Gut Microbiota, Metabolome, and Body Composition Signatures of Response to Therapy in Patients with Advanced Melanoma.

Despite the recent breakthroughs in targeted and immunotherapy for melanoma, the overall survival rate remains low. In recent years, considerable attention has been paid to the gut microbiota and other modifiable patient factors (e.g., diet and body composition), though their role in influencing therapeutic responses has yet to be defined. Here, we characterized a cohort of 31 patients with unresectable IIIC-IV-stage cutaneous melanoma prior to initiation of targeted or first-line immunotherapy via the following methods: (i) fecal microbiome and metabolome via 16S rRNA amplicon sequencing and gas chromatography/mass spectrometry, respectively, and (ii) anthropometry, body composition, nutritional status, physical activity, biochemical parameters, and immunoprofiling. According to our data, patients subsequently classified as responders were obese (i.e., with high body mass index and high levels of total, visceral, subcutaneous, and intramuscular adipose tissue), non-sarcopenic, and enriched in certain fecal taxa (e.g., Phascolarctobacterium) and metabolites (e.g., anethole), which were potentially endowed with immunostimulatory and oncoprotective activities. On the other hand, non-response was associated with increased proportions of Streptococcus, Actinomyces, Veillonella, Dorea, Fusobacterium, higher neutrophil levels (and a higher neutrophil-to-lymphocyte ratio), and higher fecal levels of butyric acid and its esters, which also correlated with decreased survival. This exploratory study provides an integrated list of potential early prognostic biomarkers that could improve the clinical management of patients with advanced melanoma, in particular by guiding the design of adjuvant therapeutic strategies to improve treatment response and support long-term health improvement.

Dietary intervention for tertiary prevention in head and neck squamous cell carcinoma survivors: clinical and translational results of a randomized phase II trial.

Background: There is a strong need for preventive approaches to reduce the incidence of recurrence, second cancers, and late toxicities in head and neck squamous cell carcinoma (HNSCC) survivors. We conducted a randomized controlled trial (RCT) to assess a dietary intervention as a non-expensive and non-toxic method of tertiary prevention in HNSCC survivors. Methods: Eligible participants were disease-free patients with HNSCC in follow-up after curative treatments. Subjects were randomized 1:1 to receive a highly monitored dietary intervention plus the Word Cancer Research Fund/American Institute for Cancer Research recommendations for cancer prevention (intervention arm) or standard-of-care recommendations (control arm). The planned sample size for the event-free survival evaluation (primary endpoint) was not reached, and the protocol was amended in order to investigate the clinical (nutritional and quality-of-life questionnaires) and translational study [plasma-circulating food-related microRNAs (miRNAs)] as main endpoints, the results of which are reported herein. Results: One hundred patients were screened, 94 were randomized, and 89 were eligible for intention-to-treat analysis. Median event-free survival was not reached in both arms. After 18 months, nutritional questionnaires showed a significant increase in Recommended Food Score (p = 0.04) in the intervention arm vs. control arm. The frequency of patients with and without a clinically meaningful deterioration or improvement of the C30 global health status in the two study arms was similar. Food-derived circulating miRNAs were identified in plasma samples at baseline, with a significant difference among countries. Conclusion: This RCT represented the first proof-of-principle study, indicating the feasibility of a clinical study based on nutritional and lifestyle interventions in HNSCC survivors. Subjects receiving specific counseling increased the consumption of the recommended foods, but no relevant changes in quality of life were recorded between the two study arms. Food-derived plasma miRNA might be considered promising circulating dietary biomarkers.

Delayed Gastric Emptying After Multivisceral Resection for Retroperitoneal Sarcoma.

INTRODUCTION: Delayed gastric emptying (DGE) is a common complication in surgery, but incidence and relevance following multivisceral resection are unknown. METHODS: Data from 100 consecutive patients treated for primary retroperitoneal sarcoma (RPS) were analyzed from our institutional prospectively maintained database from January 2019 to April 2020. DGE severity was graded according to the International Study Group of Pancreatic Surgery and classified as primary or secondary to other complications. The primary outcome was incidence and grade of clinically relevant DGE (grades B-C). Secondary outcomes were correlation with patient, tumor, and treatment characteristics, and non-DGE morbidity [Clavien-Dindo (CD) grade ≥ 3]. RESULTS: Forty-two patients developed DGE and 28 had clinically relevant DGE. DGE was primary in 10 patients and secondary in 18 patients; the most common associated complications were: infections (11/18, 61.1%), pancreatic leak (7/18, 38.9%), bleeding (6/18, 33.3%), and bowel leak (6/18, 33.3%). DGE was related to longer length of hospital stay (P < 0.001), ICU admission (P = 0.004), ICU length of stay (P = 0.001), postoperative complications (CD [Formula: see text] 3 in 14/28 in DGE patients vs 11/72 in no-DGE; P = 0.04), and re-operation (P = 0.03). With multivariate analysis, the independent risk factors for DGE were patient comorbidities (OR 1.05; 95% CI 1.01-1.1; P = 0.04) and tumor size (OR 1.05; 95% CI 1.0-1.1; P = 0.02). DISCUSSION: Following multivisceral resection, DGE is a clinically relevant event that can be caused by an underlying complication. Prompt diagnosis and treatment of both DGE and any underlying complications led to full recovery in all cases.

The Advantages of Clinical Nutrition Use in Oncologic Patients in Italy: Real World Insights.

This retrospective observational study aimed to provide insights on the use of clinical nutrition (CN) (enteral and parenteral feeding) and outcomes in an Italian real-world setting. The data source comes from administrative databases of 10 Italian Local Health Units. Patients diagnosed with malignant neoplasms from 1 January 2010 to 31 December 2015 were included. Metastasis presence was ascertained by discharge diagnosis in the hospitalization database. CN was identified by specific codes from pharmaceutical and hospitalization databases. Two cohorts were created-one for metastatic patients (N = 53,042), and one for non-metastatic patients (N = 4379) receiving CN. Two survival analyses were set for the cohort of metastatic patients-one included patients receiving CN and the second included malnourished patients. Our findings show that (1) administration of CN is associated with positive survival outcomes in metastatic patients with gastrointestinal, respiratory, and genitourinary cancer; (2) CN in malnourished metastatic patients with gastrointestinal and genitourinary cancer was associated with significant improvement in survival; (3) early administration of CN was associated with improvement in survival in non-metastatic patients with gastrointestinal cancer (HR 95%CI: 0.5 (0.4-0.6), p-value < 0.05). This study highlights the need to improve the assessment of nutritional status in oncologic patients and suggests a potential survival benefit of CN treatment in metastatic disease.

What Do We Know About the Do-It-Yourself Diets of Patients in Our Care?

This pilot study aimed to investigate dietary changes introduced after being diagnosed with cancer in a sample of 60 consecutive children and adolescents on the basis of a self-report questionnaire. The study showed that 53% of patients changed their diet, usually "to combat the tumor" (in 47% of cases). In 1 in 2 of these cases, the health care staff were not informed about any changes. This study underscores the fact that many patients and families chose to impose dietary changes that are not always discussed with their health care staff and that may risk interfering with the continuity of a patient's treatment. It is essential to have more opportunities to speak with patients and families about this issue.

Weighing the prognostic role of hyponatremia in hospitalized patients with metastatic solid tumors: the HYPNOSIS study.

Previous works linked low sodium concentration with mortality risk in cancer. We aimed at weighing the prognostic impact of hyponatremia in all consecutive patients with metastatic solid tumors admitted in a two-years period at our medical oncology department. Patients were included in two cohorts based on serum sodium concentration on admission. A total of 1025 patients were included, of whom 279 (27.2%) were found to be hyponatremic. The highest prevalence of hyponatremia was observed in biliary tract (51%), prostate (45%) and small-cell lung cancer (38.9%). With a median follow-up of 26.9 months, median OS was 2 months and 13.2 months for the hyponatremia versus control cohort, respectively (HR, 2.65; P < 0.001). In the multivariable model, hyponatremia was independently associated with poorer OS (HR, 1.66; P < 0.001). According to the multivariable model, a nomogram system was developed and validated in an external set of patients. We weighed over time the influence of hyponatremia on survival of patients with metastatic solid tumors and pointed out the possibility to exploit serum sodium assessment to design integrated prognostic tools. Our study also highlights the need for a deeper characterization of the biological role of extracellular sodium levels in tumor development and progression.

Exploiting FAsting-mimicking Diet and MEtformin to Improve the Efficacy of Platinum-pemetrexed Chemotherapy in Advanced LKB1-inactivated Lung Adenocarcinoma: The FAME Trial.

Advanced lung adenocarcinoma with inactive liver kinase B1 (LKB1) tumor suppressor protein is associated with poor response to immune checkpoint inhibitors and molecularly targeted agents, and with dismal patient prognosis. LKB1 is a central orchestrator of cancer cell metabolism, and halts tumor growth/proliferation during metabolic stress. Recent preclinical evidence suggests that LKB1-inactive lung adenocarcinoma is highly sensitive to metformin, a safe and low-cost antidiabetic compound that inhibits mitochondrial oxidative phosphorylation. The effects of metformin can be enhanced by nutrient deprivation (ie, glucose, amino acids), which reduces intracellular levels of ATP and anabolic precursors and can be achieved by the fasting mimicking diet (FMD). Noticeably, metformin also prevents resistance to cisplatin in preclinical in vitro and in vivo models of LKB1-inactive lung adenocarcinoma. Based on such preclinical evidence, the phase II FAME trial was designed to test the hypothesis that the addition of metformin, with or without cyclic FMD, to standard platinum-based chemotherapy improves the progression-free survival of patients with advanced, LKB-1 inactive lung adenocarcinoma. Enrolled patients will be randomized in a 1:1 ratio to receive cisplatin/carboplatin and pemetrexed with the addition of metformin alone (Arm A) or metformin plus FMD (Arm B). The FAME study will use a "pick-the-winner" design with the aim of establishing which of the 2 experimental treatments is superior in terms of antitumor efficacy and safety. The primary assumption of the study is that the combination of the 2 experimental treatments shall improve median progression-free survival from 7.6 months (historical data with chemotherapy alone) to 12 months. Secondary study endpoints are: objective response rate, overall survival, treatment tolerability, and compliance to the experimental treatment.

Changes in food habits in cancer patients in Italy: a survey. AIOM - SINPE - FAVO.

OBJECTIVES: The aim of this study was to investigate the prevalence of cancer patients changing their diet in relation to cancer site, sex, age and geographic distribution. Furthermore, we aimed to explore the rationale behind dietary changes and to identify sources of information in order to plan specific educational training. METHODS: Patients ≥18 y of age who accessed the Italian Cancer Patients, Families and Friends Association information points were invited to participate. An ad hoc self-report questionnaire was used. The questionnaire asked patients about changes made to the major food groups. A minimum sample of 100 patients for the most common cancers was planned. We analyzed 1257 questionnaires. We assessed the prevalence of, reasons for, and type of dietary changes. Logistic regression was used to analyze the main determinants of dietary changes. RESULTS: Of the 1257 patients, 705 (56.1%) reported changes since receiving the diagnosis of cancer. On the logistic regression analysis, age and tumor site were significantly associated with dietary changes (P <0.001), mainly in patients <50 y of age and in those with upper gastrointestinal cancers. Slightly more than half (50.8%) of patients adopted a healthier diet, with 31.3% doing so to deal with eating-related side effects and 17.9% due to cancer sites. Regardless of the reasons for changing, the most common food items to result in a decrease in consumption were alcohol, red and processed meats, and sugary drinks. Only 15% of patients reported receiving specific nutrition indication. CONCLUSION: Italian patients are attentive to the importance of diet during cancer treatment. Personal choices reflect some indications for cancer prevention as there is still a shortage of guidelines for a correct diet during treatment. Nutrition indications are rarely given within the oncologic center.

Nutritional intervention in head and neck cancer patients during chemo-radiotherapy.

OBJECTIVE: Head and neck cancer patients experience unintentional weight loss and malnutrition at diagnosis, during oncologic treatment, and after the end of therapy because of reduction of eating ability. The aim of the present study was to assess nutrition intervention efficacy in maintaining basal nutritional conditions. METHODS: Head and neck cancer patient candidates for chemoradiotherapy and requiring enteral nutrition (EN) support through gastrostomy, according to international guidelines, were included in the study. Nutritional intervention aimed to reach 30 kcal/kg/d, considering both EN and oral intake. Adjustments were made during and after treatment, aiming to maintain stable or improving nutritional indicators. Anthropometry, body composition measured by bioelectrical impedance vector analysis, and oral and EN intake were monitored at baseline (before chemoradiotherapy) and at 1, 3, and 6 mo. RESULTS: A total of 54 patients were evaluated; 35 patients completed follow-up at 6 mo and were included in the analysis. At baseline, mean weight loss in the last 6 mo was 12 ± 7.9%; mean body mass index and phase angle were 20.6 ± 3.9 kg/m2 and 4.8 ± 1.2°. Before chemoradiotherapy 21 patients (60%) were able to eat; the percentage decreased during and after treatment to 34.3% (P = 0.026) at 1 and 3 mo and at 51.4% at 6 mo. From the analysis, a mean daily energy intake of 35 ± 10 kcal/kg was needed to maintain stable body weight and phase angle during and after treatment. CONCLUSION: To preserve body weight and composition, we identified an energy requirement greater than expected both during and after chemoradiotherapy.

Urn models for response-adaptive randomized designs: a simulation study based on a non-adaptive randomized trial.

Recently, response-adaptive designs have been proposed in randomized clinical trials to achieve ethical and/or cost advantages by using sequential accrual information collected during the trial to dynamically update the probabilities of treatment assignments. In this context, urn models-where the probability to assign patients to treatments is interpreted as the proportion of balls of different colors available in a virtual urn-have been used as response-adaptive randomization rules. We propose the use of Randomly Reinforced Urn (RRU) models in a simulation study based on a published randomized clinical trial on the efficacy of home enteral nutrition in cancer patients after major gastrointestinal surgery. We compare results with the RRU design with those previously published with the non-adaptive approach. We also provide a code written with the R software to implement the RRU design in practice. In detail, we simulate 10,000 trials based on the RRU model in three set-ups of different total sample sizes. We report information on the number of patients allocated to the inferior treatment and on the empirical power of the t-test for the treatment coefficient in the ANOVA model. We carry out a sensitivity analysis to assess the effect of different urn compositions. For each sample size, in approximately 75% of the simulation runs, the number of patients allocated to the inferior treatment by the RRU design is lower, as compared to the non-adaptive design. The empirical power of the t-test for the treatment effect is similar in the two designs.

[Gastric carcinoma: an evolutionary scenario.] / Il trattamento di prima e seconda linea nel carcinoma gastrico.

Despite the progressive decline of its incidence and mortality over the past decades, gastric cancer remains the forth most common cause of cancer-related death in Europe. While historically gastric adenocarcinoma has been classified according to the Lauren classification in intestinal and diffuse subtype, the knowledge of the complex molecular mechanisms underlying its carcinogenesis has led to new molecular classifications which can represent the starting point for the development of a personalized approach also in this disease. From a clinical point of view, while the addition of trastuzumab in the therapeutic armamentarium paved the way for the introduction of targeted therapy in the first-line treatment, only recently the confirmation of the role of second-line therapy along with the approval of ramucirumab as a standard of care in this setting led to a new concept of "continuum of care" in gastric cancer. Furthermore, also the pivotal role of nutritional counseling and support both in early- and advanced-stage disease has been recently confirmed in many retrospective and prospective series.

Impact of home enteral nutrition in malnourished patients with upper gastrointestinal cancer: A multicentre randomised clinical trial.

BACKGROUND: Weight loss is frequent in patients with gastrointestinal (GI) cancer. Nutritional status deteriorates throughout anti-cancer treatment, mostly after major surgery, increasing complications, reducing tolerance and worsening the final prognosis. Enteral nutrition is safe and effective in malnourished patients undergoing major GI surgery. Randomised trials aimed at investigating the effects of home enteral nutrition (HEN) in post-surgical patients with GI cancer are lacking. This study compares HEN and counselling in limiting weight loss during oncologic treatment. PATIENTS AND METHODS: Patients with upper GI cancer and candidate to major surgery were included in the protocol when the nutritional risk screening (NRS 2002) score was ≥3. All patients were supported with enteral nutrition through a jejunostomy after surgery and randomly assigned to continue enteral nutrition or receiving nutritional counselling after discharge. Nutritional and performance status, quality of life (QoL) and tolerance to cancer treatment have been evaluated at 2 and 6 months after discharge. RESULTS: Seventy-nine patients were randomised; 38 continued enteral nutrition at home and 41 patients received nutritional counselling only. After 2 months, patients on HEN maintained their mean body weight, while patients in the nutritional counselling group showed a weight loss of 3.6 kg. Patients supported on HEN had a higher chance to complete chemotherapy as planned (48% versus 34%). QoL was not worsened by HEN. No complications were reported. CONCLUSIONS: HEN is a simple and feasible treatment to support malnourished patients with upper GI cancer after major surgery and during chemotherapy in order to limit further weight loss.

Awareness and consideration of malnutrition among oncologists: Insights from an exploratory survey.

OBJECTIVES: The attitude toward malnutrition varies considerably among oncologists and many malnourished cancer patients receive inadequate nutritional support. The aim of this brief report was to report the results of the exploratory national survey conducted by the Italian Society of Medical Oncology (AIOM) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) before publication of a consensus document aimed at evaluating current attitudes toward malnutrition and management of nutrition, among Italian medical oncologists. METHODS: Between January and July 2015, the AIOM and the SINPE conducted a national web-based exploratory survey to investigate the attitude of oncologists toward malnutrition, and the management of nutritional support, before publication of an intersociety consensus document. RESULTS: Of the 2375 AIOM members, 135 (5.7%) participated in the survey, with a satisfactory distribution across all Italian regions. Nutritional assessment and support were routinely integrated into patient care for 38 (28%) responders. According to 66 (49%) participants, nutritional assessment was carried out only at the patients' request (n = 62), or not at all (n = 4). Availability of clinical nutritionists was reported by 88 (65%) participants. For 131 responders (97%), nutritional status was decisive (n = 63) or often crucial (n = 68) in assessing whether anticancer treatment was practicable or would be tolerated. CONCLUSIONS: The low response rate may reflect the lack of awareness and consideration of nutritional issues among Italian oncologists. Although malnutrition and nutritional support seemed to be perceived by the responders as relevant factors for the efficacy of oncologic treatments, it seems that nutritional care practices may well be inappropriate. The lack of collaboration between oncologists and clinical nutritionists may be the first obstacle to overcome. Educational intersociety initiatives aimed at improving nutritional support management for cancer patients in Italy appear urgently needed.

Nutritional Support in Cancer Patients: A Position Paper from the Italian Society of Medical Oncology (AIOM) and the Italian Society of Artificial Nutrition and Metabolism (SINPE).

Malnutrition is a frequent problem in cancer patients, which leads to prolonged hospitalization, a higher degree of treatment-related toxicity, reduced response to cancer treatment, impaired quality of life and a worse overall prognosis. The attitude towards this issue varies considerably and many malnourished patients receive inadequate nutritional support. We reviewed available data present in the literature, together with the guidelines issued by scientific societies and health authorities, on the nutritional management of patients with cancer, in order to make suitable and concise practical recommendations for appropriate nutritional support in this patient population. Evidence from the literature suggests that nutritional screening should be performed using validated tools (the Nutritional Risk Screening 2002 [NRS 2002], the Malnutrition Universal Screening Tool [MUST], the Malnutrition Screening Tool [MST] and the Mini Nutritional Assessment [MNA]), both at diagnosis and at regular time points during the course of disease according to tumor type, stage and treatment. Patients at nutritional risk should be promptly referred for comprehensive nutritional assessment and support to clinical nutrition services or medical personnel with documented skills in clinical nutrition, specifically for cancer patients. Nutritional intervention should be actively managed and targeted for each patient; it should comprise personalized dietary counseling and/or artificial nutrition according to spontaneous food intake, tolerance and effectiveness. Nutritional support may be integrated into palliative care programs. "Alternative hypocaloric anti-cancer diets" (e.g. macrobiotic or vegan diets) should not be recommended as they may worsen nutritional status. Well-designed clinical trials are needed to further our knowledge of the nutritional support required in different care settings for cancer patients.

FOLFOX-4 chemotherapy for patients with unresectable or relapsed peritoneal pseudomyxoma.

PURPOSE: The standard treatment of peritoneal pseudomyxoma is based on cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The establishment of newer systemic treatments is an unmet clinical need for unresectable or relapsed peritoneal pseudomyxoma. The aim of our study was to assess the activity of chemotherapy with 5-fluorouracil and oxaliplatin (FOLFOX-4 regimen) in terms of response rate in this subset of patients. MATERIALS AND METHODS: Patients were included in a single-center, observational study and treated with FOLFOX-4 administered every 2 weeks for up to 12 cycles or until progressive disease or unacceptable toxicity. RESULTS: Twenty consecutive patients were reviewed from July 2011 to September 2013. Only partial responses were observed, with an objective response rate of 20%. Median progression-free survival and overall survival were 8 months and 26 months, respectively. Two patients were able to undergo laparotomy with complete cytoreduction and HIPEC in one case. Safety data for FOLFOX-4 were consistent with the literature. By means of a mutant enriched polymerase chain reaction, KRAS mutation was found in 16 of 19 cases (84%), and MGMT promoter methylation was found in 8 (42%, all KRAS mutant). CONCLUSION: FOLFOX-4 chemotherapy is tolerable and active in patients with peritoneal pseudomyxoma when disease is deemed unresectable or relapsed after peritonectomy and HIPEC. The identification of predictive biomarkers, such as KRAS for resistance to anti-epidermal growth factor receptor monoclonal antibodies and MGMT for response to temozolomide, is a priority for the development of evidence-based treatment strategies for peritoneal pseudomyxoma.

The nutritional risk in oncology: a study of 1,453 cancer outpatients.

PURPOSE: There is little information about the nutritional status of cancer outpatients because the practice of nutritional screening is rarely performed. This study aims to define the pattern of scores of nutritional risk in 1,453 outpatients and factors associated with a high nutrition risk score, to facilitate the identification of such patients by the oncologists. METHODS: We prospectively screened the nutritional status of cancer outpatients according to the NRS-2002 score which combines indicators of malnutrition and of severity of the disease (1-3 points, respectively). A score ≥ 3 indicates "nutritional risk". The association of the nutritional scores with some patient/tumour/therapy-related variables was investigated through univariable and multivariable linear regression models. RESULTS: Thirty-two percent of outpatients were at nutritional risk. Primary tumour site, Eastern Cooperative Oncology Group score and presence of anorexia or fatigue were significantly associated with the nutrition risk score. Depending on the combination of these variables, it was possible to estimate different probabilities of nutritional risk. CONCLUSIONS: The frequency of a relevant nutritional risk was higher than expected considering the favourably selected population. The nutritional risk was associated with common clinical variables which are usually recorded in the charts and could easily alert the oncologist on the need of a further nutritional assessment or a nutritional support.

Importance of early nutritional screening in patients with gastric cancer.

In the present study, we evaluated the relationship between nutritional status, disease stage and quality of life (QoL) in 100 patients recently diagnosed with gastric carcinoma. The patients' nutritional status was investigated with anthropometric, biochemical, inflammatory and functional variables; and we also evaluated the nutritional risk with the Nutritional Risk Screening 2002. Oncological staging was standard. QoL was evaluated using the Functional Assessment of Anorexia/Cachexia Therapy questionnaire. The statistical correlation between nutritional risk score (NRS) and oncological characteristics or QoL was evaluated using both univariable and multivariable analyses. Weight loss and reduction of food intake were the most frequent pathological nutritional indicators, while biochemical, inflammatory and functional variables were in the normal range. According to NRS, thirty-six patients were malnourished or at risk for malnutrition. Patients with NRS ≥ 3 presented a significantly greater percentage of stage IV gastric cancer and pathological values of C-reactive protein, while no correlation was found with the site of tumour. NRS was negatively associated with QoL (P < 0·001) and this relation was independent from oncological and inflammatory variables as confirmed by multivariable analysis. In the present study, we found that in patients with gastric cancer malnutrition is frequent at diagnosis and this is likely due to reduction in food intake. Moreover, NRS is directly correlated with tumour stage and inversely correlated with QoL, which makes it a useful tool to identify patients in need of an early nutritional intervention during oncological treatments.

Colobronchial fistula: an unusual complication after peritonectomy and hyperthermic intra-peritoneal chemotherapy (HIPEC).

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an innovative approach to peritoneal carcinomatosis. Due to the complexity of the combined procedure, high rates of potentially life-threatening complications have been reported. This is the first report of colobronchial fistula following CRS and HIPEC. CASE REPORT: A 70-year-old woman underwent CRS and HIPEC for papillary well-differentiated peritoneal mesothelioma. During the postoperative course, recurrent pneumonia occurred and bacteria of intestinal origin were isolated from expectorated sputum. Water-soluble contrast studies revealed direct communication between the left colon flexure and the bronchial tree. After appropriate medical and supportive therapies, the patient underwent resection of the splenic flexure and immediate anastomosis with complete recovery. CONCLUSION: Colobronchial fistula is a rare and potentially lethal complication of CRS and HIPEC. A suggestive clinical picture and contrast studies allow conclusive diagnosis to be made. Surgery is a safe and effective therapeutic option.