinum were determined by flameless atomic absorption spectrometry. ResultsTwenty patients with MPE (8 lung cancers, 7 mesotheliomas, and 5 others) were enrolled in this study. Rate of free platinum concentration relative to total platinum concentration in perfusion solution after 1hr IPHC at 43°C was 61.1±12.9%. Area under curve (AUC) of free platinum in the pleural space was calculated to be 26.3μg/mLxh, resulting in complete control of pleural effusion for 3 months after IHPC in all cases (95% confidence interval: 83–100%). While, absorption rate of total platinum from the pleural space was 33.8±17.0% (27.4±13.6mg/m2), and the maximum concentration of total platinum in serum was low, 0.66±0.31μg/mL, resulting in controllable side effects; grade 1 renal toxicity: 6 patients, grade 1 emesis: 7 patients. ConclusionsIPHC with cisplatin showed favorable pharmacokinetic profiles for an optional treatment to control malignant pleural effusion.

Preoperative intraperitoneal oxaliplatin for unresectable peritoneal carcinomatosis of colorectal origin: a pilot study.

Peritoneal carcinomatosis in colorectal cancer is an advanced stage of the disease where improved survival can be attained whenever the resection associated with hyperthermic intreperitoneal chemotherapy is possible. In unresectable cases, systemic chemotherapy is administered to obtain conversion to resectability but results have not yet been clearly evaluated. Local chemotherapy in this setting has been proven useful in several similar situations. The aim of the present pilot study was to evaluate the feasibility of pre-operative intraperitoneal chemotherapy with oxaliplatin in these patients. Six patients with unresectable peritoneal disease of colorectal origin were included in the study. An intraperitoneal implantable chamber catheter was inserted during the laparotomy that evaluated the extent of the peritoneal disease (peritoneal carcinomatosis index 25 to 39). Patients then underwent intraperitoneal chemotherapy with oxaliplatin 85 mg/m2 in combination with systemic chemotherapy (FOLFIRI or simplified LV5FU) and a targeted therapy every 2 weeks. Two catheter perfusion incidents were reported due to the abdominal wall thickness. Two patients completed the four intraperitoneal (IP) chemotherapy cycles without major toxicity. One patient developed grade 3 or 4 diarrhea requiring a short intensive care unit (ICU) stay, though it is not clear whether the event was induced by intravenous irinotecan, IP oxaliplatin or the combination of both. Grade 3 fatigue and abdominal pain were also recorded. For one patient with aggressive disease, best supportive care was initiated after the first course of chemotherapy. Our study is the first to assess intraperitoneal oxaliplatin-based chemotherapy in the preoperative setting for patients with unresectable peritoneal metastases. The tolerance was acceptable for 85 mg/m2 IP oxaliplatin combined with systemic therapy in these patients. Our results justify carrying on with a phase I/II trial to determine the recommended dose of oxaliplatin in this clinical context and its efficacy.

Paralysie diaphragmatique progressive consécutive à une chimiothérapie intra-abdominale

In patients presenting with intra-abdominal tumor and peritoneal carcinomatosis, cytoreductive surgery associated with hyperthermic chemotherapy may offer improved survival. We describe a case of diaphragmatic paralysis following that kind of procedure. A 60-year-old woman presented with respiratory insufficiency following cytoreductive surgery and intra-abdominal hyperthermic chemotherapy performed for pseudomyxoma intraperitonei. Pulmonary function assessment demonstrated a restrictive pattern. Three successive chest CT-scans demonstrated a thinning diaphragm muscle. Respiratory insufficiency eventually led to the death of our patient. We conclude in favor of a muscular degeneration of the diaphragm consecutive to the combined effect of cytoreductive surgery and intraperitoneal chemotherapy. Owing to the unusual nature of this complication, we did not consider it as a hypothesis at an early point in this patient's management. We think physicians should be aware of such a complication in order to consider it in a timely way. We recommend performing a biopsy of the diaphragm for pathology examination to assess muscular degeneration.

356. Novel nanotechnology concepts and applications to support standard cytoreductive surgery and hyperthermic intraperritoneal chemotherapy (CRS + HIPEC): A preliminary report from “2-arm cancer recurrence prevention” animal in vivo studies

356. Novel nanotechnology concepts and applications to support standard cytoreductive surgery and hyperthermic intraperritoneal chemotherapy (CRS + HIPEC): A preliminary report from “2-arm cancer recurrence prevention” animal in vivo studies

306. Survival prognostic factors in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and intraoperative hyperthermic intreperitoneal chemotherapy – A single institution experience

306. Survival prognostic factors in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and intraoperative hyperthermic intreperitoneal chemotherapy – A single institution experience

The factors affecting the survival and prognosis of patients with III~IV gastric cancer: a report of 156 cases

Objective To investigate the factors affecting the survival and prognosis of patients with stage Ⅲ~Ⅳgastric cancers. Methods A total of 156 cases of Ⅲ~Ⅳ gastric cancer was studied retrospectively from September 1, 2006 to December 31, 2012. Kaplan-Meier analysis, Log-rank univariate analysis, Cox proportional hazards model analysis were used to analyze survival and prognostic factors. Results Twelve cases were lost, to the end of the follow-up, 22 cases were alive. The median survival time was 29.3 months. 1-year, 3-year, and 5-year overall survival rates were 83.3%, 37.8%, and 21.2%, respectively. Univariate analysis showed that tumor size, tumor node metastasis (TNM) staging, curative resection, hyperthermic intraperitoneal perfusion chemotherapy (HIPEC), and postoperative chemotherapy were correlated with prognosis (P<0.05 for all). Multivariate analysis showed that TNM staging, curative resection, HIPEC, and postoperative chemotherapy were independent prognostic factors (P<0.01 for all). Conclusions TNM staging, curative resection, hyperthermic intraperitoneal perfusion chemotherapy and postoperative chemotherapy are the independent factors affecting the prognosis of stage Ⅲ~Ⅳ gastric cancer after resection. Hyperthermic intraperitoneal perfusion chemotherapy and postoperative chemotherapy can improve their survival. Key words: Stomach neoplasms; Prognosis

Clinical outcomes of cytoreductive surgery combined with intrapleural perfusion of hyperthermic chemotherapy in advanced lung adenocarcinoma with pleural dissemination.

This study aimed to investigate the safety and feasibility of intrapleural perfusion hyperthermic chemotherapy (IPHC) followed by cytoreductive surgery as a part of multimodal strategy for the treatment of advanced lung adenocarcinoma. Medical records of advanced lung cancer patients with pleural dissemination who underwent surgical treatment between 2003 and 2013 were reviewed retrospectively. Enrolled patients were divided into a surgery group comprising patients who underwent surgery only and an IPHC group, which consisted of patients who underwent surgery combined with IPHC. A total of 33 patients were enrolled in this study. Twenty-three patients underwent IPHC after surgical resection, and 10 patients underwent surgical resection only. The complication rate of the IPHC group was estimated to be 34.8% (8 cases), none of which included postoperative mortality. The complication rate of the surgery group was 40.0% (4 cases), which included one postoperative mortality. The 6-month, 1-year, and 3-year overall survival rates for the IPHC group were 95.7%, 91.3% and 38.6%, respectively, while those of the surgery group were 80.0%, 80.0% and 37.5%. The 6-month, 1-year and 3-year progression-free survival rates for the IPHC group were 87.0%, 47.8% and 24.3%, while those of surgery group were 44.4%, 33.3% and 0.0%, respectively. There were significant differences in overall survival rates between two groups (P=0.045); however, progression-free survival was not different between the two groups. IPHC combined with cytoreductive surgery for advanced lung adenocarcinoma associated with pleural seeding could be performed safely and feasible. It would be part of multimodality therapy for certain category of advanced lung adenocarcinoma. However, the long-term benefits for survival is uncertain. More extensive and precisely designed studies are warranted to further evaluate the effectiveness of IPHC.

Study of introperitoneal hyperthermic perfusion chemotherapy combined with systemic neoadjuvent chemotherapy in treatment of gastric cancer patients with peritoneal carcinomatosis

The aim of this study is to discuss the curative effect of introperitoneal hyperthermic perfusion chemotherapy(IHPC) combined with systemic neoadjuvant chemotherapy on the gastric cancer patients with peritoneal carcinomatosis. Sixty-four patients with gastric cancer and peritoneal carcinomatosis who were hospitalized in the Department of Gastrointestinal Surgery of First Hospital of Jilin University from December 2006 to December 2013. After peritoneal carcinomatosis was confirmed during laparoscopic exploration, FOLFOX6 (oxaliplatin and calcium folinate and 5-Fu) was performed for systemic chemotherapy. One course was 14 days and a complete treatment includes four courses. At the same time, patients underwent peritoneal catheter insertion and received IHPC(5-Fu 1 500 mg/m(2) and Cisplatin 35 mg/m(2) were added into 0.9% NaCl solution 2 000 ml, the infusion velocity was 35-45 ml/min, infusion time was 45-60 minutes, the temperature was controlled to 41°C). A comprehensive evaluation was taken after the fourth course of treatment before operation. Further surgical therapy was performed according to the assessment result. Sixty-four patients received IHPC combined with systemic chemotherapy. Thirty-two patients(50.0%) had partial response, 18(28.1%) stable disease, and 14(21.9%) progressive disease after chemotherapy. No severe complications or death occurred during the neoadjuvant chemotherapy. Thirty-two patients(50.0%) received radical resection, 10(15.6%) palliative operation, and another 22 patients(37.4%) didn't comply with inclusion criteria of operation. Patients receiving operation had a median survival time of 678 days, which was significantly longer than patients without operation, with a median survival time of 251(χ(2)=23.34, P=0.02). IHPC combined with systemic chemotherapy is an effective therapeutic method for gastric cancer patients with peritoneal carcinomatosis in terms of reducing preoperative tumor load and achieving radical resection.

Can hyperthermic intrathoracic perfusion chemotherapy added to lung sparing surgery be the solution for malignant pleural mesothelioma?

Can hyperthermic intrathoracic perfusion chemotherapy added to lung sparing surgery be the solution for malignant pleural mesothelioma?

The impact of neoadjuvant chemotherapy combined with tumor cell death and postoperative intraperitoneal chemotherapy on efficacy and quality of life of patients with ovarian cancer

Objective To observe the effect of neoadjuvant chemotherapy combined with tumor cells reduction and postoperative intraperitoneal perfusion chemotherapy on the efficacy and quality of life of ovarian cancer. Methods From October 2010 to October 2013 at the Department of gynecology, Taizhou Municipal Hospital, 65 cases of ovarian cancer patients for the treatment of stage Ⅲ and Ⅳ were randomly divided into intervention group (n=32) and control group (n=33). Patients in the intervention group received neoadjuvant chemotherapy after tumor cell reduction cytoreductive surgery and received postoperative intraperitoneal hyperthermic perfusion chemotherapy and conventional surgery after chemotherapy. Patients in the control group received conventional tumor cell cytoreductive surgery plus postoperative chemotherapy. Surgical status, the effectiveness of treatment, and adverse reactions were compared between two groups. Moreover, survival quality score, relapse rate, and mortality differences were compared between two groups. Results For the intervention group, operation status and effective treatment were better than the control group. The proportion of adverse reactions had no significant difference between two groups. Survival quality had no statistically significant difference between before treatment and after receiving treatment. Quality of life in the intervention group was better than that of the control group. Relapse rate, and mortality rate in the intervention group was lower than the control group. Conclusions Accepted neoadjuvant chemotherapy combined with tumor cytoreductive surgery and surgery after intraperitoneal hyperthermic perfusion chemotherapy can improve the effectiveness of treatment of ovarian cancers, and improve the quality of life, with better short-term effect. Key words: Chemotherapy, adjuvant; Tumor cells, cultured; Ovariectomy; Chemotherapy, cancer, regional perfusion; Ovarian neoplasms/TH; Quality of life

Treatment of Krukenberg tumor with hyperthermic intraperitoneal chemotherapy: A report of three cases

We report three cases of Krukenberg tumor (KT): two were synchronous and one metachronous. At presentation, the first synchronous KT patient had a palpable umbilical mass, the second had a perforated peptic ulcer, and the metachronous KT patient had an ovarian lesion, detected postoperatively. As we know, KT has a quite poor prognosis. According to some papers, surgery with chemotherapy increases survival more than 12 months. Consequently, our two synchronous KT patients received cytoreductive surgery with hyperthermic intra-abdominal chemotherapy and our metachronous KT patient received laparoscopic bilateral oophorectomy. No recurrences have so far been detected in any patient. Our patient with metachronous KT will undergo laparoscopy and hyperthermic intraperitoneal chemotherapy and our patients with synchronous KT will continue to be followed up to determine their final outcomes.