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Hepatocellular carcinoma (HCC) is the most common type of liver cancer with a high mortality rate worldwide. The percentage of HCC patients with vascular invasion is high. However, tumor thrombus in the hepatic vein (HVTT) has a lower incidence than tumor thrombus in the portal vein (PVTT). Conventionally, HCC patients with HVTT are treated the same as HCC patients with PVTT and offered sorafenib or other systemic agents. However, according to recent studies, it is evident that HCC with HVTT shows different outcomes when classified into different subgroups. In this review, we discuss the recent progress and changes in treatment of HCC with HVTT.

Background The purpose of the study was to evaluate the diagnostic value of gamma‐glutamyl transpeptidase to alkaline phosphatase ratio (GAPR) combined with gamma‐glutamyl transpeptidase to aspartate aminotransferase ratio (GAR) and alanine aminotransferase to aspartate aminotransferase ratio (AAR) in alpha‐fetoprotein (AFP)‐negative hepatocellular carcinoma (HCC). Methods A total of 925 AFP‐negative patients, including 235 HCC patients, 213 chronic hepatitis (CH) patients, and 218 liver cirrhosis (LC) patients, as well as 259 healthy controls were enrolled in this study. The differences of laboratory parameters and clinical characteristics were analyzed by Mann–Whitney U or Kruskal–Wallis H‐test. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of GAPR, GAR, and AAR in AFP‐negative HCC (AFP‐NHCC) patients. Results GAPR, GAR, and AAR were important parameters closely related to AFP‐NHCC. The combination of GAPR, GAR, and AAR was most effective in differentiating AFP‐NHCC group from control group (AUC = 0.875), AFP‐negative CH group (AUC = 0.733), and AFP‐negative LC group (AUC = 0.713). GAPR combined with GAR and AAR exhibited a larger AUC than single ratio or pairwise combination for distinguishing AFP‐NHCC group with TNMⅠstage, BCLC stage A, and tumor size less than 3 cm. The diagnostic value of GAPR combined with GAR and AAR was higher in AFP‐NHCC and was also reflected in the TNM stage, Barcelona Clinic Liver Cancer (BCLC) stage and tumor size. Conclusions GAPR combined with GAR and AAR were effective diagnostic markers of AFP‐NHCC, especially in patients with good liver function, early stage or small size., Gamma‐glutamyl transpeptidase to alkaline phosphatase ratio combined with gamma‐glutamyl transpeptidase to aspartate aminotransferase ratio and alanine aminotransferase to aspartate aminotransferase ratio were effective diagnostic markers of alpha‐fetoprotein‐negative hepatocellular carcinoma, especially in patients with good liver function, early stage or small size.

Most patients diagnosed with hepatocellular carcinoma (HCC) have advanced diseases, and many are not eligible for curative therapies. There is growing evidence suggesting that the combination treatment of PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (TKIs) is becoming a prospective trend for advanced HCC. For those HCC patients with sorafenib resistance, the efficacy of regorafenib combined with PD-1/PD-L1 inhibitors remains unclear. Herein, we represent a case of HCC with lung metastasis in the setting of Hepatitis B virus (HBV)-induced liver cirrhosis responding dramatically to the sequential treatment with regorafenib followed by PD-1 inhibitor after initial liver resection. A 51-year-old man diagnosed with alpha fetoprotein (AFP)-negative HCC underwent liver resection in September 2015 and was found to have solitary liver recurrence and multiple lung metastases in March 2017. He received microwave coagulation therapy (MCT) and trans-arterial chemoembolization (TACE) for liver tumor and treatment was started with sorafenib 400 mg twice daily for controlling lung metastases. In December 2018, an abdominal computerized tomography (CT) scan showed two new lesions in the liver. In March 2019, disease progression of lung metastases was measured and he received 160 mg regorafenib once daily. After a short period of partial response, in December 2019, due to the progression of the disease, he started treatment with regorafenib 160 mg in combination with sintilimab (PD-1 inhibitor) (200 mg, 3 weeks as a cycle). Surprisingly, after five cycles of sintilimab injection, he showed complete response in target lesions. There was no clinical evidence of disease progression, and the side-effects were mild. The current overall survival (OS) is 58 months. Data from this clinical case report suggest that sequential treatment with regorafenib followed by PD-1 inhibitor is a promising therapeutic option for sorafenib-refractory cases of HCCs., Video abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/9Hw8vlnbtNA

Severity of liver cirrhosis plays an important role in determining the safe extents of hepatectomy in patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate whether direct liver stiffness measurement can help surgeons to evaluate the severity of liver cirrhosis in HCC patients. Overall, 119 HCC patients who underwent open hepatectomy were retrospectively studied. The severity of liver cirrhosis was histologically staged using the Laennec staging system. Direct liver stiffness measurement was performed during operation using a sclerometer device named LX-C Shaw hardmeter, and its efficacy in assessing the severity of liver cirrhosis was compared with that of transient elastography (TE) and cirrhotic severity scoring (CSS) previously proposed by our team. Liver stiffness measured by LX-C Shaw hardmeter was significantly correlated with the severity of liver cirrhosis. Spearman correlation coefficients for the correlation between the severity of liver cirrhosis and direct liver stiffness measurement, TE, and CSS were 0.751, 0.454, and 0.705, respectively (all P

Hepatocellular carcinoma (HCC) is usually associated with varying degrees of cirrhosis. Among cirrhotic patients with solitary HCC in the absence of macro-vascular invasion, whether tumor size drives prognosis or not after hepatectomy remains unknown. This study aimed to investigate the prognostic impact of tumor size on long-term outcomes after hepatectomy for solitary HCC patients with cirrhosis and without macrovascular invasion. A total of 813 cirrhotic patients who underwent curative hepatectomy for solitary HCC and without macrovascular invasion between 2001 and 2014 were retrospectively studied. We set 5 cm as the tumor cut-off value. Propensity score matching (PSM) was performed to minimize the influence of potential confounders including cirrhotic severity that was histologically assessed according to the Laennec staging system. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after PSM. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival. These results were further confirmed in the PSM cohort of 235 pairs of patients. In cirrhotic patients with solitary HCC and without macrovascular invasion, tumor size may significantly affect the prognosis after curative hepatectomy.

Summary: Background: Portal hypertension (PH), which is closely associated with the severity of liver cirrhosis, has been suggested as a contraindication of liver resection for hepatocellular carcinoma (HCC). We aimed to explore the role of a potential player, histologic severity of liver cirrhosis, in affecting surgical outcomes of the patients with both HCC and PH. Methods: A total of 374 HCC patients with PH underwent resection for HCC were retrospectively reviewed. By using the Laennec staging system, the patients were divided into two groups: the mild-moderate cirrhosis (MMC) group and the severe cirrhosis (SC) group. Propensity score matching (PSM) was conducted at a 1:1 ratio between the two groups, and 89 patients were matched for each group. Short-term and long-term outcomes were compared between two groups before and after PSM. Results: The overall morbidity and 30-days mortality were significantly higher in the SC group than the MCC group (52.9% vs. 30.1%, P

Severity of liver cirrhosis is distinct from clinical portal hypertension because there exist different degrees of liver cirrhosis in hepatocellular carcinoma (HCC) patients without significant clinical portal hypertension. Whether severity of cirrhosis affects surgical outcomes for HCC patients in absence of portal hypertension or not remains unclear. This study aims to analyze the effect of cirrhotic severity on surgical outcomes for HCC patients with hepatitis B virus (HBV) infection in absence of portal hypertension. This retrospective study enrolled 166 patients who underwent curative resection for a single HCC ≤5 cm in absence of portal hypertension between February 2011 and December 2013. Liver cirrhosis was sub-classified into no/mild (no/F4A) and moderate/severe (F4B/F4C) according to the Laennec scoring system. The surgical outcomes and complications were analyzed. The surgical mortality was zero in this study. Major complications were apparently higher in the F4B/F4C group than in the no/F4A group (17.0% vs 7.4%, p <0.001). The 1-year, 3-year and 5-year overall survival (OS) rates were 98.5, 88.1 and 80%, respectively, in the no/F4A group, which were significantly higher than those in the F4B/F4C group (98.0, 69.2 and 54.7%, p = 0.001). Microscopic vascular invasion, absence of tumor capsule and severity of liver cirrhosis were independent risk factors of surgical outcomes for HCC patients without portal hypertension. In conclusion, severity of liver cirrhosis affected surgical outcomes for early-stage HCC patients independent of portal hypertension.

Although liver resection (LR) and liver transplantation (LT) are widely considered as potentially curative therapies for selected patients with hepatocellular carcinoma (HCC); however, there is still high risk of tumor recurrence in majority of HCC patients. Previous studies demonstrated that the presence of microvascular invasion (MVI), which was defined as the presence of tumor emboli within the vessels adjacent to HCC, was one of the key factors of early HCC recurrence and poor surgical outcomes after LR or LT. In this review, we evaluated the impact of current MVI status on surgical outcomes after curative therapies and aimed to explore the surgical strategies for HCC based on different MVI status with evidence from pathological examination. Surgical outcomes of HCC patients with MVI have been described as a varied range after curative therapies due to a broad spectrum of current definitions for MVI. Therefore, an international consensus on the validated definition of MVI in HCC is urgently needed to provide a more consistent evaluation and reliable prediction of surgical outcomes for HCC patients after curative treatments. We concluded that MVI should be further sub-classified into MI (microvessel invasion) and MPVI (microscopic portal vein invasion); for HCC patients with MPVI, local R0 resection with a narrow or wide surgical margin will get the same surgical results. However, for HCC patients with MI, local surgical resection with a wide and negative surgical margin will get better surgical outcomes. Nowadays, MVI status can only be reliably confirmed by histopathologic evaluation of surgical specimens, limiting its clinical application. Taken together, preoperative assessment of MVI is of utmost significance for selecting a reasonable surgical modality and greatly improving the surgical outcomes of HCC patients, especially in those with liver cirrhosis.

Liver resection (LR) is the primary treatment method for patients with hepatocellular carcinoma (HCC). Improving surgical safety and reducing surgical morbidity and mortality is important for patients receiving LR. Various devices have been developed to facilitate vascular transection to reduce intraoperative blood loss, which is considered to be a predictor of poor surgical outcomes in patients undergoing LR. Vascular staplers have been widely applied for the division of major vascular and biliary structures in the process of LR; however, when and how to use these tools remains controversial. This review aims to report the rationality and necessity of using vascular staplers in vessel transection during liver surgery. Due to the risk of intraoperative and postoperative hemorrhage and biliary fistula, the process of transection of the portal pedicle and hepatic vein is a crucial step during LR. Stapling represents a vascular dissection technique that is widely used in laparoscopic LR and has then been popularized in open LR. Advocates argue that stapler transection methods provide several advantages, including diminished blood loss, fewer transfusion requirements and shorter operative times. However, other studies have failed to demonstrate those benefits when using these tools compared with the simple clamp-crushing technique. Using the stapler vascular transection method resulted in smaller surgical margins and similar surgical outcomes compared with those of the clamp-crushing vascular transection method. However, the intraoperative use of vascular staplers may significantly increase the financial burden of liver resection for patients with HCC, while not improving short- and long-term outcomes. Therefore, it has been suggested that vascular staplers should not be routinely used in LR. The current review discussed the above points and recommended that the stapling transection of the portal pedicle and hepatic vein should be applied during laparoscopic LR in a rational manner. However, the suturing ligation method should be routinely used in open LR.

Background: Inflammatory Pseudo Tumor (IPT)-like Follicular Dendritic Cell (FDC) Sarcoma of the liver is a very rare disease and occurs mostly in the lymph nodes. Till now, only 19 cases were reported in the English literature. However, the coexistence of IPT-like Sarcoma and Non-Hodgkin’s Lymphoma(NHL) in the same patient has never been reported.Case presentation: We reported a case of a 47-year-old male patient who had a history of Hepatitis B virus (HBV) infection and presented with right upper abdominal discomfort. Nineteen years ago, he underwent liver resection of segment VII for Hepatic Non-Hodgkin Lymphoma (B-cell lymphoma). Serum alpha fetoprotein (AFP) level was normal. However, Imaging studies revealed a well-circumscribed, solid mass in the right hepatic lobe and was diagnosed as (Hepatocellular Carcinoma) HCC or Hepatic Lymphoma preoperatively. Right hemi-hepatectomy was performed on this patient. Histological report showed features of a mixture of chronic inflammatory cells and variable amounts of spindle cells. Also, Immuno-Histo-Chemical (IHC) studies demonstrated that all the tumor cells showed strong nuclear in situ labeling for EBV-encoded small RNAs (EBER) and strongly positive stainings with CD21 and CD35. The patient is still disease free after a follow-up of 40 months. Conclusions: To our knowledge, this is the first report demonstrating Hepatic IPT-like FDC Sarcoma in a patient with Primary Hepatic Non-Hodgkin Lymphoma history. In regards to treatment, complete surgical resection should be performed and would acquire excellent long-term outcomes.

Background Evaluating cirrhotic severity is essential for individualizing surgical modalities for patients with hepatocellular carcinoma (HCC). Our previous study proposed a non-invasive method named cirrhotic severity scoring (CSS) to stage liver cirrhosis. Indocyanine green retention rate at 15 min (ICG-R15) has been widely used for the preoperative evaluation of hepatic functional reserve; however, whether ICG-R15 is well correlated with cirrhotic severity, and especially whether comparable with CSS in predicting cirrhotic severity in HCC patients with Child-Pugh grade A liver function remains unknown. Methods Overall, 510 HCC patients with Child-Pugh grade A liver function undergoing hepatectomy between January 2011 and December 2014 were retrospectively studied. Cirrhotic severity was pathologically assessed using the Laennec staging system. The correlations between ICG-R15, CSS, and cirrhotic severity were analyzed. Furthermore, the performance of ICG-R15 and CSS in predicting posthepatectomy liver failure (PHLF) and 90-day mortality was compared. Results Patients with no, mild, moderate, and severe cirrhosis accounted for 15.9%, 29.2%, 35.9%, and 19.0%, respectively, in the entire cohort. ICG-R15 was found to be less than 10% in 100%, 93.3%, 86.3%, and 70.1% of the patients with no, mild, moderate, and severe cirrhosis, respectively. There was only a weak correlation between ICG-R15 and the pathological severity of liver cirrhosis (r = 0.325; P < 0.001). However, CSS showed a strong correlation with the pathological severity of liver cirrhosis (r = 0.788; P < 0.001). For those with ICG-R15 in the normal range, the accuracy of CSS in diagnosing no/mild, moderate, and severe cirrhosis was 89.1%, 72.8%, and 72.1%, respectively. In addition, CSS was superior to ICG-R15 in predicting PHLF and 90-day mortality. Conclusions CSS was more useful than ICG-R15 in the preoperative assessment of cirrhotic severity in HCC patients with Child-Pugh grade A liver function. More studies are needed to further validate CSS in patients with different Child-Pugh grades.

Rationale: Hepatic inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a very rare disease. Till now, only 19 cases were reported in the English literature. However, the coexistence of IPT-like sarcoma and non-Hodgkin lymphoma (NHL) in the same patient has never been reported. In this report, we presented a case of hepatic IPT-like FDC with hepatic NHL history of which both were successfully resected. Patient concerns: We reported a case of a 47-year-old male patient who presented with right upper abdominal discomfort. Nineteen years ago, he underwent liver resection of segment VII for hepatic NHL (B-cell lymphoma). He had a history of chronic hepatitis B virus infection. Serum alpha fetoprotein level was normal. However, imaging studies revealed a well-circumscribed, solid mass in the right hepatic lobe, he came back to the clinic because he was worried about a recurrence of the B-cell lymphoma. Diagnoses: Based on the patient's past medical history and magnetic resonance imaging results, and he was diagnosed as hepatocellular carcinoma or hepatic NHL preoperatively. Interventions: Right hemi-hepatectomy was performed on this patient. Outcomes: Histological report showed features of a mixture of chronic inflammatory cells and variable amounts of spindle cells. Also, immuno-histo-chemical studies demonstrated that all the tumor cells showed strong nuclear in situ labeling for EBV-encoded small RNAs and strongly positive stainings with CD21 and CD35. The patient tolerated the surgery well, recovered smoothly and he was discharged on postoperative day 7 (day 7). The patient is still disease free after a follow-up of over 50 months. Conclusions: To our knowledge, this is the first report demonstrating hepatic IPT-like FDC sarcoma in a patient with primary hepatic NHL history. In regards to treatment, complete surgical resection should be performed and would acquire excellent long-term outcomes.

Liver resection is the mainstay of treatment for patients with hepatocellular carcinoma and compensated cirrhosis. We investigated the relationship between the morphologic severity of cirrhosis and post-hepatectomy liver failure (PHLF) and evaluated the role of cirrhosis staging in determination of the extent limit for liver resection.The clinicopathologic data of 672 consecutive patients with Child-Pugh grade A liver function who underwent curative liver resection for hepatocellular carcinoma in Tongji Hospital from 2009 to 2013 were retrospectively reviewed. Severity of cirrhosis was staged morphologically and histologically. Risk factors for histologic cirrhosis and PHLF were analyzed. The extent limit of liver resection with reference to morphologic staging was studied.Morphologic and histologic stages were significantly correlated (τ = 0.809, P0.001). Multivariate analysis showed that morphologic staging was the most crucial factor for histologic cirrhosis (odds ratio = 26.99, 95% confidence interval = 16.88-43.14, P0.001) and PHLF (odds ratio = 11.48, 95% confidence interval = 6.04-21.82, P0.001). The incidence of PHLF was high in patients with mild cirrhosis after resection of four or more liver segments (13.6%), those with moderate cirrhosis after major resection (38.1%), and those with severe cirrhosis or severe portal hypertension after resection of two or more liver segments (63.2% and 50.0%, respectively).Morphologic severity of cirrhosis is an independent predictor of PHLF. Resection of fewer than four liver segments is justified in patients with mild cirrhosis. Major resection is not recommended in patients with moderate cirrhosis. In patients with severe cirrhosis or severe portal hypertension, only resection of fewer than two liver segments can be safely performed.

Background The optimum operative treatment for early hepatocellular carcinoma (HCC) in patients with compensated liver function remains controversial. This study aimed to assess the impact of the severity of cirrhosis on survival after liver resection (LR) and to determine the importance of the severity of cirrhosis in operative decision-making for early HCC. Methods The records of 307 patients with HCC with a solitary tumor ≤5 cm undergoing either LR or liver transplantation (LT) were reviewed retrospectively. The Child–Pugh class A patients in the LR group were stratified according to the severity of cirrhosis. Survival of each subgroup was compared with that of the LT group. Results Both the recurrence-free survival (RFS) and disease-specific survival (DSS) in the LR group were worse than those in the LT group. Stratification of the Child A patients in the LR group yielded 5-year RFS and DSS rates of 71% and 86%, respectively, for the cirrhosis-free subgroup, 58% and 79% for the mild cirrhosis subgroup, and 25% and 45% for the moderate/severe cirrhosis subgroup. There were no differences in the rates of RFS and DSS between either the cirrhosis-free or mild cirrhosis subgroup and the LT group, whereas the subgroup with moderate/severe cirrhosis had poorer RFS and DSS rates than the LT group. Conclusion LR is the best treatment for early HCC in patients without cirrhosis or with mild cirrhosis and compensated liver function, whereas LT is recommended for those with moderate/severe cirrhosis, even if their liver function is well compensated.

Rationale Portal vein thrombosis is defined as any thrombosis that develops in the portal vein system. It is considered a very rare and extremely lethal complication of hepatopancreatobiliary surgery. Patient concerns Acute portal vein thrombosis after hepatectomy in patients with hepatolithiasisis very rare. Acute portal vein thrombosis is considered as a dangerous complication after hepatectomy. It is easy to ignore the symptom of acute portal vein thrombosis. Once the appropriate time of treatment is past, it would lead to patients' death. Diagnose Acute portal vein thrombosis after hepatectomy in a patient with hepatolithiasis INTERVENTIONS:: We consider anticoagulation therapy and percutaneous transhepatic portal vein puncture and thrombectomy once the diagnosis of acute portal vein thrombosis is confirmed. Outcomes The patient's liver function continued to deteriorate, eventually resulting in death. Lessons Acute portal vein thrombosis after hepatectomy is difficult to diagnose. The management of acute portal vein thrombosis remains controversial according to its severity, location or time of discovering.

Background Severity of liver cirrhosis plays a vital role in determining an appropriate surgical strategy for HCC treatment. However, preoperative evaluation of the severity of cirrhosis has not been established in a surgical setting. This study aims to develop a model to predict the severity of cirrhosis. Methods Overall, 604 patients with hepatocellular carcinoma (HCC) and hepatitis B virus–related cirrhosis undergoing liver resection from Jan 2005 to Jun 2013 were randomly divided into either the model building group ( n = 304) or the test group ( n = 300). The severity of cirrhosis of the resected specimens was pathologically staged according to the Laennec scoring system, which sub-classified cirrhosis into either stage F4A, F4B, or F4C. Results A logistic regression analysis showed that varicosity, portal vein diameter, spleen thickness, and platelet count were significantly associated with the histologic sub-classification of cirrhosis in the model building group. Based on these four parameters, a scoring model for predicting the severity of cirrhosis was established. The model was then verified in the test group, the areas under the ROC (AUROC) for predicting mild (F4A), moderate (F4B), and severe cirrhosis (F4C) were 0.861 (95% confidence interval [CI], 0.810-0.911), 0.860 (95% CI, 0.819-0.901), and 0.968 (95% CI, 0.951-0.985), respectively. The accuracy of this model in predicting mild, moderate, and severe cirrhosis is 79.3%, 81.0%, and 85.3%, respectively. Conclusions By using this model, the severity of cirrhosis can be reliably staged preoperatively, which will provide more information on cirrhotic livers in surgical settings for the treatment of hepatitis B virus–related HCC.

Rupture of hepatocellular carcinoma (HCC) releases tumor cells and furthers peritoneal metastasis. The present study investigated the killing effects of distilled water (DW) on HCC cells and the clinical outcomes of patients undergoing liver resection with DW lavage for spontaneously ruptured HCC. Human HCC cells (BEL-7402, SMMC7721) were treated with DW, the morphological changes observed, and cell viability measured. DW-treated HCC cells were also injected intraperitoneally into nude mice, and the formation of tumor nodules and overall survival (OS) measured. The clinicopathological data of 141 consecutive patients undergoing liver resection for spontaneously ruptured HCC during 1998–2011 were retrospectively reviewed. Fifteen minutes of DW exposure caused complete cell lysis of HCC cells in vitro and completely prevented tumor formation and prolonged survival time in nude mice. Among the 141 patients, the 1-, 3-, and 5-year disease-free survival (DFS) and OS rates in patients administered DW lavage during surgery were 68.9, 24.6, and 6.6 %, respectively, and 95.1, 65.1, and 40 %, respectively, which were significantly higher than those in patients who did not (P

Hepatocellular carcinoma is the third leading cause of cancer-related death in the world, and cirrhosis is the main cause of hepatocellular carcinoma and adversely affects surgical outcomes. Liver resection, liver transplantation, and local ablation are potentially curative therapies for early hepatocellular carcinoma (HCC). There exists an obvious histological variability of severity within cirrhosis which has different clinical stages. For patients with Child-Pugh B cirrhosis and/or portal hypertension and HCC within Milan criteria, consensus guidelines suggest that liver transplantation is the best treatment of choice; liver resection is widely accepted as first-line treatment for patients with early-stage HCC and preserved liver function; and local ablation is the treatment of choice in patients with small tumors who are not candidates for surgery or can be used as a temporary treatment during the waiting period for transplantation. For patients with compensated cirrhosis or Child A cirrhosis, the selection of surgical modality based on subclassification of cirrhosis remains unclear. This review examines the current status of the selection of surgical modality for hepatocellular carcinoma treatment in cirrhotic patients and aims to emphasize the effects of the severity of cirrhosis on the selection of surgical modality for the treatment of hepatocellular carcinoma.