Hepatic encephalophaty: management and diagnostic therapeutic assistance path of Ligurian Local Health Company 3 (ASL3).

Hepatic encephalophaty (HE) is a neuropsychiatric syndrome with a prevalence in the cirrhotic population ranging from 20 to 80%. HE is a cause of inappropriate hospitalization, caregiver burdening and increased social costs. There is need to create dedicated care pathways to better manage patients and support family caregivers. The data used for the preparation of this diagnostic therapeutic assistance path (DTAP) are based on a detailed analysis of the scientific literature published before June 30, 2022 (PubMed, Web of Science, Scopus, Google Scholar). Furthermore, in the process of developing this work, we consulted in particular the guidelines/ position papers of International Society for Hepatic Encephalopathy and Nitrogen Metabolism (ISHEN), Italian Association for the Study of the Liver (AISF), European Association for the Study of the Liver (EASL), American Association for the Study of Liver Diseases (AASLD), Italian Society on Alcohol (Società Italiana di Alcologia [SIA]) and other relevant papers. DTAP was created based on the most recent recommendations of the international scientific literature. The present DTAP highlight the need for a multidisciplinary activity integrated with territorial medicine in close connection with caregivers. This guarantees improved therapeutic adherence, hospital readmission reduction, improved quality of life for patients and caregivers and a significant reduction in costs.

The Multidisciplinary Approach of Rectal Cancer: The Experience of "COMRE Group" Model.

Background: Total mesorectal excision (TME) is the gold standard to treat locally advanced rectal cancer. This monocentric retrospective study evaluates the results of laparotomic, laparoscopic and robotic surgery in "COMRE GROUP" (REctalCOMmittee). Methods: 327 selected stage I-II-III patients (pts) underwent TME between November 2005 and April 2020 for low or middle rectal cancer; 91 pts underwent open, 200 laparoscopic and 36 robotic TME. Of these, we analyzed the anthropomorphic, intraoperative, anatomopathological parameters and outcome during the follow up. Results: The length of hospital stay was significantly different between robotic TME and the other two groups (8.47 ± 3.54 days robotic vs. 11.93 ± 5.71 laparotomic, p < 0.001; 8.47 ± 3.54 robotic vs. 11.10 ± 7.99 laparoscopic, p < 0.05). The mean number of harvested nodes was higher in the laparotomic group compared to the other two groups (19 ± 9 laparotomic vs. 15 ± 8 laparoscopic, p < 0.001; 19 ± 9 laparotomic vs. 15 ± 7 robotic, p < 0.05). Median follow-up was 52 months (range: 1−169). Overall survival was significantly shorter in the open TME group compared with the laparoscopic one (Chi2 = 13.36, p < 0.001). Conclusions: In the experience of the "COMRE" group, laparoscopic TME for rectal cancer is a better choice than laparotomy in a multidisciplinary context. Robotic TME has a significant difference in terms of hospital stay compared to the other two groups.

Evaluation of Glycosylated PTGS2 in Colorectal Cancer for NSAIDS-Based Adjuvant Therapy.

Observational/retrospective studies indicate that prostaglandin-endoperoxide synthase-2 (PTGS2) inhibitors could positively affect colorectal cancer (CRC) patients' survival after diagnosis. To obtain an acceptable cost/benefit balance, the inclusion of PTGS2 inhibitors in the adjuvant setting needs a selective criterion. We quantified the 72 kDa, CRC-associated, glycosylated form of PTGS2 in 100 frozen CRC specimens and evaluated PTGS2 localization by IHC in the same tumors, scoring tumor epithelial-derived and stroma-derived fractions. We also investigated the involvement of interleukin-1 beta (IL1ß) in PTGS2 induction, both in vitro and in CRC lysates. Finally, we used overall survival (OS) as a criterion for patient selection. Glycosylated PTGS2 can be quantified with high sensibility in tissue lysates, but the expression in both tumor and stromal cells limits its use for predictive purposes. Immunohistochemistry (IHC) analysis indicates that stromal PTGS2 expression could exert a protective role on patient OS. Stromal PTGS2 was prevalently expressed by cancer-associated fibroblasts exerting a barrier function near the gut lumen, and it apparently favored the antitumor M1 macrophage population. IL1ß was directly linked to gPTGS2 expression both in vitro and in tumors, but its activity was apparently prevalent on the stromal cell population. We suggest that stromal PTGS2 could exert a positive effect on patients OS when expressed in the luminal area of the tumor.

Development of a long non-coding RNA signature for prediction of response to neoadjuvant chemoradiotherapy in locally advanced rectal adenocarcinoma.

Standard treatment for locally advanced rectal adenocarcinoma (LARC) includes a combination of chemotherapy with pyrimidine analogues, such as capecitabine, and radiation therapy, followed by surgery. Currently no clinically useful genomic predictors of benefit from neoadjuvant chemoradiotherapy (nCRT) exist for LARC. In this study we assessed the expression of 8,127 long noncoding RNAs (lncRNAs), poorly studied in LARC, to infer their ability in classifying patients' pathological complete response (pCR). We collected and analyzed, using lncRNA-specific Agilent microarrays a consecutive series of 61 LARC cases undergoing nCRT. Potential lncRNA predictors in responders and non-responders to nCRT were identified with LASSO regression, and a model was optimized using k-fold cross-validation after selection of the three most informative lncRNA. 11 lncRNAs were differentially expressed with false discovery rate < 0.01 between responders and non-responders to NACT. We identified lnc-KLF7-1, lnc-MAB21L2-1, and LINC00324 as the most promising variable subset for classification building. Overall sensitivity and specificity were 0.91 and 0.94 respectively, with an AUC of our ROC curve = 0.93. Our study shows for the first time that lncRNAs can accurately predict response in LARC undergoing nCRT. Our three-lncRNA based signature must be independently validated and further analyses must be conducted to fully understand the biological role of the identified signature, but our results suggest lncRNAs may be an ideal biomarker for response prediction in the studied setting.

Lymph node number, surface area and lymph node ratio are important prognostic indicators in neoadjuvant chemoradiotherapy treated rectal cancer.

AIMS: Neoadjuvant chemoradiotherapy (neoCRT) is recommended for locally advanced rectal cancer (RC), however, this often makes lymph node (LN) search trying. The aim of this study was to evaluate, in a large retrospective, monocentric, series of post-neoCRT-RC patients, the importance of LN number, ratio and surface area in predicting metastases, overall survival (OS) and disease free survival (DFS). METHODS: 104 patients with RC underwent total mesorectal excision, after standard neoCRT. All resected specimens were examined according to a standardised sampling/histopathological protocol. The following data regarding LNs were collected: total numbers; number with metastases; LNratio (metastatic/total); maximum diameter; surface area. RESULTS: A statistically significant association was found between LN number and DFS (p=0.0473). Finding ≤9 or >20 LNs correlated with worse prognosis compared with 10-20 (p value=0.049). LNratio (>0.2) was strongly associated with shorter DFS (HR=13.36; p value <0.0001) and OS (HR=26.06; p value <0.0001). Poor outcome, for DFS (HR=2.17, p value =0.0416) and OS (HR=1.18, p value =0.0025), was associated with increasing LN surface area. LNratio was independently associated with DFS at multivariate analysis (p value <0.0001). CONCLUSIONS: LN number, LNratio and LN surface area are important prognostic factors in neoCRT-RC and in particular finding ≤9 or >20 LNs is prognostically adverse.

Development of a predictor of one-year mortality in older patients with cancer by geriatric and oncologic parameters.

OBJECTIVES: More than 60% of the new cancer diagnoses are currently made in older adults, a highly heterogeneous population. Reliable and time-saving tools to define older adults' prognosis are needed to inform the oncologist's decisions in routine clinical practice. We sought to define a multi-domain classification tool for the prediction of all-cause one-year mortality in a cohort of older adults with solid tumors. MATERIALS AND METHODS: We conducted a single-centre, prospective study of patients with solid cancer aged 65 or older and with G8 score ≤ 14. All patients underwent a comprehensive geriatric assessment (CGA) before starting their surgical or medical treatment. One-year mortality was recorded. A CGA-based prediction tool of one-year mortality was developed and subsequently validated in two independent training and testing cohorts with a 70/30 split, respectively. RESULTS: 162 patients were enrolled. Mean patient age was 78 ±â€¯5.5 years. Forty-three percent of the patients were men. Colorectal and breast cancer were the most common diagnoses. The clinical variables selected for the development of the new classifier (MetaGENUA®) were: mini-nutritional assessment (MNA), instrumental day life activities (IADL), Cumulative Illness Rating Scale (CIRS), geriatric depression scale (GDS), age, and cancer stage. In our independent validation cohort, MetaGENUA® showed high specificity (0.86) and AUC = 0.71 (95% CI = 0.55-0.87). CONCLUSIONS: MetaGENUA® predicts one-year mortality in older patients with cancer with high specificity. As such, MetaGENUA® is predicted to reveal as a useful tool to guide the oncologist's decisions in clinical practice.

Clinico-pathological associations and concomitant mutations of the RAS/RAF pathway in metastatic colorectal cancer.

BACKGROUND: Over the past few years, next-generation sequencing (NGS) has become reliable and cost-effective, and its use in clinical practice has become a reality. A relevant role for NGS is the prediction of response to anti-EGFR agents in metastatic colorectal cancer (mCRC), where multiple exons from KRAS, NRAS, and BRAF must be sequenced simultaneously. METHODS: We optimized a 14-amplicon NGS panel to assess, in a consecutive cohort of 219 patients affected by mCRC, the presence and clinico-pathological associations of mutations in the KRAS, NRAS, BRAF, and PIK3CA genes from formalin-fixed, paraffin-embedded specimens collected for diagnostics and research at the time of diagnosis. RESULTS: We observed a statistically significant association of RAS mutations with sex, young age, and tumor site. We demonstrated that concomitant mutations in the RAS/RAF pathway are not infrequent in mCRC, and as anticipated by whole-genome studies, RAS and PIK3CA tend to be concurrently mutated. We corroborated the association of BRAF mutations in right mCRC tumors with microsatellite instability. We established tumor side as prognostic parameter independently of mutational status. CONCLUSIONS: To our knowledge, this is the first monocentric, consecutively accrued clinical mCRC cancer cohort tested by NGS in a real-world context for KRAS, NRAS, BRAF, and PIK3CA. Our study has highlighted in clinical practice findings such as the concomitance of mutations in the RAS/RAF pathway, the presence of multiple mutations in single gene, the co-occurrence of RAS and PIK3CA mutations, the prognostic value of tumor side and possible associations of sex with specific mutations.

Frailty assessment in elective gastrointestinal oncogeriatric surgery: Predictors of one-year mortality and functional status.

OBJECTIVES: Perioperative frailty assessment is still a challenge, especially in oncogeriatrics. We aimed at assessing the diagnostic accuracy of the 40 items Frailty Index (FI) as compared to the comprehensive geriatric assessment (CGA) for the prediction of one-year mortality and functional status after colorectal surgery in old-age subjects. MATERIAL AND METHODS: Ninety-nine consecutive patients aged 65 years or older who were candidate for elective gastrointestinal cancer surgery, with G8 score ≤ 14 were enrolled and subjected to CGA and to frailty stratification according to the 40-items FI. Long-term outcomes including one-year mortality and functional decline were collected. RESULTS: Mean patient age was 80.3 ±â€¯5.6 years. Colorectal cancer was the most common diagnosis. The most prevalent clinical phenotype was pre-frail. CGA and FI showed similar predictive accuracy in identifying one-year mortality after surgery and patient functional status. Our multivariate analysis indicated the pre-morbid functional status (IADL) and cancer stage as the most significant predictors of one-year mortality. CONCLUSIONS: This is the first study to investigate the prognostic accuracy of the 40-items FI as compared to CGA in a vulnerable octogenarian cancer population. Its results are consistent with patient functional status being a mediator of frailty and with both serving as intertwined markers of clinical vulnerability. In addition, according to our results, cancer and specific environmental stressors, such as surgery, are likely to affect the frailty trajectory.

Predictive values of two frailty screening tools in older patients with solid cancer: a comparison of SAOP2 and G8.

OBJECTIVES: Comprehensive Geriatric Assessment (CGA), the gold standard for detecting frailty in elderly cancer patients, is time-consuming and hard to apply in routine clinical practice. Here we compared the performance of two screening tools for frailty, G8 and SAOP2 for their accuracy in identifying vulnerable patients. MATERIAL AND METHODS: We tested G8 and SAOP2 in 282 patients aged 65 or older with a diagnosis of solid cancer and candidate to undergo surgical, medical and/or radiotherapy treatment. CGA, including functional and cognitive status, depression, nutrition, comorbidity, social status and quality of life was used as reference. ROC curves were used to compare two screening tools. RESULTS: Mean patient age was 79 years and 54% were female. Colorectal and breast cancer were the most common types cancer (49% and 24%). Impaired CGA, G8, and SAOP2 were found in 62%, 89%, and 94% of the patients, respectively. SAOP2 had a better sensitivity (AUC 0.85, p<0.032) than G8 (AUC 0.79), with higher performance in breast cancer patients (AUC 0.93) and in patients aged 70-80 years (AUC 0.87). CONCLUSIONS: G8 and SAOP2 both showed good screening capacity for frailty in the cancer patient population we examined with SAOP2 showing a slightly better performance than G8.

Targeting the Epidermal Growth Factor Receptor Can Counteract the Inhibition of Natural Killer Cell Function Exerted by Colorectal Tumor-Associated Fibroblasts.

Mesenchymal stromal cells (MSC) present in the tumor microenvironment [usually named tumor-associated fibroblasts (TAF)] can exert immunosuppressive effects on T and natural killer (NK) lymphocytes, favoring tumor immune escape. We have analyzed this mechanism in colorectal carcinoma (CRC) and found that co-culture of NK cells with TAF can prevent the IL-2-mediated NKG2D upregulation. This leads to the impairment of NKG2D-mediated recognition of CRC cells, sparing the NK cell activation through DNAM1 or FcγRIIIA (CD16). In situ, TAF express detectable levels of epidermal growth factor receptor (EGFR); thus, the therapeutic anti-EGFR humanized antibody cetuximab can trigger the antibody-dependent cellular cytotoxicity of TAF, through the engagement of FcγRIIIA on NK cells. Importantly, in the tumor, we found a lymphoid infiltrate containing NKp46+CD3- NK cells, enriched in CD16+ cells. This population, sorted and cultured with IL-2, could be triggered via CD16 and via NKG2D. Of note, ex vivo NKp46+CD3- cells were able to kill autologous TAF; in vivo, this might represent a control mechanism to reduce TAF-mediated regulatory effect on NK cell function. Altogether, these findings suggest that MSC from the neoplastic mucosa (TAF) of CRC patients can downregulate the immune cell recognition of CRC tumor cells. This immunosuppression can be relieved by the anti-EGFR antibody used in CRC immunotherapy.

Delirium, Frailty, and Fast-Track Surgery in Oncogeriatrics: Is There a Link?

BACKGROUND/AIMS: Postoperative delirium (POD) is more frequent in elderly patients undergoing major cancer surgery. The interplay between individual clinical vulnerability and a series of perioperative factors seems to play a relevant role. Surgery is the first-line treatment option for cancer, and fast-track surgery (FTS) has been documented to decrease postoperative complications. The study sought to assess, after comprehensive geriatric assessment (CGA) and frailty stratification (Rockwood 40 items index), which perioperative parameters were predictive of POD development in elderly patients undergoing FTS for colorectal cancer. METHODS: A total of 107 consecutive subjects admitted for elective colorectal FTS were enrolled. All patients underwent CGA, frailly stratification, Timed up & go (TUG) test, 4AT test for delirium screening, anesthesiologists physical status classification, and Dindo-Clavien classification. RESULTS: The incidence of POD was 12.3%. Patients' prevalent clinical phenotype was pre-frail. The multivariate analysis indicated physical performance (TUG in seconds) as the most significant predictor of POD for each second of increase. CONCLUSIONS: Only few procedure-specific studies have examined the impact of FTS for colorectal cancer on POD. This is the first study to investigate the risk factors for POD, in a vulnerable octogenarian oncogeriatric population submitted to FTS surgery and frailty stratification.

Zoledronate can induce colorectal cancer microenvironment expressing BTN3A1 to stimulate effector γδ T cells with antitumor activity.

Amino-bis-phosphonates (N-BPs) such as zoledronate (Zol) have been used in anticancer clinical trials due to their ability to upregulate pyrophosphate accumulation promoting antitumor Vγ9Vδ2 T cells. The butyrophilin 3A (BTN3A, CD277) family, mainly the BTN3A1 isoform, has emerged as an important structure contributing to Vγ9Vδ2 T cells stimulation. It has been demonstrated that the B30.2 domain of BTN3A1 can bind phosphoantigens (PAg) and drive the activation of Vγ9Vδ2 T cells through conformational changes of the extracellular domains. Moreover, BTN3A1 binding to the cytoskeleton, and its consequent membrane stabilization, is crucial to stimulate the PAg-induced tumor cell reactivity by human Vγ9Vδ2 T cells. Aim of this study was to investigate the relevance of BTN3A1 in N-BPs-induced antitumor response in colorectal cancer (CRC) and the cell types involved in the tumor microenvironment. In this paper, we show that (i) CRC, exposed to Zol, stimulates the expansion of Vδ2 T lymphocytes with effector memory phenotype and antitumor cytotoxic activity, besides sensitizing cancer cells to γδ T cell-mediated cytotoxicity; (ii) this effect is partially related to BTN3A1 expression and in particular with its cellular re-distribution in the membrane and cytoskeleton-associated fraction; (iii) BTN3A1 is detected in CRC at the tumor site, both on epithelial cells and on tumor-associated fibroblasts (TAF), close to areas infiltrated by Vδ2 T lymphocytes; (iv) Zol is effective in stimulating antitumor effector Vδ2 T cells from ex-vivo CRC cell suspensions; and (v) both CRC cells and TAF can be primed by Zol to trigger Vδ2 T cells.

The effect of preoperative chemoradiotherapy on lymph nodes harvested in TME for rectal cancer.

BACKGROUND: Adequate lymph nodes resection in rectal cancer is important for staging and local control. This retrospective analysis single center study evaluated the effect of neoadjuvant chemoradiation on the number of lymph nodes in rectal carcinoma, considering some clinicopathological parameters. METHODS: A total of 111 patients undergone total mesorectal excision for rectal adenocarcinoma from July 2005 to May 2012 in our center were included. No patient underwent any prior pelvic surgery or radiotherapy. Chemoradiotherapy was indicated in patients with rectal cancer stage II or III before chemoradiation. RESULTS: One-hundred and eleven patients were considered. The mean age was 67.6 yrs (range 36 - 84, SD 10.8). Fifty (45.0%) received neoadjuvant therapy before resection. The mean number of removed lymph nodes was 13.6 (range 0-39, SD 7.3). In the patients who received neoadjuvant therapy the number of nodes detected was lower (11.5, SD 6.5 vs. 15.3, SD 7.5, p = 0.006). 37.4% of patients with preoperative chemoradiotherapy had 12 or more lymph nodes in the specimen compared to the 63.6% of those who had surgery at the first step (p: 0.006).Other factors associated in univariate analysis with lower lymph nodes yield included stage (p 0.005) and grade (p 0.0003) of the tumour. Age, sex, tumor site, type of operation, surgeons and pathologists did not weight upon the number of the removed lymph nodes. CONCLUSION: In TME surgery for rectal cancer, preoperative CRT results into a reduction of lymph nodes yield in univariate analisys and linear regression.

Primary omental torsion: A case report.

A patient presented with an acute abdomen at the Emergency Department. The patient, a 69-year-old man, was admitted and underwent surgery with a provisional diagnosis of acute appendicitis. During surgery, omental torsion was diagnosed and the involved omentum was removed. The patient had no previous surgical history. Omental torsion is a rare cause of acute abdomen in children and adults who may present with various signs and symptoms; a preoperative diagnosis may therefore be difficult and can usually only be established during surgery.

Factors that influence 12 or more harvested lymph nodes in resective R0 colorectal cancer.

BACKGROUND/AIMS: The number of lymph nodes required for accurate staging is a critical component in colorectal cancer (CRC). Current guidelines demand at least 12 lymph nodes to be retrieved. Results of previous studies were contradictory in factors, which influenced the number of harvested lymph nodes. This study was designed to determine the factors that influence the number of harvested lymph nodes (> or = 12) in resective R0 early-stage CRC in a single institution. METHODOLOGY: Between July 2005 and December 2008, data on 225 patients who underwent surgery for CRC were retrospectively evaluated. Data for a total of 139 R0-surgery patients were collected and all the tumor-bearing specimens were fixed with node identification performed. Several possible factors that influence 12 or more harvested lymph nodes were investigated and classified into four aspects: (1) operating surgeon, (2) examining pathologist, (3) patient (age, sex, and body mass index) and (4) disease (tumor localization, tumor cell differentiation, tumor stage, type of resection). RESULTS: A total of 100 patients (71.9%) with 12 or more harvested lymph nodes and 39 patients (28.1%) with < 12 lymph nodes were analyzed. The results demonstrate that within a single institution, tumor localization, depth of tumor invasion according to Dukes stage and grading were independent influencing factors of 12 or more harvested lymph nodes. Neither the operating surgeon nor the examining pathologist had significant influence on the number of harvested lymph nodes. CONCLUSIONS: The number of harvested lymph nodes was highly variable in patients who underwent resection of R0 CRC. Neither the operating surgeon nor the examining pathologist had significant influence over the number of harvested lymph nodes. Therefore, from the viewpoint of the surgeons, disease itself is the most important factor influencing the number of harvested lymph nodes.

Colon and rectal surgery for cancer without mechanical bowel preparation: one-center randomized prospective trial.

BACKGROUND: Mechanical bowel preparation is routinely done before colon and rectal surgery, aimed at reducing the risk of postoperative infectious complications. The aim of the study was to assess whether elective colon and rectal surgery can be safely performed without preoperative mechanical bowel preparation. METHODS: Patients undergoing elective colon and rectal resections with primary anastomosis were prospectively randomized into two groups. Group A had mechanical bowel preparation with polyethylene glycol before surgery, and group B had their surgery without preoperative mechanical bowel preparation. Patients were followed up for 30 days for wound, anastomotic, and intra-abdominal infectious complications. RESULTS: Two hundred forty four patients were included in the study, 120 in group A and 124 in group B. Demographic characteristics, type of surgical procedure and type of anastomosis did not significantly differ between the two groups. There was no difference in the rate of surgical infectious complications between the two groups but the overall infectious complications rate was 20.0% in group A and 11.3% in group B (p .05). Wound infection (p = 0.18), anastomotic leak (p = 0.52), and intra-abdominal abscess (p = 0.36) occurred in 9.2%, 5.8%, and 5.0% versus 4.8%, 4.0%, and 2.4%, respectively. No mechanical bowel preparation seems to be safe also in rectal surgery. CONCLUSIONS: These results suggest that elective colon and rectal surgery may be safely performed without mechanical preparation.

Urachal tumour: case report of a poorly understood carcinoma.

BACKGROUND: Urachal carcinoma is an uncommon neoplasm associated with poor prognosis. CASE PRESENTATION: A 45-year-old man was admitted with complaints of abdominal pain and pollakisuria. A soft mass was palpable under his navel. TC-scan revealed a 11 x 6 cm tumor, which was composed of a cystic lesion arising from the urachus and a solid mass component at the urinary bladder dome. The tumor was removed surgically. Histological examination detected poor-differentiated adenocarcinoma, which had invaded the urinary bladder. The patient has been followed up without recurrence for 6 months. CONCLUSION: The urachus is the embryological remnant of urogenital sinus and allantois. Involution usually happens before birth and urachus is present as a median umbilical ligament. The pathogenesis of urachal tumours is not fully understood. Surgery is the treatment of choice and role of adjuvant treatment is not clearly understood.

Complicated small-bowel diverticulosis: a case report and review of the literature.

Here we report a case of a 60 years old woman who came to the Emergency Department of San Martino Hospital suffering from abdominal pain for about a week with high fever in the last 24 hours. The final histological examination led to the diagnosis of ileal diverticulosis associated with perforation and peritonitis with a fibrotic reaction involving the last ileal loop, the caecum and the appendix.

Small bowel metastasis from primary neuroendocrine small cell lung carcinoma.

Small bowel metastases from a primary lung carcinoma are rare. We report a case of a 76-year-old male with a primary neuroendocrine small cell carcinoma of the lung, treated by chemotherapy, who developed fever and bowel symptoms (subocclusion and pain). On CT examination, he was found to have a tumour in the small bowel. The patient then underwent abdominal surgery. At operation we found small bowel occlusion by neoplasia and we therefore resected 15 cm of ileum with a side-to-side anastomosis. Early recognition of this rare condition is important due to the fact that complicated intestinal metastases from lung carcinoma can lead to high mortality rates and poor short-term outcomes. With advances in chemotherapy and palliative care, patients with metastatic lung carcinoma can sometimes survive more than a year with a reasonable quality of life.